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By Z. Innostian. Saint Vincent College.

Previous studies do not allow a conclusion on the effect of foods rich in antioxidant com pounds purchase discount kamagra gold online, because were used different markers and administration time buy discount kamagra gold 100 mg line, and still more the age range of the postmenopausal differs considerably generic kamagra gold 100 mg with amex. With respect to the lycopene purchase discount kamagra gold on line, the following mechanism of the role of lycopene in chronic diseases has been mentioned by Agarwal and Rao [101] and Waliszewski and Blasco [102]. This highlights the importance of promote healthy lifestyles (balanced diet and moderate in tensity exercise) in vulnerable populations, such as menopausal women, in order to prevent aging induced oxidative stress-related diseases. Lycopene and its mechanism in preventing of chronic diseases (Adapted from 101 and 102). Contrary to the above has also been reported, that the exercise does not modify the antioxi dant status (although this is lower in metabolic healthy obese postmenopausal women than non-metabolic healthy obese postmenopausal women) and worse increases serum levels of thiobarbituric acid-reactive substances [107]. Conclusion The studies presented here were performed with different number of patients, methodolo gies and biomarkers, but most of them indicate that estrogen depletion induces oxidative stress and hormone replacement therapy seems to reduce it. With respect to the modifica tion of biomarkers of oxidative stress damage by food and exercise needs more research be cause so far no conclusive data have been obtained. Author details Claudia Camelia Calzada Mendoza and Carlos Alberto Jimnez Zamarripa1* 2 *Address all correspondence to: cccalzadam@yahoo. Street Salvador Daz Mirn S/N, Colony Casco de Santo Toms, Dele gation Miguel Hidalgo, C. Samuel Ramrez Moreno-psychiatric careservices- Secretaria de Salud, highway Mxico-Puebla Km 5. Review of hor monal changes during the menopausal transition: focus on findings from the Mel bourne Womens Midlife Health Project. Hot flushes, menstrual status and hormone levels in a population-based sample of midlife wom en. Significance of incidentally thick endometrial echo on transva ginal ultrasound in postmenopausal women. Intravaginaldehydroepiandrosterone (Pras terone), a physiological and highly efficient treatment of vaginal atrophy. Urinary incontinence in the elderly: part 3 of a series of articles on inconti nence. Relation ships between menstrual and menopausal attitudes and associated demographic and health characteristics: the Hilo Womens Health Study Women Health,, 50(5), 397-413. Management of menopause- associated vasomotor symptoms: Current treatment options, challenges and future directions. Bone mineral densi ty and risk of fractures in aging, obese post-menopausal women with type 2 diabetes. Relation of leptin, adiponectin and insulin resistance to bone mineral density in type 2 diabetic postmenopausal women. Periodontitis and bone mineral density among pre and post menopausal women: A comparative study. The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density. Effects of the transition from premenopause to postmenopause on lipids and lipoproteins: quantification and related parameters. Estrogen-induced improvement in coronary flow responses during atrial pacing in relation to endothelin-1 levels in postmeno pausal women without coronary disease. Insulin resistance and management of the meno pause: a clinical hypothesis in practice. Association of sex hormones and sex hormone-binding globu lin with depressive symptoms in postmenopausal women: the Multiethnic Study of Atherosclerosis. Oxidative Profile of the Menopausal Woman: Estrogens Rol in the Prevention and Treatment of Diseases. Structural basis for an drogen specificity and oestrogen synthesis in human aromatase. Hyperhomocysteinemia, oxidative stress, endothelial dysfunction in postmenopausal women. Research into Specific Modulators of Vascular Sex Hormone Receptors in the Management of Post menopausal Cardiovascular Disease. Role of estrogens in pathogenesis of age-related disease in women of menopausal age. Neuroprotective effects of oestrogen against oxidative toxicity through activation of G-protein-cou pled receptor 30 receptor. Serum -glutamyltransfer ase as Oxidative Stress Marker in Pre-and Postmenopausal Iraqi Women. Correlation of increased oxidative stress to body weight in disease-free post menopausal women. Oxidative stress, body fat composition, and endocrine status in pre- and post menopausal women. Total antioxidant capacity and superoxide dismutase activity levels in serum and gingival crevicular fluid in post-menopausal women with chronic periodontitis. Behaviour of some indica tors of oxidative stress in postmenopausal and fertile women. Decreased oxidant profile and increased antioxidant capacity in naturally postmenopausal women. Estradiol levels and oxidative bal ance in a population of pre-, peri-, and post-menopausal women. Total antioxidant status correlates with cognitive impairment in patients with recurrent depressive disorder. Effect of Chronic Administration of Estradiol, Progesterone, and Tibolone on the Expression and Phosphorylation of Glycogen Synthase Kinase-3b and the Microtubule-Associat ed Protein Tau in the Hippocampus and Cerebellum of Female Rat. Lifetime History of Depression, Type 2 Diabetes, and Endothelial Reactivity to Acute Stress in Postmenopausal Women. Homocysteine oxidative stress and relation to bone mineral density in post-menopausal osteoporosis. Association of oxidative stress, iron, and centralized fat mass in healthy post menopausal women. Study of changes in antioxidant enzymes status in diabetic post menopausal group of women suffering from cardiovascular complications. Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women. Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and carotid wall artery intima-media thickness. Duration of estrogen deprivation, not chronological age, prevents estrogens ability to enhance hippocampal synaptic physiology. Proceedings of National Academy of Science of United States of America, 107(45), 19543-19548. Womens use of hormone replacement therapy for relief of menopausal symptoms, for prevention of osteoporosis, and after hysterecto my. Updated clinical recommendations for the use of ti bolone in Asian women Climateric,13:, 317-327. Effect of short-term hormone ther apy on oxidative stress and endothelial function in African American and Caucasian postmenopausal women. Effects of hormonal replacement therapy on oxidative stress and total antioxidant capacity in postmenopausal hemodialysis patients. Oxidative stress measured by carbonyl groups level in postmenopausal women after oral and trans dermal hormone therapy. Hormone replacement therapy: relation to homocysteine and prooxidant-antioxidant status in healthy postmenopausal women Archives of Gynecology and Obstetretics,, 285(3), 733-9. Postmenopausal hormone replacement therapy use decreases oxidative protein dam age. The Effect of Hormone Replaceent Therapy on Oxidized Low Density Lipoprotein Levels and Paroxonase Activity in Postmenopausal women. Effects of oestradiol and oestroprogestin on erythrocyte antioxidative enzyme system activity in postmenopausal women. Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy. Post-menopaus al hormone therapy reduces autoantibodies to oxidized apolipoprotein B100. The benefits of hormone re placement therapy on plasma and platelet antioxidant status and fatty acid composi tion in healthy postmenopausal women. Oestradiol protects against the harmful effects of fluoride more by increasing thiol group levels than scavenging hy droxyl radicals.

Surgeon holds reel in ing the appropriate slightly for easy grasp- needed discount kamagra gold online american express, being certain that palm generic kamagra gold 100 mg with amex, feeds strand material on a reel cheap kamagra gold 100mg visa. Place reel conviently the end of the ligating beween fingers kamagra gold 100 mg overnight delivery, and the inner contents of the on the Mayo tray. For be used to prepare sufficient suture are shorter than those prepared example, if the surgeon opens the material to stay one step ahead of originally, do not be reluctant to peritoneum (the lining of the the surgeon. The goal should be to ask the surgeon if one of the abdominal cavity) and discovers have no unused strands at the end strands will serve the purpose disease or a condition that alters of the procedure. The sutures or mechanical By watching the progress of the rather than opening an additional devices must bear the responsibility procedure closely, listening to suture packet. They can only and assistants, and evaluating one more suture," and strands of perform this function reliably if the the situation; suture needs can suitable material remain which quality and integrity of the wound be anticipated. Check the label on the dispenser suture materials to understand peel overwrap down 6 to 8 inch- box for type and size of suture proper procedure to preserve es and present to the scrub material and needle(s). Maintain an adequate supply of to grasp the free end of a suture accurately and dispense only the the most frequently used sutures during an instrument tie. Rotate stock using the "first-in, follow to preserve suture tensile first-out" rule to avoid expira- 4. Read the label on the primary strength which depend upon tion of dated products and keep packet or overwrap before using whether the material is absorbable inventories current. Use aseptic technique when number of needles per packet to points for each member of the peeling the overwrap. Retain surgical team to remember and the inner contents of the primary this information during the observe in handling suture materials packet to the sterile field by procedure and/or until final and surgical needles. Do not the needle using the "no-touch" sure beween the knuckles for clamp the swaged area. Gently control, offer the sterile inner pull the suture to the right in a technique. Strands can then be armed needleholder and gently pull the strand making certain removed one at a time as needed. Surgical gut and collagen sutures for ophthalmic use must first be rinsed briefly in tepid water to avoid irritating sensitive tissues. When requesting additional handling with rubber gloves can suture material from the weaken and fray these sutures. Count needles with the as accurately as possible to circulating nurse, per hospital avoid waste. Do not pull on needles to handling fine sizes of monofila- straighten as this may cause ment material. Always protect the needle to ments, such as needleholders or prevent dulling points and forceps, except when grasping the cutting edges. Clamp the needle- free end of the suture during an holder forward of the swaged instrument tie. Clamp a rubber shod hemostat one-half the distance from the onto the suture to anchor the swage to the point. Microsurgery sutures and strand until the second needle is needles are so fine