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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis, transcription and differentiation in addition to functions in the nervous system. Deregulation of CDKs in various diseases has stimulated an intensive search for selective pharmacological inhibitors of these kinases. More than 50 inhibitors have been identified, among which >20 have been co-crystallized with CDK2. These inhibitors all target the ATP-binding pocket of the catalytic site of the kinase. The actual selectivity of most known CDK inhibitors, and thus the underlying mechanism of their cellular effects, is poorly known. Pharmacological inhibitors of CDKs are currently being evaluated for therapeutic use against cancer, alopecia, neurodegenerative disorders (e.g. Alzheimer's disease, amyotrophic lateral sclerosis and stroke), cardiovascular disorders (e.g. atherosclerosis and restenosis), glomerulonephritis, viral infections (e.g. HCMV, HIV and HSV) and parasitic protozoa (Plasmodium sp. and Leishmania sp.).
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PMID:Pharmacological inhibitors of cyclin-dependent kinases. 1223 54

This paper describes the South African cause-of-death profile in 1996, the latest year for which routine data are available. Underreporting of deaths, misclassification of causes and HIV/AIDS make face value interpretation of reported cause-of-death data difficult. Changes in subsequent years due to HIV/AIDS are considered using model projections. South Africa is undergoing a protracted bipolar transition with the coexistence of both diseases of poverty and emerging chronic diseases. In 1996 these accounted for similar proportions of the premature mortality, about 27% for males and 35% for females, with the added burden of injuries accounting for a further 35% in males and 16% in females. Tuberculosis (TB), lower respiratory tract infections, diarrhoea, HIV/AIDS, perinatal diseases, malnutrition and septicaemia contributed to the pretransitional conditions, while stroke, diabetes, ischaemic heart disease, hypertensive heart disease, asthma, chronic obstructive lung disease, cancer of the lung in men and cancer of the cervix in women contributed to the premature mortality due to non-communicable diseases. Homicide is the major cause of injury death for men while unintentional injuries are the major cause of injury death for women. Projections suggest that this triple burden (diseases of poverty, emerging chronic diseases and injuries) has now become a quadruple burden resulting from the HIV/AIDS epidemic and that without interventions to reduce mortality, by the year 2010, AIDS deaths will account for double all other causes of death combined. While efforts to improve the cause-of-death statistics are needed, the current data clearly suggest that comprehensive public health strategies to improve the health of the nation must be strengthened, and reducing the number of deaths that can be expected to result from AIDS requires urgent attention.
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PMID:South African cause-of-death profile in transition--1996 and future trends. 1224 21

This article presents a compilation of top researches conducted during the past 2 decades by the Contraceptive Technology Update. The following lists offer a brief insight into the breadth of research available to family planners: 1) the multicenter study of the lactational amenorrhea method to test its acceptability and efficacy as an introductory postpartum method; 2) the multinational study of breast cancer and depot-medroxyprogesterone acetate (DMPA) confirmed the decrease in risk of having breast cancer among women who are using DMPA; 3) several investigations on family planning particularly the new guidelines for family planning methods, contraceptive failure, and probability of conception after the 6th day of contraceptive cessation were studied; 4) researches were also made on the prevalence of Kaposi's sarcoma, Pneumocystis carinii pneumonia among young and homosexual men, and other opportunistic infections secondary to AIDS/HIV infection, and the efficacy of zidovudine in the prevention of HIV vertical transmission; 5) trials have been conducted on the mechanism of IUDs, its relation to pelvic inflammatory disease, and the negligible result of prophylactic antibiotics in the risk of having upper genital tract infection after IUD insertion; and 6) reports from researches have indicated the relationship between hormonal contraception use and breast cancer; and between ovarian cancer, stroke, acne vulgaris and oral contraceptive use. Lastly, studies on tubal sterilization have proven their efficacy in the prevention of pregnancies.
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PMID:20 years, 20 articles: studies to know. 1229 9

A major factor in the context of evaluating depression in the elderly is the role of medical problems. With aging there is a rapid increase in the prevalence of a number of medical disorders, including cancer, heart disease, Parkinson's disease, Alzheimer's disease, stroke, and arthritis. In this article, we hope to bring clarity to the definition of comorbidity and then discuss a number of medical disorders as they relate to depression. We evaluate medical comorbidity as a risk factor for depression as well as the converse, that is, depression as a risk factor for medical illness. Most of the disorders that we focus on occur in the elderly, with the exception of HIV infection. This review focuses exclusively on unipolar disorder. The review summarizes the current state of the art and also makes recommendations for future directions.
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PMID:Comorbidity of depression with other medical diseases in the elderly. 1236 69

Our current understanding of nitric oxide (NO), cyclic GMP (cGMP) and protein kinase G (PKG) signaling pathways in the nervous systems has its origins in the early studies conducted on vascular tissues during the late 1970s and early to mid-1980s. The pioneering research into the NO/cGMP/PKG pathway in blood vessels conducted by the laboratories of Drs. Ferid Murad, Louis Ignarro and Robert Furchgott ultimately led to the awarding of the 1998 Nobel Prize in Physiology or Medicine to these three scientists. On the basis of further pioneering studies by Drs. John Garthwaite, Solomon Snyder, Steven Vincent and many other neuroscientists during the late 1980s and throughout the 1990s, it became recognized that NO serves as a neurotransmitter/neuromodulator in the central and peripheral nervous systems and that certain neural cells possess a cGMP signaling pathway similar to that in vascular smooth muscle cells. Although NO (at high concentrations) is toxic and thought to participate in neuronal cell death during stroke and neurodegenerative diseases (e.g. amyotrophic lateral sclerosis, Alzheimer's disease, HIV dementia and Parkinson's disease), recent evidence suggests that NO at low physiological concentrations can act as an antiapoptotic/prosurvival factor in certain neural cells (e.g. PC12 cells, motor neurons and neurons of dorsal root ganglia, hippocampus and sympathetic nerves). The antiapoptotic effects of NO are mediated, in part, by cGMP and a downstream target protein, PKG. Other cGMP-elevating factors (e.g. atrial and brain natriuretic peptides) and direct PKG activator (e.g. 8-bromo-cGMP) also have antiapoptotic effects which have been quantified by the new capillary electrophoresis with laser-induced fluorescence detector technology. Inhibition of soluble guanylyl cyclase and lowering of basal cGMP levels cause apoptosis in unstressed neural cells (NG108-15 and N1E-115 cells). The cGMP/PKG pathway appears to play an essential role in preventing activation of a proapoptotic pathway, thus promoting neural cell survival.
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PMID:Involvement of cyclic GMP and protein kinase G in the regulation of apoptosis and survival in neural cells. 1239 44

The occurrence of stroke in patients with human immunodeficiency virus (HIV) infection has been traditionally associated with opportunistic infections and tumors, and advanced stages of immunosuppression. However, this reality is undergoing major changes. Effective antiretroviral regimens are now able to forestall the progression of HIV infection and avoid early mortality. As HIV-infected patients are growing older, clinicians are facing new challenges, including an increasing incidence of vascular complications. The use of protease inhibitors is associated with a variety of metabolic derangements that could produce accelerated atherosclerosis. Cerebrovascular hemodynamic function is impaired in HIV-infected patients with evidence of abnormal vasoreactivity even in otherwise healthy individuals. The potential contribution from these novel mechanisms should be added to the high incidence of classic vascular risk factors in the HIV-infected population and the cardiac abnormalities frequently observed in these patients. Large-scale epidemiological studies should be carried out to define the true incidence of stroke in HIV-infected patients and the factors associated with its occurrence.
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PMID:Stroke in HIV-infected patients: a clinical perspective. 1249 9

Glutamate transport is central to neurotransmitter functions in the brain. Impaired glutamate transport induces neurotoxicity associated with numerous pathological processes, including stroke/ischemia, temporal lobe epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, HIV-1-associated dementia, and growth of malignant gliomas. Excitatory amino acid transporter-2 (EAAT2) is a major glutamate transporter in the brain expressed primarily in astrocytes. We presently describe the cloning and characterization of the human EAAT2 promoter, demonstrating elevated expression in astrocytes. Regulators of EAAT2 transport, both positive and negative, alter EAAT2 transcription, promoter activity, mRNA, and protein. These findings imply that transcriptional processes can regulate EAAT2 expression. Moreover, they raise the intriguing possibility that the EAAT2 promoter may be useful for targeting gene expression in the brain and for identifying molecules capable of modulating glutamate transport that could potentially inhibit, ameliorate, or prevent various neurodegenerative diseases.
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PMID:Insights into glutamate transport regulation in human astrocytes: cloning of the promoter for excitatory amino acid transporter 2 (EAAT2). 1257 75

Immune responses protect the CNS against pathogens. However, the fact that there is little dispensable tissue in the brain makes regulation necessary to avoid disastrous immune-mediated damage. Astrocytes respond vigorously to any brain injury (e.g., tumor, stroke, AD, MS, HIV) and are postulated to play an important role in the fine tuning of brain inflammation. The authors propose that astrocytes use death receptors to modulate pro- and anti-inflammatory effects.
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PMID:Death receptors on reactive astrocytes: a key role in the fine tuning of brain inflammation? 1260 28

The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson's disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders.
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PMID:Therapeutic potential of cannabinoids in CNS disease. 1261 97

Several case reports and series described ischaemic cerebrovascular events in HIV infection. However, the exact prevalence and the clinical features of these events are unknown. We performed a cohort study on 772 consecutive HIV infected patients and evaluated the rate of transient ischaemic attacks (TIA) and of completed stroke. A total prevalence of 1.9% for TIA (0.8%) and stroke (1.2%) was calculated resulting in an annual incidence rate of 216 per 100000. The prevalence was highest in the later stages of the infection. Stroke patients had a poorer immunological state than the TIA and the cohort patients. Probable (n = 3) and possible (n = 2) vasculitis and cardiogenic embolism (n = 2) could be detected as aetiology, the remaining patients had a cryptogenic event. Our data suggest that ischaemic cerebrovascular events are more common in HIV infected patients than in the general population and that a part of these events might be caused by HIV associated vasculitis or vasculopathy.
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PMID:Ischaemic cerebrovascular events in HIV infection: a cohort study. 1264 80


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