Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RU-486 or mifepristone is best known as an antiprogestin and an abortifacient, but it has broad medical applicability. The drug is also a potent blocker of corticosteroid receptors, and it has shown promise in the treatment of breast cancer, inoperable meningioma, and cushing's disease. Cushing's is a model for the symptomatology of aging which may involve enhanced response to corticosteroid. RU-486 has reversed the osteoporosis, thinning of skin, muscle atrophy, obesity, adult onset diabetes, depression, hypertension, and immunosuppression associated with this disease. RU-486 may be of value in aiding cervical dilation, lactation, and the treatment of endometriosis. In addition, breast, bowel, kidney tumors, hepatomas, endometrial cancer, and fibrosarcomas can show corticosteroid dependency, suggesting that RU-486 may have clinical value against inoperable tumors. In a preliminary 1987 phase I study, in estrogen-positive, chemotherapy-refractory breast cancer patients in Montpelier, France, Ru-486 produced objective tumor regression (6 of 22) that was prolonged (3 months) in 4 patients. Clinical relief of bone pain was observed in 7 of 23 patients with a decline in carcinoembryonic antigen (CEA) tumor makers in 8 patients. Growing in vitro data also show that RU-486 can directly inhibit breast cancer cell proliferation. RU-486 has application for HIV infection, based on data that there is a serum factor in AIDS patients that enhances corticosteroid lympholysis. IN addition, the immune restorative action of RU-486 suggests that it could counteract the immunosuppression seen in aging, in cancer, or in viral or stress-related disease, which has recently focused clinical attention on its potential in the treatment of senile dementia and depression. Scientific conferences and workshops are needed to alert scientists, physicians, and the public to the potential medical benefits of this drug.
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PMID:RU 486: how abortion politics have impacted on a potentially useful drug of broad medical application. 150 96

Progestins counteract the positive effect of the estrogen component in oral contraceptives (OCs) on cholesterol levels thus increasing the risk of atherosclerosis. Low androgenic potency progestins do not have a negative effect, however. Other research indicates that the lower the estrogen dose in OCs the lower the risk of deep vein and superficial thrombosis. OC users, especially low dose OC users, with no other risk factors (e.g. smoking and hypertension) are not at increased risk of cardiovascular disease. Some research demonstrates elevated risk of stroke in OC users, however. Elevated cholesterol, obesity, diabetes and other factors further increases the risk of stroke. Combined OCs protect against endometrial and ovarian cancer and this effect increases with use and continues after use. Moreover OC users are not at increased risk of pituitary adenoma. Results of some studies shows an increased risk of cervical cancer, but other only demonstrates a slight increase. So far research does not indicate the following to increase breast cancer risk among OC users: early age at 1st OC use, formulation, family history, and history of benign breast disease. There is an increased risk for liver tumors in OC users, nevertheless it is rare. OCs do not raise the risk of diabetes or gallbladder disease. High dose formulations increases the risk of high blood pressure, but not so with low dose formulations. OC use does not impair, fertility, but delayed conception often occurs. Most research demonstrates no increase in pelvic inflammatory disease in OC users. OCs do not cause congenital malformations. Combined OC use is contraindicated for breast feeding mothers, but progestin only OCs can be used with no advance effects. Results of 1 study demonstrates an increase in HIV infection in OC users, but another study has opposite results. The article concludes with recommended clinical management practices.
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PMID:Reassessment of the metabolic effects of oral contraceptives. 185 68

Author surveys clinically relevant results of recent years' nutritional researches. More and more details of the etiological bases of the diet-disease relation are revealed by molecular biology, e.g. the genetic background of link between fat intake and cardiovascular diseases, the metabolism of fatty acids. The results may be used in the implementation of balanced nutrition serving for prevention and in the elaboration of recommended levels of nutrient intake. Proper nutrition starts already in the fetal life: deficient nutrient supply of the mother means a risk factor to chronic, noncommunicable diseases of adulthood. Different nutrients, components in food might be especially favourable to health status, this phenomenon is indicated in English written scientific literature by the word "nutraceutical" (in Japan "functional foods"). In the year of 1994, the buzz word of nutrition was: antioxidant. The mechanism of the development of oxidative stress, its inhibition by antioxidative agents in food and the use of it in the prevention of malignant tumors (cancers), cardiovascular diseases, cataracts and other degenerative processes of old age, were studied comprehensively. The importance of obesity, fat intake in the risk of chronic diseases constitutes a separate group of problems. Nutrition is also an important factor in the care of HIV/AIDS patients and in the inhibition of the transfer of HIV-1 between mother and fetus.
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PMID:[The use of results of scientific nutrition research in clinical practice]. 774 62

