In Vivo and In Vitro Effects of Antituberculosis Treatment on Mycobacterial Interferon-γ T Cell Response

Background: In recent years, the impact of antituberculous treatment on interferon (IFN)-c response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-c response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-c. Principal Findings: 38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-c is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-c production within the range of therapeutically achievable concentrations. Conclusions: The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-c response

Vacuolar organization in the nodule parenchyma is important for the functioning of pea root nodules

Different models have been proposed to explain the operation of oxygen diffusion barrier in root nodules of leguminous plants. This barrier participates in protection of oxygen-sensitive nitrogenase, the key enzyme in nitrogen fixation, from inactivation. Details concerning structural and biochemical properties of the barrier are still lacking. Here, the properties of pea root nodule cortical cells were examined under normal conditions and after shoot removal. Microscopic observations, including neutral red staining and epifluorescence investigations, showed that the inner and outer nodule parenchyma cells exhibit different patterns of the central vacuole development. In opposition to the inner part, the outer parenchyma cells exhibited vacuolar shrinkage and formed cell wall infoldings. Shoot removal induced vacuolar shrinkage and formation of infoldings in the inner parenchyma and uninfected cells of the symbiotic tissue, as well. It is postulated that cells which possess shrinking vacuoles are sensitive to the external osmotic pressure. The cells can give an additional resistance to oxygen diffusion by release of water to the intercellular spaces

Human polyomavirus JC replication and non-coding control region analysis in multiple sclerosis patients under natalizumab treatment

The occurrence of progressive multifocal leukoencephalopathy (PML) caused by Polyomavirus JC (JCV) in patients affected by multiple sclerosis (MS) treated with natalizumab has raised concerns about the safety of this drug. In this study, we performed a JCV-specific quantitative PCR on biological samples collected at the enrollment (t0) and every 4 months (t1, t2, t3) for 1 year and in the second year of treatment (t4, t5). Then, specific PCR products for JCV NCCR and VP1 sequences were analyzed. Moreover, JCV-specific antibodies were assessed by STRATIFY JCV® in serum at t0 and t3. After 1 year of natalizumab treatment, results showed a significant association between patients with JC viruria and positive STRATIFY JCV® with respect to those patients with no JCV-specific antibodies (p=0.0006). Moreover, at t4 the JC viremia was prevalently observed rather than JC viruria (p=0.04). Regarding NCCR sequence analysis, in peripheral blood mononuclear cells of patients STRATIFY JCV® positive at t3 and treated with 12 natalizumab infusions, NCCR sequencing revealed the presence of rearranged sequences. Finally, VP1 sequence analysis showed the prevalence of the genotypes 1A, 1B and 4. In conclusion, testing JC viruria seems to be useful to identify patients who harbor JCV with an undetectable specific humoral immune response. It may also be important to study the JCV NCCR rearrangements since they could generate neuro-invasive viral variants increasing the risk of PML onset

What is the best equation to estimate the basal energy expenditure of climacteric women?

Objectives The methods currently available for the measurement of energy expenditure in patients, such as indirect calorimetry and double-labelled water, are expensive and are limited in Brazil to research projects. Thus, equations for the prediction of resting metabolic rate appear to be a viable alternative for clinical practice. However, there are no specific equations for the Brazilian population and few studies have been conducted on Brazilian women in the climacteric period using existing and commonly applied equations. On this basis, the objective of the present study was to investigate the concordance between the predictive equations most frequently used and indirect calorimetry for the measurement of resting metabolic rate. Methods We calculated the St. Laurent concordance correlation coefficient between the equations and resting metabolic rate calculated by indirect calorimetry in 46 climacteric women. Results The equation showing the best concordance was that of the FAO/WHO/UNU formula (0.63), which proved to be better than the Harris & Benedict equation (0.55) for the sample studied. Conclusions On the basis of the results of the present study, we conclude that the FAO/WHO/UNU formula can be used to predict better the resting metabolic rate of climacteric women. Further studies using more homogeneous and larger samples are needed to permit the use of the FAO/WHO/UNU formula for this population group with greater accuracy.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[05/53935-0

Analysis of bone microarchitecture related to anthropometry in climateric women

Background: Osteoporosis is one of the most important public health problems involving a high percentage of costs in the medical care system. Reliable diagnostic techniques for an early detection of bone deterioration and studies of factors that influence its development in menopausal women are crucial. The aim of the study was to determine the relationship between bone microarchitecture and anthropometry in climacteric women.Methods: Women were recruited at the Menopause Clinic, University Hospital of FMRP/USP, and submitted to anthropometry and to the evaluation of bone quality (Ultrasound Bone Profile Index, UBPI) and quantity (Amplitude-dependent Speed of Sound, AD-SoS-) by phalangeal quantitative osteosonography (DBM Sonic BP). Descriptive analysis of the data was reported and a multiple linear regression was performed using the software SASS (R) 9.0.Results: 71 patients aged 58 +/- 7 y were studied: 28% had BMI 18.5-24.9 kg/m(2), 35% BMI 24.9-29.9 and 37% BMI > 30. Mean AD-SoS was 2059 +/- 79 m/s and mean UBPI was 0.67 +/- 0.13. Considering AD-SoS the dependent variable, there was no statistically significant relationship between age (p = 0.20), BMI (p = 0.76), fat mass by bioelectrical impedance (p = 0.42) and by anthropometry (p = 0.95). The variables had very low effect on the UBPI when it was considered the dependent variable.Conclusions: The relation between bone microarchitecture and the anthropometry of the women studied shows that, the greater the bone quantity, the better the anthropometric parameters, without statistically significance. This work was a cross-sectional study on a small sample that needs to be validated in a prospective design. (Nutr Hosp. 2012;27:612-616) DOI: 10.3305/nh.2012.27.2.5625Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP