Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

Bactérias gram negativas resistentes a antimicrobianos em alimentos

A partir de 154 espécimens de alimentos, representados por hortaliças (alface), leite e merenda escolar, obteve-se o isolamento e identificação de 400 amostras de bacilos Gram negativos. Esta amostragem se distribuiu em 339 enterobactérias (Escherichia, Shigella, Citrobacter, Klebsiella, Enterobacter, Serratia e Proteus) e 61 de gêneros afins (Acinetobacter, Flavobacterium, Aeromonas e Pseudomonas). Submetendo-se as culturas aos antimicrobianos: sulfadiazina (Su), estreptomicina (Sm), tetraciclina (Tc), cloranfenicol (Cm), canamicina (Km), ampicilina (Ap), ácido nalidíxico (Nal) e gentamicina (Gm), observou-se apenas seis estirpes sensíveis a todas as drogas e sensibilidade absoluta à Gm. A predominância dos modelos Su (27,6%) e Su-Ap (39,6%) incidiu nas enterobactérias, enquanto que, 18,0% para Ap e 9,8% para Su-Ap foram detectados nos gêneros afins. Para caracterização da resistência foram realizados testes de conjugação e a totalidade das culturas não revelou transferência para o gene que confere resistência ao ácido nalidíxico. Relevantes são as taxas de amostras R+ observadas nos bacilos entéricos, oscilando em torno de 90% (leite e merenda escolar) e alface, em torno de 70%

Coleformes fecais em águas de esgoto: II- transferência de marcadores e presença de plasmidial

Investigou-se a transferência de marcadores genéticos e a presença de DNA plasmidial em 240 culturas de Escherichia coli originárias de água de esgoto (afluente e fluentes) da Estação de Tratamento da Ilha do Governador, na cidade do Rio de Janeiro, RJ. Experimentos de conjugação com E. coli K 12 permitiram o isolamento de transconjugantes com resistência a antibióticos (Su, Sm, Tc, Cm e Ap); a metais pesados (Cu, Hg e Zn) e fatores colicinogênicos (Col Ia, Ib e V) principalmente para os coliformes isolados nos setores terminais da estação de tratamento. A distribuição de plasmídeos foi prevalente nas culturas de E. coli advindas dos efluentes, com percentuais superiores a 65.

The serological differentiation of acute and chronic schistosomiasis japonica using IgA antibody to egg antigen

Two groups of Schistosoma japonicum infected patients (acute and chronic ) and non-infected individuals were studied using IgA antibody to egg antigen (SEA) and IgG and IgM antibodies to keyhole limpet haemocyanin (KLH). The means and standard deviation of the optical density in ELISA of acute, chronic and negative groups for IgA anti-SEA were 583±124.7, 98.2±78.8 and 82.2±39. 3, respectively. There was a statistically significance between acute patients and chronic patients (P<0.01). The means and standard deviation of IgG and IgM antibodies to KLH were 501.5±150.6, 113.0±79.1, 28.8±56.3 and 413.6±148.5, 70.2±14.8, 65.3±45.3, respectively. The detection results of IgA to SEA compared with the IgG and IgM to KLH did not demonstrate a significant difference (P>0.01). The sensitivities of IgA to SEA and IgG and IgM antibodies to KLH for the detection of acute infection were 95.24%, 90.48% and 85.71%, respectively. Therefore, this study showed that the detection of IgA to SEA is also a useful new method for the serological differentiation of acute and chronic schistosomiasis japonica in humans.

Life cycle and reproductive parameters of Clerada apicicornis signoret (Hemiptera: Lygaeidae) under laboratory conditions

The life cycle of Clerada apicicornis was determined under laboratory conditions. Mean development times in days were: egg 27.2, nymph I 12.5, nymph II 12, nymph III 13.4, nymph IV 16.4, nymph V 26. The life expectancy of adults ranged from 117 to 317 days (mean 196 days). Based on a cohort of 29 females of C. apicicornis, a horizontal life table was constructed. The following predictive parameters were obtained: net rate of reproduction (Ro = 48.31), intrinsic rate of population increase (r m = 0.153), generation time (Tc = 28.20 weeks), and finite rate of population increment (lambda = 1.16). The reproductive value (Vx) for each age class of the cohort females was calculated. The following observed parameters were calculated after mortality in each stage: net rate of reproduction (R'o=13.4), intrinsic rate of population increase (r c' =0.09 ), and finite rate of population increment (lambda' =1.1). The generation time (Tc' =27.4) was estimated using the methods of Laughlin and Bengstron. A vertical life table was elaborated and mortality was described for one generation of the cohort.

