Implication of the RD(Rio)Mycobacterium tuberculosis sublineage in multidrug resistant tuberculosis in Portugal

Multidrug and extensively drug resistant Mycobacterium tuberculosis are a threat to tuberculosis control programs. Genotyping methods, such as spoligotyping and MIRU-VNTR typing (Mycobacterial Interspersed Repetitive Units), are useful in monitoring potentially epidemic strains and estimating strain phylogenetic lineages and/or genotypic families. M. tuberculosis Latin American Mediterranean (LAM) family is a major worldwide contributor to tuberculosis (TB). LAM specific molecular markers, Ag85C(103) single nucleotide polymorphism (SNP) and RD(Rio) long-sequence polymorphism (LSP), were used to characterize spoligotype signatures from 859 patient isolates from Portugal. LAM strains were found responsible for 57.7% of all tuberculosis cases. Strains with the RD(Rio) deletion (referred to as RD(Rio)) were estimated to represent 1/3 of all the strains and over 60% of the multidrug resistant (MDR) strains. The major spoligotype signature SIT20 belonging to the LAM1 RD(Rio) sublineage, represented close to 1/5th of all the strains, over 20% of which were MDR. Analysis of published datasets according to stipulated 12loci MIRU-VNTR RD(Rio) signatures revealed that 96.3% (129/134) of MDR and extensively drug resistant (XDR) clusters were RD(Rio). This is the first report associating the LAM RD(Rio) sublineage with MDR. These results are an important contribution to the monitoring of these strains with heightened transmission for future endeavors to arrest MDR-TB and XDR-TB.     

Therapeutic usefulness of antioxidant drugs in experimental intestinal reperfusion syndrome]

The intestinal reperfusion injury has been studied in Sprague-Dawley rats weighing 200 g. Intestinal ischemia has been induced by clamping the Superior Mesenteric Artery (SMA) for 120 minutes. In order to parallel clinical situations, free radical scavengers (allopurinol [ALLO]) and superoxide-dismutase [SOD] were inoculated at a low perfusion rate through the femoral vein during the last 20 minutes of the ischemic period. Both drugs have decreased the mortality rate (from 70% in control group, to 40%) and the mean percentage of damaged intestine (30.89% vs. 23.84% and 24.70%). Histologically, ALLO was less effective than SOD (12.54 control; 8.40 SOD; 11.54 ALLO). The modification of glucose, SGOT, SGPT and LDH found in all the ischemic animals shows the hepatocellular injury induced by intestinal reperfusion.     

Compared effect of n-3 and n-6 dietary fatty acids on rat intestinal acyl-CoA:cholesterol acyltransferase activity

Polyunsaturated fatty acids are known to lower plasma cholesterol concentrations. We studied their effect on intestinal acyl-CoA:cholesterol acyltransferase (ACAT) activity in rats fed either salmon oil or corn oil (17% fat) with or without 1% cholesterol. After an 8-week feeding period we confirmed the hypolipidemic effect of salmon oil and we established its ability to stimulate ACAT activity in rats fed low-cholesterol diets. The most striking effect of 1% dietary cholesterol on ACAT activity was obtained in the control group (34% enhancement), whereas cholesterol supplementation had no effect on ACAT activity in the salmon oil group. The results enable us to suggest that n-3 fatty acids have an effect per se on ACAT activity; the regulation of enzyme activity by dietary cholesterol probably involves independent processes.     

Aminoterminal pro-brain natriuretic peptide and ventricular filling pressures in heart transplant recipients.

We tested the hypothesis that, in heart transplant recipients, plasma aminoterminal pro-brain natriuretic peptide (NT-proBNP) dosage is useful for diagnosis of high ventricular loading pressures in the absence of systolic dysfunction. We studied 60 consecutive transplanted heart recipients without systolic dysfunction at 1 to 16 years after transplantation. We found that, in these patients with frequent high ventricular filling pressures, plasma NT-proBNP was highly correlated with creatininemia and not correlated with ventricular loading pressures. These results do not support the hypothesis that NT-proBNP is useful for diagnosis of isolated diastolic dysfunction in transplanted heart recipients.     

