Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some diseases and environmental exposures, including those that are risk factors for atherosclerosis, are associated with increased oxidant stress. The objective of this cross-sectional, observational study was to determine whether oxidant stress is increased during human immunodeficiency virus type 1 (HIV-1) infection or its therapy. To quantify oxidant stress, plasma F2 isoprostane (F2-IsoP) concentrations were determined by gas chromatography/mass spectroscopy. A total of 120 subjects were enrolled during routine primary care visits. The median CD4+ T cell count was 341 cells/mm3, the median HIV-1 RNA level was 3.4 log10 copies/mL, and 74% of patients were receiving antiretroviral therapy. Plasma F2-IsoP concentrations were 12-149 pg/mL (median, 31 pg/mL). In univariate analysis, higher F2-IsoP concentrations were associated with lower log10 plasma HIV-1 RNA levels (P=.009) and with efavirenz use (P=.02). Both factors remained associated with plasma F2-IsoP concentrations in multivariate analysis. Oxidant stress associated with therapeutic control of viral replication may have important implications for long-term complications of antiretroviral therapy.
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PMID:Oxidant stress is increased during treatment of human immunodeficiency virus infection. 1468 56

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
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PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

Atherosclerosis increases cardiovascular risk and the possibility of developing acute myocardial infarction (AMI) or stroke. Patients infected with human immunodeficiency virus (HIV) often present morphological and metabolic alterations (hypercholesterolemia, hypertriglyceridemia, insulin resistance, diabetes) that can increase vascular risk. The frequent coexistence of classic risk factors (atherogenic diet, smoking, physical inactivity, cocaine abuse), the progressive increase in mean age of HIV-1 infected patients, and the polymedication they receive make it difficult to estimate the direct effect that new therapies may have on cardiovascular risk. Retrospective clinical studies with diverse designs in large cohorts offer contradictory results for cardiovascular risk in the HIV-infected population. Longer observational periods are needed and the effect of other classic risk factors needs to be controlled, in order to establish the possible detrimental effect the new therapies may have on cardiovascular risk in this population.
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PMID:[Cardiovascular risk in patients with chronic HIV-1 infection: a controversy with therapeutic, clinical and prognostic implications]. 1475 7

Cardiovascular infections due to Salmonella enterica are infrequently reported, so their clinical features, prognosis, and optimal treatment are not completely known. Mortality associated with aortitis and endocarditis caused by nontyphoidal Salmonella remains exceedingly high. In this review of cases of cardiovascular infections due to Salmonella enterica studied in 2 hospitals in Madrid, we tried to assess the clinical manifestations and the procedures leading to diagnosis in addition to treatment and outcome. To complete the spectrum of infections related to cardiovascular surgery, cases of postoperative mediastinitis, pericarditis, and infections associated with cardiac devices were also included.Twenty-three patients were reviewed: 11 had mycotic aneurysms; 7 had endocarditis; 2 had device-related infections; and 3 had pericarditis, mediastinitis, and infection of an arteriovenous fistula, respectively. The risk of endovascular infection in patients older than 60 years with bacteremia due to nontyphoidal Salmonella was 23%. Most patients with aortitis had risk factors for atherosclerosis, and 6 had preexisting atherosclerotic aortic aneurysms. All except 1 patient with endocarditis had underlying cardiac disorders. Acquired immunodeficiency disease (AIDS) was a major risk factor for salmonella bacteremia in 1 patient with aortitis and 1 with endocarditis. Fever, unremitting sepsis, "breakthrough" and relapsing bacteremia were the most common clinical findings. In addition, abdominal or thoracic pain and cardiac failure and pericarditis were common features in patients with aortitis and endocarditis respectively. Computed tomography (CT) scan, arteriography, and echocardiography were the main diagnostic tools. Mortality associated with mycotic aneurysms and endocarditis due to S. enterica was 45% and 28%, respectively. Thoracic aneurysms, rupture, and shock at the time of diagnosis were associated with increased mortality in patients with aortitis. In situ bypass grafting was successfully performed in most cases. After surgery, antimicrobial therapy was continued for 4-9 weeks. No relapses were observed after a mean follow-up of 64 months. Antimicrobial therapy alone or combined with valve replacement or excision of a ventricular aneurysm was successful treatment for most patients with salmonella endocarditis. Combined medical and surgical treatment was required for patients with mediastinitis and pericarditis, and patients with device-related infections needed removal of the complete device. Diagnosis of aortitis due to nontyphoidal Salmonella should be established as early as possible to reduce mortality. Patients older than 60 years who have positive blood cultures for Salmonella along with fever and back, abdominal, or chest pain should have an extensive workup for infective aortitis. Immediate bactericidal antimicrobial therapy should be started and a CT scan should be performed on an emergency basis. If a mycotic aneurysm is found, surgical resection should follow as soon as possible. Resection of the aneurysm with in situ bypass grafting is the procedure of choice. Postoperative antimicrobial therapy for 6-8 weeks seems enough to avoid relapses. Optimal treatment of patients with endocarditis occurring on ventricular aneurysms must include resection of the aneurysmal sac. Salmonella endocarditis can be successfully treated with antimicrobials alone. Valve replacement should be reserved for patients with cardiac failure or persisting sepsis, and for those who relapse after discontinuation of antimicrobial therapy.
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PMID:The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. 1502 66

