Immunohistochemistry ofβ-neoendorphin and dynorphin in the endocrine pancreas of rat and man

Histochemistry and Cell Biology - Serial sections from araldite-embedded rat and man pancreata were investigated immunohistochemically for the presence of prodynorphin-related peptides and...     

Fair Resource Allocation to Health Research: Priority Topics for Bioethics Scholarship

This article draws attention to the limited amount of scholarship on what constitutes fairness and equity in resource allocation to health research by individual funders. It identifies three key decisions of ethical significance about resource allocation that research funders make regularly and calls for prioritizing scholarship on those topics – namely, how health resources should be fairly apportioned amongst public health and health care delivery versus health research, how health research resources should be fairly allocated between health problems experienced domestically versus other health problems typically experienced by disadvantaged populations outside the funder's country, and how domestic and non‐domestic health research funding should be further apportioned to different areas, e.g. types of research and recipients. These three topics should be priorities for bioethics research because their outcomes have a substantial bearing on the achievement of health justice. The proposed agenda aims to move discussion on the ethics of health research funding beyond its current focus on the mismatch between worldwide basic and clinical research investment and the global burden of disease. Individual funders’ decision‐making on whether and to what extent to allocate resources to non‐domestic health research, health systems research, research on the social determinants of health, capacity development, and recipients in certain countries should also be the focus of ethical scrutiny.     

Human Parechovirus Genotypes -10, -13 and -15 in Pakistani Children with Acute Dehydrating Gastroenteritis

Human parechoviruses are known to cause asymptomatic to severe clinical illness predominantly respiratory and gastroenetric infections. Despite their global prevalence, epidemiological studies have not been performed in Pakistan. In this study, we retrospectively analyzed 110 fecal specimen and found 26 (24%) positive for viral RNA with HPeV-10 (n = 3, 23%), HPeV-13 (n = 4, 31%) and HPeV-15 (n = 6, 46%) genotypes. Clinical features of patients with different HPeV genotypes were compared. All HPeV positive children were aged ≤4 years (mean 13.92 months). The male-to-female ratio was 1: 1.17 (46.2 vs 53.8%) with significant association (p = .031) to HPeV infectivity. HPeV-10 and -13 were found during summer while HPeV-15 was only detected during late winter season. Disease symptoms were more severe in children infected with HPeV-10 and -13 as compared to HPeV-15. Fever and vomiting were observed in 100% cases of HPeV-10 and -13 while only 17% patients of HPeV-15 had these complaints. Phylogenetic analyses showed that HPeV-10, -13 and -15 strains found in this study have 9–13%, 16.8% and 21.8% nucleotide divergence respectively from the prototype strains and were clustered to distinct genetic lineages. This is the first report of HPeV-15 infection in humans although first identified in rhesus macaques. The arginine-glycine-aspartic acid (RGD) motif present at the C-terminal of VP1 responsible for the viral attachment to cellular integrins was not found in all of these strains. In conclusion, these findings enhance our knowledge related to the epidemiology and genetic diversity of the HPeV in Pakistan and support the need for continued laboratory based surveillance programs especially in infants and neonatal clinical settings. Further, the parechovirus pathogenesis, cross-species transmission and disease reservoirs must be ascertained to adopt better prevention measures.     

Miospore stratigraphy of Lower and early Middle Devonian deposits from Tidikelt, Central Sahara, Algeria

The Tidikelt region forms an outstanding area for subsurface Lower Devonian stratigraphy in the central Algerian Sahara. Sediments from five boreholes have revealed abundant and diverse assemblages of miospores, acritarchs, chitinozoa, scolecodont and microplant remains. The miospores are moderately well preserved. Three new miospore species (Dibolisporites saharansis nov. sp. Hassan Kermandji, Acinosporites conatus nov. sp. Hassan Kermandji and Scylaspora tidikeltense nov. sp. Hassan Kermandji) are described. Miospore assemblages vary through the regressive and transgressive sequences. Seven miospore assemblage biozones, including six new miospore assemblage biozones (Scylaspora tidikeltense-Perotrilites microbaculatus, Dictyotriletes emsiensis-Emphanisporites spinaeformis, Apiculiretusispora arenorugosa-Camptozonotriletes caperatus, Verrucosisporites polygonalis-Dictyotriletes subgranifer, Emphanisporites annulatus-Geminospora svalbardiae, Hystricosporites microancyreus-Grandispora protea, Calyptosporites velatus-Rhabdosporites langii) are proposed for the Lower and early Middle Devonian rocks of Tidikelt Plateau. The combined use of distinctive, wide distribution cosmopolitan and Gondwanan forms as biozonal and species characteristics permits accurate subdivision, dating and correlation of Tidikelt successions with other similar miospore zones of the Lower Devonian of Europe, Canada and other parts of Gondwana plate. The miospore data provide new explanations to stratigraphic relationships of regional rock units, sedimentary cycles and stratigraphic hiatus. The miospore biozones are proposed as a provincial biozonation, which may also be applied to other Palaeozoic rocks of similar miospore content.     

Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population

In the Kingdom of Saudi Arabia (KSA), breast cancer constitutes 18% of all cancers in Saudi women. Whilst locally advanced breast cancer disease is unusual in Western countries, it constitutes more than 40% of all non-metastatic breast cancer in KSA. The relative frequency of locally advanced disease among our breast cancer population and the lack of a uniform consensus in the literature about its optimal management have prompted this retrospective analysis of the medical records of patients with Stage III breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 1981 and 1991. In all, 315 patients were identified. Their median age ±SD was 46±11.6 years which is distinctly different from the 60–65 years median age in industrial Western nations. Most patients were younger than 50 years (64%) and premenopausal (62%). Patients were approximately equally divided between Stage III A and Stage III B Patients received multimodality treatment, including surgery., adjuvant chemotherapy, tamoxifen, and adjuvant radiotherapy. Sixty-one patients were excluded from survival analysis as they were considered lost to follow-up. Of the remaining 254 patients, 73 (29%) were alive and disease free, and 18 patients (7%) were alive but, with evidence of the disease. The remaining 163 (64%) had died from breast cancer or its related complications. Their median overall survival (OS) was 54 months, (95%, Cl, 27 to 121 months) and the median progression-free survival (PFS) was 28.8 months (95% Cl, 14.2 to 113 months). Cox proportional hazard, model identified Stage III B and the number of positive axillary lymph nodes as poor predictors of OS and PFS. Radiotherapy was the only adjuvant modality that affected survival favourably. The prognosis of patients with Stage III disease remains poor despite the use of a multimodality approach. The overall young age of our patients may have contributed to the poor outcome. Moreover, the adverse effect of Stage III B disease (as compared with Stage III A) and axillary nodal status was evident. Whilst the favourable effect of radiotherapy on survival was demonstrated, the lack of independent efficacy of other modalities (adjuvant chemotherapy and tamoxifen) or the apparent deleterious effect of neoadjuvant chemotherapy should be addressed with discretion in such retrospective analysis. Optimal management of patients with locally advanced breast cancer disease should be appraised in well designed, prospective, randomised studies.     

<Emphasis Type="Italic">In vitro</Emphasis> effects of GA<Subscript>3</Subscript> on morphogenesis of CIP potato explants and acclimatization of plantlets in field

Improvement of potato has been accomplished using conventional and non-conventional approaches coupled with numerous tissue culture procedures. The aim of the present study was to assess the efficacy of gibberellic acid (GA₃) on the morphogenesis of International Potato Center (CIP) potato explants and acclimatization of plantlets in the field. Nodal segments as an explant source (1–1.5 cm) were isolated from 31 CIP potato plantlets and were inoculated into Murashige and Skoog (MS) medium supplemented with 0.0 (control), 0.1, 0.5, or 1.0 mg L^?1of GA₃. The variation in growth parameters of the cultivars was then observed. The highest shoot induction occurred in MS medium containing 1.0 mg L^?1 GA₃ with an increase in the inter-nodal distance between nodes as compared to other treatments. Higher concentration (1.0 mg L^?1) of GA₃ significantly increased plant height and root length in the treated germplasm however; this concentration was inhibitory to the number of nodes and roots per plant. The number of leaves was significantly increased in plants receiving GA₃ treatment at lower concentration (0.1 mg L^?1). The 31 CIP genotypes were transplanted to the field and checked for yield quality traits. It was concluded from the results that GA₃ had significant effects on morphogenesis and was effective in the acclimatization of CIP potato plantlets in field.     