A set of new guidelines were formulated by an expert group meeting in Sweden organized by the pharmaceutical office during March 31-April 1, 1993. It contains various methods to avoid an undesired pregnancy and also advice about postcoital contraception. Among barrier methods, the condom is the only reversible method for men with a method failure of 2 and user failure of 10. It protects against gonorrhea, chlamydia, condyloma, herpes simplex, HIV, and hepatitis B. The diaphragm can be used with a spermicide and protects to a lesser degree against chlamydia, gonorrhea, and cervical cancer. The female condom is as effective as the condom. Among spermicides, nonoxynol-9 is not only effective against sperms but also against bacteria, viruses, and certain vaginal and cervical cells. The vaginal sponge is impregnated with nonoxynol-9 and is effective up to 24 hours. The copper IUD, with a method failure of less than 1, can cause profuse menstrual bleeding, dysmenorrhea, and endometritis-salpingitis. Hormonal methods include combination pills (2-phase and 3-phase pills) and gestagen methods (high dose with 150 mg of medroxyprogesterone acetate injection every 3 months and low-dose minipills with levonorgestrel, norethisterone, or lynestrol). Mechanisms of action concern combination pills, gestagen methods, minipills, Norplant, and Levonova. Drug cross reaction can reduce effectiveness. Side effects include bleeding and amenorrhea. Risk-benefit determination is based on health effects. Possible risks are associated with breast cancer, cervical cancer, blood pressure increase, venous thromboembolism, and heart infarction. Various phases of the reproductive age include young women, lactating women, and women in the later part of the reproductive age. Special groups include those who have experienced ectopic pregnancy, infections (candida, sexually transmitted diseases: chlamydia trachomatis, HIV infections), obesity, cardiovascular diseases, diabetes mellitus, tumors of the reproductive organs, liver diseases, migraine, epilepsy, surgery, and handicapped women. Postcoital contraception is used only in need, and methods for postcoital contraception include hormonal method and the copper IUD.
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PMID:[Contraception. Recommendations from a group of experts]. 790 65

Psoriasis is a genetically inherited spectrum of skin diseases characterized by epidermal proliferation and inflammation, which are reversible. Although many have reported that psoriasis is triggered by trauma, infections, stress, drugs, etc., the epidemiology of psoriasis remains poorly understood. Linkage to human leukocyte antigen-(HLA)-Cw6 and DR7 is strong in people with early onset disease, but concordance in monozygotic twins is only 67%, emphasizing the importance of a triggering event. Other factors that have been reported to affect the course of psoriasis include upper respiratory infections, smoking, obesity, alcohol ingestion, regional enteritis, and human immunodeficiency virus infection. This manuscript reviews the clinical epidemiology of psoriasis and highlights some of the needs for further investigation into specific areas of the disease.
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PMID:Epidemiology of psoriasis: clinical issues. 800 27

To our knowledge, an association between human immunodeficiency virus infection and pseudo-Cushing's syndrome has not previously been described. We describe four HIV-infected patients with pseudo-Cushing's syndrome, characterized by striking dorsocervical and submandibular fat accumulation and central obesity. In each case, cortisol levels were either normal or suppressed adequately with administration of dexamethasone, excluding the diagnosis of true Cushing's syndrome. Immune function and weight improved significantly preceding the development of pseudo-Cushing's syndrome. Three of the four patients were taking a common protease inhibitor at the onset of symptoms, and the fourth reported the exacerbation of his symptoms with the addition of a protease inhibitor. The observed characteristic pattern of fat deposition may be attributable to a specific effect of new antiretroviral therapies or may relate to recovery independent of medication usage. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. Further research into the mechanisms of this novel phenomenon is needed.
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PMID:Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients. 967 55

Diseases in other organs may impair the male reproductive system. Acute critical conditions such as severe trauma, surgery, myocardial infarction, burns, liver failure, intoxication, or starvation are associated with suppression of gonadotropin secretion and secondary hypogonadism. With chronic illnesses, a primary testicular disorder with elevated gonadotropin levels may occur. This may be associated with increased peripheral conversion of androgens to estrogens, resulting in clinical presentation of combined androgen deficiency and estrogen excess. The association of hypogonadism and feminization with cirrhosis of the liver is a classic example. Types of hypogonadism that may occur with chronic anemia, chronic renal failure, chronic spinal cord injury, thyroid diseases, Cushing's syndrome, diabetes mellitus, obesity, HIV infection, neoplasia, and other chronic illnesses are also described. Numerous drugs have side effects on the reproductive system.
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PMID:Reproductive effects of nontesticular illness. 992 10

The development of lipodystrophy as evidenced by central obesity, "moon facies," and a "buffalo hump" is a classical feature of Cushing's disease. Recently an association of "lipodystrophy" with the use of protease inhibitors has been reported. We describe a patient with lipodystrophy secondary to protease inhibitor therapy for HIV infection.
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PMID:Protease inhibitor-induced lipodystrophy. 1018 89

Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.
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PMID:Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, infectious diseases, atherosclerosis and cancer. 1049 17

The blood-brain barrier (BBB) regulates the passage of solutes between the CNS and the blood. The BBB not only restricts the entry of serum proteins into the CNS, but it also controls the passage of nutrients, electrolytes, vitamins, minerals, free fatty acids, peptides, and regulatory proteins in both the brain to blood and blood to brain direction. The BBB performs these functions through a number of saturable and non-saturable mechanisms. For example, efflux (CNS to blood) mechanisms regulate the levels of nutrients and minerals in the CSF, detoxify the CNS, reinforce the impermeability of the BBB against circulating toxins and many drugs, secrete CNS-originating substances into the blood, and drain substances directly into the cervical lymphatic nodes. Influx mechanisms control the homeostatic environment of the CNS, supply the brain with nutrients, and help to integrate CNS and peripheral functions. These mechanisms are altered in and can be the basis for disease and many of these systems are altered in neuroAIDS. We review here examples of several diseases in which the functions of the BBB are altered, and some conditions, such as alcoholism, multiple sclerosis, obesity, and a subtype of mental retardation, where those altered functions may underlie the pathophysiology. Finally, we consider some of the ways in which these aspects of the BBB could be active in neuroAIDS, including the efflux of anti-virals, the transport of virus by adsorptive endocytosis, egress routes for HIV-1 via brain lymphatics, and the release of neurotoxins from brain endothelial cells.
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PMID:Physiology and pathology of the blood-brain barrier: implications for microbial pathogenesis, drug delivery and neurodegenerative disorders. 1060 96


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