Differences in the stability of the plasmids of Yersinia pestis cultures in vitro: impact on virulence

Plasmid and chromosomal genes encode determinants of virulence for Yersinia pestis, the causative agent of plague. However, in vitro, Y. pestis genome is very plastic and several changes have been described. To evaluate the alterations in the plasmid content of the cultures in vitro and the impact of the alterations to their pathogenicity, three Y. pestis isolates were submitted to serial subculture, analysis of the plasmid content, and testing for the presence of characteristic genes in each plasmid of colonies selected after subculture. Different results were obtained with each strain. The plasmid content of one of them was shown to be stable; no apparent alteration was produced through 32 subcultures. In the other two strains, several alterations were observed. LD50 in mice of the parental strains and the derived cultures with different plasmid content were compared. No changes in the virulence plasmid content could be specifically correlated with changes in the LD50.

Leishmania (Viannia) braziliensis growth in vitro culture relies more on folic acid availability than Leihsmania (Leishmania) amazonensis

We compared the in vitro growth of promastigotes from two Leishmania species in TC-100 and Schneider media. Leishmania (Leishmania) amazonensis replication rates were similar in both tissue culture media and reached maximum rates by 48 h. In contrast Leishmania (Viannia) braziliensis growth was significantly greater in TC-100 but maximum rates were achieved by 96 h. Folic acid appears to be the limiting factor and supplementation of Schneider media with this nutrient improved L. (V.) braziliensis replication rates and decreased the time of maximum replication to 48 h.

Effects of antifolates - co-trimoxazole and pyrimethamine-sulfadoxine - on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria

Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T), another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS - but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrolment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.

Molecular characterization of human Trypanosoma cruzi isolates from endemic areas in Panama

The present work provides information on Trypanosoma cruzi genotype circulating in endemic areas of Chagas disease in Panama. A total of 26 crude stocks of T. cruzi, isolated from the blood of persons with different clinical profiles of Chagas disease were collected and crio-conserved until used. Most of the stocks had been characterized by means of isoenzyme electrophoresis on cellulose acetate membranes. The clinical profiles of infected persons included 9 (34.6%) asymptomatic and 17 acute (65.4%) including 5 (19.2%) fatal cases, 2 under 5 years old and 3 adults. A multiplex-PCR assay based on the amplification of the non-transcribed spacer of the mini-exon gene was performed. All stocks of T. cruzi included in the study were found to correspond to Tc I group. This result supports the predominance of T. cruzi-I in the transmission cycles affecting the human population in the Republic of Panama.

Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children

The effects of pyrimethamine-sulphadoxine (PS), chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP), and amodiaquine plus pyrimethamine-sulphadoxine (AQPS) on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per µl blood) of peripheral young gametocyte (PYG), that is, < stage III to peripheral mature gametocyte (PMG), that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively) but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001). Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93) but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ), that is, (AQPS) resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

