Pharmacokinetics of Peptide mediated delivery of anticancer drug ellipticine

The amino acid pairing peptide EAK16-II (EAK) has shown the ability to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, we investigate pharmacokinetics of the formulation of EAK-EPT complexes in vivo. The developed formulation can achieve a sufficiently high drug concentration required in vivo animal models. The nanostructure and surface properties of EAK-EPT complexes or nanoparticle were characterized by transmission electron microscopy (TEM) and zeta potential measurements, respectively. 12 healthy male SD rats were divided into EPT group and EAK-EPT group randomly. Rats in EPT group were tail intravenously injected with the EPT (20 mg/kg); rats in EAK-EPT group were injected with EAK-EPT complexes (EPT's concentration is 20 mg/kg). EPT was extracted from rat plasma with dexamethasone sodium phosphate as internal standards (IS). The pharmacokinetic parameters were obtained using high pressure liquid chromatography (HPLC). Significant differences in main pharmacokinetic parameters between EPT and EAK-EPT complexes were observed, demonstrating that the complexation with EAK prolongs the residence time of the drug and enlarges the area under the concentration-time curve (AUC). This means that EAK can serve as a suitable carrier to increase the bioavailability of EPT.     

Association of T/A polymorphism in miR-1302 binding site in CGA gene with male infertility in Isfahan population

Infertility occurs in 10–15% of couples worldwide and close to half of it is caused by male factors. One of the genes that can affect male infertility is CGA. Polymorphisms in CGA gene may affect gene expression, therefore affecting male infertility by disrupting the regulation of this gene. One of the polymorphisms is the substitution of T with A in the miR-1302 binding site in the 3′ untranslated region of the CGA gene. In this study, we explored this polymorphism in Isfahan population. In this case-control study, by the use of Tetra primer-ARMS–PCR technique, rs6631 has been investigated in 224 infertile men and 196 controls. Infertile men were recruited from Isfahan Fertility and Infertility Center. Analysis of genotype and allele frequencies indicated that the differences between case and control populations were significant for rs6631 because P?=?0.00 which is above the threshold. We found a significant relationship between this polymorphism and male infertility. This study which performed for the first time in Iran suggests that polymorphism in CGA gene can affect male infertility. Also, this polymorphism has high heterozygosity, so it can be used for further studies in different populations.     

Synthesis and anticonvulsant activity of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles

A series of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles have been synthesized and evaluated as anticonvulsant agents. Compound 4b shows considerable anticonvulsant activity both in PTZ and MES models. It seems this effect is mediated through benzodiazepine receptors mechanism.     

Serum levels of interleukin-13 and interferon-gamma from adult patients with asthma in Mysore

Serum protein analysis for noninvasive quantification of airway inflammation in asthma is a promising research tool in the field of lung diseases. Cytokines are believed to have major role in inflammatory process of the airways of the lung. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4 and interleukin (IL)-13, and Th1 cells, which secrete interferon (IFN)-gamma in asthma. To test the hypothesis that serum IL-13 and IL-4 levels may be elevated whereas IFN-gamma would be decreased in this cohort of patients, a property that could make them possible candidate biomarkers in determining asthma occurrence and severity, we measured concentrations of IL-4, IL-13 and IFN-gamma in serum samples of 88 subjects (44 normal, 12 with mild asthma, 16 with moderate asthma, and 16 with severe asthma). Serum Levels of IL-4, IL-13, and IFN-gamma were determined by an enzyme-linked immune-sorbent assay (ELISA). Median serum level of IFN-gamma in asthmatic patients was 8.0pg/ml, while it was 11.4pg/ml in healthy controls. However, the difference was not significant. Among the different age groups in whom IFN-gamma was assessed, the highest median value in both cases and controls was observed in the age group of 31-40years. The median serum level of IL-13 was 40.0pg/ml in asthmatic patients and 58.25pg/ml in healthy controls. The difference was not significant. On subgroup analysis, no significant difference of IFN-gamma and IL-13 between asthma of different severities was observed. The study also revealed nonsignificant difference of serum cytokines with the duration of asthma, number of allergens, and severity of sensitization. Normal serum levels of IFN-gamma and IL-13 in asthmatic patients suggest their neutral role in the inflammatory process; however, more studies are required to establish the effect of these cytokines in adulthood asthma in different ethnic populations.     

Switching on the lights for gene therapy

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application.     

Intervention based on BASNEF model increases exclusive breastfeeding in preterm infants in Iran: a randomized controlled trial

Background

The objective of this study is to determine the effect of a consultation model, Beliefs, Attitudes, Subjective Norms and Enabling Factors (BASNEF), and the counselling steps using GATHER-Greet clients, Ask clients about themselves, Tell clients about their choices, Help clients choose, Explain what to do, and Return for follow-up-on the continuation rates of exclusive breastfeeding in mothers of premature infants.