that they may used. Use a closed needleholder or protect delicate points and nerve hook to distribute tension edges. Use knot tying techniques that may be used to transport the are appropriate for the suture needle into the microscopic material being used. Handle with special care to avoid abrasion, kinking, nicking, or instrument damage. It can be used the strength of healed tissue at been used successfully for the in conjunction with, but not in 7 days. For trauma and in closing a variety of surgical 2-octyl cyanoacrylate, marketed as post-surgical patients, infections are incisions and wounds. Approximate skin edges and use provided cosmesis equivalent to that infection or gangrene. Pat the wound dry with dry, sterile gauze direction of vital structures such to assure direct tissue contact for closed easily approximated skin edges as the eye. A doctor should also be contacted if dressing is being used, a fresh, dry bandage should the wound edges reopen or separate. The dressing should be replaced daily until the adhesive film has Apply a clean, dry bandage over the wound if fallen off or if the bandage should become wet, unless necessary to protect it. Approximate wound edges with gloved fully polymerize before applying Based Guide; F. Wait Comparing Octyl Cyanoacrylate from the skin when the dressing is approximately 30 seconds between removed, and wound dehiscence Tissue Adhesive and Sutures in applications or layers. A new tissue adhesive to remain without being evenly spread, children or other patients who may not the patient may experience a sensation be able to follow instructions for proper for laceration repair in children. Their use is edges should not be apposed by wound closure and other operative typically reserved for linear lacera- pulling on the free end of the procedures which involve suturing. This can result in unequal Each of these products has specific Furthermore, surgical tapes do not distribution of skin tensions, indications for use. Adhesive tapes approximate deeper tissues and do causing erythema or even blistering are used for approximating the not control bleeding. Skin closure tapes are an effective original tape, bisecting the alternative to sutures or staples remaining open wound with each Adhesive tapes are associated with when tensile strength and resistance strip until the space between tapes minimal tissue reactivity and yield to infection are not critical factors. They staples which are removed on the are associated with minimal tissue first to fourth postoperative day. They may be left on for to the wound and water vapor in lieu of skin sutures or used as a long periods without resulting in transmission escaping from the primary closure in conjunction with suture hatch marks. The blunt needles used for 1 the incompetent cervix ligation may also be used for this purpose. While this was its original use, umbilical tape is also used in pediatric and cardiovascular procedures to suspend small structures and vessels during the operation, but is not left in place. When healing is judged to be blood when used in an area of intervals as needed to adequate, remove each tape gross bleeding. Then, gently lift the tape away from the radiopaque thread woven into the wound surface. Their antistatic Many surgeons routinely use skin then woven carefully with a swage properties minimize the tendency of staples for closure of standard blunt needle in and out of the the tape strips to curl up. With tant to line up the wound edges Skin staples should be removed all devices, the staple creates an with the centerline indicator on the at the same time that sutures incomplete rectangle: the legs of the head of the stapler to make sure that would be removed, based on wound staple extend into the skin, and the the legs of the staple will enter the location and tension. For scalp cross-limb lies on the skin surface skin at equal distances on either side wounds, staples should be removed across the wound. Wounds closed with staples of position and the pre-cocking to close the wound while the first may be covered with a topical mechanism. Optimal visibility as assistant advances the forceps, antibiotic cream or ointment. Patients may bathe or shower important, as is the angle at which This technique is continued until the next day, but should avoid the staple enters the skin because the entire wound is everted and prolonged exposure to moisture. The ability of the that do not require extensive used to remove the staples by a staple end to swivel allows the head hemostasis and do not involve tears health care provider. Available in various materials and suture sizes, they provide a simple, reliable technique for continuous closure of the fascia of the abdominal wall. The needle of the looped suture is passed through the fascia from inside out at one end of the incision, then through the opposite wound edge from outside in, and then passed 5. The suture is threaded through passing the needle from the outside the bolster and tied. However, care Also, the skin may become necrotic leaving the knot inverted under should also be taken in the use of beneath the bolsters if the sutures the fascia. This invariably occurs if the sutures are tightly tied at the Retention suture bolsters are sterile 1 3 time of the operation, as subsequent 2 /2-inch (6cm) lengths of /16-inch tissue edema ensues. After the desired number of sutures is placed in the wound, a sterile bridge is positioned over each retention suture. The ends of the sutures are passed through the appropriate holes and tied loosely over the bridge.

