Although praziquantel (PZQ) has been used to treat schistosomiasis for over 20 years its mechanism of action remains unknown. We have developed an assay based on the transcriptional response of Schistosoma mansoni PR-1 to heat shock to confirm that while 6-week post-infection (p.i.) schistosomes are sensitive to PZQ, 4-week p.i. schistosomes are not. Further, we have used this assay to demonstrate that in mice this sensitivity develops between days 37 and 40 p.i. When PZQ is linked to the fluorophore BODIPY to aid microscopic visualization, it appears to enter the cells of intact 4 and 6-week p.i. schistosomes as well as mammalian NIH 3T3 cells with ease suggesting that the differential effects of PZQ is not based on cell exclusion. A transcriptomal analysis of gene expression between 4 and 6 weeks p.i. revealed 607 up-regulated candidate genes whose products are potential PZQ targets. A comparison of this gene list with that of genes expressed by PZQ sensitive miracidia reduced this target list to 247 genes, including a number involved in aerobic metabolism and cytosolic calcium regulation. Finally, we also report the effect of an in vitro sub-lethal exposure of PZQ on the transcriptome of S. mansoni PR-1. Annotation of genes differentially regulated by PZQ exposure suggests that schistosomes may undergo a transcriptomic response similar to that observed during oxidative stress.

Lamins are intermediate filaments that line the inner surface of the nuclear envelope, providing structural support and making contacts with chromatin. There are two types of lamins, A-and B-types, which differ in structure and expression. Drosophila possesses both lamin types, encoded by the LamC (A-type) and lamin Dm 0 (B-type) genes. LamC is nested within an intron of the essential gene ttv. We demonstrate that null mutations in LamC are lethal, and expression of a wild-type LamC transgene rescues lethality of LamC but not ttv mutants. Mutations in the human A-type lamin gene lead to diseases called laminopathies. To determine if Drosophila might serve as a useful model to study lamin biology and disease mechanisms, we generated transgenic flies expressing mutant LamC proteins modeled after human disease-causing lamins. These transgenic animals display a nuclear lamin aggregation phenotype remarkably similar to that observed when human mutant A-type lamins are expressed in mammalian cells. LamC aggregates also cause disorganization of lamin Dm 0 , indicating interdependence of both lamin types for proper lamina assembly. Taken together, these data provide the first detailed genetic analysis of the LamC gene and support using Drosophila as a model to study the role of lamins in disease.

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The body's defense against schistosome infection can take many forms. For example, upon developing acute schistosomiasis, patients often have fever coinciding with larval maturation, migration and early oviposition. As the infection becomes established, the parasite comes under oxidative stress generated by the host immune system. The most common treatment for schistosomiasis is the anti-helminthic drug praziquantel. Its effectiveness, however, is limited due to its inability to kill schistosomes 2 -4 weeks post-infection. Clearly there is a need for new antischistosomal drugs. We hypothesize that gene products expressed as part of a protective response against heat and/or oxidative stress are potential therapeutic targets for future drug development. Using a 12,166 element oligonucleotide microarray to characterize Schistosoma mansoni genes induced by heat and oxidative stress we found that 1,878 S. mansoni elements were significantly induced by heat stress. These included previously reported heat-shock genes expressing homologs of HSP40, HSP70 and HSP86. One thousand and one elements were induced by oxidative stress including those expressing homologs of superoxide dismutase, glutathione peroxidase and aldehyde dehydrogenase. Seventy-two elements were common to both stressors and could potentially be exploited in the development of novel anti-schistosomal therapeutics.

Achillea millefolium L. is cultivated in Iran and widely used in traditional medicine for gastrointestinal disorders. The aim of this study was to determine the effect of hydroalcoholic extract of A. millefolium on the contraction and relaxation of isolated ileum in rat. In this experimental study, aerial parts of A. millefolium were extracted by maceration in ethanol 70% for 72h. Terminal portion of ileum in 100 male Wistar rats was dissected and its contractions were recorded isotonically in an organ bath containing Tyrode solution (37 ºC, pH 7.4) under one gram tension. Acetylcholine (1mM) and KCl (60mM) were used to create isotonic contractions. Propranolol and Nω-Nitro-L-arginine methylester hydrochloride (L-NAME) were used to investigate the mechanisms of action prior to giving the extract to the relevant groups. Data were compared by ANOVA and Turkey's post hoc test.. The results showed that the ileum contraction was induced by KCl and acetylcholine induced contraction was significantly reduced by A. millefolium extract. The cumulative concentrations of A. millefolium relaxed the KCl and acetylcholine induced contractions (n=14, p<0.001). The inhibitory effect of extract on contraction induced by KCl and acetylcholine was not significantly affected neither by propranolol (1μM) nor by L-NAME (100 μM). There was no significant difference in the rate of relaxation by propranolol and L-NAME between the two groups. In conclusion, A. millefolium can inhibit contraction of smooth muscle of ileum in rat, and it can be used for eliminating intestinal spasms. These results suggest that the relaxatory effect of A. millefolium on ileum contractions can be due to the blockade of voltage dependent calcium channels. In addition, the β-adrenoceptors, cholinergic receptors and nitric oxide production are not powerful actors in inhibitory effect of A. millefolium. So, the nitric oxide and adrenergic systems may also be involved in the antispasmodic effect of A. millefolium.

Background:Hepatitis B virus is one of the important viral causes of liver inflammation with high worldwide prevalence and important hepatic and extra hepatic complications.Objectives:The aim of this study was to investigate the prevalence and risk factors of hepatitis B in Chaharmahal and Bakhtiari province, Iran.Patients and Methods:For this descriptive, analytical, population-based study, 3000 participants older than 15 years were enrolled according to the clustering method. After obtaining written informed consent and taking required blood samples, we gathered data on demographic status and probable transmission routes of disease using questionnaire between 2012 and 2013. The data was analyzed using SPSS software (descriptive parameters and chi-square). P value below 0.05 was considered as statistically significant.Results:The mean age of participants was 38.4 ± 16.3. The seroprevalence rate of hepatitis B was found to be 1.3% (95% CI, 0.95%-1.81%). Prevalence of HBeAg among HBsAg positive participants was 2.5% (only 1 of 40). Seroprevalence was higher in male group (2.5 times higher than women), age group of over 55 years, farmers, and non-public occupations. Positive seroprevalence was associated with a history of renal disease, familial transmission, transfusion, surgery in hospital, circumcision, contact with hepatitis B infected individuals, imprisonment, intravenous (IV) drug abuse, and smoking (P < 0.05). Nevertheless, the highest odds ratio (OR) was obtained for history of renal disease (OR = 7.64: 3.01-18.4), followed by imprisonment (OR = 5.4: 1.86 -15.7) and IV drug abuse (OR = 5.68: 1.3-24.7).Conclusions:Chaharmahal and Bakhtiari province could be categorized as a low endemic region for hepatitis B infection, with a seroprevalence similar to that in other provinces of western Iran. Vaccination seems to influence its decrease, especially in adolescents and youth. More surveillance and attention to risk factors are suggested to identify high-risk groups and to implement vaccination.

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