Are there differences in disease progression and mortality among male and female HIV patients on antiretroviral therapy? A meta-analysis of observational cohorts.

Studies examining the sex differences in morbidity and mortality among HIV/AIDS patients have yielded inconsistent results. We conducted a meta-analysis of sex differences in disease progression and mortality among HIV/AIDS patients. Medical literature databases from inception to August 2014 were searched for published observational studies assessing sex differences in immunologic and virologic response, disease progression and mortality among HIV-infected patients. Random effects meta-analyses of 115 eligible studies were conducted to obtain pooled estimates of outcomes and heterogeneity was explored in sub-group analyses. Pooled estimates showed an increased risk of progression to AIDS (relative risk [RR]=1.11,95% CI=1.02-1.21) and all-cause mortality (RR=1.23, 95% CI=1.17-1.29) among males compared to females. All-cause mortality differed by sex only in low and middle income countries. The risk of AIDS-related mortality (RR=1.03, 95% CI=0.82-1.30), immunologic failure (RR=1.19,95% CI: 0.97-1.47), virologic suppression (RR=0.98, 95% CI=0.84-1.14), virologic failure (RR=1.26, 95% CI=0.99-1.61) and the change in CD4 cell count (Weighted mean difference [WMD] = -5.15, 95% CI= -13.57 to 3.28) did not differ by sex. These findings were modified by disease severity, adherence and use of highly active antiretroviral therapy. We conclude that HIV-related disease progression and survival outcomes are poorer in males.

Seroprevalence of hepatitis C infection in HIV patients using a rapid one-step test strip kit.

BACKGROUND: Hepatitis C virus (HCV) and HIV are transmitted via similar routes making co-infection with these viruses a common event. In addition, HIV infection and related immunosupression in patients with hepatitis C may be associated with more rapid progression of liver disease to cirrhosis, end-stage liver disease and death. OBJECTIVE: The study is to determine the seroprevalence of HIV/HCV co-infection rate. METHODS: A cross -sectional study was carried out from January to March 2010 at the HIV clinic of the Lagos State University Teaching Hospital. About 5 mls of blood sample was collected from each consenting participant. Sera were subjected to HCV rapid kit as recommended by the manufacturer (Dia Spot HCV one step test strip). The descriptive data was given as means +/- standard deviation (SD). The chi-squared test was used for analytical assessment. The differences were considered statistically significant when P value obtained was < 0.05. RESULTS: The overall seroprevalence rate of HIV/HCV coinfection was 3.3%. Only 6 of 194 female HIV subjects screened tested positive for HCV (3.1%), while 3 of 73 male subjects tested positive for HCV (4.1%) (P value 0.001). None of the 9 co-infected HIV/HCV participants (both male and female) had CD4 count of 350 and above, 3 had a count of 1-100 cells/il., 4 had 100-200, while 2 had 201-350. CONCLUSION: There is the need to include hepatitis C screening routinely in all HIV-infected patients undergoing pre-HAART evaluation in HIV clinics in order to lower liver-related morbidity and mortality associated with them.

Effects of methyllycaconitine and related analogues on bovine adrenal alpha3beta4* nicotinic acetylcholine receptors.

Adrenal secretion and binding studies were performed using ring E analogues of methyllycaconitine to assess structural determinants affecting activity on bovine adrenal alpha3beta4* nicotinic receptors. The most potent analogues are as potent as many inhibitors of adrenal secretion. Our data support the potential use of methyllycaconitine analogues to generate nicotinic receptor subtype-specific compounds.

Structure-activity studies with ring E analogues of methyllycaconitine. Synthesis and evaluation of enantiopure isomers of selective antagonist at the alpha3 nicotinic receptor.

