Ncm 104 Lecture Notes

NCM 104 DERMATOLOGIC DISORDERS I. REVIEW OF THE INTEGUMENTARY SYSTEM SKIN – also known as the integument which means covering – largest organ system – barrier between external and internal environment FUNCTIONS OF THE SKIN 1) Protection – protects from trauma (Mechanical, Radiation, Thermal) – thickened skin on palms and soles provides additional covering against trauma r/t constant use – Intact skin – primary defense (prevents invasion of microorganisms) – secretions(from sebaceous gland) are oily and slightly acidic (prevents/limits the mult. of mcgs) 2) Maintenance of Homeostasis prevents excessive loss of water and electrolytes 3) Thermoregulation – affected by: > production of perspiration (dehydration fever) > activity > constriction (v dissipation of heat) and dilation of blood vessels > external BT -body’s core temperature 4) Reception of stimuli – area in the brain – SOMATOSENSORY CORTEX â₠¬â€œ abundance of free nerve endings and receptors * NOCICEPTOR – pain * END-ORGAN OF RUFFINI/PACINIAN CORPUSCLE – pressure * MECHANORECEPTOR – machanical * MEISSNER’S CORPUCLES (MERKEL DISCS/CELLS) – touch 5) Synthesis of vitamin D – helps the uptake of Ca2+ and PO4 in intracellular level with the aid of sunlight activates Vitamin D to D3 (Cholecalciferol) 6) Immunity/processing of antigenic substances – immunologically mediated defenses against microorganisms Ex. Langerhans cells Keratinocytes 7) Provide an outward appearance or cosmetic adornment – acceptance of the appearance of the skin, hair, or nail is critical to psychosocial being 8) Excretion – skin has a vital role in elimination of Na+ and H2O for homeostasis (maintaining balance in the internal environment) STRUCTURES OF THE SKIN LAYERS OF THE SKIN 1) EPIDERMIS – avascular in nature – Thickness: 0. 04 mm (eyelids- thinnest) to 1. mm (palms and soles- thickest) 4 Cell types of the Epidermis a) Keratinocytes – 95% – Produces Keratin – insoluble protein – helps create a waterproof barrier – function in immunity – control water loss b) Melanocytes – located at the base of the epidermis – Produces Melanin – responsible for skin color and absorption of UV light – the darker you are, the more protection against cancer – acts as an umbrella covering that shields DNA from UV c) Merkel’s cell – It is located at the basal layer of the epidermis but can usually be located only with the use of an electron microscope – one of the receptors scarcely located in the palms, soles, oral and genital epithelium d) Langerhan’s cell – play a role in cell-mediated immune responses in coordination with T cell – originates in the bone marrow and migrates into the epidermis Layers of the Epidermis a) Stratum Germinativum/Basale â⠂¬â€œ innermost – cells are columnar in shape – where melanin is found in greatest amount – lies close to the dermis layer – cells at the basale layer receives nutrition from the dermis via diffusion and undergo mitosis every 19 days and older cells are pushed upward undergoing changes in shape and chemical composition through a process known as keratinization ) Stratum Spinosum – cells are irregularly-shaped known as prickle cells (have sharp cytoplasmic projection at the covering) c) Stratum Granulosum – cells are nucleated granular cells which contain keratohyalin granules (contain lipids with desmosomal connections which helps to form waterproof barrier) water loss from the body *not responsible for water loss in the pores d) Stratum Lucidum – thin transparent layer Skin moisture-can only be seen in thick skin like the palms and soles immunity e) Stratum Corneum – composed of dead keratinized cells (contain keratin -acidic in nature) – serves as a durable overcoat of the body DESQUAMATION – natural process of breaking apart of dead skin cells; for every 35-35 days, an individual will have a new epidermal skin Epidermal Appendages a) Eccrine glands – sweat-producing gland – thermoregulation – can be found throughout the skin but with some exemptions – numerous on palms, soles, axilla and forehead – not found in: Vermillion border(junction of the pink area of lips surrounding skin) Lips, Ears, Nailbeds, Glans penis,Labia minora b) Apocrine glands – function is not clearly known – abundant in the axilla, breast, areola, anoogenital area, ear canal, and eyelids c) Sebaceous glands release of sebum (has lubricating and bactericidal effect) – can be found all throughout the skin except on the palms, soles, and axilla d) Hair – a non-viable protein end-product – found in all skin surfaces except palms and soles e) Nails †“ horny scales of the epidermis 2) DERMIS – a dense-layer of tissue beneath the epidermis – gives the skin most of its substances and structures – 1—4 mm (thickest dermis is found in the back) – has characteristics for: ->WOUND HEALING: because it contains fibroblast, macrophages, mast cells, lymphocytes -> MAINTENANCE OF EQUILIBRIUM: because it contains lymphatic, vascular, and nerve supply Layers of the Dermis a) Papillary Layer -upper dermal region with finger-like projections -contains: >papillary loops (provide nutrients to the epidermis) >Pain receptors b) Reticular Layer – deepest skin layer – contains BV, sweat glands, and deep pressure receptor (Pacinian corpuscles) – abundant phagocytes are located – as one ages, depleted collagen and elastic fibers -collagen for TOUGHNESS OF EPIDERMIS – Elastic fiber for SKIN ELASTICITY 3) SUBCUTANEOUS FAT/ HYPODERMIS – AKA adipose layer – Functions: * S ource of energy * Hormone metabolism * Insulation from extreme hot and cold Cushion to trauma -specialized layer of connective tissue -absent in the: eyelids, scrotum, areola, tibia ASSESSMENT OF CLIENTS WITH INTEGUMENTARY DISORDERS A) SUBECTIVE DATA HISTORY TAKING – assess for pre-existing factors 1) Chief complaint (if Derma conditions already exists) – Assessment on itchiness, dryness, rashes, lesions, ecchymosis, lumps & mass – Changes in skin, hair, and nails – Onset of the condition – Other accompanying symptoms with known cause (pain, fever, swelling, redness) – Alleviating factor such as cold weather 2) Past Health History – Hx of previous derma disease Previous trauma and symptoms; interventions – Other systemic illnesses relevant to the skin such as immunologic, endocrine, vascular, renal, or hepatic conditions – Age of onset – Particular season/month of the year – Treatment done – Immuniza tion status – Recent exposure to insects/childhood diseases 3) Known exposure to communicable disease (school, neighbourhood) 4) Travel to foreign countries/places – possible environmental factors that the patient is exposed to Ex. Poison ivy 5) Medications currently being taken/ has recently finished – Photosensitivity drugs- causes sunburn-like rashes in areas of exposureEx. Phenothiazides Tetracyclines Diuretics Sulfonamides – topical preparations containing derivatives of ingredients which are known as sensitizing Ex. Neomycin Ethylaminobenzoate/ benzocaine Diphenhydramine HCl 6) Occupation and recreational activities – exposure to irritants and chemicals either in the home or environment Ex. Prolonged exposure to the sun Unusual cold exposure 7) Allergies – medications or foods – assess if after ingestion, complains of itchiness, burning, or eruption of rashes – substances that cause local, skin irritations/lesions with di rect contact Ex. Textile, Metal (Ni), Wool Allergic reaction could trigger skin discoloration & eruption of rashes, skin irritation *oral corticosteroids which may cause Acne breakouts, Thinning of the skin, Stretch marks, and Other systemic manifestations if this is used at high dose or routinely 8) Family health history – Family lifestyle and living environment – Genetically transmitted Derma conditions such as: * Alopecia * Psoriasis * Atopic dermatitis – Systemic diseases with derma manifestations such as: * DM * LE * Blood dyscrasia 9) Habits (the patient as an individual) – hygiene practices – products/cosmetics use – changes in clothing or bedding diet (sufficient intake of nutrients like H2O, vitamins and dietary fats) -Exercise -Sleep patterns which affect circulation, nourishment, and repair of the skin B) OBECTIVE DATA – appraise the entire skin surface on head-to-toe including oral mucosa – appraise thoroughly †“ use INSPECTION, PALPATION, OLFACTION PHYSICAL APPRAISAL 1) Color – areas of irregular pigmentation (hypo/hyperpigmentation) – Paleness/pallor – Cyanosis – Jaundice – Assess sclera for a very dark person 2) Texture – palpation (stroke the patient with the fingertips lightly to assess texture) – NORMAL: Smooth, Soft, Resilient, No areas of lumps, No unusual hickening/thinning 3) Moisture – hydration level of the skin for both wetness(Fluidity) and oiliness(Sebum) – assess INTERTRIGINOUS AREAS (parts which have skin-to-skin contact like axilla & groin) – NORMAL: Well-hydrated but not excessively moist 4) Temperature – use the dorsum of the hand – compare hypothermia/hyperthermia with the area on the opposite side – NORMAL: uniformly warm 5) Turgor – skin’s elasticity – the time it takes for the skin and underlying tissue to return to its original contour after being pinch ed up (usually on the abdominal area) -older individuals: v skin turgor – NORMAL: 3 sec ) Odor – NORMAL: free from pungent odors – usually present in the axilla, skin folds, open wounds related to presence of bacteria in the skin 7) Presence and characteristics of Lesions MANIFESTATIONS OF SKIN DISORDERS 1) LESIONS PRIMARY LESIONS– first lesions to appear on the skin and has a recognizable structure in response to some changes in the external and internal environment A. Erythema – redness and inflammation (skin/mucous membrane) – result of dilation and congestion of superficial capillaries – Ex. Nervous blush, Sunburn B. Macule – unelevated change in color – flat – 1mm-1cm – circumscribed Ex. Freckles, measles, petechiae, flat moles PATCHES – larger than 1 cm and may have irregular shape – Portwine birthmarks, Vitiligo (White Patches) C. Papule – small, circumscribed, solid elevation, 1 mm-1cm – Ex. Warts, Acne, Pimple, Elevated moles D. Vesicle – circumscribed round or oval – thin translucent mass – filled with serous fluid or blood – 1mm-1cm – Ex. Herpes simplex, Early chicken pox, Small burn blisters E. Bullae – Large blisters (larger than vesicle) – Ex. 2nd degree burn, Herpes simplex (Big) F. Pustule – Vesicle or bullae filled with pus – Ex. Acne vulgaris, Impetigo G. Nodule elevated solid hard mass that extends deeper into the dermis than a papule – have a circumscribed border – 2cm – irregular border – Ex. Malignant melanoma, Hemangioma I. Wheal – reddened localize collection of edema fluid – irregular in shape – varies in size – Ex. Hives, Mosquito bites J. Plaque – raised lesion formed from merging of papules and nodules – >1cm – Ex. Psoriasis, Rubeolla K. Cyst – elevated, encapsulated, fluid-filled mass arising from SC tissues – 1cm or larger – Ex. Sebaceous cyst, Epidermoid cyst L. Comedo – accumulation of sebum and keratin within a hair follicle – occurs due to clogging 2 types: Open comedo (black head) Closed comedo (white head) M. Telangiectasia – permanent dilation of capillaries in the skin SECONDARY LESIONS – develop/occur if changes occur in the primary lesions – relate to client’s health status, environment, & status of the epidermal layer – possible causes: Scratching, Rubbing, Medications, Natural disease progression, Process of involution or Healing A. Crust (SCAB) – a rough dry area formed by the coagulation of drying plasma or exudates – could be a dried sebum, serum, blood, or pus on skin surface producing a temporary barrier to the environment – Ex. Impetigo, Eczema, Healing of burns/LesionsB. Scales – dried fragments of sloughed epidermal cells – irregular in shape an d size – colors vary from White, Tan, Yellow, to Silver -Ex. Dandruff, Dry skin, Psoriasis C. Ulcer – depressed lesion in which entire epidermis and upper layer of dermis are lost – could be due to trauma or tissue destruction – irregular in shape and exudative – Ex. Stasis ulcer D. Fissure – deep linear split through epidermis into dermis – Ex. Tinea pedis E. Scar – Mark left on skin after healing F. Hyperkeratotic Plaque (Callus/ â€Å"Kalyo†) – excessive thickness of the epidermal layer caused by chronic friction or pressure ) PRURITUS – unpleasant skin sensation that provoke the desire to scratch – Skin, Certain MM, Eyes, Perineum, Nostril, External ear canal – r/t mechanical stimulation of chemical mediator – r/t systemic disease – Chicken pox, Severe liver disease, DM , Uremia 3) PAIN – stimulation of