chlamdAs with other organ systems, the vulnerability of the nervous system to infectious agents increases with aging. Several different infectious agents can cause neurodegenerative conditions, with prominent examples being human immunodeficiency virus (HIV-1) dementia and prion disorders. Such infections of the central nervous system (CNS) typically have a relatively long incubation period and a chronic progressive course, and are therefore increasing in frequency as more people live longer. Infectious agents may enter the central nervous system in infected migratory macrophages, by transcytosis across blood-brain barrier cells or by intraneuronal transfer from peripheral nerves. Synapses and lipid rafts are important sites at which infectious agents may enter neurons and/or exert their cytotoxic effects. Recent findings suggest the possibility that infectious agents may increase the risk of common age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and stroke. While scenarios can be envisioned whereby viruses such as Chlamydia pneumoniae, herpes simplex and influenza promote damage to neurons during aging, there is no conclusive evidence for a major role of these pathogens in neurodegenerative disorders. In the case of stroke, blood vessels may be adversely affected by bacteria or viruses resulting in atherosclerosis.
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PMID:Infectious agents and age-related neurodegenerative disorders. 1516 5

Cardiovascular dysfunction appears to be an important complication of human immunodeficiency virus (HIV) infection and is being reported with greater frequency. There have been recent reports in the literature of HIV patients who suffer from vascular lesions such as large artery vasculopathy secondary to vasculitis, as well as accelerated atherosclerosis of the coronary arteries. The latter has been linked to patients on protease inhibitors that are used as part of a highly active antiretroviral therapy (HAART) regimen and have also been implicated in a lipodystrophy syndrome. We report a rare case of an HIV-infected patient on HAART who presented with a large ascending aortic aneurysm associated with symptomatic severe aortic regurgitation. A noteworthy finding on pathological analysis of the aorta was an etiology of accelerated atherosclerosis rather than the more expected vasculitis.
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PMID:HIV disease and an atherosclerotic ascending aortic aneurysm. 1534 2

Endothelial dysfunction is a critical initial step of atherogenesis that subsequently contributes to the progression and clinical manifestations of atherosclerosis. The use of human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) agents has been associated with increased cardiovascular events and worsening of multiple coronary heart disease risk factors including dys-lipidemia, insulin resistance, and endothelial dysfunction. Endothelial dysfunction may be caused by HIV infection itself as well as treatment-related effects of the antiretroviral agents used to treat HIV. The available evidence suggests that PIs may induce endothelial dysfunction via their effects on both lipid and glucose metabolism. Studies in healthy subjects confirm a role for reduced endothelial nitric oxide production in the endothelial dysfunction associated with the PI indinavir. Further work is needed to determine the relative tendencies of other antiretroviral agents to induce endothelial dysfunction, the physiologic mechanisms involved, and the contribution of the metabolic and body shape changes associated with HIV treatment-related lipodystrophy, and to establish effective interventions for endothelial dysfunction in HIV-infected patients.
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PMID:Clinical aspects of endothelial dysfunction associated with human immunodeficiency virus infection and antiretroviral agents. 1547 Feb 73

