Anti-HCV positivity in sexual partners and offspring of patient with chronic hepatitis C

We investigated the seroprevalence of HCV in stable sexual partners and offspring of chronic hepatitis C patients, and aimed to determine the risk factors involved. 191 anti-HCV and HCV RNA positive subjects who coinhabited with their spouse and/or offspring were included. Risk factors of index cases for disease transmission, liver biopsy results, anti-HCV and HCV-RNA in spouses and/or offspring were evaluated. Together with index cases, a total of 404 family members including 174 stable sexual partners and 230 offspring were included. The most common risk factors among index cases were dental procedures (73.8%), history of surgery (64.9%), and blood transfusions (24.1%). Anti-HCV positivity was established in 11 (2.7%) of the total 404 family contacts--6 sexual partners and 5 offspring. HCV seropositivity was significantly higher in the spouses of index cases with severe hepatitis C compared to those with mild to moderate hepatitis C (p=0.008), but there was no statistically significant correlation between the severity of liver disease in index cases and anti-HCV positivity in their offspring. In conclusion, anti-HCV seropositivity in the spouses and children of patients who are HCV-RNA positive HCV carriers does not appear to be higher than the HCV seroprevalence in our country.     

Metabolism of murine and human embryos: search for a growth indicator in vitro culture medium

Ham's F-10 medium was analyzed biochemically before and after growth of murine and human embryos. Ham's F-10 medium (280 mosm/kg, pH 7.4) alone, by means of reverse-phase high-performance liquid chromatography, demonstrated one major hydrophilic peak, which eluted at 4 to 8 minutes in a 10% to 48% acetonitrile gradient. This peak showed a single peptide of 50 kilodaltons in one-dimensional polyacrylamide gel electrophoresis and size exclusion high-performance liquid chromatography. After the growth of two-cell murine embryos to eight-cell embryos or blastocysts, the major hydrophilic peak was greatly reduced or absent in the culture medium, and in turn a major hydrophobic peak appeared that eluted at 29 minutes. The major hydrophobic peak could not be focused in one-dimensional polyacrylamide gel electrophoresis, but a high content of polar and nonpolar amino acids was revealed in N-terminal sequencing and mass spectrometric analysis. This shift in the peaks was not detected when embryos were cultured in the presence of 0.02% sodium azide. In vitro culture of human zygotes from the pronuclear stage to two to eight cells caused a similar disappearance of the major hydrophilic peak concomitant with the appearance of one to three major hydrophobic peaks in the culture medium. We conclude that the change in profile of culture medium from hydrophilic to hydrophobic peaks on high-performance liquid chromatography is indicative of the metabolic pattern of murine and human embryos. These data also indicate that murine and human embryos do not secrete any major peptide during their development in vitro.     

Contraceptive vaccines

The world's population is growing at a tremendous rate, affecting growth and development. Apart from this population growth, unintended pregnancies resulting in elective abortions continue to be a major public health issue. In over half of these unintended pregnancies, the women have used some type of contraception. Thus, there is an urgent need for a better method of contraception that is acceptable, effective and available. The contraceptive choices available to women at this time include steroid contraceptives, intrauterine devices, barrier methods, spermicides, natural family planning, male and female sterilisation, and recently available emergency contraceptives. Contraceptive vaccines (CVs) may provide viable and valuable alternatives that can fulfill most, if not all, properties of an ideal contraceptive. Since both the developed and most of the developing nations have an infrastructure for mass immunisation, the development of vaccines for contraception is an exciting proposition. The molecules that are being explored for CV development either target gamete production (gonadotropin releasing hormone, follicle-stimulating hormone and luteinising hormone), gamete function (zona pellucida [ZP] proteins and sperm antigens) or gamete outcome (human chorionic gonadotropin [hCG]). Disadvantages of CVs targeting gamete production are that they affect sex steroids and/or show only a partial effect in reducing fertility. CVs targeting gamete function are better choices. Vaccines based on ZP proteins are quite efficacious in producing contraceptive effects. However, they invariably induce oophoritis affecting sex steroids. Sperm antigens constitute the most promising and exciting targets for CVs. Several sperm-specific antigens have been delineated in several laboratories and are being actively explored for CV development. Antisperm antibody-mediated immunoinfertility provides a naturally occurring model to indicate how an antisperm vaccine will work in humans. Vaccines targeting gamete outcome primarily focus on the hCG molecule. The hCG vaccine is the first vaccine to undergo phase I and II clinical trials in humans. Both the efficacy and the lack of immunotoxicity have been reasonably well demonstrated for this vaccine. The present studies focus on increasing the immunogenicity and efficacy of this birth control vaccine.     

Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan

Malik S, Kakar N, Hasnain S, Ahmad J, Wilcox ER, Naz S. Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan. Mutations in IRF6 cause Van der Woude syndrome (VWS), one of the most common syndromes associated with cleft lip (CL) with or without cleft palate (CP). The presence of pits on the lower lip of patients is the most characteristic feature of the syndrome. We have identified three novel and seven previously reported IRF6 mutations in 12 of 16 unrelated families segregating VWS from Pakistan. The three newly identified mutations include a frameshift (c.568delG) and two missense mutations c.295G>A (p.G99S) and c.1219T>C (p.S407P). Recent functional studies on IRF6 and the three‐dimensional structure of IRF5 carboxy (C) terminus, a protein encoded by a paralog of IRF6, shed light on the p.S407P substitution. Additionally, the identification of the same mutations responsible for VWS in Pakistan, as reported in other global populations worldwide, marks these residues as mutational hotspots and indicates their essential role in structural stability or function of IRF6. This is the first study of VWS in Pakistan and we estimate that 1 in 100 patients with CL with or without CP (CL/P) are affected in the Pakistani population predominantly from the Punjab area.     

Role of Ocimum sanctum leaf extract on dietary supplementation in the transgenic Drosophila model of Parkinson＇s disease

AIM： To evaluate the effect of Ocimum sanctum leaf extract on the dietary supplementation in the transgenic Drosophila model of Parkinson＇s disease. METHOD： The effect of Ocimum sanctum leaf extract was studied on the transgenic Drosophila model of flies expressing normal human alpha synuclein（h-αs） in the neurons. O. sanctum extract at final concentrations of 0.042 8 × 10-4, 0.87 × 10-4, and 1.85 × 10-4 g·mL-1 of diet were established and the flies were allowed to feed for 21 days. The climbing assay and lipid peroxidation were taken as parameters for the study. RESULTS： The supplementation of O. sanctum extract showed a dose-dependent significant delay in the loss of climbing ability and reduction in oxidative stress in the brain of PD model flies. CONCLUSION： The results of the present study showed that the O. sanctum extract is potent in reducing the PD symptoms in transgenic Drosophila model.