Papillary vasoproliferative changes in cat scratch disease.
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Biomedical subjects
Publications and source records attributed to C Ly.
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OBJECTIVE: To evaluate body composition changes using bioelectrical impedance analysis and skinfold thickness measurements in infants from tropical areas who become stunted between 4-18 months of age. DESIGN AND MEASUREMENTS: Follow-up study. Extracellular water to total body water ratio index (length(2)/resistance at low to high frequency), peripheral fat (tricipital and subscapular skinfold thickness), and length-for-age index were studied at 4 and 18 months of age. SETTINGS: Low-income areas in four tropical regions (Congo, Senegal, Bolivia and New Caledonia). SUBJECTS: Infants were included in the analysis provided they were neither stunted nor wasted at 4 months. Two groups of infants were compared, those that were stunted at 18 months (n=61) or not (n=170). RESULTS: The extracellular water to total body water ratio index and the sum of skinfold thickness measurements were similar in the two groups at 4 months, and only the extracellular water to total body water ratio index was significantly different at 18 months. When no stunting appeared between 4 and 18 months, the change in the extracellular water to total body water ratio index was not linked with variations in length-for-age, and presented the expected pattern of variation in body water compartments. When stunting occurred, variation in length-for-age was related to significant changes in the extracellular water to total body water ratio index, the biggest increase in the proportion of extracellular water being found in the most stunted infants. Variations in the sum of the two skinfold thickness measurements presented the expected pattern for the 4-18 months growth and did not differ between the two groups. CONCLUSIONS: Multifrequency resistances suggested that stunting was associated with a lack of the expansion of the intracellular compartment that is expected during normal growth of cell mass, together with preserved fat mass. SPONSORSHIPS: Supported by grant 92L0623 from the French Ministry of Research, and by Institut de Recherche pour le Développement (IRD).
Heavy metals are increasingly being implicated as causative agents in neurodegenerative diseases such as Alzheimer's disease (AD). Cobalt, a positively charged transition metal, has previously been shown to be in elevated levels in the brain of AD patients compared with age-matched controls. In this study, we investigate the effects of cobalt as an inducer of oxidative stress/cell cytotoxicity and the resultant metabolic implications for neural cells. We show that cobalt is able to induce cell cytotoxicity (reduced MTT metabolism) and oxidative stress (reduced cellular glutathione). The pre-treatment of cells with the pineal indoleamine melatonin, prevented cell cytotoxicity and the induction of oxidative stress. Cobalt treatment of SHSY5Y cells increased the release of beta-amyloid (Abeta) compared with untreated controls (ratio Abeta 40/42). Melatonin pre-treatment reversed the deleterious effects of cobalt. These findings are significant as cobalt is an essential nutritional requirement, usually bound to cobalamin (vitamin B12), for all animals which in the unbound form could lead to neurotoxicity.
We report a highly sensitive and rapid strategy for characterizing biological toxins based on capillary electrokinetic chromatography with multiphoton-excited fluorescence. In this approach, aflatoxins B1, B2, and G1 and the cholera toxin A-subunit are fractionated in approximately 80 s in a narrow-bore electrophoretic channel using the negatively charged pseudostationary phase, carboxymethyl-beta-cyclodextrin. The aflatoxins--highly mutagenic multiple-ringed heterocycles produced by Aspergillus fungi--are excited at the capillary outlet through the simultaneous absorption of two to three 750-nm photons to yield characteristic blue fluorescence; cholera toxin A-subunit, the catalytic domain of the bacterial protein toxin from Vibrio cholera, is excited through an unidentified multiphoton pathway that apparently includes photochemical transformation of an aromatic residue in the polypeptide. The anionic carboxymethyl-beta-cyclodextrin, used to chromatographically resolve the uncharged aflatoxins, enhances emission from these compounds without contributing substantially to the background. Detection limits for these toxins separated in 2.1-micron-i.d. capillaries range from 4.4 zmol (approximately 2700 molecules) for aflatoxin B2 to 3.4 amol for the cholera toxin A-subunit. Larger (16-micron-i.d.) separation capillaries provide concentration detection limits for aflatoxins in the 0.2-0.4 nM range, severalfold lower than achieved in 2.1-micron capillaries. These results represent an improvement of > 10(4) in mass detectability compared to previously published capillary separations of aflatoxins and demonstrate new possibilities for the analysis of proteins and peptides.
