Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a continuing effort to design small-molecule inhibitors of dihydrofolate reductase (DHFR) that combine the enzyme-binding selectivity of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine (trimethoprim, TMP) with the potency of 2,4-diamino-5-methyl-6-(2',5'-dimethoxybenzyl)pyrido[2,3-d]pyrimidine (piritrexim, PTX), seven previously undescribed 2,4-diamino-5-[2'-methoxy-5'-(substituted benzyl)]pyrimidines were synthesized in which the substituent at the 5'-position was a carboxyphenyl group linked to the benzyl moiety by a bridge of two or four atoms in length. The new analogues were all obtained from 2,4-diamino-5-(5'-iodo-2'-methoxybenzyl)pyrimidine via a Sonogashira reaction, followed, where appropriate, by catalytic hydrogenation. The new analogues were tested as inhibitors of DHFR from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), and Mycobacterium avium (Ma), three life-threatening pathogens often found in AIDS patients and individuals whose immune system is impaired as a result of treatment with immunosuppressive chemotherapy or radiation. The selectivity index (SI) of each compound was obtained by dividing its 50% inhibitory concentration (IC(50)) against Pc, Tg, or Ma DHFR by its IC(50) against rat DHFR. 2,4-Diamino-[2'-methoxy-5'-(3-carboxyphenyl)ethynylbenzyl]pyrimidine (28), with an IC(50) of 23 nM and an SI of 28 in the Pc DHFR assay, had about the same potency as PTX and was 520 times more potent than TMP. As an inhibitor of Tg DHFR, 28 had an IC(50) of 5.5 nM (510-fold lower than that of TMP and similar to that of PTX) and an SI value of 120 (2-fold better than TMP and vastly superior to PTX). Against Ma DHFR, 28 had IC(50) and SI values of 1.5 nM and 430, respectively, compared with 300 nM and 610 for TMP. Although it had 2.5-fold lower potency than 28 against Ma DHFR (IC(50) = 3.7 nM) and was substantially weaker against Pc and Tg DHFR, 2,4-diamino-[2'-methoxy-5'-(4-carboxyphenyl)ethynylbenzyl]pyrimidine (29), with the carboxy group at the para rather than the meta position, displayed 2200-fold selectivity against the Ma enzyme and was the most selective 2,4-diamino-5-(5'-substituted benzyl)pyrimidine inhibitor of this enzyme we have encountered to date. Additional bioassay data for these compounds are also reported.
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PMID:New 2,4-diamino-5-(2',5'-substituted benzyl)pyrimidines as potential drugs against opportunistic infections of AIDS and other immune disorders. Synthesis and species-dependent antifolate activity. 1499 35

Emergence of Staphylococcus aureus small colony variants (SCVs) has been associated with antibiotic use, particularly with trimethoprim-sulfamethoxazole (TMP-SMZ). In this study, 634 specimens of 125 patients with AIDS were prospectively screened for S. aureus with normal phenotype and for S. aureus SCVs. Charts of these patients were reviewed for previous prophylaxis with TMP-SMZ often used as long-term pneumocystosis prophylaxis. Thirty-seven patients (29.6%) harbored S. aureus in their anterior nares, three of these patients (8.1%) had S. aureus SCVs. Interestingly, TMP-SMZ does not appear to select for S. aureus SCVs in nasal swabs of these patients.
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PMID:Effect of trimethoprim-sulfamethoxazole prophylaxis in AIDS patients on the formation of the small colony variant phenotype of Staphylococcus aureus. 1502 28

We present a 46-year-old African-American man with AIDS who was admitted on two different occasions within three weeks for signs and symptoms of meningitis after using trimethoprim/sulfamethoxazole (TMP/SMX). TMP/SMX is primarily used for the treatment of pneumocystis carinii pneumonia prophylaxis in AIDS patients. Drug-induced aseptic meningitis (DIAM) is commonly seen with nonsteroidal anti-inflammatory drugs (NSAIDS), antibiotics (with TMP/SMX being the most frequently implicated), intravenous immunoglobulins and OKT3 antibodies. However, the implication of TMP/SMX inducing aseptic meningitis has been underreported to FDA/MEDWATCH program. This might be due to the fact that it has also been used to treat bacterial meningitis from organisms like Listeria monocytogenes, which is a common pathogen in the elderly and in infants. We reviewed the literature in an attempt to characterize the pattern and predictors of TMP/SMX-induced aseptic meningitis.
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PMID:Trimethoprim-sulfamethoxazole-induced aseptic meningitis. 1657 15

