Is Ischemia Involved in the Pathogenesis of Murine Cerebral Malaria?

Sequestration of parasitized erythrocytes in the central nervous system microcirculation and increased cerebrospinal fluid lactate are prominent features of cerebral malaria (CM), suggesting that sequestration causes mechanical obstruction and ischemia. To examine the potential role of ischemia in the pathogenesis of CM, Plasmodium berghei ANKA (PbA) infection in CBA mice was compared to infection with P. berghei K173 (PbK) which does not cause CM (the non-CM model, NCM). Cerebral metabolite pools were measured by (1)H nuclear magnetic resonance spectroscopy during PbA and PbK infections. Lactate and alanine concentrations increased significantly at the terminal stage of CM, but not in NCM mice at any stage. These changes did not correlate with parasitemia. Brain NAD/NADH ratio was unchanged in CM and NCM mice at any time studied, but the total NAD pool size decreased significantly in the CM mice on day 7 after inoculation. Brain levels of glutamine and several essential amino acids were increased significantly in CM mice. There was a significant linear correlation between the time elapsed after infection and small, progressive decreases in the cell density/cell viability markers glycerophosphocholine and N-acetylaspartate in CM, indicative of gradual loss of cell viability. The metabolite changes followed a different pattern, with a sudden significant alteration in the levels of lactate, alanine, and glutamine at the time of terminal CM. In NCM, there were significant decreases with time of glutamate, the osmolyte myo-inositol, and glycerophosphocholine. These results are consistent with an ischemic change in the metabolic pattern of the brain in CM mice, whereas in NCM mice the changes were more consistent with hypoxia without vascular obstruction. Mild obstructive ischemia is a likely cause of the metabolic changes during CM, but a role for immune cell effector molecules cannot be ruled out.     

Prevalence of schistomasiasis lesions detected by ultrasonography in children in Molodo, Mali

AIM: To study schistomasiasis infection in school children in Molodo, an irrigated rice growing region of Mali, by determining the prevalence of schistomasiasis and lesions identified by ultrasonography among children living in this region. METHODS: This cross sectional study included 346 children aged 7 to 14 years selected at random from five schools in Molodo. We tested for hematuria using urine dipsticks and searched for Schistosoma haematobium eggs in urine and S. mansoni eggs in stools. Ultrasonography of the liver, spleen and urinary tract was performed. RESULTS: The prevalences of Schistosoma haematobium and S. mansoni infection were 72% (range: 66.9-76.6%) and 68.2% (range: 60.9-71.2%) respectively; 55.1% of the children had co-infection. Ultrasonography of the urinary tract revealed an irregular bladder wall as the most frequent abnormality (3.4% of children). Abdominal ultrasonography demonstrated type B hepatic fibrosis in four children (1.1%), type C in one (0.3%) and type D in one (0.3%). CONCLUSION: Few schistosomiasis lesions were detected by ultrasonography compared with the prevalence of S. haematobium and S. mansoni infections. This observation is probably related to mass treatment programs conducted during a national anti-schistosomiasis program.     

Genetic diversity and genotype multiplicity of Plasmodium falciparum infections in symptomatic individuals in the maritime region of Togo

Objective To assess the genotype prevalence and the multiplicity of Plasmodium falciparum infections in the maritime region of Togo. Methods We enrolled 309 symptomatic individuals aged from 6 months to 15 years from Bè/Lomé and Tsévié, two malaria endemic zones. The number and the proportions of merozoite surface proteins 1, 2 and 3 genotypes in patients were determined using capillary electrophoresis genotyping. We further investigated the possible association between transaminases and homocysteine, and the severity of the disease. Results Of the 309 samples genotyped, 210 tested positive to msp‐1, 227 to msp‐2 and 193 to msp‐3. The nested PCR revealed 22 different alleles for the allelic family msp‐1, 33 for msp‐2 and 13 for msp‐3. At each locus, the family distribution was 54.58% of K1, 25% of MAD20 and 20.42% of RO33 for msp‐1, and 51.71% and 48.29% of FC27 and 3D7, respectively, for msp‐2. For all these allelic variants, the distribution was associated with neither the severity of malaria nor the zone of habitation. Pearson correlation coefficients between either the levels of homocysteine or the transaminase and the severity of the disease were very low. Conclusion The severity of malaria was not associated with higher multiplicity of infections and did not appear restricted to particular genotypes. More comprehensive explorations including immunity, genetic factors, nutritional and sociologic status of the population could clarify the situation.     

