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Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004

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OBJECTIVE: To assess the efficacy of lamivudine treatment on hepatitis B e antigen (HBeAg) and/or hepatitis B surface antigen (HBsAg) seroconversion, on other virological and serological markers of response including hepatitis B virus (HBV) DNA and serum aminotransferases, and the safety of lamivudine treatment in hepatitis B patients. PATIENTS: This phase III open-label study evaluated the virological and biochemical response to lamivudine in 70 Portuguese patients with HBeAg positive chronic hepatitis B. Patients were treated with lamivudine 100mg once daily for 12 months. METHODS: Antiviral activity was assessed by measuring alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels at all protocol visits, and hepatitis B serology and HBV DNA were performed at baseline and at month 12 visits. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. RESULTS: The primary endpoint was virological response at month 12, defined as loss of detectable HBeAg from serum with a reduction of HBV DNA to undetectable levels, and this was observed in 19/69 (27.5%) of patients. Almost half of the patients were HBV DNA negative by this time. Mean ALT values decreased steadily during treatment and by 12 months 61% of patients had values within the normal range. HBeAg seroconversion (HBeAg negative, HBeAb positive) was achieved in 27.9% of patients by 12 months, although all patients remained HBsAg positive. CONCLUSION: Lamivudine was well tolerated and the incidence of adverse events was similar to those reported in previous studies. Lamivudine treatment resulted in virological and biochemical improvements in HBeAg positive chronic hepatitis B patients, with HBeAg seroconversion in one-third of patients.

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The diagnosis of schistosomiasis is made by identification of Schistosoma in stool and urine, or by colonic or hepatic biopsies. The authors demonstrate in this paper, however, that it is also possible to suspect this disease by colonoscopy, i.e., by macroscopic observation of the vascular alterations in the mucous membrane of parasite infected patients. Out of 33 patients -21 with schistosomiasis and 12 with other intestinal parasitoses--the endoscopist correctly diagnosed Schistosomiasis in 18 (85.7%) patients, although he had no previous experience of the diagnosis. Since this infection is widespread throughout the world, these endoscopic findings are important; they may help the physician correctly diagnosis schistosomiasis in non-endemic areas where the diagnosis may not be suspected.

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Cultured retina cells from chick embryos took up [3H]putrescine and approx 10.8% of the incorporated amine was converted into [3H]GABA. The putrescine-derived GABA accumulated in a pool that was released in the medium at a rate corresponding to 3.66% of the total [3H]GABA in the cell at incubation intervals of 12 min. Treatment of cultures with L-glutamate (500 microM) promoted a 5-7 fold increase in the rate of [3H]GABA efflux which was totally independent on the presence of calcium ions in the superfusing medium. (+)-5-Methyl-10,11-dihydro-5h-Dibenzo(A,D)cyclohepten-5,10- Iminihydrogenmaleate (MK 801) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 100 microM, inhibited the glutamate evoked release of GABA by 78 and 73% respectively. N-methyl-D-aspartate (NMDA, 100 microM), elicited the release of putrescine-derived GABA only when magnesium ions were removed from the superfusing medium with 2 mM EGTA. In the presence of 1 mM MgCl2, NMDA was totally ineffective in inducing the release. As for glutamate, AMPA (R,S)-alpha-Amino-3-hydroxy-5-methyllisoxazole-4-propionicacid+ ++ hydrobromide (100 microM) also induced the release of GABA synthesized from putrescine. Our data show that putrescine is an important source of GABA in the embryonic CNS and that GABA synthesized from putrescine can be released in the extracellular space when cells are stimulated by L-glutamate through the activation of excitatory amino acid (EAA) receptors.

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