Designing research funding schemes to promote global health equity: An exploration of current practice in health systems research

International research is an essential means of reducing health disparities between and within countries and should do so as a matter of global justice. Research funders from high‐income countries have an obligation of justice to support health research in low and middle‐income countries (LMICs) that furthers such objectives. This paper investigates how their current funding schemes are designed to incentivise health systems research in LMICs that promotes health equity. Semi‐structured in‐depth interviews were performed with 16 grants officers working for 11 funders and organisations that support health systems research: the Alliance for Health Policy and Systems Research, Comic Relief, Doris Duke Foundation, European Commission, International Development Research Centre, Norwegian Agency for Development Cooperation, Research Council of Norway, Rockefeller Foundation, UK Department of International Development, UK Medical Research Council, and Wellcome Trust. Thematic analysis of the data demonstrates their funding schemes promote health systems research with (up to) five key features that advance health equity: being conducted with worst‐off populations, focusing on research topics that advance equitable health systems, having LMIC ownership of the research agenda, strengthening LMIC research capacity, and having an impact on health disparities. The different types of incentives that encouraged proposed projects to have these features are identified and classified by their strength (strong, moderate, weak). It is suggested that research funders ought to create and maintain funding schemes with strong incentives for the features identified above in order to more effectively help reduce global health disparities.     

Inhibitor effect of omeprazole in isolated human myometrial smooth muscle.

The aim of the present study was to investigate the effect of omeprazole, an H+-K+-ATPase inhibitor, in myometrial smooth muscle strips from women undergoing elective caesarean section at term. Isolated myometrial strips taken with informed consent were obtained from eight pregnant women undergoing elective caesarean section at term (not in labour) and mounted in organ baths for recording of isometric tension. We recorded the effect of increasing concentrations of omeprazole on spontaneous and Ca2+-induced contractions of myometrial smooth muscle and on contractions of myometrial smooth muscle pretreated with indomethacin (3 x 10(-6) M) and L-NAME (3 x 10(-5) M). Omeprazole (10(-4)-10(-3) M) decreased the amplitude and frequency of spontaneous contractions in a time- and concentration-dependent manner in all myometrial smooth muscle isolated from pregnant women. The decrease in amplitude of contractions in myometrial smooth muscle reached statistical significance beginning from the concentration of 3 x 10(-4) M. Addition of indomethacin (3 x 10(-6) M) and L-NAME (3 x 10(-5) M) in to the organ baths 30 min before did not change relaxation responses to omeprazole. When 8 mM Ca2+-precontracted in Ca2+-free medium myometrial smooth muscle were exposed to increasing concentrations of omeprazole (10(-5)-10(-3) M), omeprazole produced relaxation responses in a time- and concentration-dependent manner, reaching statistical significance at 10(-4) M. These results show: (1) omeprazole time- and concentration-dependently decreased spontaneous contractile activity in myometrial smooth muscle isolated from pregnant women, (2) omeprazole-induced relaxations was not influenced by indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME), suggesting that it is not mediated by cyclooxygenase products and nitric oxide, and (3) omeprazole brought about time- and concentration-dependently relaxation of myometrial smooth muscle precontracted by 8 mM Ca2+ in Ca2+-free medium. This effect of omeprazole may be due to blockade of the calcium channels.     

Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes.

We examined whether lung inflammatory mediators are increased during exercise and whether pharmacological blockade can prevent exercise-induced arterial hypoxemia (EIAH) in young athletes. Seventeen healthy athletes (9 men, 8 women; age 23 +/- 3 yr) with varying degrees of EIAH completed maximal incremental treadmill exercise tests after administration of fexofenadine, zileuton, and nedocromil sodium or placebo in a randomized double-blind crossover study. Lung function, arterial blood gases, and inflammatory metabolites in plasma, urine, and induced sputum were assessed. Drug administration did not improve EIAH or gas exchange during exercise. At maximal exercise, oxygen saturation fell to 91.4 +/- 2.6% (drug trial) and 91.9 +/- 2.1% (placebo trial) and alveolar-arterial oxygen difference widened to 28.1 +/- 6.3 Torr (drug trial) and 29.3 +/- 5.7 Torr (placebo trial). Oxygen consumption, ventilation, and other exercise variables were similarly unaffected by drug treatment. Although plasma histamine increased with exercise, values did not differ between trials, and urinary leukotriene E(4) and 11beta-prostaglandin F(2alpha) levels were unchanged after exercise. Postexercise sputum revealed no significant changes in markers of inflammation. These results demonstrate that EIAH in young athletes is not attenuated with acute administration of drugs targeting histamine and bioactive lipids. We conclude that airway inflammation is of insufficient magnitude to cause impairments in gas exchange and does not appear to be linked to EIAH in healthy young athletes.