Dynamic not isometric training blunts osteo-renal disease and improves the sclerostin/FGF23/Klotho axis in maintenance hemodialysis patients: a randomized clinical trial.

This study compared the effectiveness of dynamic resistance training (DRT) versus isometric RT (IRT) on osteogenesis and hormonal mechanisms involved in maintenance hemodialysis (MHD) patients. One hundred and ninety-three MHD patients were randomized into three groups: control (CTL) (n = 60), DRT (n = 66), and IRT (n = 67). A first visit was required for an anamnesis to evaluate the number of medications, biochemical, and anthropometric measurements (dialysis adequacy, creatinine, urea, body mass, height, and body mass index). Grip strength, bone mineral density (BMD), and renal-bone markers were assessed pre- and postprotocol. The DRT and IRT training was 6 mo with a frequency of three times per week, on alternate days. Each training session consisted of three sets of 8 to 12 repetitions at lower and moderate intensities. Both training sessions were prescribed approximately 1 h prior to dialysis. Statistical significances were adopted with P < 0.05. There was a greater dropout in the IRT group (24%) as compared with the DRT group (14%), which in turn had less adverse clinical effects (67%, 24%, and 61% for CTL, DRT, and IRT, respectively). DRT promoted gains in BMD in different body locations, in addition to increasing pro-osteogenic factors (Klotho and calcitriol) and reducing those related to bone loss, such as sclerostin, FGF23, and PTH. There was an improvement in Ca × PO43 for DRT, whereas these benefits did not occur in the IRT group (P < 0.05). These novel findings suggest that the DRT generates biopositive adaptations in bone tissue in MHD and can be used as a nonpharmacological strategy to improve BMD.NEW & NOTEWORTHY This study shows, for the first time, the effect of dynamic and isometric resistance training on bone mineral density in hemodialysis patients, providing a new understanding of the possible participation of the sclerostin/FGF23/Klotho axis, vitD, PTH, and calcium × phosphate product in this process. However, isometric resistance training may not be sufficient to induce these benefits. Therefore, this study supports the potential therapeutic role of dynamic resistance training counteracting chronic kidney disease-mineral and bone disorder.

Strain classification of Mycobacterium tuberculosis isolates in Brazil based on genotypes obtained by spoligotyping, mycobacterial interspersed repetitive unit typing and the presence of large sequence and single nucleotide polymorphism.

Rio de Janeiro is endemic for tuberculosis (TB) and presents the second largest prevalence of the disease in Brazil. Here, we present the bacterial population structure of 218 isolates of Mycobacterium tuberculosis, derived from 186 patients that were diagnosed between January 2008 and December 2009. Genotypes were generated by means of spoligotyping, 24 MIRU-VNTR typing and presence of fbpC103, RDRio and RD174. The results confirmed earlier data that predominant genotypes in Rio de Janeiro are those of the Euro American Lineages (99%). However, we observed differences between the classification by spoligotyping when comparing to that of 24 MIRU-VNTR typing, being respectively 43.6% vs. 62.4% of LAM, 34.9% vs. 9.6% of T and 18.3% vs. 21.5% of Haarlem. Among isolates classified as LAM by MIRU typing, 28.0% did not present the characteristic spoligotype profile with absence of spacers 21 to 24 and 32 to 36 and we designated these conveniently as "LAM-like", 79.3% of these presenting the LAM-specific SNP fbpC103. The frequency of RDRio and RD174 in the LAM strains, as defined both by spoligotyping and 24 MIRU-VNTR loci, were respectively 11% and 15.4%, demonstrating that RD174 is not always a marker for LAM/RDRio strains. We conclude that, although spoligotyping alone is a tool for classification of strains of the Euro-American lineage, when combined with MIRU-VNTRs, SNPs and RD typing, it leads to a much better understanding of the bacterial population structure and phylogenetic relationships among strains of M. tuberculosis in regions with high incidence of TB.

Multidrug resistant Mycobacterium tuberculosis: a retrospective katG and rpoB mutation profile analysis in isolates from a reference center in Brazil.

BACKGROUND: Multidrug resistance is a critical factor in tuberculosis control. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a national reference center. METHODS AND FINDINGS: Ninety-nine multidrug resistant isolates from 12 Brazilian states were studied. Drug-resistance patterns were determined and the rpoB and katG genes were screened for mutations. Genotypic diversity was investigated by IS6110-RFLP and Luminex 47 spoligotyping. Mutations in rpoB and katG were seen in 91% and 93% of the isolates, respectively. Codon 315 katG mutations occurred in 82.8% of the isolates with a predominance of the Ser315Thr substitution. Twenty-five isolates were clustered in 11 groups with identical IS6110-RFLP patterns while 74 showed unique patterns with no association between mutation frequencies or susceptibility profiles. The most prevalent spoligotyping lineages were LAM (47%), T (17%) and Haarlen (12%). The Haarlen lineage showed a higher frequency of codon 516 rpoB mutations while codon 531 mutations prevailed in the other isolates. CONCLUSIONS: Our data suggest that there were no major multidrug resistant M. tuberculosis strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance. In addition, drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment.