C: Hypercoagulablity Definition: Hypercoagulability is any alteration of the coagulation pathway that predisposes to thrombosis order 100 mg kamagra gold with amex. Hypercoagulability is a less common cause of thrombosis & & it can be divided into: 1 purchase kamagra gold once a day. Morphology of Thrombi Thrombi may develop any where in the cardiovascular system safe 100mg kamagra gold. The differences between arterial & venous thrombi are: Arterial thrombi Venous thrombi a) Arise at the site of endothelial injury a) Arise at area of stasis b) Grow in a retrograde fasion purchase kamagra gold 100mg without a prescription, against b) Grow in the direction of blood flow from its site of attachment. B: Embolization: The thrombus may dislodge and travel to other sites in the vasculature. Death of a tissue due to a decreased blood supply or drainage is called infarction. D: Organization and recanalization Organization refers to the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts into the fibrin-rich thrombus. Organization is accompanied by the formation of capillary channels across the thrombus, re-establishing lumen continuity to some extent. The recanalization eventually converts the thrombus into a vasscularized mass of tissue which is later on incorporated as a subendothelial swelling of the vessel wall. Clinical significance of thrombi Thrombi are significant clinically because: - They cause obstruction of arteries and veins & - They are possible source of emboli. Venous Thrombosis (Phlebothrombosis) Venous thrombosis affects veins of the lower extremity in 90% of cases. Superficial venous thrombosis - Usually occurs in saphenous venous system, particularly when there are varicosities. This is because deep venous obstruction is rapidly offset or releaved by collateral bypass channels. Pregnancy & puerperal states increase coagulation factors & reduce the synthesis of antithrombotic substances. Migratory thrombophlebitis is a condition that affects various veins throughout the body & is usually of obscure aetiology, but sometimes it is associated with cancer, particularly pancreatic cancer. Arterial Thrombosis - The rapid flow of arterial blood prevents the occurrence of thrombosis unless the vessel wall is abnormal. Atheromatous plaques produce turbulence and may ulcerate & cause endothelial injury, both of which can lead to thrombosis. These thrombi may narrow or occlude the lumen of arteries such as the coronary and cerebral arteries. A thrombus develops in the atrium in patients with atrial fibrillation & dilatation superimposed on mitral stenosis. Embolism Definition:- An embolus is a detached intravascular solid, liquid or gaseous mass that is carried by blood to sites distant from its point of origin. Causes of embolism: An embolus can arise from: o Thrombus (99% of emboli arise from a thrombus. Such an embolus is called thromboembolus) o Platelets aggregates o Fragment of material from ulcerating atheromatous plaque o Fragment of a tumour o Fat globules o Bubbles of air o Amniotic fluid o Infected foreign material o Bits of bone marrow o Others. Unless otherwise specified, the term embolism should be considered to mean thromboembolism. Such an embolus is derived from a thrombus in the systemic veins or the right side of the heart. The thromboembolus will travel long with the venous return & reach the right side of the heart. Depending on the size of the embolus and on the state of pulumonary circulation, the pulmonary embolism can have the following effects: 1. If the thrombus is large, it may block the outflow tract of the right ventricle or the bifurcation of the main pulumonary trunk (saddle embolus) or both of its branches, causing sudden death by circulatory arrest. Sudden death, right side heart failure (cor pulmonale), or cardiovascular collapse occurs when 60% or more of the pulumonary circulation is obstructed with emboli. If the embolus is very small (as in 60-80% of the cases), the pulmonary emboli will be clinically silent. Embolic obstruction of medium sized arteries manifests as pulmonary haemorrhage but usually does not cause infarction