Stability-indicating methods for the determination of sertaconazole nitrate by micelle-enhanced spectrofluorimetry and TLC-densitometry

Two sensitive and selective stability-indicating methods were developed for the determination of sertaconazole nitrate (Ser-NO3), in the presence of its acid, alkaline and oxidative degradation products. The first method was based on measuring the fluorescence intensity of the drug at λex/λem = 231 nm/312 nm. The influence of micelle medium on the fluorescence emission was studied. The nonionic surfactant of Triton® X-100 showedstrong sensitizing effect for the fluorescence. The fluorescence intensity plot was linear over concentrations 0.5–5 μg mL-1 with mean percentage recoveries 100.59 ± 1.49 %. The second method was based on TLC separation of the drug from its degradation products followed by densitometric measurement of the intact drug spot at 302 nm. The developing system used for separation was chloroform-acetone-33 % ammonia (14:2:0.1 v/v/v). The linear range was 1–8 μg/spot with mean percentage recoveries 100.07 ± 1.97 %. The methods were validated according to ICH guidelines. Statistical analysis of the results revealed high accuracy and good precision. The suggested procedures could be used for the determination of sertaconazole nitrate in drug substance and drug products as well as in presence of its degradation products

The effect of ruminal incubation of bioactive yeast (Saccharomyces cerevisiae) on potential rumen degradability of Panicum maximum and Centrosema pubescens in West African dwarf sheep

The rising interest in the use of organic and inorganic substances in manipulating rumen function for improved fermentative activity has provided avenues for the inclusion of various species of yeast cultures in ruminant diets. In this study, we investigated the effect of bioactive yeast (Saccharomyces cerevisiae), on rumen degradative function of the West African Dwarf Sheep (WADS) in terms of fermentable organic matter, crude protein and crude fiber of Panicum maximum and Centrosema pubescens. Three inclusion levels of Saccharomyces cerevisiae, 200, 500 and 800 milligrams were infused into the rumen of three groups (A, B and C), of three WAD sheep each. Another group (D) of same animal number served as the control. In vivo rumen potential degradability studies, using the nylon bag technique was performed using Panicum maximum and Centrosema pubescens in all the groups. The result of the study showed  that bioactive yeast improved the potential rumen degradability of crude protein, crude fibre and organic matter fractions of Panicum maximum and Centrosema pubescens in a rather dose dependent manner compared to the control. There was a significant correlation (r = 0.56) between degradability, dose and time of incubation for crude fibre and organic  matter fractions but not for crude protein. These observations suggest that regulated dietary inclusion of bioactive yeast can be used to bioengineer the rumen towards efficient fibre breakdown, particularly forages of poor protein quality and high fibre content, for efficient production of volatile fatty acids as well as probably enhancing other aspects of rumen functions.Keywords: Bioactive Yeast, Degradability, Forages, Rumen, WADS

Cost-effectiveness of a market-based home fortification of food with micronutrient powder programme in Bangladesh

Objective: We estimated the cost-effectiveness of home fortification with micronutrient powder delivered in a sales-based programme in reducing the prevalence of Fe deficiency anaemia among children 6–59 months in Bangladesh. Design: Cross-sectional interviews with local and central-level programme staff and document reviews were conducted. Using an activity-based costing approach, we estimated start-up and implementation costs of the programme. The incremental cost per anaemia case averted and disability-adjusted life years (DALY) averted were estimated by comparing the home fortification programme and no intervention scenarios. Setting: The home fortification programme was implemented in 164 upazilas (sub-districts) in Bangladesh. Participants: Caregivers of child 6–59 months and BRAC staff members including community health workers were the participants for this study. Results: The home fortification programme had an estimated total start-up cost of 35·46 million BDT (456 thousand USD) and implementation cost of 1111·63 million BDT (14·12 million USD). The incremental cost per Fe deficiency anaemia case averted and per DALY averted was estimated to be 1749 BDT (22·2 USD) and 12 558 BDT (159·3 USD), respectively. Considering per capita gross domestic product (1516·5 USD) as the cost-effectiveness threshold, the home fortification programme was highly cost-effective. The programme coverage and costs for nutritional counselling of the beneficiary were influential parameters for cost per DALY averted in the one-way sensitivity analysis. Conclusions: The market-based home fortification programme was a highly cost-effective mechanism for delivering micronutrients to a large number of children in Bangladesh. The policymakers should consider funding and sustaining large-scale sales-based micronutrient home fortification efforts assuming the clear population-level need and potential to benefi