Low frequency of mutated methylenetetrahydrofolate reductase 677C-->T and 1298A-->C genetics single nucleotide polymorphisms (SNPs) in Sub-Saharan populations.

5,10-Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are two of the key enzymes in the folate/vitamin B12-dependent remethylation of homocysteine to methionine. The frequencies of MTHFR single nucleotide polymorphisms (SNPs), 677C-->T, 1298A-->C, 1317T-->C and of MTR, 2756A-->G, have been widely studied in Caucasians, but they have never been reported simultaneously in a large population from Sub-Saharan Africa. Presently, we report the prevalence of these SNPs and their relationship to homocysteine in 240 subjects recruited in West Africa. The frequencies of the mutant genotypes 677TT (0.8%) and 1298CC (2%) were lower than that usually observed in Caucasians, while the frequency of the mutant 1317CC was higher (16%). We formed a systematic association of the mutated MTHFR 677C-->T SNP with a 1298A/1317T common haplotype. The MTHFR mutant genotype 677TT was associated with an intermediate hyperhomocysteinemia (92.4 +/- 6.0 micromol/l) higher than that described in Caucasians. The 2756A-->G SNP in the MTR was similarly distributed in Africans compared to Caucasians. In conclusion, the MTHFR 677TTor 1298CC genotypes are much rarer in Africans than in Caucasians. The 677TT low frequency may be related to the high effect of this mutation on homocysteine metabolism in the environmental conditions of this African region.     

Donation after Cardiac Death Kidneys with Low Severity Pre-Arrest Acute Renal Failure

The widening gap between supply and demand for renal transplantation has prompted many centers to use donors after cardiac death. Some of these donors exhibit signs of acute renal failure (ARF) prior to cardiac arrest. Concern has been expressed about poor quality of graft function from such donors. In response to this perception, we reviewed 49 single renal transplant recipients from category III donors after cardiac death between 1998 and 2005, at our center. All kidneys but one had hypothermic machine perfusion and viability testing prior to transplantation. According to the RIFLE criteria, nine recipients had kidneys from donors with "low severity pre-arrest ARF". The remainder of the recipients were used as control group. There was no statistical significant difference in delayed graft function and rejection rates between these two groups. Recipients GFR at 12 months was 44.4 +/- 17.1 and 45.2 +/- 14.7 (mL/min/1.73m(2)) from donors with ARF and without ARF, respectively (p = 0.96). In conclusion, low severity ARF in kidneys from controlled after cardiac death donors can be a reversible condition after transplantation. Short-term results are comparable to the kidneys from same category donors without renal failure, providing that some form of viability assessment is implemented prior to transplantation.     

In Vitro antimycotic activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. against opportunistic filamentous fungi

Xanthorrhizol was isolated from the rhizome of Curcuma xanthorrhiza (Zingiberaceae) and its in vitro activity against opportunistic filamentous fungi was evaluated using the NCCLS (M38-A) standard method. Xanthorrhizol was found to be active against all the species tested, namely Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Fusarium oxysporum, Rhizopus oryzae and Trichophyton mentagrophytes: the MICs being 2.0, 2.0, 2.0, 4.0, 1.0 and 1.0 microg/mL, while the MFCs were 4.0, 4.0, 4.0, 8.0, 2.0 and 2.0 microg/mL, respectively. The susceptibility of six species of filamentous fungi to xanthorrhizol was comparable to that of the commercial antifungal, amphotericin B. Xanthorrhizol also has activity to inhibit the conidial germination of all tested species. The results strongly suggest that xanthorrhizol can be developed as a natural antifungal agent.