Body composition and bone measurements in intra-uterine growth retarded and early postnatally undernourished male and female rats at the age of 6 months: comparison with puberty

Undernutrition in early life may permanently change body structure, physiology and metabolism and leads to chronic diseases in later life. To test whether malnutrition during different critical time periods around birth in the rat has long-lasting effects on body composition and skeletal growth, we examined body weight and body composition in pubertal rats and adult rats of 6 months after pre- and postnatal malnutrition. Prenatal malnutrition or intra-uterine growth retardation (IUGR) was induced by ligation of the uterine arteries on day 17 of gestation and postnatal food restriction (FR) by litter enlargement to 20 pups per mother from day 2 after birth until weaning (day 24). Pubertal markers were balanopreputial separation (BPS) in the male and vaginal opening (VO) in the female. IUGR as well as FR resulted in a persistent growth retardation. From birth in IUGR rats and from day 4 after birth in FR rats until 6 months of age body weight in male and female rats was significantly lower compared with controls (P < 0.01 and P < 0.05). Although total body bone mineral content (TBBMC) did not differ between male IUGR rats and controls at BPS, at the age of 6 months TBBMC was significantly lower (P < 0.01) compared with controls. At BPS as well as at 6 months of age, TBBMC was significantly lower in male FR rats compared with controls (P < 0.05 and P < 0.01). In the female IUGR rats TBBMC was significantly lower compared with controls at VO (P < 0.01) and 6 months (P < 0.05). TBBMC in the female FR rats was significantly lower at VO (P < 0.01), but did not differ from controls at the age of 6 months. For both IUGR and FR male and female rats these differences disappeared after adjusting for body weight. Body composition in terms of total fat mass, percentage fat and percentage lean did not differ from controls in male and female IUGR rats at 6 months and the same results were observed in the female FR rats. However, in the male FR rats, total fat mass and percentage fat were significantly lower compared with controls (P < 0.01 and P < 0.05), while the percentage lean mass was significantly higher (P < 0.05). We conclude that different critical time periods of malnutrition around birth have different effects later in life on growth, which do not disappear at least after 6 months of life. With respect to body composition, only in the FR male rats, differences are found in total fat mass and the balance of percentage fat mass and lean mass. At time of puberty and at the age of 6 months bone mass adjusted for body weight does not seem to be affected by perinatal undernutrition.     

Impact of information leaflets on HIV test uptake amongst GUM clinic attendees: an update

In the Sexual Health Strategy, the targets of HIV testing uptake in genitourinary medicine clinics (GUM) are set at 40% by year 2004 and 60% by 2007. We assessed the uptake of HIV test amongst GUM clinic attendees, more than six months after introducing an information leaflet in place of verbal pre-test counselling (PTC). The uptake rate was significantly higher than in a previous audit conducted in the same year, two weeks after introduction of the leaflets (62% vs 50%, P =0.001).     

Alpha 2-adrenergic receptor inhibition of cAMP accumulation is transformed to facilitation by tumor necrosis factor-alpha

Activation of the alpha(2)-adrenergic receptor on neurons regulates the activity of neurons. Inhibition of forskolin-stimulated cAMP accumulation induced by alpha(2)-adrenergic receptor activation is altered following exposure of the neuron SH-SY5Y cell line to tumor necrosis factor-alpha (TNF). Acute (5 and 15 min) exposure to TNF induces a transformation in alpha(2)-adrenergic regulation of cAMP accumulation from inhibition to facilitation. These findings support an autocrine role for the regulation of TNF production from neurons.     

