Microarray analysis of gene expression induced by sexual contact in Schistosoma mansoni

<p>Abstract</p> <p>Background</p> <p>The parasitic trematode <it>Schistosoma mansoni </it>is one of the major causative agents of Schistosomiasis, a disease that affects approximately 200 million people, mostly in developing countries. Since much of the pathology is associated with eggs laid by the female worm, understanding the mechanisms involved in oogenesis and sexual maturation is an important step towards the discovery of new targets for effective drug therapy. It is known that the adult female worm only develops fully in the presence of a male worm and that the rates of oviposition and maturation of eggs are significantly increased by mating. In order to study gene transcripts associated with sexual maturation and oviposition, we compared the gene expression profiles of sexually mature and immature parasites using DNA microarrays.</p> <p>Results</p> <p>For each experiment, three amplified RNA microarray hybridizations and their dye swaps were analyzed. Our results show that 265 transcripts are differentially expressed in adult females and 53 in adult males when mature and immature worms are compared. Of the genes differentially expressed, 55% are expressed at higher levels in paired females while the remaining 45% are more expressed in unpaired ones and 56.6% are expressed at higher levels in paired male worms while the remaining 43.4% are more expressed in immature parasites. Real-time RT-PCR analysis validated the microarray results. Several new maturation associated transcripts were identified. Genes that were up-regulated in single-sex females were mostly related to energy generation (i.e. carbohydrate and protein metabolism, generation of precursor metabolites and energy, cellular catabolism, and organelle organization and biogenesis) while genes that were down-regulated related to RNA metabolism, reactive oxygen species metabolism, electron transport, organelle organization and biogenesis and protein biosynthesis.</p> <p>Conclusion</p> <p>Our results confirm previous observations related to gene expression induced by sexual maturation in female schistosome worms. They also increase the list of <it>S. mansoni </it>maturation associated transcripts considerably, therefore opening new and exciting avenues for the study of the conjugal biology and development of new drugs against schistosomes.</p

Tentativa de controle de Hymenolepis nana através de tratamentos clínicos repetidos, com praziquantel, em uma comunidade fechada

Praziquantel was used repeatedly in an orphanage to determine its effectiveness in controlling hymenolepis. At the same time, the possible mechanisms of the transmission of this parasitosis were studied. The first group examined consisted of 161 people of which 109 were the orphanage children, who varied in age from days or months to eight years, and 52 adults, employees of the institution. Stool tests of all were made about every two months, using the Hoffman, Pons and Janer method; cure control was carried out by the same method seven to fourteen days after treatment. Every two weeks, H. nana eggs were searched for under the finger nails of the children, in insects, in domestic wastes, on door knobs and refrigerator handles, and on toilet flush knobs and strings. Water collected from rinsed urinals and shower floors was also tested. Eggs and larva of helminths and protozoa cysts were found in domestic waste and cockroaches and on door knobs. H. nana eggs were found in puddles of water left on shower floors and the rinse water of urinals. Every patient whose feces had H. nana eggs was treated with a single oral 25mg/kg dose of praziquantel, taken after lunch. In the four groups treated (66 patients in all), no important side effects were observed, and follow-up indicated 100% cure. For the 5th and last treatment, a group of both positive and negative (for H. nana) people was divided into sub-groups and treated with one (25mg/kg) or two doses of the medicine for a period of four days (total: 50mg/kg). Follow-up examination two months after treatment showed that only six patients were still eliminating eggs of the parasite; all belonged to the sub-group treated with a single dose of the drug. In spite of the treatments given an of the high percentage of cure, control of hymenolepiasis was not achieved.Foi feita tentativa de controle do Hymenolepis nana em uma comunidade fechada utilizando-se o praziquantel em repetidos tratamentos. Concomitantemente, foram estudados os prováveis mecanismos de transmissão da parasitose. A comunidade trabalhada possuia inicialmente 161 pessoas, sendo 109 crianças internas, com idade variando de dias e/ou meses a 8 anos, e de 52 adultos, funcionários da instituição. O diagnóstico parasitológico foi realizado aproximadamente de 2 em 2 meses em toda a população, pelo método de Hoffman, Pons e Janer, e o controle de cura, pelo mesmo método, entre o 7.º e o 14.º dia. Quinzenalmente foram realizadas pesquisas para ovos de H. nana no leito ungueal das crianças, em insetos, no lixo doméstico, nas maçanetas das portas e geladeiras, nos botões e cordões de descarga. Posteriormente examinou-se água recolhida dos urinóis e do chão do "box" do chuveiro. Todos os pacientes eliminando ovos de H. nana nas fezes foram tratados com praziquantel, após exame clínico, na dose única oral de 25mg/kg, após o almoço. Em 4 tratamentos realizados (66 pacientes), não foram observadas reações colterais importantes, e o controle de cura foi sempre de 100%. No 5.º e último tratamento, grupos de pacientes positivos e negativos para H. nana foram divididos em subgrupos e tratados com uma dose da droga (25mg/kg) ou duas doses espaçadas de 4 dias (total: 50mg/kg). No levantamento realizado dois meses após o tratamento, foram encontrados apenas 6 indivíduos eliminando ovos do parasita. Estes pertenciam ao subgrupo de crianças com himenolepíase tratado com uma única dose da droga. Ovos e larvas de helmintos e cistos de protozoários foram encontrados no lixo doméstico, insetos (baratas) e maçanetas de portas, enquanto ovos de H. nana só foram achados em água aspirada do "box" do chuveiro e da lavagem dos urinóis. Apesar da elevada percentagem de cura e dos vários tratamentos realizados, não se conseguiu o controle da himenolepíase