Nociceptor 4) SWELLING – due to release of chemical mediato rs 5) REDNESS – due to hyperemia 6) SYSTEMIC ss – fever (release of pseudothermoregulators), leucocytosis (^WBC) DIAGNOSTIC TESTS 1) LAB TEST a. Tzanck smear – Named after Arnault Tzanck – Aka Chickenpox test/ Herpes skin test A microscopic assessment of fluid and cells from vesicles or bullae – Top of vesicle is cut with the use of scalpel then a smear is taken from the base of vesicle using the scalpel – Differentiates vesicular disorders – may identify a virus (-) reaction – vesicle from burns (+) H. Simplex or Acantholytic cells; varicella virus; multinucleated giant cells b. KOH test – done if the causative agent is suspected to be a fungus – the specimen (smear) is treated with 10-20% of KOH before microscopic study Normal or (-) result shows no Fungi (No dermatophytes/yeast) c. Culture – done to identify the specific microorganisms to determine specific antibiotic treatment 2) SKIN BIOPSY – ex . Dermal punch biopsy – a sample of skin tissue is removed, processed, & examined under a microscope – 4 types: 1. Excision Biopsy – entire skin area is cut 2. Punch Biopsy – a small cylinder of skin is removed 3. Shave biopsy – outermost part of a lesion is shaved off with a scalpel 4. Aspiration biopsy – indicated for fluid-filled lesion 3) WOOD’S LIGHT EXAMINATION – Skin is viewed under UV light through a special glass (Wood’s glass ) to identify superficial infections of the skin – Place the patient in a dark room before examination 4) SKIN TESTING used to identify substances causing the allergy – 3 ways: 1. Scratch test – aka Puncture/Prick test – Pricking the skin 2. Intradermal test – Similar to Tuberculin test *DURATION OF TEST FOR BOTH SCRATCH AND INTRADERMAL TEST IS 5-10 MINS OR 15 MINS 3. Patch Test – the allergen is placed on a patch then placed on the skin – D uration: 48 hours (2 days) 4 TYPES OF HYPERSENSITIVITY REACTIONS TYPE I (ANAPHYLACTIC/IMMEDIATE HYPERSENSITIVITY) – may involve the skin (disorders such as urticarial or eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea/ rhinitis), bronchopulmonary tissues (asthma), GIT (gastroenteritits) rxn may range from minor inconveniences to death (r/t bronchopulmonary constriction-vO2) – takes 15 to 30 minutes from the time of exposure – delayed onset of type I = 10 to 12 hours – mediated by Ig E – primary cell components : Mast cell and Basophil TYPE II (CYTOTOXIC HYPERSENSITIVITY) – may affect variety of organs and tissues – reaction time: minutes to hour after exposure – mediated by Ig G and Ig M – ex. Drug-induced haemolytic anemia Granulocytopenia Thrombocytopenia TYPE III (IMMUNE-COMPLEX HYPERSENSITIVITY) – the type of reaction is considered as GENERAL – ex. Serum sickness may involve individual organ suc h as the skin (SLE and Arthus reaction), kidneys, lungs, blood vessels and joints – reaction time: 3 to 10 hours – mediated by soluble immune complexes particularly Ig G TYPE IV (CELL-MEDIATED/ DELAYED TYPE) – ex. Mantoux test (PTB test), PPV test, tuberculin test – 48 to 72 hours (2 to 3 days) II. SKIN DISORDERS A. DERMATITIS/ECZEMA – Inflammation of the epidermal layer – Rashes are characterized by itching and redness Types: I. Contact Dermatitis – Inflammatory reaction either caused by Allergens or Irritants – utilize PATCH TEST to identify the cause – 2 TYPES BASED ON ETIOLOGY: Irritant Contact Dermatitis – Most common – There is no allergic reaction but there is inflammation that occurs because of either a PHYSICAL or CHEMICAL IRRITANTS – Manifestations: > Lesions appear sooner > Appear on exposed areas – Ex. Mechanical (glass fiber, wool) Chemical (cleaning compounds, perfume) Physical ( clothing, stuff toy) * Allergic Contact Dermatitis – A Delayed type (TYPE 4) of hypersensitivity rxn from contact with allergens – Immune-mediated response by previously sensitized Lymphocytes to specific antigen (allergen) – Ex. Drugs (Penicillin, Sulfonylamides) Metals (Nickel)Spandex Rubber Bra – MANAGEMENT OF CONTACT DERMATITIS: 1. Topical corticosteroids – use BID for 2 weeks – causes thinning of the skin 2. Oral Antibiotics – if lesions develop into 2’ lesion or if 2’ infection sets in 3. Oral Antihistamines, Topical Antipruritic agents, Colloid oatmeal baths – to control itching – NURSING INTERVENTIONS 1. Avoiding irritants and sensitizing substances 2. Wear appropriate clothing 3. Wear gloves 4. Use mild soap products II. Atopic Dermatitis – Genetically-based skin disorder that is both chronic and relapsing ( bec. it involves type 1 rxn) – Strongly linked with asthma and hay fever Most common in children Immunologic irregularity (Cytokines and inflammatory mediators) v Vasoconstriction of Superficial vessel v vProtective barrier function of the skin – FOCUS OF NURSING CARE in managing atopic dermatitis is geared toward addressing the social and emotional disturbances and sleep pattern disturbance – EXACERBATING FACTORS: * Change in temperature COLD – Dry skin HOT – Vasodilation > Inflammation> Itching & Redness * Other irritants * Physiologic Stress – direct stress to the area * Exercise – loss of H2O > Dryness – MANAGEMENT OF ATOPIC DERMATITIS (SYMPTOMATIC ONLY; NO CURE): 1. Hydrating the Skin Cornerstone of management – Apply moisturizer 3-4x a day to reestablish hydration of the S. corneum 2. Corticosteroid a. Systemic b. Topical * – Educate on: * Proper Application (Only apply to area being affected) * Duration of Use (BID X 2 weeks) * Side effects: Thinning of the skin Jeopardizing the immune sys tem – Application of WET WRAPPINGS – To enhance absorption and – Helps decrease pruritus 3. Protopic ointment (tacrolimus); pimecrolimus (Elidel) – IMMUNOMODULATORS (block T cell activation) – Indication: Moderate to Severe atopic dermatitis – Side effects: Itching, Burning, Irritation for few days Avoid sunlight/ artificial sunlight for prolonged periods (photosensitivity rxn) 4. Antihistamines – for itchiness 5. Antibiotic – if secondary infection sets in III. Seborrheic Dermatitis – Eczematous eruptions typically occur in hairy areas – Sebaceous gland in which there is an increase amount and alteration in the quality of sebum/serum – Usually occurs on Scalp, Eyebrow, Central chest, Face, Genital skin fold – PREDISPOSING FACTORS: 1. Family history of skin diseases 2. Winter months – symptoms usually worsen (drying effect) 3. Over growth of yeast organisms ( secondary to fungal infection) Inf lammatory changes Around sebaceous glands and hair follicles) v Red, greasy scales (Characteristic symptom > scale) – MANAGEMENT: 1. Mild – Tar, Selenium, Zinc, or Ketoconazole shampoo preparations > Have antibacterial effect on the normal flora found at the hair follicles 2. Chronic – Topical corticosteroids > To flatten thick, scaly plaques (SCALP) – Low potency topical steroids/ topical antifungal agents (FACIAL) IV. Stasis Dermatitis – Eczematous eruption common in lower extremities occurring in older persons – PREDISPOSING FACTORS: 1. Varicosities (venous insufficiency) 2. Poor circulation vVenous return (From legs) Substances remain in the tissues v Irritation, brawny colored skin associated with edema v Itching (May or May not occur) v Scratches v Break in the epidermis (Stasis ulcer) v 2’ infection – MANAGEMENT (prevention of predisposing factors): 1. Treatment of peripheral vascular conditions 2. Prevent constriction o f the circulation 3. Treat lower extremity edema * Elevate lower extremity (CI: Cardio/Pulmonary problems) * Compression stockings * Unna boots (bandage application on the lower extremities) 4. Topical corticosteroids – To address itching and scratches V. Lichen Simplex Chronicus Usually occurs in the Wrist, Ankles, and Back of the skull (Easily reached) – A localized, well-circumscribed eczematous eruption caused by repeated rubbing and scratching – Aka ITCH-SCRATCH CYCLE – PREDISPOSING FACTOR: Stress where scratching becomes habitual and worse at NIGHT – elephant skin B. ACNE – An inflammatory disease of sebaceous follicle marked with comedone, macules, and papules TYPES: I. Acne Vulgaris – Occurs on the Face, Neck, Upper chest, & Buttocks – Common among adolescents (80%) & may occur in adults – PREDISPOSING FACTORS: 1. Stress (activation of hormone production) 2.Heredity (familial tendency of androgen imbalance) 3. En docrine (hormonal imbalances) 4. Diet (free fatty acids) Puberty [^Androgen] (Sebaceous glands undergo enlargement) v Produce sebum v Binds with debris (Keratin, Bacteria, Cell fragments) v Plug hair follicle v Comedo (open/close) v Inflammation (Papules, Pustules, Nodules, Cyst) – MANAGEMENT: 1. Topical Benzoyl Peroxide Retinoids Retinoid-like drugs such as Adapaline, Tretinoids, Azeleic acid Antibiotics such as Clindamycin, Erythromycin, & Sulfa-based agents *Don’t self-medicate 2. Systemic Antibiotic – indicated for inflammatory acne lesionsIsotretinoin (Accutane) – vitamin A analog – Side effx: Dry lips & conjunctiva, and skin hairloss, muscle ache, photosensitivity, mood disturbance – prevents pregnancy, ^Risk of birth defects 3. Intralesional therapy – NURSING CARE: 1. Keep hands and hair away from face 2. Avoid exposure to oil and greases a. Eat well-balanced diet b. Wash face 2 or 3X a day with mild cleanser c. Use only water- based cosmetics II. Acne Rosacea – Characterized as a RED facial rash which mostly affect 30-60 y/o – It has both vascular and acne component – Chronic, localized eruption with vascular and acne characteristic – PREDISPOSITION: . Affects women more than men ( S/S is more severe in female) 2. Fair complexion individuals are more inclined 3. Familial predisposition – CHARACTERISTICS: 1. Red papules (sometimes pustules) – usually located on nose, forehead, cheeks, chin, rarely involves trunk and upper limbs 2. Blushing or flushing (â€Å"Red face†) – telangiectasia 3. Dry and flaky facial skin 4. Enlarged unshapely nose with sebaceous hyperplasia (the pores will become prominent) and rhinophyma (fibrous thickening) 5. Eye symptoms – eyelid inflammation/ conjunctivitis *Appearance of Lesion: DOME-SHAPED (no black/white heads; no deep cyst/lumps) MANAGEMENTS: 1. Antibiotics (Tetracycline) including doxycycline and minocycline – Duration : 6-12 weeks – to reduce inflammation (redness, papules, pustules and eye symptoms) 2. Topical: metronidazole/ Azeleic acid cream or lotion – applied 2x a day directly to the affected area 3. Nutraceuticals / clonidine – ? -2 recepto agonists > reduce vasodilation > vflushing/redness in the area 4. Anti-inflammatory drugs (diclofenac) – to reduce discomfort and redness on the affected skin – NURSING INTERVENTIONS: 1. Avoid oil-based facial creams 2. Use water-based make-up 3. Never apply a topical steroid (to the rosacea) . Protect yourself from the sun. (Use light oil-free facial sunscreens) 5. Keep your face cool: minimize your exposure to hot or spicy foods, alcohol, hot showers and baths and warm rooms. C. PSORIASIS – A genetically determined, chronic, epidermal, proliferative, not curable dse *control fast cellular proliferation – aka PAPULO-SQUAMOUS LESION > scaly in characteristic – a chronic, recurren t, erythematous inflammatory disorder involving keratin synthesis – History: 1841 – Viennese dermatologist known as Ferdinand von Hebra coined the term psoriasis from Greek word â€Å"psora† which means â€Å"to itch† – INCIDENCE:Men and women are equally affected Occurs in all ages but is less common among children and elderly Commence at early adulthood (18-24) Increased incidence among Whites Decreased among Japanese, American Indians, West African origin – exacerbated by several factors – manifestations usually appear between 15 and 35 years old – CAUSE: unknown But with high link to alteration in cyclic nucleotide and possible immunologic abnormality – CONTRIBUTORY FACTORS: 1. Immune-mediated condition – The condition is believed to be caused by faulty signals in the body’s immune system – the body tends to overreact and accelerate the growth of skin cells the T cells abnormally trigger inflamma tion in the skin (accelerates skin cells to grow faster and to pile up on the outer surface of the skin> the skin does not desquamate but piles up) *Normally, skin cells mature and sheds off every 28-30 days Cytokines (Lymphokines) v ^Platelet, Neutrophils, Basophils v Release of Histamine v Inflammation 2. Genetic – It has been appreciated by physicians that it occurs in families – high rates among monozygotic twins – known to be linked with inherited genes or other immune-mediated conditions – when both parents have psoriasis, a child may have 40% probability of developing the disease

