Validated HPLC and HPTLC Methods for Simultaneous Determination of Some α1 -Adrenoreceptor Blockers

Alpha-blockers (alfuzosin, tamsulosin, doxazosin, prazosin and terazosin) relax the smooth muscles in the prostate and are indicated for the symptomatic treatment of benign prostatic hyperplasia due to evidence of their positive and rapid effect on lower urinary tract symptoms. Our objective was to develop and validate simultaneous estimation of these drugs. Same class of drugs may have almost same functional groups and therefore research focused on development of RPLC and HPTLC method for simultaneous quantitative determination. The separation was achieved in HPLC method on a C18 column, a UV detector at 230 nm and a elution was performed under a gradient mobile phase composed of (A) ACNdiethylamine (0.05 mL), (B) methanol, (C) 10 mM ammonium acetate and (D) Water. For HPTLC method separation was achieved by using mobile phase chloroform and methanol in the ratio 9.5:0.5. Both of the validated methods can be utilized for the assay of these α1 adrenoreceptors in pharmaceutical industries.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Targeting IκappaB kinases for cancer therapy

The inhibitory kappa B kinases (IKKs) and IKK related kinases are crucial regulators of the pro-inflammatory transcription factor, nuclear factor kappa B (NF-κB). The dysregulation in the activities of these kinases has been reported in several cancer types. These kinases are known to regulate survival, proliferation, invasion, angiogenesis, and metastasis of cancer cells. Thus, IKK and IKK related kinases have emerged as an attractive target for the development of cancer therapeutics. Several IKK inhibitors have been developed, few of which have advanced to the clinic. These inhibitors target IKK either directly or indirectly by modulating the activities of other signaling molecules. Some inhibitors suppress IKK activity by disrupting the protein-protein interaction in the IKK complex. The inhibition of IKK has also been shown to enhance the efficacy of conventional chemotherapeutic agents. Because IKK and NF-κB are the key components of innate immunity, suppressing IKK is associated with the risk of immune suppression. Furthermore, IKK inhibitors may hit other signaling molecules and thus may produce off-target effects. Recent studies suggest that multiple cytoplasmic and nuclear proteins distinct from NF-κB and inhibitory κB are also substrates of IKK. In this review, we discuss the utility of IKK inhibitors for cancer therapy. The limitations associated with the intervention of IKK are also discussed

The co-occurrence of anemia and cardiometabolic disease risk demonstrates sex-specific sociodemographic patterning in an urbanizing rural region of southern India

BACKGROUND/OBJECTIVES: To determine the extent and sociodemographic determinants of anemia, overweight, metabolic syndrome (MetS), and the co-occurrence of anemia with cardiometabolic disease risk factors among a cohort of Indian adults. SUBJECT/METHODS: Cross-sectional survey of adult men (n=3,322) and non-pregnant women (n=2,895) aged 18 y and older from the third wave of the Andhra Pradesh Children and Parents Study that assessed anemia, overweight based on Body Mass Index, and prevalence of MetS based on abdominal obesity, hypertension, and blood lipid and fasting glucose measures. We examined associations of education, wealth and urbanicity with these outcomes and their co-occurrence. RESULTS: The prevalence of anemia and overweight was 40% and 29% among women, respectively, and 10% and 25% among men (P<0.001), respectively, while the prevalence of MetS was the same across sexes (15%) (P=0.55). The prevalence of concurrent anemia and overweight (9%), and anemia and MetS (4.5%) was highest among women. Household wealth was positively associated with overweight and MetS across sexes (P<0.05). Independent of household wealth, higher education was positively correlated with MetS among men (OR (95% CI): MetS: 1.4 (0.99, 2.0)) and negatively correlated with MetS among women (MetS: 0.54 (0.29, 0.99)). Similar sex-specific associations were observed for the co-occurrence of anemia with overweight and MetS. CONCLUSION: Women in this region of India may be particularly vulnerable to co-occurring anemia and cardiometabolic risk, and associated adverse health outcomes as the nutrition transition advances in India

Association of Hip Bone Mineral Density and Body Composition in a Rural Indian Population:The Andhra Pradesh Children and Parents Study (APCAPS)