We report a case of dual Mycobacterium tuberculosis (TB) and Pneumocystis jiroveci (carinii) (PCP) lymphadenitis in a patient with HIV who had been receiving trimethoprim-sulfamethoxazole (TMP-SMX) as systemic prophylaxis for PCP. This patient was successfully treated with antituberculosis medications and TMP-SMX. Our review of the literature identified this as the first reported case of dual TB and PCP lymphadenitis in an HIV-infected host and highlights the potential limitations of TMP-SMX prophylaxis.
AIDS Patient Care STDS 2006 Jan
PMID:Dual infection with Mycobacterium tuberculosis and Pneumocystis jiroveci Lymphadenitis in a Patient with HIV infection: case report and review of the literature. 1642 50

Daily prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) significantly decreases morbidity and mortality among people living with HIV. Some clinicians are reluctant to use TMP-SMZ in pregnant and breastfeeding HIV-infected women because of concerns about the possible teratogenicity when used in the first trimester and about its potential to induce hyperbilirubinemia near term and during early breastfeeding. We systematically reviewed evidence regarding the toxicity of TMP-SMZ prophylaxis in pregnant and breastfeeding women to help guide practice in resource-limited settings. We identified relevant literature by searching PubMed and MEDLINE via OVID, Embase, and Science Citation Index for data on hyperbilirubinemia, kernicterus, and teratogenicity associated with administration of sulfonamides and TMP-SMZ through July 2005. We also reviewed the reference lists of identified articles. Most studies demonstrated that TMP-SMZ was not associated with hyperbilirubinemia when administered to mothers during pregnancy and breastfeeding. No cases of kernicterus were reported in neonates after maternal ingestion of sulfonamides. There is mixed evidence linking ingestion of TMP-SMZ and other sulfonamides in early pregnancy to elevated risks of oral clefts, neural tube defects, and cardiovascular and urinary tract abnormalities, although some sources found that supplementation with folic acid might ameliorate this potential risk. Existing guidelines recommend that HIV-infected pregnant women receive prophylaxis, but they differ with regards to stage of disease at which to initiate treatment, need for CD4+ T-lymphocyte testing, and prophylaxis during the first trimester. Existing data indicate that the risk of serious injury to neonates from maternal use of daily TMP-SMZ prophylaxis during pregnancy and breastfeeding is small. Given the substantial benefits of TMP-SMZ prophylaxis for HIV-infected women living in resource-limited settings, this review indicates that it is safe to abide by the WHO guidelines recommending daily TMP-SMZ prophylaxis for HIV-infected pregnant women.
AIDS Rev
PMID:Systematic review of the safety of trimethoprim-sulfamethoxazole for prophylaxis in HIV-infected pregnant women: implications for resource-limited settings. 1673 49

We report a case of rhabdomyolysis associated with the use of trimethoprim-sulfamethoxazole (TMP-SMX) in a newly diagnosed AIDS patient with presumed Pneumocystis jiroveci (formerly named Pneumocystis Carinii) pneumonia. The present case is significant because of the paucity of similar cases in the literature and the relative frequency with which TMP-SMX is used today.
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PMID:Trimethoprim-sulfamethoxazole associated rhabdomyolysis in a patient with AIDS: case report and review of the literature. 1677 45

In patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), the most common cause of focal intracranial lesion is Toxoplasma gondii infection. T. gondii encephalitis is an easily and effectively treatable disease, with promising outcomes. T. gondii has the potential to form a focal infection niche anywhere in the central nervous system, thus allowing for a colorful clinical picture. In this report, we attempted to present five HIV/AIDS cases with central nervous system toxoplasmosis demonstrating five different neurological presentations. The ages, gender and clinical findings of the patients who were admitted to our Infectious Diseases Clinics were as follows; 35 years old male patient with delirium, 49 years old male patient with focal dystony, 32 years old female patient with facial paralysis and monoparalysis, 53 years old male patient with Wernicke syndrome, 32 years old male patient with epilepsy. Cerebral toxoplasmosis were diagnosed by clinical findings and imaging techniques. The patients were treated with trimetoprim-sulfametoxazol (TMP-SMZ) and haloperidol, only TMP-SMZ, clindamycin and daraprim, TMP-SMZ and levotiracetam, TMP-SMZ and phenytoin, respectively, with recovery in neurological and radiological symptoms. In conclusion, until proven otherwise, HIV/AIDS patients presenting with focal neurological complaints should be accepted as having central nervous system toxoplasmosis.
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PMID:[The colorful clinical spectrum of cerebral toxoplasmosis in five HIV positive cases: what comes out of Pandora's box?]. 1677 62

We investigated regularly swabs of adults dispenzarised at Mary Immaculate Clinic of Trnava University in Nairobi providing free health care for about 50 000 population of Mukuru Slums. 20 patients who were treated for AIDS by our clinic (those who started HAART before Free National AIDS Cooperation Programme - NASCOP) were assessed after 1, 2 and 3 years (18 of 20 completed the survey, other 2 loss of follow up, probably died. Exposure to other molecules can select resistant mutants. Previous exposure to TMP/SMX was similar in both groups and therefore was not responsible for the difference between resistance patterns.
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PMID:Etiology and resistance patterns of respiratory isolates in Kenyan adults with AIDS from slum population. 1803 Feb 79

Data are controversial as to the role of menarche age as a risk factor of high-risk human papillomavirus (HR-HPV) infections. The objective of this study was to analyse the risk estimates for age at menarche as determinant of cervical intraepithelial neoplasia (CIN) and HR-HPV infections. A cohort of 3187 women were stratified into three groups according to their age at menarche: (i) women <13 years of age; (ii) those between 13 and 14 years and (iii) women >15 years of age. These groups were analysed for predictors of (a) HR-HPV, (b) high-grade CIN and (c) outcome of HR-HPV and cytological abnormalities during prospective follow-up. All the three groups had identical prevalence of HR-HPV, Papanicolaou smear abnormalities and CIN grades. In contrast to menarche age itself, the time from menarche to the first intercourse (TMI), to the first pregnancy (TMP) and to the first delivery (TMD) were all significant (P = 0.0001) predictors of HR-HPV (but not CIN2) in univariate analysis, but lost their significance in a multivariate model. Outcome of cervical disease and HR-HPV infection was unrelated to menarche age, the latter and the three intervals being not predictors of CIN2 in a multivariate model. In conclusion, age at menarche and the intervals between menarche and (i) onset of sexual activity, (ii) first pregnancy and iii) first delivery, are not independent predictors of HR-HPV infections and CIN2 in multivariate analysis.
Int J STD AIDS 2008 Jan
PMID:Age at menarche is not an independent risk factor for high-risk human papillomavirus infections and cervical intraepithelial neoplasia. 1827 41

The rationale to screen for glucose-6-phosphate dehydrogenase (G6PD) deficiency in HIV-infected individuals is their increased likelihood to receive oxidant drugs and subsequent potential of hemolytic events. However, current guidelines regarding who should be screened are conflicting. The authors examined the prevalence of G6PD deficiency and the frequency of hemolytic events in an urban HIV clinic. They used data from a military database as a comparison. In both cohorts, a relatively high number of black females were found to be G6PD deficient (10% and 13%), which was similar to the rate in men (15% and 12%). No white females were G6PD deficient. The authors identified 8 drug-related hemolytic events in HIV clinic patients. Two patients necessitated blood transfusions; both were triggered by trimethoprim/sulfamethoxazole (TMP/SMX). Although G6PD screening prior to the use of TMP/SMX is not often considered by clinicians, the authors' finding of 2 hemolytic events requiring transfusion suggests this would be beneficial.
J Int Assoc Physicians AIDS Care (Chic)
PMID:Prevalence and significance of G6PD deficiency in patients of an urban HIV clinic. 1834 24


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