Complex Coacervation of Lysozyme and Heparin: Complex Characterization and Protein Stability

No HeadingPurpose. To characterize complex coacervates/flocculates of lysozyme and heparin in terms of binding stoichiometry and to determine the effect of complexation on protein structure and stability.Methods. Insoluble lysozyme-heparin complexes were formed at pH 7.2 and the binding stoichiometry determined using a solution depletion method. Protein structure was determined by infrared spectroscopy and intrinsic fluorescence. Protein stability was evaluated using differential scanning calorimetry and followed in a 12-weeks storage stability study at 37C.Results. Binding stoichiometry between heparin and lysozyme was found to be dependent on ionic strength of the solution. At low ionic strength (I 0.01) about 11 lysozyme molecules could bind to a 17 kDa heparin chain, 3 to a 6 kDa chain, and less than 2 to a 3 kDa chain. At higher ionic strength (I 0.1), only 7 lysozyme molecules could bind to a 18 kDa heparin chain.. Above ionic strengths of approximately 0.32 M, no insoluble complexes were observed. Infrared spectroscopy and intrinsic fluorescence did not show any major changes in protein structure upon complexation to heparin. In contrast, differential scanning calorimetry showed a large decrease in the melting temperature of the protein, from 77C to 61C. Moreover, after 12-weeks storage at 37C, only 60% protein recovery was observed for the complexes, with no loss of protein for the uncomplexed protein.Conclusions. Heparin has multiple binding sites for lysozyme, amounting to at most one lysozyme molecule per 3 disaccharide units of heparin. Complexation decreased lysozyme stability, suggesting that heparin has a higher affinity for the unfolded state than the native state. Similar destabilization may occur for other proteins upon interaction with highly charged polymeric compounds or surfaces.     

Evaluation of exposure to man-made vitreous fibers by nasal lavage

The objectives of this study were to develop a biomonitoring method for the assessment of exposure to man-made vitreous fibers (MMVF), to examine the level of exposure to MMVF in the prefabricated house industry, and to study nasal inflammatory reactions and respiratory symptoms associated with MMVF among workers. Nasal lavage was performed on workers from two factories, and concentrations of MMVF were measured by electron microscopy. Cytokines (IL-6, IL-8, TNF-alpha, and IFN-gamma) were also assayed and inflammatory cells (lymphocytes, eosinophils, neutrophils, and macrophages) were counted microscopically. Concentrations of airborne fibers (longer than 5 microm) were measured for comparison. Moreover, the exposure to MMVF and the related symptoms were studied with a structured questionnaire. In nasal lavage samples, the mean concentration of MMVF (length >1.5 microm) was 3260 f/ mL in Factory 1, 1680 f/mL in Factory 2, and below 500 f/mL in the control group. About 52% of the retained fibers were longer than 100 microm. The group-specific mean concentrations of MMVF in nasal lavage samples correlated with production rates and airborne fiber levels in both plants. The airborne concentrations of MMVF both in the breathing zone and fixed-point samples were low (below 0.1 f/cm(3)). No significant differences in the biological response (inflammatory cells, cytokines) were found between the groups exposed and the control group. The workers complained of some irritation of the skin, eyes, and upper respiratory tract, which could be reduced by appropriate protective equipment. It is concluded that nasal lavage can be used as a biomonitoring method in the assessment of MMVF exposure.     

Cytokines and adhesion molecules in duodenal mucosa of children with delayed-type food allergy

OBJECTIVES: The aim was to investigate the expression of cytokines, adhesion molecules, and activation and proliferation markers in duodenal biopsies from children with delayed-type food allergy (FA). METHODS: Seven children with untreated FA (uFA), seven children with treated FA (tFA) to cow milk and/or cereals, and five normal controls furnished duodenal biopsy specimens. Additionally, five pediatric patients with celiac disease were included, serving exclusively as positive controls for in situ hybridization. Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), adhesion molecules, and activation markers were detected by immunohistochemistry, and expression of IFN-gamma and IL-4 messenger RNA was revealed by in situ hybridization. RESULTS: uFA patients had a higher density of IFN-gamma positive cells in the lamina propria than did tFA patients and controls (P = 0.053 and P = 0.018). Moreover, the uFA patients exhibited a higher proportion of crypt cells in mitosis than did tFA patients (P = 0.026), and stronger staining of HLA-DR in the crypts and increased density of gammadelta-T cell receptor-positive intraepithelial lymphocytes than did controls (P = 0.048 and P = 0.010). The densities of alpha(4)beta(7) positive cells in the lamina propria tended to be higher in controls than in uFA or tFA patients (P = 0.106, P = 0.073). Expression of IL-4 mRNA was significantly higher in celiac patients than in the other study groups (uFA P = 0.006, tFA P = 0.010; controls P = 0.029), and celiac patients showed higher expression of IFN-gamma mRNA than did tFA patients or controls (P = 0.017 and P = 0.016). CONCLUSIONS: As expected, Th1 dominance was present in the lamina propria of children with delayed-type FA. It may cause activation of epithelial cells and increase their turnover.     

