Unsymmetrical 1,3-disubstituted urea derivatives as α-chymotrypsin inhibitors

The objective of this study was to synthesize potent and/or novel inhibitors for α-chymotrypsin activity. Eighteen derivatives of N-methylphenyl-N′-(alkyl/aryl) urea (1–18) were synthesized, and their inhibitory effects on α-chymotrypsin enzyme were evaluated. Two compounds exhibited potent inhibitory activities. The most potent, N-(2-methylphenyl)-2-oxo-1-pyrrolidinecarboxamide (15) having a methyl group at ortho position was the most active inhibitor with an IC₅₀ value of 8.10 ± 0.14 μM, which was comparable to standard chymostatin (IC₅₀ = 8.24 ± 0.11 μM). A slightly less potent, N-(2-acetylphenyl)-N′-(3-methylphenyl) urea (10), exhibited an IC₅₀ of 13.6 ± 0.23 μM. Compounds 3, 4, 7, 11, and 13 exhibited moderate activities. The results demonstrated that α-chymotrypsin inhibition is related to the position of the methyl group and the presence of substituent at the nitrogen of the urea bridge. The inhibitory trend suggests that α-chymotrypsin inhibitory activity declines with ortho > meta > para substitution order. In conclusion, our data suggest that the compound 15 may serve as a lead compound for further designing of other potent or novel α-chymotrypsin inhibitors.     

Synthesis of novel pyrazolobenzothiazine 5,5-dioxide derivatives as potent anti-HIV-1 agents

A new series of pyrazolobenzothiazine-based carbohydrazides was prepared in a facile way, starting with commercially available sodium saccharine. The final products were sufficiently characterized by spectroscopic techniques. In addition, compound 5k was confirmed with X-ray crystallography as well. All the compounds were screened for anti-HIV-1 and cytotoxicity activities. Overall, out of 15 compounds, seven exhibited good activity with EC₅₀ values <20 μM. Compounds 5c, 5d, 5g, 5j and 5k appeared as the potent anti-HIV-1 agents with EC₅₀ values <5.0 μM. The structure–activity relationship would facilitate the discovery of new molecules with better profile of HIV inhibition activity.     

Enhanced electrochemical response of a modified glassy carbon electrode by poly(2-vinlypyridine-b-methyl methacrylate) conjugated gold nanoparticles for detection of nicotine

Poly(2-vinylpyridine-b-methylmethacrylate) coated gold nanoparticles [P(2VP-MMA)-AuNPs] were prepared and characterized by UV-Vis, FTIR, AFM, and zetasizer analysis. Investigation of the potential of the synthesized poly(2-vinylpyridine-b-methylmethacrylate) coated gold nanoparticles [P(2VP-MMA)-AuNPs] for detection of nicotine is the main focus of the current study. P(2VP-MMA)-AuNPs were coated on a glassy carbon electrode (GCE) for electrochemical detection of nicotine by cyclic voltammetry. The effect of molar mass of individual P2VP blocks and total molar mass of the block copolymer is evaluated in the context of an enhanced electrochemical response of the modified GCE for its sensing ability of nicotine in both aqueous and organic media. The electrochemical detection of nicotine is significantly enhanced by modification of the GCE with P(2VP-MMA)-AuNPs.

Poly(2-vinylpyridine-b-methylmethacrylate) coated gold nanoparticles [P(2VP-MMA)-AuNPs] are employed for enhancement of electrochemical response of glassy carbon electrode for nicotine.     

Water intake and risk of type 2 diabetes: A systematic review and meta-analysis of observational studies

Background and aimsThe association of water intake with type 2 diabetes mellitus (T2DM) is still unclear. Therefore, the aim of this systematic review and meta-analysis was to synthesize the knowledge about the relationship between water intake and the risk of T2DM.MethodsWe conducted a systematic search in PubMed and Scopus up to June 2018 for observational studies. Risk ratios (RR)s and 95% confidence intervals (95% CI)s were calculated and fixed effects models were used.ResultsOverall, 6 studies were included in the meta-analyses. There was an inverse relationship between water intake and risk of T2DM (RR: 0.94; 95% CI: 0.91–0.97, P < 0.001) with low heterogeneity (I2 = 24%, P = 0.24).ConclusionOur findings indicated that the intake of water was correlated with reduced risk of type 2 diabetes in women and men. These results support the current recommendations of water intake as an inseparable part of a diet with the lowest risk of diabetes mellitus.     

The sponge/Matrigel angiogenesis assay

It has become increasingly clear that definitive tests for angiogenesis require in vivo assays. Recently, the Matrigel plug assay has become the method of choice for many studies involving in vivo testing for angiogenesis. In this assay, test angiogenesis-inducing compounds such as bFGF or tumor cells are introduced into cold liquid Matrigel which, after subcutaneous injection, solidifies and permits penetration by host cells and the formation of new blood vessels. Assessment of angiogenesis in the Matrigel plug is achieved either by measuring hemoglobin or by scoring selected regions of histological sections for vascular density. We now describe a modification of the Matrigel plug assay which permits a more precise visualization of the angiogenic reaction, provides directional information, requires no histological analysis, and lends itself to photographic documentation and image analysis protocols. We illustrate the assay by describing dose- and time-dependent responses to tumors of murine and human origin, to angiogenesis-inducing factors such as bFGF (FGF-2) and VEGF and to anti-angiogenic agents such as endostatin. The method has been used as well to demonstrate blood vessel recruitment by embryonic chick aortic arch rudiments. Additionally it has been able to detect strain-dependent differences in susceptibility to angiogenic stimulation.     

Girl Child Marriage and Its Effect on Fertility in Pakistan: Findings from Pakistan Demographic and Health Survey, 2006–2007

Child marriage (before 18 years) is prevalent in Pakistan, which disproportionately affects young girls in rural, low income and low education households. Our study aims to determine the association between early marriage and high fertility and poor fertility health indicators among young women in Pakistan beyond those attributed to social vulnerabilities. Nationally representative data from Pakistan Demographic and Health Survey, 2006–2007, a cross-sectional observational survey, were limited to ever-married women aged 20–24 years (n = 1,560; 15 % of 10,023) to identify differences in poor fertility outcomes [high fertility (three or more childbirths); rapid repeat childbirth (<24 months between births); unwanted pregnancy (any ever); pregnancy termination (any stillbirth, miscarriage or abortion ever)] by early (<18) versus adult (≥18) age at marriage. Associations between child marriage and fertility outcomes were assessed by calculating adjusted odds ratios (AORs) using logistic regression models after controlling for demographics, social equity indicators (education, wealth index, rural residence), contraception use, marriage duration and culture-specific factors (husband’s desire for more children, son preference). Overall, 50 % of ever-married women aged 20–24 years in Pakistan were married before the age of 18 years. Girl child marriage was significantly (p < 0.001) associated with low social equity indicators (poverty, rural residence, and no formal education). Adjusted logistic regression models showed that girl child marriage was significantly associated with high fertility (AOR 6.62; 95 % CI 3.53–12.43), rapid repeat childbirth (AOR 2.88; 95 % CI 1.83–4.54), unwanted pregnancy (AOR 2.90; 95 % CI 1.75–4.79), and pregnancy termination (AOR 1.75; 95 % CI 1.10–2.78). Girl child marriage affects half of all ever-married women aged 20–24 years in Pakistan, and increases their risk for high fertility and poor fertility health indicators, highlighting the need of increasing the age of marriage among women in Pakistan. Efforts to eliminate girl child marriage by strict law enforcement, promoting civil, sexual and reproductive health rights for women can help eliminate girl child marriage in Pakistan.