The Appropriateness and Applicability of Behaviorism to Human Relations

The theoretical conceptualities of behaviorism cover the prime angle of behavioral perspective in aim of explaining the motives of action, rationale of attitude, and prime associates of human dimensions. The school of behaviorism covers the therapeutic interventions guided by objective and empirical approach. The concepts of behaviorism envelopes the diverse and dynamic character of human behavior that aims to discover possible patterns and links that may further organize human actions.Various theoretical frameworks that govern the behavioral concept have provided an approach to explain human actions. The theories that have aroused in this firm are Pavlov's classical conditioning, Watson's learned neuroses, and B. F. Skinner's operant conditioning, which are the skeletal backbone of behavioral perspective. With further application of the said conceptual pattern, noted limitations have also been observed. Behavior involves gradual statutory progression, which can be learned and unlear ned through suggested behavioral patterns.By learning these behavioral cues, one may possess the capabilities of predicting the probable angles of action that enhances human relations. According to the theoretical framework of Ivan Pavlov, creatures including humans possess the capacity to form their behavioral pattern through reconditioning, which popularly known as the framework of classical conditioning. Pavlov has started his experiment on the behavioral paradigm, which clearly involves animal subjects and their cravings for their needs.Nature justifies that creatures possess their necessities in order to maintain living, while classical conditioning proves that certain stimuli are triggered in response to these needs, and possess modifiability that depends on the dynamic nature. Another theoretical framework proposed is John Watson’s neuroses and behavioral modifications. 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Behavior theory maintains that human actions are initiated and developed through learning experiences.The major premise of behavior theory is that individuals change their behavior depending on the reactions it obtains from others: Behavior is supported by rewards and extinguished by negative consequence s or responses. The condition of the learned behavior is strengthened by reward and avoidance of punishment or weakened by lack of reward and aversive stimuli. Whether a given behavior pattern persists depends on the differential reinforcement – the rewards and punishments attached to that behavior and the rewards and punishments attached to alternative behavior.By the conceptual patterns of behaviorism school, the possibility of improving human relations could be present. As humans interact with each other, they utilize variant types of actions and attitudes that are primarily lead by their won behavioral aspect. Taking an example in the view of behavioral deviances, the conditioning of such deviant promotion modifies the personality of the person. These experiences include personally observing other individuals behaving erratically and aggressively to obtain some goal or watching people being rewarded for violent actions on television, movies or other media sources.People l earn to act aggressively when, as children, they model their behavior after the violent acts of adults. Later in life, these violent behavior patterns persist in social relationships. One example is a boy who sees his father repeatedly striking his mother with impunity is likely to become a battering parent and husband. As for human relations, the conditioning of behavior provides development of understanding on how people act and behave, which is essential especially in consideration of probable positive and negative actions.Taking behavioral perspective in account, the possibility of predicting the rationale for action, comprehension of reasons for action, and understanding of the personality of the person are all possible; hence, reducing chances of conflicts, and probable improvements of behavior through modification and conditioning. However, such theories propose limitations especially in the perspective of every individual’s unique character; since, cultural, upbringin g, and social environment varies among individuals. Human relation needs to consider as well other factors that influence behavior, such as physical, emotional, social, and cultural dimension.

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Good Country People by Flannery O'Conner - Essay Example The story begins with Mrs Hopewell's analysis of Mrs Freeman's limited facial expressions, but therein she reveals also the limits of her own thinking. Her thoughts of the Freemans are laced with some scorn, but she humors them because they are "good country people" and of use to her. Mrs Hopewell's daughter Hulga, who had lost her leg in a shooting accident, is openly rude to Mrs Freeman, but the good countrywoman was never troubled even by "a direct attack, a positive leer, blatant ugliness to her face." The author, however, does not attempt to present any rosy picture of country people. Mrs Freeman is shown to poke her very sharp nose into everything, with "a special fondness for the details of secret infections, hidden deformities, assaults upon children." Her children, Glynese and Carramae, whom Hulga secretly refers to as Glycerin and Caramel, have all the worst qualities of the girls of their age in the town, but the story is not primarily about the Freemans. The story line follows the thread of one particular 'good' country man's attitude to these city folk. The irony of his point of view is revealed in full only at the very end of the story.

Fairy Tales and Gender Roles Essay Example | Topics and Well Written Essays - 1500 words

Fairy Tales and Gender Roles - Essay Example They seem to brig inspiration to the reader or viewer of the fairy tale. Fairy tale stories are meant to describe a life that is none existent. Sometimes they show a legendary figure who emerged as a result of a historical event (Greenway, Jennifer, and Erin, 14). They are used as a teaching tool in schools and can bring about the much needed knowledge by students about how this came to be. Fairy tales do not usually focus outside certain aspects like places, people, and certain religion. They derive their story more from a certain time in life: in that they do not dwell on the present, instead, they are more of a past time in history. They are characterized by a beginning, â€Å"once upon a time†, and an ending, â€Å"†¦happily ever after† (Greenway, Jennifer, and Erin, 33). In this essay, attention will be focused on one of the most famous fairy tales, Snow White. This fairy tale teaches and shows a lot, despite being a fairy tale that is based on fantasy. This l iterary piece of writing contains certain attributes that relate to gender roles, values that are important to both sexes, the existence of evil and the influence that the fairy tale has on society. In the film, the house chores are done by a happy Snow White who entertains herself by singing loudly. Here, the film goes on to show that such a girl, who at the time is cleaning and cooking, is happy despite her work. She is in a joyful mood despite working for people who do not treat her in accordance to how she is supposed to be treated. At this point, it is safe to say that she is doing chores usually designed for a woman. From the cooking, doing the dishes and cooking, women play their role in society without questioning why they are doing it. Snow White, despite the jobs being tiresome, performs her duties without complaining (Greenway, Jennifer, and Erin, 15). She has come to understand her role in society. In society, women are bound to perform certain tasks in their homes, or i n places they live. It goes on to show that they have accepted that as their role and that it is them that should perform them. The film was produced during the great depression when women were not allowed to work in farms and industries, but were to stay at home and do house chores (Stahly and Robert, 97). The film depicts women values such as being industrious, dutiful and longsuffering by snow white way of living and handling issues. From this, a lesson can be learnt; that even though women play their roles since it is they that should, they have other characteristics that are bound to grow on other people. When Snow White accidentally came upon a cottage in the middle of the forest after being released by the queens’ servant, she goes in, at this point showing her curiosity, and falls asleep till she is discovered by the dwarves. Her curiosity brought upon her good fortune. It could have brought her disaster, since entering a house whose owner(s) is not present could lead to certain consequences. Meeting with the seven dwarves, playing her role in ensuring they ate at the required moment and cleaning, goes on a long way to show just how women’s roles fit into society. Traditional and modern society have one thing in common; in that the roles that each member of the opposite sex performs. Snow White shows how women are supposed to be like in

Business Ethics, Invisble Hand Essay Example | Topics and Well Written Essays - 750 words

Business Ethics, Invisble Hand - Essay Example A business's biggest interest is profit maximization. All businesses, be it a small-scale or a large corporation or enterprise, seek to maximize their profitability as much as they can. After and in accordance to this, a firm aims to minimize costs. It is not hidden that when businesses attempt to achieve these aims, they crush many ethical values such as responsibility to the society in the form of, perhaps, pollution control guidelines. They leave, to the society, negative externalities only so that they can earn profits. Under such circumstances, you cannot expect a business to care for the environment or the people around them. True, that firms satisfy our material needs and this does lead to the general good. But in providing us with these services and goods, they will do whatever it takes to get to that level of profit maximization and cost minimization. I do not think that the 'invisible hand' furthers us to greater public welfare because firms forget all about ethics when it comes to power and profits. To support this, let's take the example of California's power market. The electricity industry was freed of regulations so that competition could be promoted and that the invisible hand could work. However, the opposite happened. They failed to provide the service; there were blackouts and prices were also very high. The sellers kept developing new ways of abusing the system until the State intervened (Shaw, W.H., 2004). My second argument is that with globalization taking its toll increasingly and hence, with competition growing immensely, it has become extremely important for firms to maintain and raise their positions in the global market. One would think that competition increases efficiency, along with which, prices are decreased. In any case, the customer, or the society as a whole, benefits. However, this is not usually the case. Globalization emphasizes on competition, true. But as a result it creates awareness in the society, gives customer choices, makes them powerful and hence, demanding. All this put together, puts great pressure on a firm operating in the free global market. Mostly, an average customer is not going to think of buying from a firm who is socially responsible and who has value for ethical guidelines and how it treats its employees or competitors. A customer would want to buy from a firm who provides the good or service, they don't care how, they just want the service. This leads to many businesses sacrificing their ethical values and moving towards the bigger motive of profit earning. Many businesses today in third world countries, especially, adhere to such unethical practices. An example of the water industry in Pakistan can be taken. Such filthy water is provided in the homes of people than many suffer from diseases such as hepatitis, yellow fever etc due to this. Conclusion In the end, it is important to note that not all firms yield to such unethical practices and not all situations demand such practices. Today, 'going green' is also a way of earning profits. However, the arguments presented above do take place and the society is exploited as a result. There are both sides to the pictures. It is only up to the business

Sources of Demographic Data Case Study Example | Topics and Well Written Essays - 1000 words

Sources of Demographic Data - Case Study Example The demographic analysis may also encompass nationality, religion, education, and ethnicity (Murdock, 2006). All these elements are usually vital for the government for planning on different government developmental issues. Nonetheless, all the demographic data that are used in the analysis of population and its structure are usually obtained through numerous sources including census, administrative records, and surveys.  The population census is a collective process that used to collect, evaluate, analyze, compile, and publish data; otherwise, it is the disseminating demographics, social and economic data within a specific time to all persons in a country or within a well-delimited section or part of a country. Census usually involves the collection of data concerning every person within a set of living quarters in the whole country or part of a country. It usually allows estimates for small population and geographic or subpopulation to be used in the final tally (Murdock, 2006). Census processes are usually vital for their bass population figures that usually used to calculate fundamental rates, especially from the civil registration data. It also supplies sample surveys with sample frames. Additionally, censuses are usually vital for securing legislation requirements, political funding and supports, as well listing and mapping all the households. Therefore, census usually has structured steps including formulation of questionnaires that include all the areas of interest including age, sex, education, ethnicity, nationality, household information, and profession among other areas of interest. It is worth noting that census processes are usually complex and expensive. Moreover, not all information can be gathered using a single census period; thus, the questionnaires of any census period are usually designed differently in light of what the final users of the data are interested in.