The four diastereomers 4a-d of methyllycaconitine (MLA) analogue 3 ( R =(CH(2))(3)Ph, R'=CH(3)) have been synthesized in enantiomerically pure form by coupling both (S)- and (R)-2-(methylsuccinimido)benzoic acid (5a and 5b) with both (S)- and (R)-3-hydroxymethyl-N-(3-phenyl) propylpiperidine (6a and 6b) using TBTU. These compounds were assayed for potency as nicotinic acetylcholine receptor (nAChRs) antagonist. All the four diastereomers showed the same potency at both the alpha3 and alpha7 receptors as racemic compound 3. This indicates that the binding at nicotine acetylcholine receptors (nAchRs) is probably non-stereospecific.

Synthesis and biological evaluation of some novel 4H-benzopyran-4-one derivatives as nonsteroidal antiestrogens.

The preparation and characterization of some novel 2- and 3-substituted-7-methoxy-4H-1-benzopyran-4-one are presented. The synthesized compounds were evaluated for their uterotrophic, antiuterotrophic and antiimplantation activities in mature female albino rats. 3-Benzyl-7-methoxy-4H-1-benzopyran-4-one (14) showed the highest uterotrophic activity (87%) based on dry uterine weight gain. The antifertility activity, as assessed by the post-coital antiimplantation activity test, was of weak potency for most compounds (14-29%). Among the products, the 2-(4'-methoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one (19) exhibited the highest antiestrogenic activity of 65%. It also elicited 31% of the uterotrophic activity of estradiol.

Antilipidemic agents, Part. IV: Synthesis and antilipidemic testing of some heterocyclic derivatives of hexadecyl and cyclohexyl hemisuccinate esters.

Two main classes of novel esters containing a hexadecyl or cyclohexyl group and various heterocyclic rings, like quinazolines, triazoles, thiadiazoles and pyrazoles have been synthesized. The first class involves the synthesis of the hexadecyl ester derivatives; namely 3-substituted-2-(hexadecyloxycarbonylpropionylthio)-4(3H)-quinazol inones 4a-c; 4-substituted-3-(4-pyridyl)-5-(hexadecyloxycarbonylpropionylthio)- 4H- 1,2,4-triazoles 6a-c; 5-substituted-2-(hexadecyloxycarbonylpropionylamino)-1,3,4-thiadia zoles 8a-c, 4-[4-(hexadecyloxycarbonyl)phenyl]azo-5-hydroxy-3-methyl-1-phen ylpyrazole 16; and 1-[4-(hexadecyloxycarbonyl) phenyl]-3-methyl-2-pyrazolin-5-one 19. The second class comprises the synthesis of the cyclohexyl ester derivatives; namely 3-substituted-2-(cyclohexyloxycarbonylpropionylthio)-4(3H)-quinazo linones 11a, b, 4-substituted-3-(4-pyridyl)-5-(cyclohexyloxycarbonylpropionylthio) -4 H-1,2,4-triazoles 12a, b and 5-isopropylthio-2-(cyclohexyloxycarbonylpropionylamino)-1,3, 4-thiadiazole 13. The antihypercholesterolemic as well as antihyperlipidemic activities of representative compounds have been studied. All the compounds tested resulted in a decrease in the lipid indices (cholesterol, LDL-cholesterol, HDL-cholesterol and serum triglycerides levels) studied in mice. Compounds 4b, 11a and 12a showed the highest antihyperlipidemic activity; their activities were almost equal to that of beta-sitosterol which was used as a standard.

Novel triazolo[4,3-a]quinazolinone and bis-triazolo[4,3-a:4,3'-c]quinazolines: synthesis and antitoxoplasmosis effect.

Several quinazoline derivatives containing substituted thiosemicarbazido and S-methylisothiosemicarbazido groups at the 2-position and at both the 2- and 4-positions have been synthesized. Treatment of the S-methylthiosemicarbazides with morpholine or diethylamine did not give the corresponding guanidines. Instead, they underwent cyclodesulfurization into the condensed ring systems, [1,2,4]triazolo[4,3-a]quinazolinones and bis-[1,2,4]triazolo[4,3-a:4'.3'-c]quinazolines. Evaluation of the products for antitoxoplasmosis effect by studying the ultrastructure morphology of the organisms using scanning electron microscopy (SEM) indicated their efficacy in causing structural deformity of Toxoplasma gondii. Such a deformity plays an important role in obstructing the entry of the organisms into host cells.