because of dual blood inflow to the area from the bronchial circulation. In turn, two thirds of intracardiac mural thrombi are associated with left ventricular wall infarcts and another quarter with dilated left atria secondary to rheumatic valvular heart disease. The major sites for arteriolar embolization are the lower extremities (75%) & the brain (10%), with the rest lodging in the intestines, kidney, & spleen. The emboli may obstruct the arterial blood flow to the tissue distal to the site of the obstruction. The infarctions, in turn, will lead to different clinical features which vary according to the organ involved. Fat Embolism Fat embolism usually follows fracture of bones and other type of tissue injury. Although traumatic fat embolisms occur usually it is as symptomatic in most cases and fat is removed. But in some severe injuries the fat emboli may cause occlusion of pulmonary or cerebral microvasculature and fat embolism syndrome may result. Fat embolism syndrome typically begins 1 to 3 days after injury during which the raised tissue pressure caused by swelling of damaged tissue forces fat into marrow sinsosoid & veins. Air embolism Gas bubbles within the circulation can obstruct vascular flow and cause distal ischemic injury almost as readily as thrombotic masses. Air may enter the circulation during: Obstetric procedures Chest wall injury In deep see divers & under water construction workers. Generally, in excesses of 100cc is required to have a clinical effect and 300cc or more may be fatal. The bubbles act like physical obstructions and may coalesce to form a frothy mass sufficiently large to occlude major vessels. Amniotic fluid embolism It is a grave but un common, unpredictable complication of labour which may complicate vaginal delivery, caesarean delivery and abortions. The amniotic fluid containing fetal material enters via the placental bed & the ruptured uterine veins. The onset is characterized by sudden severe dyspnea, cyanosis, hypotensive shock followed by seizure & coma of the labouring mother. As discussed in this & the previous subtopics, the potential consequence of thromboembolic events is ischemic necrosis of distal tissue, known as infarction. Infarction Definition: An infract is an area of ischemic necrosis caused by occlusion of either the arterial supply or venous drainage in a particular tissue. Other mechanisms include [almost all of them are arterial in origin]: Local vasospasm Expansion of atheroma due to hemorrage in to athermotous plaque. The effect of such a dual blood supply is that if there is obsrtuction of one of the arterial supplies, the other one may offset the rapid occurrence of infarction in these organs unlike the renal & splenic circulations which have end arterial supply. Infarction caused by venous thrombosis is more likely to occur in organs with single venous outflow channels, such as testis &ovary. B: Rate of development occlusion Slowly developing occlusions are less likely to cause infraction since they provide time for the development of collaterals. Neurons undergo irreversible damage when deprived of their blood supply for only 3 to 4 minutes. D: Oxygen content of blood Partial obstruction of the flow of blood in an anaemic or cyanotic patient may lead to tissue infarction. Types of infarcts Infarcts are classified depening on: A) the basis of their colour (reflecting the amount of haemorrhage) into: 1. Anemic (White) infarcts B) the presence or absence of microbial infection into: 1. Red infarcts occur in: a) Venous occlusions as in ovarian torsion b) Loose tissues such as the lung which allow blood to collect in infarct zone. White infarcts occur in: a) Arterial occlusion in organs with a single arterial blood supply. Morphology of infarcts Gross: All infarcts are wedge-shaped with the occluded vessel at the apex and the periphery of the organ forming the base of the wedge. Following inflammation, some of the infarcts may show recovery, however, most are ultimately replaced with scars except in the brain. Microscopy: The dominant histologic feature of infarction is ischemic coagulative necrosis.

Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function order kamagra gold online from canada. Gene prole analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors cheap kamagra gold master card. Higher levels of 25- hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women buy kamagra gold 100mg low cost. Parental smoking at home and the risk of childhood-onset multiple sclerosis in children discount kamagra gold 100mg with visa. The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis. Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated. Autocatalytic cleavage of myelin basic protein: an alter- native to molecular mimicry. Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope. Alterations in type I hemidesmosome components suggestive of epigenetic control in the salivary glands of patients with Sjogrens syndrome. Epigenetics in autoimmune disorders: highlights of the 10th Sjogrens syndrome sym- posium. Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Autoimmune diseases and autoantibodies in the rst degree relatives of patients with systemic sclerosis. Predictors of the scleroderma phenotype in broblasts from systemic sclerosis patients. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Epigenetic investigation of variably X chromosome inactivated genes in monozygotic female twins discordant for primary biliary cirrhosis. Identication and characterization of a 14 kDa human protein as a novel parvulin-like peptidyl prolyl cis/trans isomerase. Evidence for a major role of heredity in Graves disease: a population-based study of two Danish twin cohorts. High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: a possible explanation for the female predisposition to thyroid autoimmunity. Ulcerative colitis and Crohns disease in an unselected population of monozygotic and dizygotic twins. Aberrant methylation of the eyes absent 4 gene in ulcerative colitis-associated dysplasia. Methylation of the oestrogen receptor gene in non-neoplastic epithelium as a marker of colorectal neoplasia risk in longstanding and extensive ulcerative colitis. Methylation status of genes in non- neoplastic mucosa from patients with ulcerative colitis-associated colorectal cancer. Ulcerative colitis-associated colorectal cancer is frequently associated with the microsatellite instability pathway. Rates vary in different parts of the world, reecting a genetic basis for many of these conditions. There are hotspots where incidence rates may increase, and this is believed to be inuenced by environmental or other T. There is also a role for gender in autoimmunity, with the prevalence in women being signicantly higher than in men [2]. In some conditions, such as scleroderma and autoimmune thyroiditis, this gender bias has been traced to an imbalance in X-chromosome inactivation, known as the X chromosome inactivation skew theory [3]. This is evidence that not only genetics, but epigenetics may play a role in the pathogenesis of autoimmune diseases. Phenotypic variation within each of the autoimmune diseases may indeed be a function of epigenetic inuences on a baseline level of gene expression [4e6]. Because epigenetic modi- cations are reversible [7], this also opens the door for potential treatments to be developed that will reverse the epigenetic changes that contribute to the pathogenesis of the disease. The treatment of autoimmune diseases has undergone several very signicant paradigm changes over the past century. With a better understanding of the mechanisms of this group of diseases have come newer and more innovative modes of therapy. The discovery of cortisone, initially called Compound E in the 1940s was hailed as a wonder drug after the successful treatment of a woman with rheumatoid arthritis at the Mayo Clinic. These are the biological agents, which are synthesized by genetic engineering and have proven to be 226 extremely effective in the control of these diseases. The earliest biological agent to treat rheu- matoid arthritis was rituximab, introduced in 1986. Other biologics used to treat autoimmune diseases such as Crohns disease include the tumor necrosis factor alpha inhibitors. Although generally considered safer than chronic corticosteroid use, the potential for serious side effects can occur. More recently, a new strategy towards the treatment of autoimmune disease has been intro- duced. This strategy is based on observations that epigenetics may play a role in the devel- opment of autoimmunity. The bulk of experience in the use of the epigenetic drugs has so far been in the treatment of cancer (Box 12. This experience has led to a great deal of promise for a similar application in the treatment of autoimmunity. Interestingly, the use of cortico- steroids in the treatment of these illnesses may be intertwined with the development of epigenetic drugs because of the impact of epigenetic drugs on the glucocorticoid receptor [9,10]. Epigenetic drugs may also play a role in treatment of other inammatory diseases states such as asthma [11,12] as well as other classes of disease, including neurologic [13] or psychiatric [13,14] disorders. The challenges may be different, since the target genes and cells that have gone awry may be different depending on disease states, but the principles that lead to the development of epigenetic drugs are similar. Epigenetics describes changes in gene expression which are stable and heritable, but reversible. On the other hand, the knowledge that we need to devise ways to specically target the gene or cell responsible for the disease is still not available. Epigenetics in Human Disease clinically valuable in treating autoimmune diseases, a greater success would arise from the ability to target the effect of epigenetic drugs directly to the cells in which dysregulation of transcription occurs. The successful targeting of the control of a single gene or cell type may be associated with a lower risk of side effects, since genes irrelevant to the disease will be spared. The fact that epigenetic changes are believed to be reversible indicates that drugs known to affect gene transcription may be used to restore normal transcription and lead to resolution of clinical symptoms. The existence of a role of chromatin and histone modication in the regulation of gene expression is a common phenomenon of many cell types and genes. Epigenetic modication is involved in the regulation of various proinammatory cascades responsible for many disease states, including infection, cancer, and autoimmune diseases. It is at the core of most inammatory processes and its activation is closely linked to a number of histone acetyltransferases. Histone deacety- 228 lases remove acetyl groups from lysine residues forming compact and condensed chromatin which is transcriptionally silenced. The hallmark of these processes is reversibility, although early on it was not believed to be so. The primary site of action is at the histone tail, which is near the amino terminus of the protein. In general, opening the chromatin, as occurs through acetylation is associated with increased gene expression. They act on a variety of cells and signaling pathways to regulate chromatin architecture and immunologic function [21].