Inhibition of HIV and HSV infection by vaginal lactobacilli in vitro and in vivo

Background

The vaccine industry is one of the most important health-related industries. It can be affected by accession to the World Trade Organization (WTO) because of probable dramatic changes in the business environment. Iran has already initiated accession negotiations.

Purpose of the study

In this paper, we investigate the position of, challenges to, and opportunities for vaccine manufacturing in Iran with regard to accession to the WTO.

Methods

This is a qualitative and cross sectional study. To collect information, we designed a questionnaire and interviewed some of the vaccine industry??s key opinion leaders in Iran. Before the interviews were conducted, the questionnaires were sent to these individuals by email.

Results

According to the interviewees, the country??s main challenges with regard to accession to the WTO are the lack of firm internal intellectual property (IP) rules, not being recognized as pre-qualified by the World Health Organization (WHO), the use of old equipment, and a lack of cooperation with global vaccine companies.

Major conclusions

Iran??s local vaccine industry, with a long history and international reputation that could be used as an advantage, is faced with several challenges, such as problems with keeping up with Current Good Manufacturing Practice (cGMP), a lack of adequate and meaningful investment in research and development (R&D), and limitations on private sector participation in the production of vaccines. Gradual privatization of the industry, improved international relations, utilization of the R&D power of small hi-tech companies, consistent education of human resources, and modernization of infrastructures and equipment are among the suggested solutions.     

Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors

Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen deprivation therapy of primary prostate cancer can be mediated by reactivation of the androgen receptor (AR). One important mechanism mediating this AR reactivation is intratumoral conversion of the weak adrenal androgens DHEA and androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA and androstenedione are synthesized by the adrenals through the sequential actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC. However, the significance of intratumoral CYP17A1 and de novo androgen synthesis from cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor resistance/relapse, remain to be determined. We report that AR activity in castration-resistant VCaP tumor xenografts can be restored through CYP17A1-dependent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes selective pressure for increased intratumoral expression of CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1 inhibitors. Supporting the clinical relevance of this mechanism, we found that intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent, but that AR activity in these cells is still steroid dependent and mediated by upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis. Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may remain steroid dependent and therefore responsive to therapies that can further suppress de novo intratumoral steroid synthesis.     

Protective effects of aqueous and ethanolic extracts of Portulaca oleracea L. aerial parts on H2O2-induced DNA damage in lymphocytes by comet assay

The comet assay is a standard method for measuring DNA damage. In this study, the protective effects of ethanolic and aqueous extracts of Portulaca oleracea L. (P. oleracea) on human lymphocyte DNA lesions were evaluated with the comet assay. Lymphocytes were isolated from blood samples taken from healthy volunteers. Human lymphocytes were incubated in H(2)O(2) (50,100, and 200 μM), aqueous extract (0.05, 0.1, 0.5, 1, and 2.5mg/ml), and ethanolic extracts (0.05, 0.1, 0.5, 1, and 2.5mg/ml) of P. oleraceae aerial parts alone with a combination of H(2)O(2) (100 μM) with either 1 or 2.5mg/ml of both extracts at 4°C for 30 minutes. The extent of DNA migration was measured using the alkaline single cell gel electrophoresis approach assay, and DNA damage was expressed as percentage tail DNA. We found that the aqueous extract of P. oleracea significantly inhibited DNA damage, while there was no effect of the ethanolic extract. These data suggest that the aqueous extract of P. oleracea can prevent oxidative DNA damage to human lymphocytes, which is likely due to antioxidant constituents in the extract.     

Retinal vessel segmentation using a multi-scale medialness function

Recently, automated segmentation of retinal vessels in optic fundus images has been an important focus of much research. In this paper, we propose a multi-scale method to segment retinal vessels based on a weighted two-dimensional (2D) medialness function. The results of the medialness function are first multiplied by the eigenvalues of the Hessian matrix. Next, centerlines of vessels are extracted using noise reduction and reconnection procedures. Finally, vessel radii are estimated and retinal vessels are segmented. The proposed method is evaluated and compared with several recent methods using images from the DRIVE and STARE databases.     

A clinic‐based screening of mutations in exons 31, 34, 35, 41, and 48 of LRRK2 in Iranian Parkinson's disease patients

We present results of mutation screening of exons 31, 34, 35, 41, and 48 of LRRK2 in 205 Iranian Parkinson's disease patients. Sixteen percent of the cases were familial. Although age was not a factor in patient recruitment, the Iranian cohort was relatively young (average age at onset of disease: 48.9 years). A notably high male to female ratio (2.96:1) and earlier age at onset (by 2.9 years) in men were observed. A known disease‐associated variation, c.C4321T causing R1441C, and IVS31 + 3A > G, a variation that may be associated, were observed. Therefore, disregarding IVS31 + 3A > G, disease status in at least 0.5% of our young cohort and in 3.5% of the familial cases was associated with a mutation in the five exons of LRRK2 screened. Interestingly, the variation causing p.G2019S was not observed. © 2009 Movement Disorder Society     

Identification of four novel potentially Parkinson's disease associated LRRK2 variations among Iranian patients

The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson's Disease patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low.     

Coagulase gene polymorphism of Staphylococcus aureus isolated from clinical and sub-clinical bovine mastitis in Isfahan and Chaharmahal va Bakhtiari provinces of Iran

Mastitis is a common disease in dairy cattle and is an inflammatory response of the breast tissue to bacterial attack to this tissue. Mastitis causes considerable loss to the dairy industry, among the several bacterial pathogens that can cause mastitis; Staphylococcus aureus is probably the most lethal agent because it causes chronic and deep infection in the mammary glands that is extremely difficult to cure. Several virulence factors including coagulase gene are produced by S. aureus and may contribute to its pathogenicity. This study was conducted to investigate the coagulase gene polymorphism of S. aureus isolated from clinical and sub-clinical bovine mastitis milk samples in Isfahan and Chaharmahal va Bakhtiari provinces of Iran. Amplification of the coagulase gene from 86 S. aureus strains isolates by specific primers showed 31 specimens contained 970?bp fragment, and 11 strains contained 730?bp fragment relevant to coa gene (coagulase) in PCR. After enzymatic digestion with AluI, 31 specimens contained three bands: 320, 490, and 160?bp (genotype I) and 11 specimens contained two bands: 490 and 240?bp (genotype VIII) in the RFLP.     

Immunomodulatory effects of astragalus polysaccharide on Human peripheral blood mononuclear cells co-cultured with cervical cancer cell line

OBJECTIVE:To investigate immunomodulatory ef-fects of Astragalus polysaccharides (APS) on the co-culture of peripheral blood mononuclear cells(PBMCs) with HeLa ...