Prolactin releasing peptide has high affinity and efficacy at neuropeptide FF2 receptors

Neuropeptide FF (NPFF) and prolactin-releasing peptide (PrRP) are two members of the RFamide peptide family. In this study we investigated whether these RFamide peptides, which have common structural features in their C-terminal RFamide motif and share several physiologically important functions, could exert their effects through the same set of receptors. The affinity and functional activity of several related RFamide peptides were determined at the human neuropeptide FF receptor subtype 2 (hNPFF2) and the human prolactin-releasing peptide (hPrRP) receptors. The full-length human prolactin releasing peptide 31 (hPrRP31) had significantly higher efficacy compared with NPFF and its stable analog, (1DMe)Y8Fa, at the hNPFF2 receptor. In contrast, NPFF and (1DMe)Y8Fa were not efficacious at the hPrRP receptor. Our study indicated a generally relatively low level of discrimination for RFamide peptides at the NPFF receptor, whereas the hPrRP receptor clearly preferred PrRP or very closely related peptides. The seemingly promiscuous binding of the RFamide peptides to the NPFF receptor was further confirmed by receptor autoradiography. PrRP may thus signal through the NPFF receptors in vivo.     

Human resources for health in Palestine: a policy analysis. Part II. The process of policy formulation and implementation

This article is the presentation of part II of the analysis aiming at providing an insight and better understanding of human resources for health development within a conflicting and transitional context. This part focuses on the human resources for health (HRH) policy development in Palestine taking into consideration the critical elements in policy formulation and implementation, such as sound data based policy and planning, key stakeholders, role and implications of international cooperation. Moreover, it examines recent progress of HRH policy and constraints for implementation. Part I addresses the current situation and recent developments in HRH in Palestine.     

Organochlorines,lead, and mercury in Akwesasne Mohawk youth

Most humans have detectable body burdens of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and p,p'-dichlorophenyldichloroethylene p,p'-DDE), a metabolite of p,p'-dichlorodiphenyltrichloroethane (DDT). Native American communities may be at increased risk of exposure through subsistence-based diets and greater physical contact with contaminated soil and water. In this article we describe the levels of toxicants (PCBs, p,p'-DDE, HCB, mirex, lead, and mercury) among youth 10-17 years old (n = 271) of the Akwesasne Mohawk Nation. Ultratrace, congener-specific PCB analysis of human serum quantitated 83 PCB congeners (plus 18 as pairs/triplets), in addition to p,p'-DDE, HCB, and mirex, and included all major Aroclor-derived congeners typically present in human samples. Twenty congeners (in 16 chromatographic peaks) were detected in 50% or more of the individuals sampled [geometric mean (GM) of the sum of these congeners = 0.66 ppb]. Thirteen congeners (in 10 peaks) were detected in 75% or more of the samples (GM = 0.51 ppb). Of the 20 congeners detected in 50% or more of the samples, 17 had five or more chlorine substitutions. International Union for Pure and Applied Chemistry congeners 118, 101(+90), and 153 were detected in nearly all participants (GM = 0.06 ppb, 0.05 ppb, 0.09 ppb, respectively). p,p'-DDE and HCB were detected in 100% and 98% of the samples (GM: p,p'-DDE = 0.37 ppb; HCB = 0.03 ppb). Mirex was detected in approximately 46% of the samples (GM = 0.02 ppb). No cases of elevated lead level were observed. One participant had a mercury level marginally higher than the U.S. Environmental Protection Agency's current level of concern (0.50 microg/dL). Although differences in analytic methods and participant ages limit comparability, toxicant levels from the Mohawk youth are lower than those associated with severe food contamination (Yusho and Yu-cheng) but similar to other chronically exposed groups.