Insights into the population structure of Mycobacterium tuberculosis using spoligotyping and RDRio in a southeastern Brazilian prison unit.

Tuberculosis (TB) is still a serious public health problem, continuing to be an important threat for confined populations. We used spoligotyping to estimate the genotypic clades of Mycobacterium tuberculosis isolates from inmates in two blocks in a southeastern Brazilian prison unit, with TB incidence rate of 8185/100.000. The Latin American Mediterranean (LAM) clade is well represented in the country, and the LAM specific molecular markers, RD(Rio) large sequence polymorphism and the SNP on the Rv3062 [ligB(1212)], were used to characterize spoligotype signatures from prison isolates. Typing of RD(Rio) and ligB increase LAM clade from 66.7% (n=72/108) to 69.4% (n=75). The LAM2 SIT17 (n=23) and SIT179 (n=12) signatures comprised one third of all isolates, followed by Haarlem (11.5%, n=12), T (8.7%, n=9) and X (5.7%, n=6) clades. Strains with unknown signatures represented 5.5% (n=6), and four (3.7%) did not match any lineage. We observed RD(Rio) among 64 (59.2%) isolates, and 54 (50%) were of the LAM clade. In particular, the LAM2/RD(Rio) sub-lineage was significantly associated with clustering (p=0.02) and its frequency was higher (32%) when compared to that of the previous general TB cases in RJ (4.29%). Overall cluster frequency defined by spoligotyping/IS6110-RFLP was 62%. The two evolutionary markers helped to evaluate some LAM signature misconceptions and demonstrate that LAM2/RD(Rio) was found with high frequency, hitherto being unnoticed. All these data, allied to high clustering, imply that public health measures to minimize the escalation of TB in prison is essential, and both spoligotyping as well as RD(Rio) would be useful tools to monitor the effects of the measures with respect to M. tuberculosis lineage variation.

Use of tacrolimus and the development of posttransplant diabetes mellitus: a Brazilian single-center, observational study.

INTRODUCTION: Posttransplant diabetes mellitus (PTDM) is considered to be a serious complication of kidney transplantation that may reduce patient and graft survival. The immunosuppressant tacrolimus (TAC) increases the risk of developing PTDM. PURPOSE: We sought to estimate the risk of PTDM among renal transplant recipients treated with TAC, to identify other risk factors for PTDM, and to describe its consequences. METHODS: We retrospectively analyzed 413 recipients of ages >or=18 years who were free of diabetes before kidney transplantation. They were treated with TAC, cyclosporine (CyA), or sirolimus (SIR) plus steroid therapy with a minimum follow-up posttransplant of 6 months. PTDM was diagnosed according to American Diabetes Association guidelines. RESULTS: The mean age was 42.3 years and 230 (55.7%) were male. The initial immunosuppression for 171 (41.4%) patients was TAC; 221 (53.5%), CyA; and 21 (5.1%), SIR. PTDM occurred in 85/413 (20.6%) of patients. The median time to PTDM development was 54 days posttransplant. The cumulative incidence of PTDM was 24.6% and 17.2% for TAC and CyA treatment groups, respectively. In the intention-to-treat analysis, the proportion of patients receiving TAC who developed PTDM was significantly higher than that of CyA (HR = 1.6 [1.01-2.42]; P = .04). The Kaplan-Meier method showed that 78.5% patients taking TAC were free of PTDM at 6 months compared with 88.8% taking CyA (P = .003). The other independent risk factors were body mass index (BMI; P < .0001); recipient age (P < .0001) and acute rejection episodes (AE; P = .01). Three-year actuarial graft survivals were 85.5% for PTDM patients compared with 93.3% for those without diabetes (P = .021); patient survivals, 88.9% and 96.7%, respectively (P = .017). CONCLUSION: The incidence of PTDM is associated with TAC use, recipient age, BMI, and ARE. Therefore, PTDM is an important risk factor for graft loss and mortality.

Drug-nutrient interactions in elderly people.

PURPOSE OF REVIEW: The presence of multiple diseases, polypharmacy, malnutrition, and impaired metabolism in elderly individuals increases the risks of adverse events related to drug-food interactions. Some considerations for elderly people influenced by drug-food interactions are reviewed. RECENT FINDINGS: When investigating pharmacokinetic and pharmacodynamic modifications in the elderly, other factors have to be considered, such as anorexia, dementia, depression, intolerance, gastrointestinal-tract disorders, social and economic factors, reduced abilities (visual and manual) and difficulties in chewing or swallowing. Specific reference is made herein to the health status of the elderly Brazilian population based on the observations of our research group. In addition, the most common diseases (such as cancer, coronary heart disease, dementia, diabetes mellitus, hypertension and osteoporosis), the drugs usually prescribed to treat them, and the adverse nutritional reactions that occur in older patients are summarized. SUMMARY: In order to develop a correct drug prescription plan and nutritional intervention to avoid any kind of undesirable drug-food interaction effect, it is necessary to adequately diagnose the disease and often re-evaluate the chosen treatment, identify disease stages and the necessary therapies to minimize the number of drugs administered, and select a reasonable nutritional assessment.