Structural requirements for imidazo[1,2-a]pyrazine derivatives as Aurora A kinase inhibitors and validation of the model

Aurora kinases belong to the family of serine/threonine kinases. They are divided into three subclasses, Aurora A kinase, Aurora B kinase, and Aurora C kinase and are reported to be vital for cell proliferation. Abnormal expression of these enzymes leads to cancer. Predictive CoMFA and CoMSIA based quantitative structure activity relationship models have been developed on 51 imidazo[1,2-a]pyrazine derivatives reported previously by Merck Research Laboratories. AutoDock was used for docking of the most active compound (34) and the conformation thus obtained was used for the alignment of 3D structures. The developed (CoMSIA-SEHD) model showed good predictive ability with predictive squared correlation coefficient (r ²) value of 0.752. The best model was validated systematically using different validation parameters. The CoMSIA model gave useful information to understand features required to modify and develop new potential Aurora kinase inhibitors.     

Maculosin,a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

ContextStreptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities.ObjectiveThis study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed.Materials and methodsThe compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay.ResultsEthyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 µg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12–KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C₁₄H₁₆N₂O₃ as determined by the [M + H]⁺ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC₅₀, 2.16 ± 0.05 µg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC₅₀, 4.8 ± 0.05 µg/mL). No toxicity was observed for maculosin (LD₅₀, <128 µg/mL) in brine shrimp lethality assay (BSLA) up to the compound’s antioxidant activity (IC₅₀) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD₅₀ value of 8.63 ± 0.15 µg/mL.ConclusionsMaculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.     

Synthesis and pharmacological investigation of novel 1-alkyl-4-(4-substituted aryl/heteroaryl)-1,2,4-triazolo [4,3- a] quinazolin-5 (4H)-ones as a new class of H1-antihistaminic agents

A series of novel 1-alkyl-4-(4-substituted aryl/heteroaryl)- 1,2,4-triazolo [4,3-a] quinazolin-5(4H)-ones were synthesized by the cyclization of 2-hydrazino-3-(4-subst. aryl/heteroaryl) quinazolin-4(3H)-one with various carbon donors. The starting material, 2-hydrazino-3-(4-subst. aryl/heteroaryl) quinazolin-4(3H)-one, was synthesized from 4-subst. arylamine/ heteroarylamine by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly, whereby the compound 1-methyl-4-(2-py-ridyl)-1,2,4-triazolo[4,3-a] quinazolin-5(4H)-one (II) was found to be more potent (percent protection 71.43 %) when compared to the reference standard, chlorpheniramine maleate (percent protection 71 %). Compound II showed negligible sedation (8 %) when compared to chlorpheniramine maleate (25 %). Hence it could serve as prototype molecule for further development as a new class of H1-antihistamines.     

Child sexual abuse in Tanzania: much noise,little justice

Every day in Tanzania, newspapers report horrible stories of the sexual abuse of children. This serious situation has aroused calls for stricter punishment of perpetrators, but little is being done to help the abused children. A 1997 analysis of these reports by the Tanzania Legal Human Rights Center has revealed that the majority of the perpetrators are adult males who are close to their victims and who hold positions of respect in society. The sexual abuse of children is fundamentally an expression of power over a child's life, and Tanzanian children have little control over their lives and are usually disciplined with corporeal punishment. Tanzanian children are accustomed to seeing men hurt weaker people without censure, and the children do not have the status to defend themselves against physical, psychological, or sexual abuse. Thus, child sexual abuse is an inevitable consequence in a society where children have no voice. It is impossible to condone physical and verbal abuse while condemning sexual abuse, and punishing the abusers will not solve the problem. Instead, perpetrators must be held accountable and made to understand the seriousness of their actions. In order to make amends to their victims, they should be required to pay for the child's health care and education and to perform mandatory community service to make children safer. Children must be given the opportunity to learn that they can say no to adults and refuse to accept abuse.     

Trends in socioeconomic and nutritional status of children younger than 6 years in India

The main aims of this study are to find out the trends in the (a) prevalence of undernutrition and severe anemia and (b) degree of association of undernutrition and severe anemia in children younger than 6 years in India with some socioeconomic variables. Using the Reproductive and Child Health Survey data, z score of weight for age and hemoglobin status were analyzed to understand the state and agewise variation and their association with the sociodemographic variables through logistic regression. The prevalence of malnutrition according to both the criteria was first seen to increase, attain a maximum value at some age between 12 and 48 months, and then decrease. Statewise distribution showed a close link between the stage of development and the prevalence of malnutrition-prevalence rate being less for developed states. The rates were also less for the Northeastern states of India. The regression analysis clearly points out that children with illiterate mothers, of lower age groups, or from low standard of living households are more prone to become malnourished. The economic growth alone is not sufficient for substantially reducing malnutrition. It is necessary to improve the rate of literacy, especially of women, to reduce the prevalence of malnutrition and anemia among children. It is not only economic development but also overall human development that is needed in India.     

