The covalently bound polymers of peptidoglycan and group-specific polysaccharide (PG-APS) were isolated from the cell walls of group A streptococci. Arthritis was induced in rats with a single intraperitoneal injection of an aqueous suspension of PG-APS fragments derived by sonication. The joint lesions induced with this polydisperse suspension followed a bimodal pattern consisting of an acute phase, which reached a peak 5 days after injection and then receded, followed by a chronic, remittent, erosive arthritis lasting several months. The relative severities of the acute and chronic phases could be manipulated by selection of the size of PG-APS fragments. The fragments of PG-APS obtained by sonic treatment were resolved on the basis of size into three major populations by sucrose gradient or differential centrifugation. Based upon light scattering and gel filtration, the average molecular weight of the largest family of fragments was estimated to be about 500 x 106, the intermediate fragments were 50 x 106 daltons, and the predominant size in the smallest population was 5.3 x 106 daltons. The larger fragments induced negligible acute inflammation, but chronic disease became apparent 5 to 9 weeks after injection. The smallest fragments induced the most severe acute inflammation, with relatively little late, chronic joint disease. The particles of intermediate size induced moderate acute inflammation and the most severe chronic, erosive joint lesions. A single injection of fragments of the isolated peptidoglycan moiety of the PG-APS induced only a moderate acute inflammation ofjoints, with no apparent capacity to maintain the injury and induce chronic disease.

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Rats were lactationally exposed to low- (0.2%) and high-level (1%) lead (Pb) from postnatal day 1 (PND1) through PND21 through the drinking water of the mother. The levels of catecholamines, epinephrine, norepinephrine and dopamine and the activity of the enzyme monoamine oxidase (MAO) were determined in the cerebellum, hippocampus and cerebral cortex in young (1-month-old) and adult (3-month-old) rats. Pb-exposure decreased the activity of mitochondrial MAO in all the brain regions in a dose-dependent manner. The synaptosomal catecholamines (epinephrine, norepinephrine and dopamine), however, increased with low level (0.2%) Pb-exposure and significantly decreased with high level (1%) Pb-exposure in both the age groups. In general, the young rats seem to be more vulnerable to Pb-neurotoxicity. These data suggest that Pb-exposure perturbs the aminergic system in the cerebral cortex, cerebellum and hippocampus and may contribute to the cognitive and behavioural impairments observed in Pb-exposed rats.

Exposure to low-levels of lead (Pb) during early development has been implicated in behavioral abnormalities and cognitive deficits in children. The present study is focused on developmental changes in hippocampus and cerebellum of rats following perinatal exposure to Pb. Pregnant rats were exposed to 0.2% Pb-acetate from gestation day 6 (GD 6) through postnatal day (PND) 21 and the activity levels of acetylcholinesterase (AChE) were estimated in cerebellum and hippocampus of pups at specific time points for 5 weeks. In both the brain regions, Pb-exposure decreased AChE activity with an increase in age. Histochemical observations conducted in 35 days old rat brain showed decreased AChE activity conspicuously in stratum oriens and dentate gyrus of hippocampus, and molecular and granule cell layers of cerebellum. In vitro studies conducted in 35 days old rat brain showed a considerable decrease in the specific activity of AChE at high concentrations (50-100 microM) of Pb in a concentration-dependent manner. However, at low concentrations (5-20 microM), Pb failed to produce such changes. In the presence of eserine (physostigmine), the specific inhibitor of AChE, the inhibitory effect of Pb was potentiated and this was more pronounced at low-concentrations of Pb. The behavioral responses in open-field also showed a significant decrease in both Pb exposed as well as eserine administered rats. These data suggest that low-level perinatal Pb-exposure induces alterations in cholinergic system in the cerebellum and hippocampus of developing brain even after the withdrawal of Pb-exposure, that may contribute to behavioral and learning deficits.

Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of this compound hampers an effective in vivo cancer study. We prepared new ionic derivatives of betulinic acid with higher water solubilities, without losing the structural integrity and functionality of this compound. As a result, these new ionic derivatives have shown much higher inhibitory effects against different cancer cell lines such as melanoma A375, neuroblastoma SH-SY5Y and breast adenocarcinoma MCF7. For A375 cell lines, the derivative 5 exhibited a low IC50 value of 36 μM (vs 154 μM for betulinic acid); for MCF7 cell lines, the derivative 5 also exhibited a low IC50 value of 25 μM (vs 112 μM for betulinic acid). The high cytotoxicity of these new derivatives can be linked to their greatly improved water solubility. Our assay method used little DMSO in aiding the dissolution of these derivatives to demonstrate the advantage of improved water solubility and to mimic the in vivo study conditions. The cell viability studies based on both MTT and LDH assay methods have confirmed the high inhibitory effect of our ionic derivatives of betulinic acid (particularly 4 and 5) against different cancer cells.