Borna disease virus (BDV), a nonsegmented, negative-stranded (NNS) RNA virus, causes central nervous system (CNS) disease in a broad range of vertebrate species, including felines. Both viral and host factors contribute to very diverse clinical and pathological manifestations associated with BDV infection. BDV persistence in the CNS can cause neurobehavioral and neurodevelopmental abnormalities in the absence of encephalitis. These BDV-induced CNS disturbances are associated with altered cytokine and neurotrophin expression, as well as cell damage that is very restricted to specific brain regions and neuronal subpopulations. BDV also targets astrocytes, resulting in the development of prominent astrocytosis. Astrocytes play essential roles in maintaining CNS homeostasis, and disruption of their normal activities can contribute to altered brain function. Therefore, we have examined the effect of BDV infection on the astrocyte's physiology. We present here evidence that BDV can establish a nonlytic chronic infection in primary cortical feline astrocytes that is associated with a severe impairment in the astrocytes' ability to uptake glutamate. In contrast, the astrocytes' ability to uptake glucose, as well as their protein synthesis, viability, and rate of proliferation, was not affected by BDV infection. These findings suggest that, in vivo, BDV could also affect an important astrocyte function required to prevent neuronal excitotoxicity. This, in turn, might contribute to the neuropathogenesis of BDV.
Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious i.v. antithrombotic agents.
The design, synthesis and SAR of sulfonamidopyrrolidinone fXa inhibitors incorporating a new benzamidine isostere, namely aminoisoquinolines, is described. These inhibitors have higher Caco-2 cell permeability than comparable benzamidines and attain higher levels of exposure upon oral dosing. The most potent member 14b (fXa Ki=6 nM) is selective against other serine proteases of interest (>600 fold).
BACKGROUND: Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis. METHODS AND RESULTS: RPR101511A is a novel compound which selectively and potently inhibits the cell-free and in situ PDGFr-TK and PDGFr-dependent proliferation and chemotaxis in vascular smooth muscle cells (VSMC). To evaluate the effect of RPR101511A (30 mg. kg-1. d-1 BID for 28 days following PTCA) on coronary restenosis, PTCA was performed in hypercholesterolemic minipigs whose left anterior descending (LAD) coronary artery had been injured by overdilation and denudation, yielding a previously existing lesion. Angiographically determined prePTCA minimal lumen diameters (MLD) were similar in vehicle and RPR101511A-treated pigs (1.98+/-0.09 versus 2.01+/-0.08 mm) and increased to the same extent in the 2 groups following successful PTCA (2.30+/-0.06 versus 2.52+/-0.13). At termination, there was an average 50% loss of gain in the vehicle-treated group but no loss of gain with RPR101511A (2.16+/-0. 05 versus 2.59+/-0.11, P<0.001). Morphometric analysis of the LAD showed that RPR101511A caused a significant decrease in total intimal/medial ratio (0.96+/-0.58 versus 0.67+/-0.09, P<0.05). CONCLUSIONS: RPR101511A, which acts by inhibition of the PDGFr-TK, completely prevented angiographic loss of gain following PTCA and significantly reduced histological intimal hyperplasia.
The authors review a number of critical issues in the structural reform of animal health services for both small and non-commercial livestock producers in Africa and highlight several problems that others concerned with the privatisation of this service area have tended to neglect. Most notably, attention is called to the following: a) the need to retain a central role for paraprofessionals in the new delivery system b) the important and problematic relationship between the veterinary and paraveterinary professions c) the importance of developing state contracting procedures for assisting the private delivery of animal health services that will avoid the problems of local monopoly d) the central role that professionalism will have to play in this area, if collective goods and the public interest are to be served.