Novel steroidal 1,4-diketones and pyridazine derivatives as potential antiestrogens.

A series of steroidal 1,4-diketone derivatives was synthesized by acid-catalyzed condensation of 2-acetylestradiol-17 beta-acetate with substituted phenylglyoxals. Conversion of the products into the corresponding pyridazine derivatives was achieved by reaction with hydrazine hydrate. The synthesized compounds were evaluated for their uterotrophic, antiuterotrophic, and antifertility activities in mature female albino rats. Among the compounds tested, the phenyl 2, p-bromophenyl 3, and p-methoxyphenyl 5 diketone derivatives displayed uterotrophic activity of 72%, 72%, and 91%, respectively. The gradation of antiestrogenic activity was assessed in vivo by the inhibition of the estrone-stimulated uterine growth. Compounds 2-5 showed moderate antiestrogenic activity of 53-56%. None of the tested compounds elicited antifertility activity as assessed by the post-coital antiimplantation activity test.

Detection of Herpes Simplex Virus and candida infection with special emphasis on their possible role in human Squamous Cell Carcinoma and its variants.

Sixty seven cases of human oral S.C.C. with its intra oral variances were investigated microbiologically, histopathologically, histochemically and immunologically. Yeasts were isolated from 85% of examined cases. "Candifast test" showed that Candida albicans was the commonest form of the detected fungi, followed by C. parapsilosis and C. tropicalis, while the least in frequency was the Torulopsis glabrata. Yeasts were more detected in females, elders and tobacco smokers. Two cases of well differentiated S.C.C. were surprisingly detected, and for the first time in literature, associated with a specific granulomatous reaction and showed positively impregnated fungi. While negative reactions for fungi were noticed in all lymphoepitheliomas, almost all the verrucous carcinoma were positive. Viral inclusion bodies were demonstrated for the first time by MT. This method was rapid, economic and could be used as a pilot study before applying the more specific monoclonal antibody techniques or in-situ hybridization methods. Comparing the results of HSV hybridization with that of candida infection we found that both could be detected in some cases. The results indicate that viral and fungal factors may be synergetic in the development of oral carcinomas.

Synthesis and antimicrobial activity of some tetramethylenethieno[2,3-d]pyrimidine derivatives.

A series of tetramethylenethieno[2,3-d]pyrimidine derivatives has been synthesized and tested for its antimicrobial properties. All the synthesized compounds were found to exhibit in vitro antibacterial and/or antifungal activity. The highest activity was elicited by 4-benzolhydrazino-5,6-tetramethylenethieno[2,3-d]pyrimidine (9) showing MIC value of 7.81 micrograms/ml against E. Coli and C. albicans, while its MBC value was half that of nystatin. Compound 16 was almost as potent as nystatin exhibiting a minimum bactericidal concentration (MBC) value of 15.62 micrograms/ml.

Synthesis and antimicrobial activity of some thiazolinyl tetrahydrobenzo[b]thiophenes and thiazolinyl tetrahydrobenzothieno[2,3-d]pyrimidin-4-ones.

Two series of novel 3-carbethoxy-2-(3',4'-disubstituted-2',3'- dihydrothiazol-2'-ylidenamino)-4,5,6,7-tetrahydrobenzo[b] thiophenes (3a-o) and 2-methyl-3-(3',4'-disubstituted-2',3'-dihydrothiazol-2'-ylidena mino-5,6,7,8- tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H) ones (8a-o) have been synthesized and tested for antimicrobial activity. All members of the series have been found to exhibit in vitro antibacterial and/or antifungal activities. Activity was optimized by cyclization to the thienopyrimidin-4-ones. In particular, compounds 8e and 8fd were the most active against the 3 tested microorganisms. Their antifungal activity was higher than that exhibited by nystatin while their MIC was found to be nearly equal to that of nystatin.