BACKGROUND: Fat mass is variably associated with bone mass, possibly due to differential mechanical and biological effects of fat mass. We examined the association of fat mass with bone mass in a lean population. OBJECTIVE: To investigate association between hip bone mineral density and fat and lean mass in a cross-sectional study from southern India. DESIGN: The Andhra Pradesh Children and Parents Study is a prospective cohort study in Hyderabad, India. In 2009-2012, the study collected data on anthropometric measures, bone mineral density (BMD), fat mass, and lean mass measured by dual-energy x-ray absorptiometry, and socioeconomic data of the adult participants (n = 1760; mean age = 34.9 years old for women; 2130 and 32.3 for men). RESULTS: The median BMI (kg/m2) was 20.1 kg/m2. Women had relatively higher fat mass as compared to men. In models adjusted for lean mass, there was an association between hip bone mineral density and fat mass in women (β (95% confidence interval): premenopausal 0.025 (0.006 to 0.045); postmenopausal 0.045 (0.014 to 0.076)) but not in men (0.001 (-0.012 to 0.0014)). The association between hip BMD and fat mass was stronger in postmenopausal than premenopausal women. Hip BMD was consistently associated with lean mass, in both men and women. CONCLUSIONS: In this relatively lean population, lean mass was more consistently associated with hip BMD than fat mass. Weight gain through lean mass improvement may be a more reliable public health strategy for strengthening bone health in transitional settings

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Cultural and leadership predictors of corporate social responsibility values of top management: A GLOBE study of 15 countries.

This paper examines cultural and leadership variables associated with corporate social responsibility values that managers apply to their decision-making. In this longitudinal study, we analyze data from 561 firms located in 15 countries on five continents to illustrate how the cultural dimensions of institutional collectivism and power distance predict social responsibility values on the part of top management team members. CEO visionary leadership and integrity were also uniquely predictive of such values. Journal of International Business Studies (2006) 37, 823–837. doi:10.1057/palgrave.jibs.8400230

Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival

<p>Abstract</p> <p>Background</p> <p>We have engaged in an international program designated the <it>Bank On A Cure</it>, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma.</p> <p>We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, <it>n </it>= 70) versus long term progression-free survivors (greater than 3 years, <it>n </it>= 73) in two phase III clinical trials.</p> <p>Results</p> <p>Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes.</p> <p>Conclusion</p> <p>A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS.</p

High-Order SNP Combinations Associated with Complex Diseases: Efficient Discovery, Statistical Power and Functional Interactions

There has been increased interest in discovering combinations of single-nucleotide polymorphisms (SNPs) that are strongly associated with a phenotype even if each SNP has little individual effect. Efficient approaches have been proposed for searching two-locus combinations from genome-wide datasets. However, for high-order combinations, existing methods either adopt a brute-force search which only handles a small number of SNPs (up to few hundreds), or use heuristic search that may miss informative combinations. In addition, existing approaches lack statistical power because of the use of statistics with high degrees-of-freedom and the huge number of hypotheses tested during combinatorial search. Due to these challenges, functional interactions in high-order combinations have not been systematically explored. We leverage discriminative-pattern-mining algorithms from the data-mining community to search for high-order combinations in case-control datasets. The substantially improved efficiency and scalability demonstrated on synthetic and real datasets with several thousands of SNPs allows the study of several important mathematical and statistical properties of SNP combinations with order as high as eleven. We further explore functional interactions in high-order combinations and reveal a general connection between the increase in discriminative power of a combination over its subsets and the functional coherence among the genes comprising the combination, supported by multiple datasets. Finally, we study several significant high-order combinations discovered from a lung-cancer dataset and a kidney-transplant-rejection dataset in detail to provide novel insights on the complex diseases. Interestingly, many of these associations involve combinations of common variations that occur in small fractions of population. Thus, our approach is an alternative methodology for exploring the genetics of rare diseases for which the current focus is on individually rare variations

Cellulose nanofiber backboned Prussian blue nanoparticles as powerful adsorbents for the selective elimination of radioactive cesium

On 11 March 2011, the day of the unforgettable disaster of the 9 magnitude Tohoku earthquake and quickly followed by the devastating Tsunami, a damageable amount of radionuclides had dispersed from the Fukushima Daiichi’s damaged nuclear reactors. Decontamination of the dispersed radionuclides from seawater and soil, due to the huge amounts of coexisting ions with competitive functionalities, has been the topmost difficulty. Ferric hexacyanoferrate, also known as Prussian blue (PB), has been the most powerful material for selectively trapping the radioactive cesium ions; its high tendency to form stable colloids in water, however, has made PB to be impossible for the open-field radioactive cesium decontamination applications. A nano/nano combinatorial approach, as is described in this study, has provided an ultimate solution to this intrinsic colloid formation difficulty of PB. Cellulose nanofibers (CNF) were used to immobilize PB via the creation of CNF-backboned PB. The CNF-backboned PB (CNF/PB) was found to be highly tolerant to water and moreover, it gave a 139 mg/g capability and a million (106) order of magnitude distribution coefficient (Kd) for absorbing of the radioactive cesium ion. Field studies on soil and seawater decontaminations in Fukushima gave satisfactory results, demonstrating high capabilities of CNF/PB for practical applications.National Science Foundation (U.S.) (DMR-1507806