Critical Review & Appraisal of one published Research Study Essay

Critical Review & Appraisal of one published Research Study - Essay Example Themes in the literature tend to lean toward identifying the consequences and causes of domestic violence (Johnson and Ferraro, 2000). Crime studies tend to demonstrate a bias in favour of women as the primary victims of domestic violence (Straus, 1999). The reality is however, that men are victims of domestic violence (Straus, 1999). In fact, the Home Affairs Committee (2009: 133) of the House of Commons commented that ‘men are the forgotten victims of domestic violence’. It is the reality that men are victims of domestic violence and the fact that the Home Affairs Committee acknowledged the neglect of male victims of domestic violence that prompted my interest in research on this subject. I selected a peer reviewed article by Dobash and Dobash (2004) because it provides empirical evidence of why much of the focus on domestic violence tends to be biased in favour of women as the primary victims. The research was based on a mixed methods approach involving 95 couples where both partners had reported violence against one another. This research is important to me because it helps me in my future career plans in social and community development by shedding light on the social construction of domestic violence as a problem primarily for women. The article selected is: Dobash, R.P. and Dobash, R. E. (2004). ‘Women’s violence to men in intimate relationships.’ British Journal of Criminology, 44: 324-349. In selecting the article by Dobash and Dobash (2004) I began by entering key terms in the search engine provided by several databases online. The databases selected were Jstor, Springer, Wiley, Google Scholar, Sage, Karger Open Access, Elsevier, Taylor & Francis Group, and Exlibris. I also conducted a general search of Google. The key words entered into the search engines were ‘domestic violence against men’, ‘domestic violence against men in the UK,’ ‘men as victims of domestic violence’ and ‘men as victims of domestic

Gender representations in The Big Bang Theory Essay

Gender representations in The Big Bang Theory - Essay Example This study aims at giving insight on how the use of gender representation is utilized in The Big Bang Theory to attract a large audience. As indicated by the title, this project explores the gender representations in The Big Bang Theory. There have been other studies about this subject too. However, what makes The Big Bang Theory a classical study is the controversial sexist position it adapts. This is the reason why this research aims at conducting a scientific inquiry on the unbalanced gender portrayal. One of the sets of questions that urgently require addressing is the relationship of discourses of gender in the media. For instance, what contributes to the popularity of The Big Bang Theory show notwithstanding the unsurpassed gender misrepresentation overriding in the show? This study will compare, contrast, investigate, examine, develop, and evaluate the subject matter. An proper indulgent of the facts contributing to the popularity of the show is quite significant as it would i ndicate the exact reasons as to why the various attempts to fight for egalitarianism have never been prolific. . It is beneficial to gain an appreciation regarding gender representations, the values and ideologies presented in The Big Bang Theory as this might aid in formulation and implementation of effective policies to circumvent the menace, change people’s psychological perspectives on gender and improve societal welfare and amalgamation.

Critique of a Speech or Presentation (or editorial Essay

Critique of a Speech or Presentation (or editorial - Essay Example conomy, education, health, and foreign affairs, and in maximizing pathos to appeal to the emotions of understanding and hopefulness, although his ethos is tarnished with the disconnection between his promises of jobs and the reality of unemployment and dissatisfaction with his policies and reforms. Obama effectively uses logos to help voters understand the difference between his vision and the Republican vision. He reminds voters that they have a responsibility in choosing the right vision, which can be attained through thinking reasonably about what Republicans had done in the past. As former leaders, their policies contributed to the 2008 recession. Obama asserts his vision early in his speech: â€Å"Ours is a fight to restore the values that built the largest middle class and the strongest economy the world has ever known† (1). He is saying that the Republican vision does not offer a tangible road to the protection of the middle class and economic development. He argues that Republican policies are unclear: â€Å"They want your vote, but they don’t want you to know their plan† (2). This is effective if the voters will appreciate that it is better to take a more tangible new road from Obama than an unknown, possibly repetitive road from Republicans. More over, Obama appeals to reason when he emphasizes that people should not go back to Republicans, who have been doing the same things: â€Å"And that’s because all they had to offer is the same prescription they’ve had for the last thirty years† (2). Obama effectively reminds people that his road to economic recovery is new and ongoing. Furthermore, Obama underlines the importance of moving on and not comparing his work with past Republican administrations. He jokes about the tax resolutions of Republican administrations: â€Å"Have a surplus? Try a tax cut. Deficit too high? Try another† (2). Obama influences voters to understand that he is moving away from these tested-and-failed actions. He will continue his

Furman v. georgia Essay Example for Free

Furman v. georgia Essay The death penalty or capital punishment has been part of our humanity for years and years. Existed since ancient times, according to people a person who has committed an atrocious act, was sentence to death penalty or capital punishment. The death penalty begins back in the 18th century B.C. in the code of king Hammaurabi of Baylon; who was accused of committing 25 crimes. In years past, the punishments where more crucial then today, the execution procedures had no boundaries, forms of killing where endless. Drowning, whacking, â€Å"damnatio ad Bestia† which was death cause by a wild animal, dismemberment: dividing the body into quarter-usually with an ax, throwing then off a high place, impalement: one of the most crucial consisting in beating them with a stick, buried alive, the guillotine: decapitation, wretch they refer as the â€Å"quick, clean and humane† way of doing the killing, death by torture, stoning crucifying was also consider a death penalty act. Jesus Christ was crucified in Jerusalem part of his punishment for being the son of God. Within times pass the process change a little to decapitation, execution, hanging, electrocution, execution by gas and the one use to date lethal injection. (1. History of death penalty) One of the cases that reach the Supreme Court and change the laws in the United States about the death penalty was the case of Furman v. Georgia in 1971. William Henry Furman claimed that his sentencing violated his rights guaranteed by the 14th amendment. (The 14th Amendment was passed after the American Civil War, and was designed to prevent states from denying due process and equal protection under the law to their citizens. And was dividing into sections: the first section of the amendment was to revolutionize federalism, stated that no state could â€Å"deprive any person of life, liberty, or property without due process of law; nor deny to any person within its jurisdiction. The equal protection of the laws, gradually the Supreme Court interpreted the amendment to mean the guarantees of the bill of rights apply to the states as well as the national government.) (2. Our documents) Furman’s v. Georgia: Furman was a 26year old man with very little education. A man that struggle his whole life about making a living, was very depressed and moody all the time there were days when he didn’t have anything to eat, and that’s when he started breaking into homes to be able to survive. He was caught a couple of times but was giving a light or suspended sentence. A psychiatrist had already diagnosed him with emotionally disturbed and mentally impaired. But was still entering homes in order to live. On August 11, 1967 Furman enter a home and was going through some things when he heard a noise and try to escape the home, some said he drop the gun and when it hit the ground it shot and others said he felt and the gun discharge killing Mr. William Joseph Micke Jr. a husband and father of 5 children. The death was truly a tragic, it was an accident that resulted in murder, and his carrying a gun was to protect himself in case or to even scare a person and be able to run without any incidents. Furman despite of his conditions was convicted of murder and sentence to death in a one day trial. Although Furman did not intend to kill the resident he regales committed murder during the commission of a felony, and was an aggravating factor, and the one in particular which made him eligible for the death penalty (3. Murderpedia) When the trial approached he pleaded not guilty by means of insanity, which was the advice of his appointed attorney. The court at that time order another psychiatric test and the physicians who examined agreed that he was mentally deficient and in the report they concluded that Furman experienced mild to moderate psychotic episodes associate with convulsive disorder. After a few weeks in a hospital assigned by the court, the Dr. said he knows what’s right from wrong and that he was competent to stand trial for murder. Although killing was an accident, the state of Georgia at the time authorized that the death penalty be giving weather a murder took place during the commission of a felony. Furman had one thing going against him at all times; he was a black man in the 60s and 70s and most blacks guilty of committing murder in that state was a reason enough to sentence to death penalty. In 1972 the case reach the Supreme Court which they rule 5-4 that the death penalty as then administered violated the 8th amendment proscription against cruel and unusual punishment and the 14th amendment equal protection clause. The courts typically issue the decision with a majority opinion written and sign by one of the justices. On occasion the court will issue a per curiam decision which takes the form of a brief, unassigned opinion. All 9 judges had different opinions, although 5 justices voted to reverse the death sentences, there concurring opinions revealed that it was shaky coalition. Each majority justice, Mr. Douglas, Mr. Stewart, Mr. White, Mr. Marshall, and Mr. Brennan, wrote a separate concurring opinion supporting the majority decision. Each believed that Furman had indeed been deprived of his constitutional rights. The justices could not agree on an argument striking down the death penalty across the board, however. This unusual procedure reflected not only the intense differences of opinion within the majority, but also the difficulty of deciding the constitutionality—or presumed lack thereof—of the death sentence. The four dissenters, Chief Justice Burger and Justices Blackmun, Powell, and Rehnquist, also wrote extensive opinions expressing their views against the majority opinion. Several argued taking the position of judicial restraint that the death penalty was a matter for the people to decide, through their legislatures. Others argued that emotional appeals were not appropriate in Supreme Court opinions. Finally, the dissenters were disturbed by the erosion of federalism and the unnecessarily invasive judicial activism practiced by the justices of the Warren Court. They said that it was disproportionally applied to the â€Å"poor and despised† that it was applied in an arbitrary and capricious fashion.† Justice Douglas was the man that came up with the idea to review the historic of the death sentence penalty for both America and England. This justice noticed that the laws was extremely unfair because it was applied only to the minorities, the outcast and the smaller population in the country. He decide that the death penalty was unusual and against Gods Plan. Furman centered on the convictions and death sentences of 3 African American men. His case ended changing the way they see each individual case. (4. Law Cornell My opinion on this case is that everyone should be treaty equally, his intent was to commit a crime of robbery not a murder. Unfortunaly we are all aware that the criminal justice system in the United States is imperfect and that we are aware of the flaws that exist within our system. I would of punished him with many years in prison but not the death penalty due to it wasn’t his intentions. Furman did not outlaw the death penalty. It just required states to prevent random, racial, unfair results by giving juries management to apply the death penalty fairly. After Furman, most states modified their death penalty laws. The new laws created a two-phase system for death penalty cases. In the first phase, the jury decides if the defendant is guilty of murder. In the second phase, the jury hears new evidence to decide if the defendant deserves the death penalty. The new laws gave juries guidance for making this decision. (1,2,3,4) Following the case of Furman v. Georgia in 1972, the Supreme Court ruled that the death penalty systems were unconstitutional violations of the Eighth Amendment’s prevention on â€Å"cruel and unusual† punishments. After this case many states changed their death penalty laws. Four years later in Gregg v. Georgia (1976), the Court reaffirmed the death penalty as constitutional. Troy Gregg had been found guilty of murder and armed robbery and sentenced to death. He asked the Court to go further than it had in the Furman case, and rule the death penalty itself unconstitutional. The Court refused to do so. The Court found that Georgia’s system for applying the death penalty was â€Å"judicious† and â€Å"careful.† Gregg had gone through two trials – one to determine guilt and one for sentencing. Further, specific jury findings of â€Å"aggravating circumstances† were necessary to impose the death penalty. There was therefore no Eighth Amendment violation, and the death penalty was constitutional. (5. Georgia encyclopedia/ 6. Lectlaw) Gregg v. Georgia took place on March, 1976. The case dealt with administrative law; this legal field controls the â€Å"due process† clause of the United States Constitution. The due process clause is defined as the government’s obligation to respect and uphold the legal rights of American people during and after they are arrested. Both the Federal and state governments are required to protect and preserve a person’s human rights and liberties. All governments of the United States are required to treat citizens in a fair and respectful manner during the arrest process. When he appealed his sentence as cruel and unusual and a violation of the Eighth Amendment, the US Supreme Court in a 7-2 decision upheld the sentence. The court ruled that the death penalty was an appropriate punishment in extreme criminal cases and that Georgia had settled appropriate values and other precautions to guide a jurys considerations in capital cases. He was sentence to death penalty do to the fact that he entered the house armed so he meant danger to the community and that his purpose was to commit the crime. The United States Supreme Court stated that the execution of Troy Leon Gregg was Constitutional due to the fact that Mr. Gregg was tried, head and sentenced through a formal judicial system. The night before he was supposed to be killed, Gregg escaped from prison and was killed in North Carolina following a fight. (7 law cornell) In this case the court upheld the constitutionality of the death penalty, defending statutes that guide judges and juries in the decision to issue the death sentence. The Court did, however, state that the madatory use of the death penalty would be prohibited under the Eighth Amendment as cruel and unusual punishment. The defendent in this case, Gregg, had been convicted on two counts of armed robbery and two counts of murder. The jury was instructed by the trial judge, who was following Georgia state law, to return with either a decision of life imprisonment or the death penalty. Justice Byron stated in his opinion that Gregg had failed in his burden of showing that the Georgia Supreme Court had not done all it could to prevent discriminatory practices in the forming of his sentence. This decision became the first time the Court stated that punishment of death does not invariably violate the Constitution. (8. Death penalty)