A realistic estimation of the cost of government campaigns to control rinderpest and contagious bovine pleuropneumonia is essential in order to determine profitable fees for private veterinarians with a health mandate in Senegal. A cost analysis of a vaccination campaign, organised by the Veterinary Services in Senegal between 1995 and 1996, involving 547,735 cattle, was conducted. Revenue and total costs were 50 CFA francs and 110 +/- 37 CFA francs per head, respectively. Staff-related costs accounted for 39.41% +/- 7.62% of the total cost. The gross and net margins corresponded to the average subsidies of 42 +/- 27 CFA francs and 60 +/- 37 CFA francs, respectively. Simulations showed better relative efficiency for private veterinarians who vaccinate at a price of between 97 and 84 CFA francs per head. Economies of scale varied from 8 to 13 CFA francs per head when the vaccination team increased the number of animals initially vaccinated (16,000 head) by 25% and 44%, respectively. This indicates that a fee of 125 CFA francs per head should guarantee the profitability of compulsory vaccination for private veterinarians.
The effect of supplementation on growth was tested by means of four similar controlled randomized trials in the Congo (n = 120), Senegal (n = 110), Bolivia (n = 127), and New Caledonia (n = 90). Four-month-old infants were randomly allocated to supplement or control groups. A cereal-based precooked porridge was offered twice daily for 3 mo and consumption was monitored. Both groups were free to eat local food. At 7 mo of age, all infants were still breast-fed in the Congo, Senegal, and Bolivia compared with 47% in New Caledonia. Mean daily consumption of the supplement varied among countries (558-790 kJ/d). Mean length at 4 mo was lowest in Bolivia, higher in Senegal and the Congo, and near the National Center for Health Statistics reference in New Caledonia. The mean 4-7 mo length increment was 0.48 cm higher for supplemented than for control infants in Senegal (P < 0.05), whereas weight increments did not differ. No significant effect was found in the other countries.
Developing countries frequently see their currency depreciated to varying degrees. The consequences of such monetary disturbances on the nutrition of young children are not well known, though children are the most vulnerable in nutritional terms. One year after the 50% devaluation of the CFA Franc (communauté financière africaine, "African Financial Community"), which took place on 12 January 1994 simultaneously in fourteen countries, nine of which are on the UNDP list of least developed countries, we wanted to find out the long-term effects of the devaluation, and the strategies that families had adopted to cope with it. In Brazzaville, Congo, in December 1994, an epidemiological survey was conducted on a representative sample of 893 children between the ages of 4 and 12 months in two districts, and indicators of child nutrition were established. A comparable survey had been conducted in December 1993, before the devaluation. In Senegal, in the absence of a previous survey which could be used in comparison, a qualitative survey using RAP methodology, was conducted in January 1995 in two towns near the capital. In three districts in each of these towns, a cluster of ten plots was chosen at random and surveyed, with a combination of semi-structured individual interviews with mothers (n = 60) and group interviews with all the women together (n = 6). The information was put together with interviews of 25 local traders selling food. In the Congo, comparison of the two surveys shows that the practice of breast-feeding had hardly changed, nor had the age at which baby food was introduced (90% of children of 4-5 months take semi-solid and solid foods); on the other hand, more children are being given the ordinary family meal earlier, at 6-9 months. The proportion of baby foods based on commercially imported flour has fallen (from 32% in 1993 to 18% in 1994), and has been replaced with local products based on maize; this change is more marked among poorer families. The low nutritional value of such preparations is in part compensated by the addition of sugar, though less milk is added (28% in 1994 as opposed to 43% in 1993). In Senegal, mothers do not seem to have changed their breast-feeding practices either, the age at which baby foods are introduced, or the number of times they are provided daily. The most important change is the drop in quality of food given to children, and the poorer family food for the older children. The partial switch from imported products to local produce was an expected consequence of devaluation; it is clearly confirmed here for nutrition of young children, with the consequent loss of nutritional quality (a reduction in energy density and in nutrients). The first thing needed is, therefore, an improvement in local manufacture of food supplements of good nutritional quality, for young children. Mothers also complain of the increased difficulty in managing a family diet so as to take account of economic needs, cultural values and nutrition. They therefore criticize a number of nutritional education messages that are clearly no longer appropriate to the new economic context. Finally the fact that young children are getting poorer quality nutrition is worrying for the future: if it lasts, the nutritional status of children will deteriorate; whenever possible, monitoring must be established so that measures can be taken when necessary to forestall any dramatic deterioration that would endanger the health of the children.
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