Cigarette smoking worsens systemic inflammation in persons with metabolic syndrome

Background Emerging data suggests that the combination of smoking and metabolic syndrome (MetS) markedly increases cardiovascular disease risk well beyond that of either condition. In this study we assess if this interaction can be explained by an additive increase in the risk of systemic inflammation by MetS and cigarette smoking. Methods We evaluated 5,503 healthy non-diabetic Brazilian subjects (mean age of 43 ± 10 years, 79% males). Participants were divided into sub-groups of smokers and non-smokers with or without MetS. High-sensitivity C reactive protein (hs-CRP) was measured to assess degree of underlying inflammation. Results Overall (19%) had hs-CRP \u3e 3 mg/L. In adjusted regression analyses, compared to non-smokers, there was a 0.19 mg/L (95% CI: 0.05, 0.32) increase in hs-CRP among smokers in the entire population and 0.63 mg/L (95% CI: 0.26, 1.01) increase among smokers with MetS while there was no significant increase among smokers without MetS (β = 0.09 95% CI: -0.05, 0.24). In a fully adjusted logistic regression model, smokers compared to non-smokers were 55% more likely to have elevated hs-CRP in the entire population (OR 1.55, 95% CI: 1.25, 1.92) and more than twice as likely to have elevated hs-CRP if they had MetS ( OR 2.05, 95% CI: 1.40, 3.01) while the risk was non-significant among those without MetS (OR = 1.29, 95% CI: 0.98, 1.69). Conclusion The study demonstrates an additive effect of cigarette smoking on the risk of systemic inflammation in MetS thus highlighting the need for determining smoking status among those with MetS and aggressively targeting smoking cessation in this population

Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer

BACKGROUND: IL-1beta has been implicated in inflammatory episode. In view of the inflammatory nature of cancer cachexia, we determined the predictive value of IL-1B-31 T/C, -511 C/T, +3954 C/T and IL-1RN VNTR gene polymorphisms on the occurrence of cachexia associated with locally advanced gastric cancer. METHODS: The study included 214 patients and 230 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of polymerase chain reaction products. RESULTS: The overall frequencies of IL-1B-31 T, -511 T, +3954 T and IL-1RN VNTR alleles in patients with locally advanced gastric cancer were all comparable with those in controls. No significant differences were found in the distribution of IL-1B-31 T, -511 T and IL-1RN VNTR between patients with cachexia and without. Patients with cachexia showed a significantly higher prevalence of IL-1B+3954 T allele than those without (P = 0.018). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the IL-1B+3954 CT genotype was associated with an odds ratio of 2.512 (95% CI, 1.180 – 5.347) for cachexia. CONCLUSION: The IL-1B+3954 T allele is a major risk for cachexia from locally gastric cancer. Genetic factors studied are not likely to play an important role in the determination of susceptibility to locally advanced gastric cancer