Impact of Boxer Rebellion on Chinas World Relations

Impact of Boxer Rebellion on Chinas World Relations What impact did the Boxer Rebellion have  on China’s relations with the rest of the world? The Boxer Rebellion instigated an unprecedented coordinated military response from international powers after The Righteous and Harmonious Fists more commonly known as the Boxers had mutilated and slaughtered thousands of Chinese Christian converts, Western missionaries and foreign nationals.[1] The atrocities occurred between 1898 and 1900 when the Boxers began targeting their perceived enemies in the Shandong region of China before spreading north to Beijing. The Boxers could not differentiate between the Christian missionaries’ desire to proselytise China’s peasants and forced westernisation. This paper contends that the Boxer Rebellion both wounded and opened relations between China and the outside world. Clearly, the discriminate violence of the Boxers shocked and angered the international community.[2] Therefore, far from achieving their objective of purging China from globalisation and the westernisation of Chinese peasants, it caused the world to hone in on Chin a. Inadvertently the Boxer Rebellion opened international relationships with China and the outside world. Countries like the United States refrained from argumentative dialogue and began to have meaningful diplomatic discussions with the Chinese government. Nevertheless, the Boxer Protocol, signed in 1901, seriously affected China’s relationship with the world. The protocol virtually bankrupted China’s economy. The Qing Dynasty was forced to pay three hundred and thirty three million United State dollars indemnity to foreign countries affected by the Boxer’s violence.[3] The Boxer Rebellion like the majority of insurrections has no narrative from the insurgents. The historiographies of rebellions are a combination of texts of victims, politicians, historians and other academics as in the case the Boxer Rebellion. The majority of eyewitness accounts are usually anonymous but reveal the harsh reality of death associated with insurrections. Cohen gives a perfect ex ample of this when he cites an eyewitness account of a Chinese individual who witnessed the scene of death during the Boxer Rebellion in Tianjing in 1900, the eyewitness describes the atrocities of the rebellion, they declare, ‘There are many corpses floating in the river. Some were without heads, others were missing limbs. The bodies of women often had their nipples cut off and their genitalia mutilated†¦ There were also bodies in shallow areas by the banks with flocks of crows pecking away at them. The smell was so bad we had to cover our noses the whole day. Still, no one came out to collect the bodies for burial. People said that they were all Christians who had been killed by the Boxers and the populace dare not get involved.’[4] Boyd contends that ‘most Westerners went to China to make money or to make converts.’[5] Neither reason was popular with the Righteous Harmonious Fists (Boxers). They viewed themselves as representatives of the Chinese peasantry and rigorously opposed all foreigners. Although, by the end of the nineteenth century, China’s population had reached three hundred and fifty million the majority of Chinese peasants had never encountered foreigners or Western missionaries.[6] Nevertheless, the Boxers held a strong belief that foreigners and Christian missionaries were responsible for the breakdown in the fabric of simple Chinese peasant society and they dishonoured their traditional spiritual and community. Furthermore, the Boxers attributed China’s natural disasters such as flood, drought and famine to the corruption of Christianity. Drought followed the great flood of the Yellow River in 1898 and left two million peasants starving and desperate. The Boxers a bott om up organisation without official leadership saw themselves as representatives of the peasantry in the Shandong region of northern China.[7] Likewise, the missionaries imposed power in the villages they occupied and they were involved in legal decision-making. The missionaries infuriated the Boxers even more because they were not just content to proselytise Christianity they also rejected Confucianism.[8] Harrison contends that the Boxers believed Catholic missionaries posed the greatest threat to Chinese morality. She argues that the Boxers targeted villages where the well-established Catholic missionaries had taken on the role of officials. The Boxers believed that because central government had failed to tackle the issue of village politics and moral issues they would take the law into their own hands.[9] However, this argument is neutralised by the excessive violence and murder of Catholics committed by the Boxers in the villages of central Shanxi.[10] The Boxers believed they were impervious to pain; they could withstand attack from both sword, and bullet. Their strange beliefs made them merciless fighters and a therefore a dangerous enemy of foreigners, Chinese Christian converts and missionaries. Even if their beliefs were well founded and justifiable, their methods of resolving their perceived problems were inexcusable and crude.[11] The Boxers fervent mystical beliefs are not a new phenomenon because allegedly, in preceding years Chinese peasants had experienced similar supernatural powers following natural disasters. Male peasants believed that they acquired special ‘religious’ spiritual powers to overcome the disasters.[12] However, the Boxers method of dealing with the threat was incomprehensible. Fleming’s contentious claim that at the beginning of the Boxer regime, ninety percent of the Boxers were just peasants in ‘fancy dress’ is debateable. However, he declares that as time went by thei r ‘sartorial costume’ of red and yellow turbans and sashes became less important and the majority of Boxers held strong political ideologies.[13] Following the suppression of the Boxer’s by the international counterinsurgency force,[14] each nation affected by Boxer violence sought retribution. However, some nations were less harsh than others were. For example, the United States highlighted this in their response. Secretary of State John Hay fearing China’s partition by European nations following the Boxer Rebellion issued a memorandum in July 1900 to those countries affected by the rebellion. Hay suggested that they should continue to support China’s ‘administrative and territorial integrity.’[15] In reality the United States were protecting their own trading interests in China. Furthermore, the United States practised a strict anti-imperialistic foreign policy.[16] However, the United States outward support of the Qing Dynasty was a contradiction of their policies towards Chinese immigrants. Ironically, the Chinese Exclusion Act 1882 and the Geary Act 1892 effectively prevented Chinese peop le from entering America.[17] After the suppression on the Boxer Rebellion, China supported American military presence in Beijing to repel any further rebellions following the defeat of the Boxers. The United States politely refused and withdrew from China in October 1900. The commander of the American counterinsurgency force stated, ‘Let us hope that this generous, charitable, and magnanimous treatment of the vanquished may prove an example to the nations of the world, and a step forward in the world’s progress toward a higher and nobler humanity. We are glad to know that this work is appreciated to you. It is needless to tell you, however, that the United States does not maintain an army for the purpose of furnishing the city of Peking with good municipal government, and as a business proposition your appeal for the United States forces to remain longer in Peking has little to stand upon.[18] Britain was slow to respond to the Boxer Rebellion.[19] However, retrospectively the Boxer Rebellion caused Britain to adopt a more vigorous foreign policy. Indeed, because of the inadequacies of the Prime Minister and Foreign Secretary Lord Salisbury in dealing with the Boxer Rebellion, the Conservative government made significant changes to the Diplomatic Service.[20] Sir Claude MacDonald the British minister in Beijing despite being fully aware of the Boxers violence against foreigners, Christian converts and missionaries in northern China refused to contemplate that the Boxer would spread across China.[21] Indeed, Otte contends that Britain’s blasà © attitude to the Boxer violence only changed after the siege of Beijing legation district that began on June 14th 1900. For fifty-five days, the Boxers laid siege to the square mile legation district in Beijing.[22] When the multilateral counterinsurgency force finally arrived in Beijing in August 1900, they displayed to the world for the first time that a sense of unity was possible. The multilateral force consisted of all the nations who had personnel in the legation. The force consisted of approximately twenty thousand troops. The Japanese were the dominant force with ten thousand troops. Japan demonstrated to China and the world that the importance of China was truly international and not just Eurocentric.[23] Furthermore, the multilateral force with the aim of rescuing the personnel and their families from the Beijing Legation district were given different instructions from their governments. German emperor Kaiser Wilhelm II commanded his troops to show no mercy to the Boxers after they had murdered the German Minister in Beijing Baron von Ketteler. The Kaiser declared to his troops before they left Bremerhaven, ‘Just as the Huns a thousand years ago, under the leadership of Attila, gained a reputation by virtue of which they still live in historical tradition, so may the name of Germany become known in such a manner in China, that no Chinese will ever again to look askance at a German.’ [24] Clearly, the Boxer Rebellion affected relations with Germany and this was borne out by the first point in the Boxer Protocol, it declared, ‘†¦Ã¢â‚¬ ¦.Prince of the First Rank, Chun, was appointed Ambassador of His Majesty the Emperor of China, and directed in that capacity to convey to His Majesty the German Emperor the expression of the regrets of His Majesty the Emperor of China and of the Chinese Government at the assassination of his Excellency the late Baron von Ketteler, German Minister†¦Ã¢â‚¬ ¦. The Chinese Government has stated that it will erect on the spot of the assassination of his Excellency the late Baron von Ketteler, commemorative monument worthy of the rank of the deceased, and bearing an inscription in the Latin, German, and Chinese languages which shall express the regrets of His Majesty the Emperor of China for the murder committed†¦[25] The first article of the Boxer Protocol clearly highlights China’s humiliation. Germany like other governments wanted to punish and embarrass China after the Boxer Rebellion. The proceeding articles in the protocol all required apologies, monument erections, the destruction of Chinese arms and fortresses, and the forfeiture of land to foreign powers.