Starting from the very simple molecule sulfamic acid, O-substituted-, N-substituted-, or di-/tri-substituted sulfamates may be obtained, which show specific biological activities which were or started to be exploited for the design of many types of therapeutic agents. Among them, sulfamate inhibitors of aminoacyl-tRNA synthetases (aaRSs) were recently reported, constituting completely new classes of antibiotics, useful in the fight of drug-resistant infections. Anti-viral agents incorporating sulfamate moieties have also been obtained, with at least two types of such derivatives investigated: the nucleoside/nucleotide human immunodeficiency virus (HIV) reverse transcriptase inhibitors, and the HIV protease inhibitors (PIs). In the increasing armamentarium of anti-cancer drugs, the sulfamates occupy a special position, with at least two important targets evidenced so far: the steroid sulfatases (STSs) and the carbonic anhydrases (CAs). An impressing number of inhibitors of STSs of the sulfamate type have been reported in the last years, with several compounds, such as 667COUMATE among others, progressing to clinical trials for the treatment of hormone-dependent tumors (breast and prostate cancers). This field is rapidly evolving, with many types of new inhibitors being constantly reported and designed in such a way as to increase their anti-tumor properties, and decrease undesired features (for example, estrogenicity, a problem encountered with the first generation such inhibitors, such as EMATE). Among the many isozymes of CAs, at least two, CA IX and CA XII, are highly overexpressed in tumors, being generally absent in the normal tissues. Inhibition of tumor-associated CAs was hypothesized to lead to novel therapeutic approaches for the treatment of cancer. Many sulfamates act as very potent (low nanomolar) CA inhibitors. The X-ray crystal structure of the best-studied isozyme, CA II, with three sulfamates (sulfamic acid, topiramate, and EMATE) has recently been reported, which allowed for a rationale drug design of new inhibitors. Indeed, low nanomolar CA IX inhibitors of the sulfamate type have been reported, although such compounds also act as efficient inhibitors of isozymes CA I and II, which are not associated with tumors. A large number of anti-convulsant sulfamates have been described, with one such compound, topiramate, being widely used clinically as anti-epileptic drug. By taking into consideration a side effect of topiramate, an anti-epileptic drug leading to weight loss in some patients, it has recently been proposed to use this drug and related sulfamates for the treatment of obesity. The rationale of this use is based on the inhibition of the mitochondrial CA isozyme, CA V, involved in lipogenesis. Some sulfamates were also shown to possess potent inhibitory activity against acyl coenzyme A:cholesterol acyltransferase, an enzyme involved in cholesterol metabolism. One such agent, avasimibe, is in advanced clinical trials for the treatment of hyperlipidemia and atherosclerosis. Thus, the sulfamate moiety offers very attractive possibilities for the drug design of various pharmacological agents, which are on one hand due to the relative ease with which such compounds are synthesized, and on the other one, due to the fact that biological activity of most of them is impressive.
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PMID:Sulfamates and their therapeutic potential. 1547 25

Current antiretroviral therapy protocols enable long-term survival of HIV-infected patients, decreasing the risk of infectious complications. Three classes of anti-HIV treatments are available. With longer survival, unusual cardiovascular complications related to iatrogenic biological anomalies (dyslipidemia and impaired glucose tolerance) have appeared among this young population which is exposed to usual risk factors of atherosclerosis. Antiretroviral therapies are suspected to cause these complications, inducing maturity-onset diabetes in 4 to 20% of patients, impaired glucose tolerance in 15 to 60%, hypertriglyceridemia in 15 to 74% depending on the survey, and hypercholesterolemia in 20 to 60%, especially in case of associated lipodystrophia. A lipid battery including total cholesterol, HDL, and triglycerides, and 12-h fasting blood glucose should be obtained before initiating antiretroviral therapy. Any anomalous finding should be followed carefully with regular surveillance every 3 to 6 months and search for other causes of secondary dyslipidemia. In the event of casual and persisting elevation of LDL-cholesterol levels, a statin treatment can be introduced. For secondary prevention, irrespective of the context, recommendations currently merge with the consensus applying to the general population. These patients require careful surveillance of cardiovascular risk factors and a specific care in addition to treatment of their immunodeficiency.
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PMID:[Antiretroviral therapy and cardiovascular risk]. 1552 82

Prolonged treatments with inhibitors of human immunodeficiency(HIV)-encoded protease (ARPI) have been reported to induce early atherosclerotic events. Our in vitro study indicates that alpha-tocopherol may prevent drug-induced premature atherosclerosis since it interferes with CD36 scavenger receptor over-expression induced by ritonavir in monocytes. The mechanism of CD36 upregulation by ritonavir involves inhibition of the ubiquitin-proteasome system and alpha-tocopherol is able to normalize proteasome activity. These findings suggest that ARPI combined with early alpha-tocopherol supplementation may decrease the drug-induced atherosclerotic risk.
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PMID:HIV protease inhibitors-induced atherosclerosis: prevention by alpha-tocopherol. 1581 62


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