Hepatic stereology of schistosomiasis mansoni infected-mice fed a high-fat diet

High-fat diets induce weight gain and fatty liver in wild-type mice. Schistosomiasis mansoni infection also promotes hepatic injury. This study was designed to quantify hepatic alterations in schistosomiasis mansoni-infected mice fed a high fat-rich chow compared to mice fed a standard rodent chow, using stereology. Female SW mice fed each either high-fat diet (29% lipids) or standard chow (12% lipids) over 8 months, and then were infected with Schistosoma mansoni cercariae. Four experimental groups were studied: infected mice fed a high-fat diet (IHFC) or standard chow (ISC), uninfected mice fed a high-fat diet (HFC) or standard chow (SC). Mice were sacrificed during early infection (9 weeks from exposure). The following hepatic biometry and the stereology parameters were determined: volume density (hepatocytes [h], sinusoids [s], steatosis [st] and hepatic fibrosis [hf]); numerical density (hepatocyte nuclei - Nv[h]); absolute number of total hepatocyte N[h], normal hepatocyte N[nh], and binucleated hepatocyte N[bh], percentage of normal hepatocyte P[nh] and binucleated hepatocyte P[bh]. IHFC and HFC groups exhibited TC, HDL-C, LDL-C, and body mass significantly greater (p < 0.05) than control group. No significant differences were found regards liver volume (p = 0.07). Significant differences were observed regards P[nh] (p = 0.0045), P[bh] (p = 0.0045), Nv[h] (p = 0.0006), N[h] (p = 0.0125), N[bh] (p = 0.0164) and N[nh] (p = 0.0078). IHFC mice group presented 29% of binucleated hepatocytes compared to HFC group (19%), ISC group (17%) and SC (6%). Volume density was significantly different between groups: Vv[h] (p = 0.0052), Vv[s] (p = 0.0025), Vv[st] (p = 0.0004), and Vv[hf] (p = 0.0007). In conclusion, schistosomiasis mansoni infection with concurrent high-fat diet promotes intensive quantitative changes in hepatic structure, contributing to an increasing on hepatic regeneration.

Congenital transmission of Trypanosoma cruzi in central Brazil. A study of 1,211 individuals born to infected mothers

Transmission of Trypanosoma cruziduring pregnancy is estimated to occur in less than 20% of infected mothers; however, the etiopathogenesis is not completely understood. The Centre for Studies on Chagas Disease provides confirmation of T. cruziinfection for individuals living in central Brazil. In this retrospective hospital-based study, all requests for diagnosis of T. cruziinfection in individuals less than 21 years old from 1994-2014 were searched. We end with 1,211 individuals and their respective infected mothers. Congenital transmission of infection was confirmed in 24 individuals (2%) in central Brazil, an area where the main T. cruzi lineage circulating in humans is TcII. This low prevalence of congenital Chagas disease is discussed in relation to recent findings in the south region of Brazil, where TcV is the main lineage and congenital transmission has a higher prevalence (approximately 5%), similar to frequencies reported in Argentina, Paraguay and Bolivia. This is the first report to show geographical differences in the rates of congenital transmission of T. cruziand the relationship between the prevalence of congenital transmission and the type of Tc prevalent in each region.

Descripción del ARN de transferencia mitocondrial para Serina (UCN) de Lutzomyia columbiana (Diptera, Psychodidae)

Lutzomyia columbiana es un flebotomíneo considerado como vector sospechoso de Leishmania mexicana y Leishmania braziliensis en Colombia. Este insecto pertenece al grupo verrucarum, que incluye algunos taxones isomórficos, lo que ha estimulado la búsqueda de marcadores moleculares que permitan, además de diferenciar las especies, estudiar sus relaciones de parentesco. En este artículo se describe por primera vez la estructura putativa del ARN de transferencia mitocondrial para serina que reconoce el codón UCN (ARNtSer) de Lu. columbiana. El ADN genómico fue extraído, amplificado y secuenciado a partir de seis especímenes colectados con cebo humano. La estructura secundaria del ARNtSer fue inferida con el programa tRNAscan-SE 1.21. El gen ARNts consistió de 67 pares de bases (pb), encontrándose un solo haplotipo en los seis individuos secuenciados. El ARNtSer de Lu. columbiana mostró 7 apareamientos intracatenarios en el brazo aceptor del aminoácido, 3 en el brazo dihidrouridina (DHU), 5 en el brazo del anticodón y 5 en el brazo ribotimidina-pseudouridina-citosina (TøC). El tamaño de las lupas correspondió a 5 nucleótidos en la DHU, 7 en la anticodón, 4 en la variable y 7 en la TøC. Lu. columbiana se distingue del resto de especies de Lutzomyia y Phlebotomus secuenciadas a la fecha por la presencia de una guanina en la posición nucleotídica 64, que produce un apareamiento no canónico tipo uracilo-guanina en el brazo aceptor. Se necesitan más estudios para confirmar la utilidad del ARNtSer como marcador molecular para la discriminación de especies de flebotomíneos.