[26] However, as previously mentioned, the most damaging article in the protocol was the three hundred and thirty three million dollar indemnity with four percent interest. Undoubtedly, the multilateral troops took revenge on the Boxers and their supporters, Boyd contends that rumours of looting, rape, and torture committed by multilateral troops spread throughout Beijing. [27] Schoppa argues that the Boxer Protocol is the lowest point in Chinese international relations and their ultimate humiliation. The protocol signed on the 7th September 1901 between China and the Powers of Germany, Austria-Hungary, Belgium, Spain, United State s, France, Great Britain, Italy, Japan, Netherlands, and Russia was yet another unequal treaty that humiliated the Chinese government. The terms of the protocol not only restricted China’s domestic privileges, they increased foreign interests in China. Therefore, the fifty years of humiliation that began with China’s defeat in the Opium Wars extended into a new millennium. Therefore, the Boxer Protocol crippled Chinese spirit, economy and international prestige.[28] Although, the Boxer Rebellion and the consequent protocol severely damaged China domestically and their international reputation it instigated the dismantlement of their biggest burden, the corrupt Qing Dynasty. The Empress Dowager Cixi deceived the international community by pretending that her troops were suppressing the Boxers. However, the reality was that she despised foreign intervention as much as the Boxers did. She cleverly encouraged the Boxers to turn the Chinese peasantry and country against the foreigners. The Boxers declared ‘Support the Qing, destroy the Foreigners.’ Foreigners included missionaries and Chinese Christian converts. As Esherick contends, the Boxer Rebellion was not a true rebellion, as they did not oppose the Chinese Qing government.[29] The rebellion failed to resemble the excepted definition as ‘an organized armed resistance to an established ruler or government.’[30] Once the Qing dynasty realised that counterinsurgency would overthrow the Boxers they soon renounced their involvement so they could continue in the eyes of the West as a legitimate government.[31] However, inevitably the Boxer Rebellion demonstrates that China’s international relations were damaged by the more primitive actions the Boxers and the more sophisticated and sinister intervention of the Qing Dynasty.[32] In conclusion, the Boxer Rebellion clearly left an indelible mark on China both domestically and internationally. The ruthless action of the Boxers against foreigners, Chinese Christian converts, and missionaries was viewed by the outside world as unjustified and inexcusable. The Boxers clearly believed that they were acting in the best interests of peasants who made up the majority of the Chinese population. Their violent activities led to the Boxer Protocol in 1901 that almost bankrupted China through the huge financial reparations. The further articles of the protocol heaped further humiliation on China and allowed international powers access to prominent trading areas. However, arguably inadvertently the Boxer Rebellion prevented China from being colonised by major international powers. The Boxer Rebellion undoubtedly stirred the United States to intervene in order to save their trading rights in China. They sent a clear message to Britain, Germany, France, Italy, Japan, and Russ ia to support China’s administrative and territorial integrity. Furthermore, the Boxer Rebellion was the catalyst for disintegration of the dishonest Qing Dynasty. Although, the Qing Dynasty under Empress Dowager Cixi supported the Boxers it was not to protect the interests of China’s peasantry. Even though the Boxer Rebellion eventually instigated improved foreign diplomacy, it is indisputable that their actions not only led to the massacres of foreigners, Chinese Christians and missionaries it led to thousands of deaths of their own people. The international counterinsurgency forces showed no mercy when they exacted retribution on the Boxers and their sympathisers. The ease in which the Boxers and Imperial guard were defeated by the multilateral counterinsurgency forces compelled the Chinese government to modernise their military. The Boxer Rebellion reiterated the Eurocentric ideology that the Chinese are uncivilised. Furthermore, the rebellion alienated the western community from China even though it inadvertently improved international diplomacy and rid China of the corrupt Qing Dynasty that ultimately led to China becoming a republic in 1912. The ease in which the Boxers and Imperial guard were defeated by the multilateral counterinsurgency forces compelled the Chinese government to modernise their military. Bibliography Books Boyd, J., A Dance with Dragon. The Vanished of Peking’s Foreign Policy (London: I. B. Tauris Co. Ltd, 2012). Cashman, D., America in the Age of the Titans: The Progressive Era and World War I (New York: New York University Press, 1998). Cohen, Paul, in ‘Humanising the Boxers’, in Bickers, R. Tiedemann, R. (eds), The Boxers, China, and the World (Plymouth: Rowman Littlefield Publishers Ltd, 2007), pp. 179-197. Cullinane, M., Liberty and American Anti-Imperialism: 1898-1909 (New York: Palgrave MacMillian, 2012). Durschmeid, E,. Beware the Dragon, China: 1,000 Years of Bloodshed (London: Carlton Publishing Group, 2008). Esherick, J., The Origins of the Boxer Uprising (Oakland: University of California Press). Fleming, P., The Siege at Peking (Edinburgh: Birlinn Ltd, 2001). Harrison, Henrietta, in ‘Humanising the Boxers’, in Bickers, R. Tiedemann, R. (eds), The Boxers, China, and the World (Plymouth: Rowman Littlefield Publishers Ltd, 2007), pp. 1-15. Otte, Thomas, ‘Heaven knows where we shall finally drift’: Lord Salisbury, the Cabinet, Isolation, and the Boxer Rebellion’ in Kennedy, G. Neilson, K. (eds), Incidents and International Relations: People, Power, and Personalities (Connecticut: Praeger Publishers, 2002). Schoppa, K., The Columbia Guide to Modern Chinese History (New York: Columbia University Press, 2000). Seonnichsen, J., The Chinese Exclusion Act of 1882 (Santa Barbara: Greenwood Publishing Group, 2011). Spence, J., The Searching of Modern China (London: Century Hutchinson Ltd, 1990). Steiner, Z., The Foreign Office and Foreign Policy, 1898-1914 (Cambridge: Cambridge University Press, 1970). Journals Oulett, ‘Multinational counterinsurgency: the Western intervention in the Boxer Rebellion 1900-1901’ Small Wars Insurgencies. 20: 3.4 (2009): pp. 507-527. Radio broadcast Bragg, M., ‘The Boxer Rebellion’ In our Time. BBC radio 4 archive broadcast (21.30, 9 March 2009) Internet source ‘Rebellion.’ Oxford English Dictionary (03 April 2014). Available online: http://www.oed.com/view/Entry/159201?isAdvanced=falseresult=1rskey=nNKkrE Date accessed: 02 April 2014. ‘Boxer Protocol, 1901, Peace Agreement between the Great Powers and China 09/07/190’ (03 April 2014) Available online: http://china.usc.edu/(S(ivfmlzuvquerbb45edthpbze)A(irVj2QZVywEkAAAAYWQzZmNiZGMtZTBhNC00MDc1LTg5ZTItOGQ4OGU4MGI0NTk3Uo36FF2grKtLe_4GD64z6sKQqsw1))/ShowArticle.aspx?articleID=420 Date accessed: 03 April 2014 1 [1] Oulett, ‘Multinational counterinsurgency: the Western intervention in the Boxer Rebellion 1900-1901’ Small Wars Insurgencies. 20: 3.4 (2009): p. 511. [2] Durschmeid, E,. Beware the Dragon, China: 1,000 Years of Bloodshed (London: Carlton Publishing Group, 2008)p. 172. [3] Spence, J., The Searching of Modern China (London: Century Hutchinson Ltd, 1990), p. 235. [4] cited by Cohen, Paul, in ‘Humanising the Boxers’, in Bickers, R. Tiedemann, R. (eds), The Boxers, China, and the World (Plymouth: Rowman Littlefield Publishers Ltd, 2007), p. 186 [5] Boyd, J., A Dance with Dragon. The Vanished of Peking’s Foreign Policy (London: I. B. Tauris Co. Ltd, 2012), p. xvi. [6] Fleming, P., The Siege at Peking (Edinburgh: Birlinn Ltd, 2001), p. 36. [7] Bragg, M., ‘The Boxer Rebellion’ In our Time. BBC radio 4 archive broadcast (21.30, 9 March 2009) [8] Ibid. [9] Harrison, Henrietta, in ‘Humanising the Boxers’, in Bickers, R. Tiedemann, R. (eds), The Boxers, China, and the World (Plymouth: Rowman Littlefield Publishers Ltd, 2007), p. 12 [10] Harrison, Henrietta, in ‘Humanising the Boxers’, p. 7 [11] Oulett, ‘Multinational counterinsurgency: the Western intervention in the Boxer Rebellion 1900-1901’, p. 508. [12] Bragg, M., ‘The Boxer Rebellion’ In our Time [13] Fleming, The Siege at Peking, p.36. [14] Oulett, ‘Multinational counterinsurgency: the Western intervention in the Boxer Rebellion 1900-1901’, p. 508. [15] Cashman, D., America in the Age of the Titans: The Progressive Era and World War I (New York: New York University Press, 1998), p.436. [16] Cullinane, M., Liberty and American Anti-Imperialism: 1898-1909 (New York: Palgrave MacMillian, 2012), p. 4. [17] Seonnichsen, J., The Chinese Exclusion Act of 1882 (Santa Barbara: Greenwood Publishing Group, 2011), p. xiv. [18] cited in Oulett, ‘Multinational counterinsurgency: the Western intervention in the Boxer Rebellion 1900-1901’. p. 518. [19] Otte, Thomas, ‘Heaven knows where we shall finally drift’: Lord Salisbury, the Cabinet, Isolation, and the Boxer Rebellion’ in Kennedy, G. Neilson, K. (eds), Incidents and International Relations: People, Power, and Personalities (Connecticut: Praeger Publishers, 2002), p. 30. [20] Steiner, Z., The Foreign Office and Foreign Policy, 1898-1914 (Cambridge: Cambridge University Press, 1970), p. 180. [21] Otte, Thomas. ‘Heaven knows where we shall finally drift’: Lord Salisbury, the Cabinet, Isolation, and the Boxer Rebellion’, p. 26 [22] Otte, Thomas. ‘‘Heaven knows where we shall finally drift’: Lord Salisbury, the Cabinet, Isolation, and the Boxer Rebellion’, p. 29 [23] Bragg, M., ‘The Boxer Rebellion’ In our Time [24] Fleming, The Siege at Peking, pp. 135-136 [25] ‘Boxer Protocol, 1901, Peace Agreement between the Great Powers and China’ (09/07/1901). Available online: http://china.usc.edu/(S(ivfmlzuvquerbb45edthpbze)A(irVj2QZVywEkAAAAYWQzZmNiZGMtZTBhNC00MDc1LTg5ZTItOGQ4OGU4MGI0NTk3Uo36FF2grKtLe_4GD64z6sKQqsw1))/ShowArticle.aspx?articleID=420 Date accessed: 03 April 2014 [26] Fleming, The Siege at Peking, pp. 250-251 [27] Boyd, J., A Dance with Dragon. The Vanished of Peking’s Foreign Policy, p. 22. [28] Schoppa, K., The Columbia Guide to Modern Chinese History (New York: Columbia University Press, 2000), p. 171. [29] Esherick, J., The Origins of the Boxer Uprising (Oakland: University of California Press), p. xiv. [30] ‘Rebellion.’ Oxford English Dictionary. 2014, Available online: http://www.oed.com/view/Entry/159201?isAdvanced=falseresult=1rskey=nNKkrE Date accessed: 02 April 2014. [31] Ibid. [32] Esherick, The Origins of the Boxer Uprising, p. 312