Diffractive Phenomena and Shadowing in Deep-Inelastic Scattering

Shadowing effects in deep-inelastic lepton-nucleus scattering probe the mass spectrum of diffractive leptoproduction from individual nucleons. We explore this relationship using current experimental information on both processes. In recent data from the NMC and E665 collaboration, taken at small x << 0.1 and Q^2 < 1 GeV^2, shadowing is dominated by the diffractive excitation and coherent interaction of low mass vector mesons. If shadowing is explored at small x > 1 GeV^2 as discussed at HERA, the situation is different. Here dominant contributions come from the coherent interaction of diffractively produced heavy mass states. Furthermore we observe that the energy dependence of shadowing is directly related to the mass dependence of the diffractive production cross section for free nucleon targets.Comment: 12 pages Latex, 8 figure

Competing biosecurity and risk rationalities in the Chittagong poultry commodity chain, Bangladesh

This paper anthropologically explores how key actors in the Chittagong live bird trading network perceive biosecurity and risk in relation to avian influenza between production sites, market maker scenes and outlets. They pay attention to the past and the present, rather than the future, downplaying the need for strict risk management, as outbreaks have not been reported frequently for a number of years. This is analysed as ‘temporalities of risk perception regarding biosecurity’, through Black Swan theory, the idea that unexpected events with major effects are often inappropriately rationalized (Taleb in The Black Swan. The impact of the highly improbable, Random House, New York, 2007). This incorporates a sociocultural perspective on risk, emphasizing the contexts in which risk is understood, lived, embodied and experienced. Their risk calculation is explained in terms of social consent, practical intelligibility and convergence of constraints and motivation. The pragmatic and practical orientation towards risk stands in contrast to how risk is calculated in the avian influenza preparedness paradigm. It is argued that disease risk on the ground has become a normalized part of everyday business, as implied in Black Swan theory. Risk which is calculated retrospectively is unlikely to encourage investment in biosecurity and, thereby, points to the danger of unpredictable outlier events

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Antibody Responses to NY-ESO-1 in Primary Breast Cancer Identify a Subtype Target for Immunotherapy

The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)− invasive ductal carcinomas of high grade, including both HER2− and HER2+ tumors. In line with these results, we detected ESO expression in 20% of primary HR− BC, including both ESO Ab+ and Ab− patients, but not in HR+ BC. Interestingly, whereas expression levels in ESO+ BC were not significantly different between ESO Ab+ and Ab− patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR− (HER2− or HER2+) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy

Inhibition of Casein Kinase 2 Modulates XBP1-GRP78 Arm of Unfolded Protein Responses in Cultured Glial Cells

Stress signals cause abnormal proteins to accumulate in the endoplasmic reticulum (ER). Such stress is known as ER stress, which has been suggested to be involved in neurodegenerative diseases, diabetes, obesity and cancer. ER stress activates the unfolded protein response (UPR) to reduce levels of abnormal proteins by inducing the production of chaperon proteins such as GRP78, and to attenuate translation through the phosphorylation of eIF2α. However, excessive stress leads to apoptosis by generating transcription factors such as CHOP. Casein kinase 2 (CK2) is a serine/threonine kinase involved in regulating neoplasia, cell survival and viral infections. In the present study, we investigated a possible linkage between CK2 and ER stress using mouse primary cultured glial cells. 4,5,6,7-tetrabromobenzotriazole (TBB), a CK2-specific inhibitor, attenuated ER stress-induced XBP-1 splicing and subsequent induction of GRP78 expression, but was ineffective against ER stress-induced eIF2α phosphorylation and CHOP expression. Similar results were obtained when endogenous CK2 expression was knocked-down by siRNA. Immunohistochemical analysis suggested that CK2 was present at the ER. These results indicate CK2 to be linked with UPR and to resist ER stress by activating the XBP-1-GRP78 arm of UPR

The challenge of admitting the very elderly to intensive care

The aging of the population has increased the demand for healthcare resources. The number of patients aged 80 years and older admitted to the intensive care unit (ICU) increased during the past decade, as has the intensity of care for such patients. Yet, many physicians remain reluctant to admit the oldest, arguing a "squandering" of societal resources, that ICU care could be deleterious, or that ICU care may not actually be what the patient or family wants in this instance. Other ICU physicians are strong advocates for admission of a selected elderly population. These discrepant opinions may partly be explained by the current lack of validated criteria to select accurately the patients (of any age) who will benefit most from ICU hospitalization. This review describes the epidemiology of the elderly aged 80 years and older admitted in the ICU, their long-term outcomes, and to discuss some of the solutions to cope with the burden of an aging population receiving acute care hospitalization