An experimental morphometric study of neutral lipid accumulation in skeletal muscles

The neutral lipid content of skeletal muscle fibers was determined by computing the lipid accumulation index (LAI) on transverse cryostat sections stained with Oil Red O. The LAI was defined as: (total area of neutral lipid droplets in a fiber) × 100/(total cross-sectional area of a fiber). The biceps, diaphragm, and soleus muscles were studied in 3 groups of guinea pigs: normal animals, animals fasted for 48 hours, and animals subjected to muscle denervation and then fasted for 48 hours. and animals, subjected to muscle denervation and then fasted for 48 hours. In normal animals, the highest mean LAI was found in the diaphragm (4.93) in comparison with lower values in the biceps (2.25) and soleus (2.09). After fasting, these values were markedly increased; there was also a concomitant increase in plasma free fatty acid (FFA) concentration. Prior denervation further increased the LAI in biceps and soleus but reduced it in the diaphragm. Type 2A fibers tended to show high lipid accumulation when the plasma FFA concentration was high. Type 2B fibers never accumulated much lipid under any circumstances. Type 1 fibers varied in their response in the different muscles.     

Iodine deficiency in Papua New Guinea (sub-clinical iodine deficiency and salt iodization in the highlands of Papua New Guinea)

Data on the status about iodine nutrition in children in Papua New Guinea (PNG) are scarce. This study attempts to determine the mean daily per capita consumption of salt, the iodine content of salt in the households and retail shops and the urinary iodine concentration in children (6-12 years) in Hella Region, Southern Highland Province (SHP), PNG. The mean daily consumption of salt was 2.62 +/- 1.29 g. The iodine content of salt was >30 p.p.m. in 95 per cent of households and 100 per cent of retail shops. The median urinary iodine concentration of 48.0 mg/l for all the children indicates moderate iodine deficiency. The median urinary iodine concentrations for the male (67.0 mg/l) and female (44.0 mg/l) children indicate mild and moderate iodine deficiency, respectively. 68.42 per cent of the male and 81.82 per cent of the female children have urinary iodine concentration <100 mg/l, indicating that iodine deficiency is a potential public health problem in the Hella region. These results indicate a need for further assessment of the implementation of the universal salt iodization strategy for the elimination of iodine deficiency in the SHP, PNG.     

Sample size calculations based on generalized estimating equations for population pharmacokinetic experiments

We present a method for calculating the sample size of a pharmacokinetic study analyzed using a mixed effects model within a hypothesis testing framework. A sample size calculation method for repeated measurement data analyzed using generalized estimating equations has been modified for nonlinear models. The Wald test is used for hypothesis testing of pharmacokinetic parameters. A marginal model for the population pharmacokinetic is obtained by linearizing the structural model around the subject specific random effects. The proposed method is general in that it allows unequal allocation of subjects to the groups and accounts for situations where different blood sampling schedules are required in different groups of patients. The proposed method has been assessed using Monte Carlo simulations under a range of scenarios. NONMEM was used for simulations and data analysis and the results showed good agreement.     

What have we learned? Coordination

This paper outlines each aspect of coordination as it relates to the responses made by various organizations in the disaster-affected areas. It is a synthesis of the presentations and discussions pertaining to coordination during the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO), in Phuket, Thailand, 04-06 May 2005. Coordination is defined, and two important questions are answered: (1) What coordination was done well?; and (2) What coordination could have been done better?     

Acceptability, feasibility and affordability of infant feeding options for HIV-infected women: a qualitative study in south-west Nigeria

The objective of this study was to explore the acceptability, feasibility, affordability, safety and sustainability of replacement feeding options for HIV-infected mothers in Ile-Ife, in south-west Nigeria. Six focus group discussions were conducted with a purposive sample of mothers, fathers and grandmothers. The HIV status of all participants was unknown to investigators. All text data were analysed using the Text-based Beta Software program. With regard to the acceptability of replacement feeds, respondents perceived the stigma associated with not breastfeeding to be an important consideration. In this community, breastfeeding is the norm--even though it is not necessarily exclusive. For infected mothers who choose to breastfeed exclusively and then to wean their infants before 6 months of age, respondents did not anticipate early cessation of breastfeeding to be problematic. Respondents noted that acceptable replacement foods included infant formula, soy milk and cow's milk. Barriers to replacement feeding that were mentioned included: the high costs of replacement foods and fuel for cooking; an unreliable supply of electrical power; poor access to safe water; and poor access to storage facilities. The research confirms the difficulty of replacement feeding for HIV-infected mothers in sub-Saharan Africa. The results also provide the basis for new issues and hypothesis for future research in other communities with similar socio-cultural and economic characteristics.     

Clinical Audit of Antenatal Service Provision in Nigeria

We audited records of 365 pregnant women whose mean age was 25.6 ± 5.6 years. Their mean gestational age at booking was 29.3 ± 2.7 weeks; their mean number of antenatal visits was 4.2 ± 2.3. Weight, blood pressure, and urine were checked on 97.3%, 95.1%, and 86.3% of the women respectively. Hemoglobin estimation was done on 19.2% of women; 34.8% received two doses of tetanus toxoid. Malaria prophylaxis and iron and folate supplements were provided to 263 (72.1%) and 293 (80.3%), respectively. Late booking was common, and antenatal service was inadequately equipped. Early booking and full implementation of preventive treatments are recommended. Support for detection of anaemia and immunization service is desirable.     

Structure determination of glycogen synthase kinase-3 from Leishmania major and comparative inhibitor structure-activity relationships with Trypanosoma brucei GSK-3

Glycogen synthase kinase-3 (GSK-3) is a drug target under intense investigation in pharmaceutical companies and constitutes an attractive piggyback target for eukaryotic pathogens. Two different GSKs are found in trypanosomatids, one about 150 residues shorter than the other. GSK-3 short (GeneDB: Tb927.10.13780) has previously been validated genetically as a drug target in Trypanosoma brucei by RNAi induced growth retardation; and chemically by correlation between enzyme and in vitro growth inhibition. Here, we report investigation of the equivalent GSK-3 short enzymes of L. major (LmjF18.0270) and L. infantum (LinJ18_V3.0270, identical in amino acid sequences to LdonGSK-3 short) and a crystal structure of LmajGSK-3 short at 2 ? resolution. The inhibitor structure-activity relationships (SARs) of L. major and L. infantum are virtually identical, suggesting that inhibitors could be useful for both cutaneous and visceral leishmaniasis. Leishmania spp. GSK-3 short has different inhibitor SARs than TbruGSK-3 short, which can be explained mostly by two variant residues in the ATP-binding pocket. Indeed, mutating these residues in the ATP-binding site of LmajGSK-3 short to the TbruGSK-3 short equivalents results in a mutant LmajGSK-3 short enzyme with SAR more similar to that of TbruGSK-3 short. The differences between human GSK-3β (HsGSK-3β) and LmajGSK-3 short SAR suggest that compounds which selectively inhibit LmajGSK-3 short may be found.