Advanced Glycation End Products (AGE) for Diabetes

Advanced Glycation End Products (AGE) for Diabetes Diabetes mellitus is a syndrome which defined as a group of metabolic diseases characterized by hyperglycemia, that result from insufficient production of insulin, or body cells poorly respond to the insulin that is produced, or both. Insulin is a hormone produced in the pancreas and secreted in the blood to maintain blood glucose in the body through enables body cells to absorb glucose, to turn into energy. If the body cells enable to absorb the glucose, the glucose will accumulates in the blood (hyperglycemia), leading to many and different potential medical complications (Harmel Mathur, 2004). Diabetes have several categories but the majority of cases fall into two categories which are type 1 diabetes mellitus and type 2 diabetes mellitus. These two types are powerful and highly independent risk factors causing coronary artery disease, stroke, peripheral arterial disease and organ damage and dysfunction including eyes and nerves (Harmel Mathur, 2004). Type 1 Diabetes Mellitus: Type 1 diabetes mellitus resulting from pancreas failure to produce insulin hormone. Person at risk of developing type 1 can be identified by doing serologic test markers that showing evidence of autoimmune destruction of beta cells (islet cells) of the pancreas which is responsible for insulin production. Type 1 diabetes is manifested in childhood and early adulthood, but can patient present at any age (Goroll Mulley, 2009). Type 2 diabetes mellitus: Patients with type 2 diabetes mellitus are prone with wide range of series complications. Type 2 is characterized by high blood glucose due to insulin resistance and relative insulin deficiency. There are 20.8 million people in United State with type 2 diabetes mellitus. Type 2 diabetes traditionally is seen in elderly people. However it is diagnosed in obese children. Many studies shows that type 2 diabetes mellitus are associated with high calorie diet, physical inactivity and life style (Feinglos Bethel, 2008). Other Types of Diabetes: There are other types of diabetes but they are less common but patients who are underlying defect or disease process can be identified in a relatively specific manner. These types are Genetic defects of beta-cell function, Diseases of the exocrine pancreas e.g Fibrocalculous pancreatopathy, Endocrinopathies and cystic fibrosis and Uncommon forms of immune-mediated diabetes. Diabetes mellitus complications: Diabetic complications can be grouped into macrovascular and microvascular disease. Macrovascular diseases are result from atherosclerosis which develops in earlier age in patient with diabetes. There are several factors contribute to atherosclerosis such as lipidemia, hypertension, increased platelets adhesion and aggregation, elevated factor V, factor VII and fibrinogen concentration. Macrovascular diseases are seen in both type one and two of diabetes mellitus and they include coronary heart disease, Ischemic stroke and peripheral vascular disease (which can lead to ulcers, gangrene and amputation) (Winter Signorino, 2002). Whereas, Microvascular complications is seen in type one diabetes mellitus. Hyperglycemia damages the basement membrane of capillaries in the retina and glomerulars which leads to retinopathy and neuropathy. Microvascular diseases include neuropathy (nerve damage), nephropathy (kidney disease) and vision disorders (eg retinopathy, glaucoma, cataract and corneal disease). Furthermore there are other complications of diabetes include infections, metabolic difficulties, dental disease, autonomic neuropathy and pregnancy problems (Winter Signorino, 2002). Several clinical research show a strong relationship between hyperglacemia and diabetic microvascular complications in both type 1 and type 2 diabetes. High glucose and insulin resistance play important roles in the pathogenesis of macrovascular complications due to atherosclerosis. Diabetes-specific microvascular disease in the retina, glomerulus and vasa nervorum has same pathophysiological features. Intracellular hyperglycaemia causes abnormalities in blood flow and increased vascular permeability which leads to decreased activity of vasodilators such as nitric oxide, increased activity of vasoconstrictors such as angiotensin II and endothelin-1, and elaboration of permeability factors such as vascular endothelial growth factor (VEGF) (Brownlee, 2001). There are several factors which contribute the formation of inflammation, atherosclerosis and diabetes mellitus complication. These factors are hyperglycemia, accumulation of advanced glycation endproducts, dyslipidemia and oxidative stress which lead to endothelial dysfunction resulting in thrombotic complications and cardiovascular (Altman, 2003). In type 1 diabetes mellitus, high blood glucose is usually as result of low level of insulin secretion whereas in type2 hyperglycemia is caused by resistance of insulin at the cellular level. Low insulin levels or insulin resistance enable the body to convert glucose into glycogen (a starch-as source of energy which stored in the liver). In type 1 diabetes, pancreatic beta cells are attacked by auto-immune which cause infiltration of inflammatory cells and increased expression and secretion of S100-calcium binding protein and high-mobility group protein 1 (HMGP1) through inflammatory cells which consequently lead to islet damage and increased blood glucose level, subsequent accumulation of AGE (Bierhaus Nawroth, 2009). Comparing to T1D, in type 2 diabetes mellitus, different metabolic disturbances stimulates inflammatory cells to secretes RAGE ligands, which cause low-grade inflammation and increased oxidative and carbonly stress, all these play roles in promoting AGE formation and RAGE expression in respective organs (Bierhaus Nawroth, 2009). Insulin resistance and Inflammation: In diabetic patients with hyperglycemia, cause by 1) impaired insulin secretion by the pancreatic ß-cells, 2) muscle insulin resistance, and 3) hepatic insulin resistance all play central roles in the development and progression of glucose intolerance. As I mention before, type 2 diabetes mellitus (T2DM) is characterized by insulin resistance in liver and muscle and impaired insulin secretion. Also include deranged adipocyte metabolism and modified fat topography in the pathogenesis of glucose intolerance in T2DM. Fat cells are resistant to insulins antilipolytic effect, which result in increased plasma free fat acid levels. Long period of increasing plasma fat fee acid stimulates gluconeogenesis, promote hepatic and muscle insulin resistance, and impairs insulin secretion in genetically predisposed patients. These pathways of FFA-induced are known as lipotoxicity. Fat cells Dysfunction makes excessive amounts of insulin resistance-inducing, inflammatory, and atherosclerotic-provoking cytokines and fails to secrete normal level of insulin-sensitizing adipocytokines. Enlarged fat cells are insulin resistant and have minimized capacity to store fat. When storage capacity of adipocyte is exceeded, lipid overflows into muscle, liver, a nd perhaps ß-cells, resulting in muscle, hepatic insulin resistance and impaired insulin secretion. In type 2 diabetics, the ability of insulin to stop lipolysis and to decrease the plasma FFA levels is markedly impaired. It is clearly that chronic elevated levels of plasma free fat acid leads to insulin resistance in muscle and liver, and impair insulin secretion. In addition to FFA in plasma, increase stores of triglycerides in muscle and liver which correlate closely with the presence of insulin resistance in tissues. The triglycerides in liver and muscle are in a state of constant turnover, and the metabolites of intracellular triglyceride lipolysis impair action of insulin in liver and muscle (Bays et al, 2004). This pathway of events has been referred to as lipotoxicity . The accumulation of lipid in dipocytes leads to activate NADPH oxidase which increases the production of reactive oxygen species (ROS). The mechanisms increased production of cytokines including TNF-ÃŽ ±, IL-6 and monocyte chemoattractant protein-1 and reduce the production of adiponectin (Shoelson et al, 2006). Furthermore accumulation of lipid activates the protein response to increased ER stess in fat and liver. All these have accumulated to induce lipotoxicity as an important cause of ß-cell dysfunction (Bays et al, 2004). Receptor for advanced glycation end products (RAGE): RAGE is type I transmembrane receptor of the immunogloblin superfamily. It is a receptor for advanced glycation endproducts (AGE). It is about 45-KD a protein and it is consist of 403 amino acids in human, rate and mouse. Its extracellular region consists of one V-type (variable) immunoglobulin domina, which followed by two C-type (constant) immunoglobulin dominas (Basta, 2004). Its name drive from its ability to bind AGE and also it is known as AGER. It is located within the major histocompatibility complex (MHC) class III region on chromosome 6, which contains numbers of genes involved predominantly in inflammatory and immune responses and several components of complements. Beside AGE, RAGE is able to bind several ligands therefore is called a pattern-recognition receptor. These ligands are high-mobility group protein 1 (HMGP1), S100-calicum binding protein (S100b) which is family of pro-inflammatory cytokines and it can be found in any inflammatory lesion and vascular walls of diabetics patients, amyloid-ß-protein and macrophage-1 glycoprotein (CD11B/CD18). RAGE plays role in diabetes and other metabolic disease. The interaction of RAGE and its ligands cause pro-inflammatory activation. It is involved in several diseases such as innate immune response, mediating immune and inflammatory response, cancer promoting and progressing and microvascular and mi crovascular diseases (Bierhaus Nawroth, 2009). Moreover, RAGE expression is increased in the cells of the vascular walls, at the site where AGEs and S100/calgranulins are accumulated, including endothelium vascular smooth muscle cells, glomerular mesangial cells and mononuclear phagocytes. This destrbution of RAGE and its ligands leads to increased cellular activation, causing further raised expression of the receptor (Basta et al, 2004). Recently the studies have been proved that RAGE and its ligands accumulate in diabetes and contribute to its pathology. Serum levels of S100A8/9 and S100A12 increased in type 2 diabetic patients. Also, evidence was provided by raised serum levels HMGB1 were linked to coronary artery disease in type 2 diabetes. In addition the studies which have been done in streptozotocin-induced diabetic rats proved that diabetes increased amyloid-beta-peptide (1-40) levels in the brain. Furthermore, CML-modification of S100A8 and S100A9 are seen in inflammatory bowel disease and promote RAGE-mediated sustained inflammatory. Moreover, Carboxylated N-glycans on RAGE eases binding of HMGB and mediates ligation of S100A8/A9 to subpopulation of RAGE on colon cancer cells (Bierhaus Nawroth, 2009). Advanced Glycation End products (AGE) and its biochemical mechanism production: There are various pathways involved in stimulation of atherosclerosis in diabetes mellitus. However the most important one is formation and deposition of AGEs through nonenzymetic reaction between extracellular protein and glucose and it accumulates within cells of the vascular walls, in the extracellular space, kidney, nerves and retina (Basta et al, 2004). Possible mechanism of AGEs formation arise from intracellular auto-oxidation of glucose to glyoxal, decompounding of the Amadori product (glucose-derived 1-amino 1-deoxyfructose lysine adducts) to 3-deoxyglucosone and fragmentation of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate to methylglyoxal. These reactive intracellular dicarbonyls (glyoxal, methylglyoxal and 3-deoxyglucosone) which can react with amino groups of intracellular and extracellular proteins to form AGEs (pyrraline, pentosidine, CML, crossline) (Balasubramanyam et al, 2002). Several experimental studies evidenced that advanced glycation end products can alter vascular wall homeostasis in atherogenic through different ways which are: AGEs and mononuclear phagocytes Interaction: The binding of AGEs with mononuclear phagocytes MPs induces the activation of platelet-derived growth factor, insulin-like growth factor-1, and pro-inflammatory cytokines, such as IL-1ß and TNF-ÃŽ ±. Furthermore the interaction of AGEs with its receptor (RAGE) in the mononuclear phagocytes promotes cell migration (chemotaxis) (Basta et al, 2004). AGEs and vascular smooth muscle cells Interaction: Interaction of AGE with smooth muscle cells (SMCs) exhibits the proliferative activity and production of fibronectin. SMC growth are indirectly mediate by cytokines or growth factors which induced by AGEs in the MPs. Transforming growth factor-ß (TGF-ß) act as an intermediate factor in AGE-induced fibronectin formation by SMC(Basta et al, 2004). AGEs with vascular endothelium Interactions: alterations of vascular permeability and of adhesive properties As result its unique position and numerous properties, the vascular endothelium has important role in the regulation of extracellular permeability, the maintenance of blood fluidity, metabolism of hormones and vasoactive mediators and the regulation of vascular growth and tone. The endothelium is exposed to AGEs located on circulating proteins and cells (such as, diabetic RBCs), also those found in the underlying subendothelial matrix. Receptors for AGEs present on the endothelial cell surface, and mediate both the uptake and AGEs transcytosis, and the internal signal transduction. AGE-RAGE interaction leads to alteration of barrier function and an increased permeability of endothelial cells interact with AGEs and increased migrate of macromolecules through the endothelial monolayer. The increase in permeability is associated by alterations of the physical integrity of the endothelium, as shown by the destruction of structures and alterations of cellular morphology (Basta et al, 2004 ). Also, it has been proved that AGEs cause alterations of endothelial anti-hemostatic functions in vitro, through a reduction of thrombomodulin expression and accompanied with induction of tissue factor expression. The promoting of tissue factor and the decreasing in thrombomodulin activity change the dynamic endothelial features with regard to hemostasis from those of an anticoagulant to those of a procoagulant surface (Basta et al, 2004). Intraction of AGEs with endothelial RAGE also causes the depletion of cellular antioxidant defense mechanisms (such as glutathione, vitamin C) and the generation of reactive oxygen species. As a result of the increased cellular oxidative stress, NF-ÃŽ ºB activation occurs, thus inducing the expression of NF-ÃŽ ºB-regulated genes including, in addition to the procoagulant tissue factor, adhesion molecules, such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1); this past may prime diabetic vasculature towards enhanced interaction with circulating monocytes. Furthermore, the incubation of endothelial cells with EN-RAGE or S100B results in VCAM-1 induction, in a RAGE-dependent manner, as sustained by the inhibitory effect of anti-RAGE IgG or soluble RAGE (Basta et al, 2004). Alterations of endothelium-dependent vasodilatation AGEs linked to the vascular matrix may quench bioavailability of nitric oxide (NO), which is an important regulator of vascular tone inducing smooth muscle cell relaxation. Studies provided that, AGE inhibits NO activity, when it added to NO in vitro. Studies on animal exterminate induced diabetes show that an alteration of endothelium-dependent dilatation occurs in short period, within 2 months, from diabetes induction. A direct reaction between NO radical and other free radicals which are formed during the reactions of AGEs assumable leads to inactivation of NO. In parallel, advanced glyaction end products promote the expression of the potent vasoconstrictor endothelin-1 changing endothelial function towards vasoconstriction (Basta et al, 2004).