Evidence of an oxidative challenge in the Alzheimer's brain

Alzheimer's disease may arise from or produce oxidative damage in the brain. To assess the responses of the Alzheimer's brain to possible oxidative challenges, we assayed for glutathione, glucose-6-phosphate dehydrogenase, catalase and superoxide dismutase in twelve regions of Alzheimer's disease and aged control brains. In addition, we determined levels of malondialdehyde to evaluate lipid peroxidation in these brain regions. Most brain regions showed evidence of a response to an oxidative challenge, but the cellular response to this challenge differed among brain regions. These data suggest that the entire Alzheimer's brain may be subject to an oxidative challenge, but that some brain areas may be more vulnerable than others to the consequent neural damage that characterizes the disease.     

Cardiorespiratory Studies in Patients with Pulmonary Tuberculosis

Cardiorespiratory studies in 13 young females and 11 middle-aged men with localized acute pulmonary tuberculosis revealed evidence of significant resting hyperventilation and reduction in the dynamics of ventilation indicative of restrictive lung disease. Indices of intrapulmonary mixing and pulmonary diffusing capacities were normal, as were alveolar-arterial pCO₂ gradients.The ventilation/perfusion ratios were slightly elevated in both groups, while pulmonary artery pressure and total pulmonary vascular resistance (TPVR) showed a rise in the males only.Both groups showed an increase in actual QBF flows and a resultant significant decrease in arterial pO₂, which suggests that the areas of tuberculous infection are metabolically active.     

Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities

ABSTRACT: BACKGROUND: Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance. METHODS: The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Jurua valley in the Amazon region. Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008. RESULTS: The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95%CI 0.20 [EN DASH] 0.58) for the P. falciparum malaria incidence rates, 0.67 (95%CI 0.50 [EN DASH] 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95%CI 0.41 [EN DASH] 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported. CONCLUSIONS: In the remote region of the Jurua valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria.     

Association Mapping Provides Insights into the Origin and the Fine Structure of the Sorghum Aluminum Tolerance Locus,AltSB

Root damage caused by aluminum (Al) toxicity is a major cause of grain yield reduction on acid soils, which are prevalent in tropical and subtropical regions of the world where food security is most tenuous. In sorghum, Al tolerance is conferred by SbMATE, an Al-activated root citrate efflux transporter that underlies the major Al tolerance locus, Alt_SB, on sorghum chromosome 3. We used association mapping to gain insights into the origin and evolution of Al tolerance in sorghum and to detect functional variants amenable to allele mining applications. Linkage disequilibrium across the Alt_SB locus decreased much faster than in previous reports in sorghum, and reached basal levels at approximately 1000 bp. Accordingly, intra-locus recombination events were found to be extensive. SNPs and indels highly associated with Al tolerance showed a narrow frequency range, between 0.06 and 0.1, suggesting a rather recent origin of Al tolerance mutations within Alt_SB. A haplotype network analysis suggested a single geographic and racial origin of causative mutations in primordial guinea domesticates in West Africa. Al tolerance assessment in accessions harboring recombinant haplotypes suggests that causative polymorphisms are localized to a ∼6 kb region including intronic polymorphisms and a transposon (MITE) insertion, whose size variation has been shown to be positively correlated with Al tolerance. The SNP with the strongest association signal, located in the second SbMATE intron, recovers 9 of the 14 highly Al tolerant accessions and 80% of all the Al tolerant and intermediately tolerant accessions in the association panel. Our results also demonstrate the pivotal importance of knowledge on the origin and evolution of Al tolerance mutations in molecular breeding applications. Allele mining strategies based on associated loci are expected to lead to the efficient identification, in diverse sorghum germplasm, of Al tolerant accessions able maintain grain yields under Al toxicity.     

Partial purification and immobilization of ribonuclease T2.

A simple procedure, consisting of water extraction, heat treatment at pH 2.0, negative adsorption on DEAE-cellulose at pH 4.9, and concanavalin A-Sepharose chromatography, was developed for the partial purification of ribonuclease (RNase) T2 from taka-diastase powder with an overall yield of 5.5%. The partially purified enzyme when coupled to aminoethyl Bio-Gel P-60, retained 12-16% of the activity of the soluble enzyme. Temperature stability studies on RNase T2 bound to matrices, activated with increasing concentrations of glutaraldehyde, and the influence of lysine modification on the activity of the soluble enzyme revealed that the low activity observed for the gel-bound enzyme is probably due to the masking of the active site of the enzyme as a result of the involvement of lysine residues, situated near the active site, during coupling. Immobilization did not affect the pH and temperature optima of RNase T2. On repeated use, the bound enzyme retained approximately 55% of its initial activity after six cycles. These results are discussed, taking into consideration the factors affecting immobilized enzymes.