Obstetric care practice in Birbhum District, West Bengal, India.

BACKGROUND: The study area is the Birbhum district of the State of West Bengal in India. It is one of the backward districts in India. OBJECTIVE: The paper investigates the existing pattern of obstetric health care practices and the factors associated with the utilization of such care. METHOD: The present analysis includes 495 adult married women of both rural and urban areas of nine Blocks of Birbhum district. Besides performing chi2 tests to see the association of the relevant individual and household characteristics, logistic regression was also carried out to measure the effect of these characteristics on the use of obstetric health care. RESULTS: In Birbhum district of West Bengal 65 percent mothers go to doctors for antenatal check-up during their pregnancy, but only 26 percent mothers deliver their babies in institutions and 30 percent mothers get the help of professional health assistants during delivery. Educated women have emphasized role in the practice of obstetric health care. Husband's education and the standard of living of the family also have some effect on the practice of antenatal check up, place of delivery and assistance of health professional. While most of the family background variables have significant effect on the practice of antenatal check up, these variables do not have much effect on the choice of delivery or seeking assistance of health professionals. Contrary to the popular belief the working status of women does not have favourable influence on the obstetric health care practices. In developing countries like India, it is the poverty, which compels the women to take jobs-that too in low paid jobs especially in rural backward areas. CONCLUSION: The status of literacy of mothers and standard of living of the family are of prime importance in improving the obstetric health care practices.     

Married men's first time experiences of early childbearing and their role in sexual and reproductive decision making: a qualitative study from rural Vietnam

Male partners' involvement in women's sexual and reproductive health has been increasingly emphasised in international health. A qualitative approach with open-ended qualitative interviews was used to explore young, married men's first time experiences of early childbearing, their sexual and reproductive decision making and the meanings they make of their role as husbands and fathers. The results offer a nuanced picture of the men's vulnerability in becoming young fathers and having to assume their role as family decision-makers, while still being inexperienced in matters related to the health of their wives and newborn child. Constraints to gender equality and traditional norms and values continue to pose barriers to both young men and women making independent decisions in relation to marriage and childbearing. Men's involvement is necessary in healthcare programmes designed to improve women's sexual and reproductive health and the health of the newborn. Young, first-time fathers, in particular, need support and empowerment.     

Embryotoxicity and fetotoxicity of orally administered hexavalent chromium in mice

The embryotoxic and fetotoxic potential of hexavalent chromium (Cr⁺⁶) in mice was investigated by administering 250, 500, and 1000 ppm of potassium dichromate daily through drinking water during the entire gestation period. An increase in embryonic deaths was observed; however, in the mothers treated with the highest dose, there was complete absence of implantation sites. No major abnormality was observed in the fetuses except that Cr⁺⁶ exposure increased the incidences and types of external and skeletal malformations. It is concluded that oral exposure to Cr⁺⁶ causes dose-dependent embryolethal effects in mice.     

The association between aneurysm formation and systemic hypertension in Takayasu's arteritis

We have studied the incidence and patterns of aneurysm formation in 88 consecutive patients with Takayasu's arteritis by utilizing digital subtraction pan-aortoarteriography by the intravenous and/or intra-arterial route. Seventy-two patients underwent initial intravenous angiography of which 64 (89%) were diagnostic. All the intra-arterial studies (n = 24) were diagnostically adequate. Arterial aneurysms were seen in eight patients (9.1%) and the saccular variety (75%) was the most common. Clinical and angiographic features of these eight patients were compared with those of the remaining patients. No major differences were observed except that longstanding uncontrolled hypertension was present in all patients with aneurysm formation. In comparison, hypertension was observed in 30 (49.2%) of the remaining 61 patients in whom clinical details were available. Angiographic localization of the aneurysm is important since there are no clinical features that distinguish these patients and rupture of a strategically located aneurysm can prove fatal. The association between hypertension and aneurysm formation suggests that hypertension in these patients should be aggressively managed at the onset of disease. In this regard percutaneous transluminal renal angioplasty may prove a possible management adjunct.