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  These four mechanisms promote and alter vascular wall homeostasis. When mononuclear phagocytes migrate to the site of immobilized AGEs in the tissue, their migrations allow them to interact with AGE -modified surface and become activated. This mechanism cause attracting and retaining MPs in tissue where AGEs deposit. Migration and activation of MPs and T cells (inflammatory cells) promote and cause chronic vascular inflammation through alter vessel wall (Basta et al, 2004). Promotion of atherogenesis pathways by AGEs: AGEs are most important factors in endothelial dysfunction in diabetic patients through binding its receptor (RAGE). Advanced Glycation Endproducts stimulate the expression of proinflammatory cells and molecules (Altman, 2003). AGEs can be seriously deleterious to the function of blood vessel walls in various ways. First it causes blood vessel dysfunction through cross bridges among vessel macromolecules. Secondly of damage is that accumulation of AGEs lead circulating blood cells to adhere to the vascular walls which promote atherosclerosis. Third way is through binding different receptors which have been recognized on various cell types such as macrophages, endothelial cells, and smooth muscle cells, renal and neuronal cells (Basta et al, 2004). Hyperglycaemia Mechanisms-caused damage: Hyperglycemia diverse microvascular and macrovascular complications in diabetic patients through several mechanisms such as increased formation and accumlation of advanced glycation end-product (AGE); activation of protein kinase C (PKC) isoforms; and increased generation of reactive oxygen species (Bonke et al,2008) Increased production advanced glycation end-products AGE promote atherogenesis pathway through accumulation of AGEs and AGEs ligation to RAGE on endothelial cells and macrophages induce inflammation through activating pro-inflammatory cytokines including TNF-ÃŽ ±, 1L-6 a L-1ß, induction of reactive oxygen species (ROS) and through increased oxidative stress which lead to degradation of IKBs (IKBs is normally bound to NF-KB to prevent translocation of NF-KB to nucleus). ROS activates NF-KB which results in translocation of NF-KB to nucleus. Activation of NF-KB cause pathological change of gene expression which is highly related to inflammation, immunity and atherosclerosis, increased expression of inflammatory mediators which lead to insulin resistance and increased RAGE expression as well (Basta et al, 2004). Mechanisms by which intracellular production of advanced glycation end-product (AGE) precursors damages vascular cells. Cellular functions are altered by dicarbonyl advanced glycation end products. Alteration of extracellular matrix proteins results in abnormal interactions with other matrix proteins and with integrins. Alteration of plasma proteins by AGE precursors generate ligands that bind to AGE receptors, inducing conversion of gene expression in endothelial cells, mesangial cells and macrophages. Activation of protein kinase C: The protein kinace C (PKC) family compromises at least eleven isoforms, nine are induced by the lipid second messenger diacylglycerol (DAG). Altered DAG-PKC pathway play an important role in diabetic complications. Intracellular hyperglycaemia raises the amount of DAG which activate PKC in cultured vascular cells and in the retina and renal glomeruli of diabetic animals. Hyperglycaemia may also activate PKC isoforms indirectly by AGEs bind receptors and increased activity of the polyol pathway, possibly through increased reactive oxygen species (ROS). AGE stimulated diacylglycerol (DAG) and activate protein kinase C (PKC) in VSMC. PKC is one of important signal transduction elements involved with multiple cell response. In early studies of diabetes, retinal and renal blood flow abnormalities are due to activation of PKC-ß isoforms perhaps through depressing nitric oxide production or increasing endothelin-1 activity. Abnormal activation of protein kinase C has several pathogenic c onsequences: It leads to decreased production of nitric oxide in smooth muscle cells and glomerular mesangial cells that is induced by hyperglycemia (Brownlee, 2001). Activation of PKC causes inhibition of insulin-stimulated expression of mRNA for endothelial nitric oxide synthase (eNOS) in cultured endothelial cells. Hyperglycaemia activates PKC to increased endothelin-1, permeability of endothelia cells and increased expression of the vascular permeability angiogenesis factor (VEGF) in smooth muscle cells (Brownlee, 2001). Increased generation of reactive oxygen species: Increased generation of reactive oxygen species (ROS) is another possible pathways of diabetes complications especially nephropathy complication. Production of Reactive oxygen species can be result from the activation of various enzymes, including NADPH oxidase, nitric oxide (NO) synthase, and myeloperoxidase, with arising evidence that NADPH oxidase is the major cytosolic source of ROS generation in diabetes. NADPH has homologues that are present within the kidney, namely nox-3, seen in fetal kidney, and nox-4, which is predominately expressed in the renal cortex. AGE bind RAGE induces signal transduction and activate NADPH oxidase in endothelial cells. The interaction between AGE-RAGE enhances production of the cytokine vascular endothelial growth factor (VEGF), which is directly induced by NADPH oxidase and is associated with the pathogenesis of albuminuria in diabetes (Bonke et al, 2008). Diabetes mellitus control and treatment: Both type 1 and 2 diabetes mellitus are characterized by elevated blood glucose level due to insufficiency of insulin level. Therefore, diabetes patients need to reduce blood glucose level through healthy diet, drugs such as (hypoglycemic tablets and anti-atherosclerosis drugs), insulin injection and regular physical exercise. Healthy Diet: In general, healthy diet for diabetes patients should include: limit fats (especially saturated fats and trans-fat acid), proteins and cholesterol. Also, patient should consume a lot of fiber and vegetables. Patients with insulin-producing or insulin synthesis treatment should monitor their blood glucose level to avoid hyperglycemia. For example, adults and teenager patients should maintain their blood glucose level between 80-120 mg/dl, and 100-200 mg/dl for children under 12 year old. Type 1 diabetes patients should test their blood glucose level four to more per day. However, in type 2 diabetes, patients recommend to measure blood glucose level 1 to 2 times daily, because glucose level in type 2 diabetes is more stable than in type 1. Such important tests are important during diet plans and treatment. For example, glycosylated hemoglobin test (HbA1 c) is an indicator for carbohydrate level. Micro and macroalbuminuria indicates of the proteinuria and renal function, for instance if the teat showed high level of proteinuria then the patient need to lowering protein intake (Flaws et al, 2002). Exercise: Physical exercise is important to manage diabetes complications. Regular exercise improves the status of both type 1 and 2 diabetes through transporting sugar to muscles, improving blood circulation, and increasing insulin receptors. Exercise has specific effects on diabetes patients include: reducing blood glucose level during and after exercise, increased insulin sensitivity, reduced triglyceride level and increased good cholesterol (HDL) (Flaws et al, 2002). However, diabetes patients may have several risks associated with exercise which include: hypoglycemia if patient under treatment with hyperglycemia agents, hyperglycemia and ketosis in insulin-deficient patients, and exacerbation of cardiovascular disease. Therefore, patients who are over 30 year old should be examined before doing physical exercise. These examinations include: cardiovascular exams such as blood pressure, blood lipid and ECG, and neurological evaluation such as eye exam (Flaws et al, 2002). Anti-inflammatory drugs Various drugs in recent clinical practice have been used as anti-inflammatory agents such as thiazolidinedione (TZD) class of PPARÃŽ ³ agonists and members of statin class of HMG CoA reductase inhibitors. Both of them have importane anti-inflammatory properities and both have action on glucose homeostasis and cholesterol redusing (Shoelson et al, 2006). TZDs are used to induced insulin sensivity and decresed hyperglicemia in patient with type 2 diabetes mellitus. TZDs drugs inculde pioglitazone, rosiglitazone and troglitazone. The role of TZDs is through binding and activiting PPARÃŽ ³ to induce a number of gene expression products in a dipocyte. TZDs action are attributed to fatty acid in the a dipose tissue. TZD decreases circulating free faty acid and keep faty acid out of musle and liver because accumalte of fatty acide in these tissue lead to insulin resistance. In addition, PPARÃŽ ³ is not only present in dipocyte but also in it is expressed in macrophages and other immune cells response, hepatocyte, endothelial cells and vascular smooth mucsle cells (VSMC). TZD play role in reduce the expression of targets gene for cytokines, growth factors, proliferation and migration of cells, and cell cycle progression (Shoelson et al, 2006). Rosigliatozone: Rosigliatozone decreses the inflammatory markers such as serum C-reactive protein, metalloproteinase-9, white blood cell, tumer necrosis factor-ÃŽ ± and serum amyloid-A in type two diabetes mellitus (Altman, 2003). Group of studies done on Diabetes Rodents: The recent research has demonstrated that rosiglitizone, a PPARÃŽ ³ agonist, attenuates diabetes associated atherosclorosis. The reaserch has studied the direct antiathersclosis effects of PPARÃŽ ³ afer long beriod of therapy in an experiment of insulin deficiency. This study show that rosiglitezone has no effect on glucose level in both control or diabetes mice. However, rosiglitizone , PPARÃŽ ³ (acting as insulin sinstiser) significally decresed plasma insulin level in control mice (Calkin et al, 2005). In addition to Calkin study and his collegous, another study shows that rosiglitazone increase the insulin content and iselt cells number and total mass of pancreas in diabetes rats. However, it is unknown if this is adirect effect of rsiglitazone by activation of PPARÃŽ ³ mediated pathway in islets or indirect effect of normalizing the hyperglicemia (Sanchez et al, 2002). Increaesd secration rate of proinsulin relative to insulin is one oa acommon feature in type 2 diabetes mellitus. The normal range of proinsulin in normal subjects is about 2 to 4% of the total amount of insulin and in type 2 diabetes proinsulin rate is about 15%. Curently the studies has been demonstrated that rosiglitazone in type 2 diabetes decrease proinsulin secretion. Proinsulin has been associated with activity of carboxypeptidase E. Fricker and collegous have evidenced that carboxypeptidase are present in secretory pathway and participate in peptide processing. CarboxypeptidaseB has similler feature as carboxypeptidaseE but the precursor sequence of carboxypeptidaseB has been seen in an adult mouse islet cells. Thus suggest that rosiglitazone may has primery effect on increasing the expression of carboxypeptidaseB precursor protein resulting in increse proinsulin to insulin conversion (Sanchez et al, 2002). Further more, rosiglitizone did not affect fasting insluin level in diabetic mice due to streptozotocin which induce insulin insufficency. Also, another group of study has curently demonstrated that short period of treatment with rosiglitizone decreased plaque area in diabetic mice but had no determination if effects seen were linked to insulin sensitization (Calkin et al, 2005). More current sutdies have evedanced that rosiglitezone treatment in diabetes mice reduce gene expression of the NF-KB subunit p65. Further study has shown that rosiglitizone has no direct effect o glucose-induce upregulation of oxidative stress. Same study had investigated RAGE expression acording to preveious finding that first of all, RAGE expression increse oxidative stress and secondly rosiglitezone which used in culture media alter RAGE expression. The study had shown, the expression of RAGE gene wasnt altered by rosiglitizone (Calkin et al, 2005). Some study showed no significant alteretion in gene expression after TZDs treatment. This is because of almost studies were not preformed in human adipose tissue in vivo but they used adipose tissue of rodents and adipocyte cell line. Actually under such study we should consider about some facts that, for example rosiglitazone dose which used in rodents study (10 mg/kg) is higher than human dose about 100-fold. furthermore, TZD may has an action on gene expressed in rodents but it is not necessarily to has same action on human gene. For example carbonic anhydrase 3 protein raised 2-fold after treated the mice with rosiglitazone, however there was no increasing in carbonic anhydrase 3 mRNA in human adipocyte. Although there were similarities in the action of TZD-induced insulin sensitivity, there may be TZD action has different mechanisms on experimental models and human (Kolak et al,2007). Therfore, Im going to discuss about the studies which have been done on human adipose tissue and there findings. Group of studies done in human patient with type 2 diabetes: Overactivity of ubiquitin-proteasome system is associated with the inflammation and atherosclerotic plaques in type 2 diabetes. Study by Marfella and his colegous on human diabetes patients has been shown that the PPAR-ÃŽ ³ agonist rosiglitazone reduce ubiquitin-proteasome activity and thuss prevent plaque progression to unstable phenotype in diabetes individulas (Marfella et al, 2006). Also, same study shows, the production of O2- by monocytes is reduced after rosiglitazone treatment. Thus proteasome reduction is induced by inhibition of oxidative stress and polyubiquitination. As oxidative stress induce insulin resistence through NF-kB activation, rosiglitazone enhance insulin sensivity and plaque stability in diabetes patien through reducing oxidative stress and ubiquitin-proteasome activity. Further possibility that, NF-KB activation is inhibited by rosiglitazone through a PPAR-ÃŽ ³ independent pathway. PPAR-ÃŽ ³ agonist inhibits NF-KB translocation and subsequent DNA binding through inhibits immune response which induce degradation of IKBs (Marfella et al, 2006). Rosiglitazone have significant effects on metabolism of faty acid and lowering circuliting non-esterified fatty acid. Therfore rosiglitazone prevent islet cells through reducing fatty acid exposure (Sanchez et al, 2002) Kolak and his colleagues investigated the gene of expression in human adipose tissue in vivo in type two diabetes mellitus, befor and after tratment with rosigliatozone and metformin. Reosigliatozone modulates expression of gene which involved in free faty acid synthesis and storage, protein strcture, inflammatory cells inculde macrophage and gene associated in glucose transport and insulin sensivity. Whereas metformin has no effect on these gene (Kolak et al, 2007). TZD decrease the expression of RAGE endothelial protien. From preveious finding, TNF-ÃŽ ± increase the expression of RAGE on endothelial cells, so