Methods

This is a randomized controlled clinical trial carried out on 124 mothers with premature infants hospitalized in Fatemieh Hospital, city of Hamadan, in 2014. Participants were randomly assigned to either the intervention or control groups. The initial demographic questionnaire carried out in both groups included three questions about the continuation of exclusive breastfeeding, BASNEF, a checklist related to the lactation performance documented by mothers and the weight gain of their infants. Five breastfeeding consultation sessions based on the BASNEF model and counselling steps using GATHER, were held for the mothers in the intervention group for five consecutive days. Then follow-up weight gain and the questionnaire completion were performed in both groups at 1, 2, 3 and 4 months after the intervention.

Results

Baseline characteristics were similar in the two groups. There were no significant differences between both groups in the rate of exclusive breastfeeding, lactation performance and infant weight at baseline. The intervention group had significantly higher rates of exclusive breastfeeding, 72.6% versus the control group of 16.1%, at the end of the 4 month follow-up. Also the intervention group had significantly higher mean scores of lactation performance (8.62?±?2.08 vs 6.40?±?1.84 in the control group) and infant weight (5694.80?±?779.43 vs 4760.17?±?859.12 in the control group) at the end of the 4 month follow-up.

Conclusion

Breastfeeding consultation of mothers based on the BASNEF model and using GATHER counselling steps increased the rate of exclusive breastfeeding, lactation performance and weight gain of premature infants. Therefore, breastfeeding counselling sessions are recommended for all mothers of premature infants.

Trial registration

Iranian Registry of Clinical Trials number IRCT2014111013405N6 and date registered, January 5, 2015.

     

Factors Affecting Gender Differences in the Association between Health-Related Quality of Life and Metabolic Syndrome Components: Tehran Lipid and Glucose Study

Objective

Using structural equation modeling, this study is one of the first efforts aimed at assessing influential factors causing gender differences in the association between health-related quality of life (HRQoL) and metabolic syndrome.

Methods

A sample of 950 adults, from Tehran Lipid and Glucose Study were recruited for this cross sectional study in 2005–2007. Health-related quality of life was assessed using the Iranian version of SF-36. Metabolic syndrome components (MetSCs) and physical and mental HRQoL were considered as continuous latent constructs explaining the variances of their observed components. Structural equation modeling was performed to examine the association between the constructs of MetSCs and the physical and mental HRQoL within the two gender groups.

Results

Based on the primary hypothesis, MetSCs and HRQoL were fitted in a model. The negative effect of MetSCs on HRQoL was found to be significant only in the physical domain and only in women. The proportion of all the cardio-metabolic risk factors as well as subscales of physical HRQoL that have been explained via the two constructs of MetSCs and HRQoL, respectively, were significantly higher in women. Physical activity in both men (β = 3.19, p<0.05) and women (β = 3.94, p<0.05), age (β = -3.28, p<0.05), education (β = 2.63, p<0.05) only in women and smoking (β = 2.28, p<0.05) just in men, directly affected physical HRQoL. Regarding the mental domain, physical activity (β = 3.37, p<0.05) and marital status (β = 3.44, p<0.05) in women and age (β = 2.01, p<0.05) in men were direct effective factors. Age and education in women as well as smoking in men indirectly affected physical HRQoL via MetSCs.

Conclusion

Gender differences in the association between MetSCs and physical HRQoL could mostly be attributed to the different structures of both MetSCs and physical HRQoL constructs in men and women. Age and smoking are the most important socio-behavioral factors which could affect this gender-specific association in the mental domain.     

Genetically modified crops and small-scale farmers: main opportunities and challenges

Although some important features of genetically modified (GM) crops such as insect resistance, herbicide tolerance, and drought tolerance might seem to be beneficial for small-scale farmers, the adoption of GM technology by smallholders is still slight. Identifying pros and cons of using this technology is important to understand the impacts of GM crops on these farmers. This article reviews the main opportunities and challenges of GM crops for small-scale farmers in developing countries. The most significant advantages of GM crops include being independent to farm size, environment protection, improvement of occupational health issues, and the potential of bio-fortified crops to reduce malnutrition. Challenges faced by small-scale farmers for adoption of GM crops comprise availability and accessibility of GM crop seeds, seed dissemination and price, and the lack of adequate information. In addition, R&D and production costs in using GM crops make it difficult for these farmers to adopt the use of these crops. Moreover, intellectual property right regulations may deprive resource poor farmers from the advantages of GM technology. Finally, concerns on socio-economic and environment safety issues are also addressed in this paper.