Pharmacokinetics of the low molecular weight heparin enoxaparin during 48 h after bolus administration as an anticoagulant in haemodialysis.

BACKGROUND: The interest of low molecular weight heparins (LMWH) regarding bleeding risk is controversial in renal failure patients. In haemodialysis patients, there are very few data on the pharmacokinetics of LMWH after the end of the session. The aim of the study was to evaluate the duration of anticoagulation after bolus administration of the LMWH enoxaparin at the start of haemodialysis. METHODS: The pharmacokinetics of enoxaparin were studied during the 48 h following a single bolus injection at the start of the dialysis session in 30 chronic haemodialysis patients. Pharmacokinetics were determined using a population approach (Non Linear Mixed Effects Modelling). RESULTS: A single injection of enoxaparin at 60 U IU/kg (4000 +/- 455 IU) led to an anti-Xa activity higher than 1.2 IU/ml during the first 2 h of the session, and between 0.4 and 1.2 IU during the third and fourth hours. After the end of the session, anti-Xa activity remained higher than 0.4 IU/ml up to 10 h after injection, and higher than 0.1 IU/ml up to 24 h. The pharmacokinetic model showed that only weight improved the predicted vs observed anti-Xa activity plot. The model was used to simulate single and multiple dosing with decreased enoxaparin doses. Whatever the procedure, anti-Xa activity remained high (>0.22 +/- 0.99 UI/ml) up to 12 h after the start of the dialysis session. CONCLUSIONS: These results suggest that haemodialysis patients receiving the LMWH enoxaparin during dialysis are at risk of bleeding up to 10 h after the injection.     

Effect of wheat bran, pectin and cellulose on the secretion of bile lipids in rats

We assayed the lipid content of bile from rats that had been fed either a standard diet (5% fat) or a high fat diet (25% fat, 1.2% cholesterol) in the presence or in the absence of various dietary fibers (namely, wheat bran, pectin and cellulose). The cholesterol concentration in bile from rats fed the high fat diet plus wheat bran or pectin was lower than that of the rats fed the high fat, high cholesterol diet without fiber. Bile phospholipids did not vary significantly from one group to another. In comparison to the standard diet, the high fat, high cholesterol diet led to a greater ratio of primary to secondary bile salts and a higher level of glycoconjugates. The observed differences may be explained by a variation in the metabolism of bile salts brought about by the difference in diet.     

Changes in cerebral calcium, sodium and potassium after single or repeated administration of lithium in the rat

A single administration (IP) of lithium chloride in the rat induces a decrease in erythrocyte calcium, proportional to the lithium level (p less than 0.01) and a diminution in cerebral calcium (p less than 0.001) which is accompanied by decrease in cerebral sodium and potassium levels (p less than 0.001). Repeated administration (IP + VO) has the same cerebral effects. The authors report that the reversible decrease in calcium, sodium and potassium, resulting from an increase in cerebral lithium levels, can be demonstrated on sampling at 1.30 and 3 hours (IP), or at 12 hours (VO). These results are relevant to the treatment of manic illnesses using calcium antagonists.     

BRCA1-2 mutations in breast cancer: identification of nine new variants of BRCA1-2 genes in a population from central Western Spain

We carried out a mutational analysis of BRCA1 and BRCA2 genes in 103 individuals from a population in Western Central Spain and we identified nine new variants: two truncating mutations in BRCA2 [2604C>A (Y792X), 8873del4], three missense mutations in BRCA2 [677A>G (H150R), 958G>A (D224N) and 3398A>G (K1057R], and four silent mutations, two in BRCA1 [1115T>G (R332R) and IVS24+36 C>G], and two in BRCA2 [2583T>A (I785I) and 7854G>A (T2542T)]. In two unrelated families of our population, we identified the BRCA1 1806C>T (Q563X) mutation, which is considered to be a Swedish founder mutation. BRCA1 1806C>T (Q563X) and BRCA2 3036del4 gene mutations were the most frequent in our series.