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Menezes A.M.B.,Federal University of Pelotas | Wehrmeister F.C.,Federal University of Pelotas | Hartwig F.P.,Federal University of Pelotas | Perez-Padilla R.,National Institute of Respiratory Diseases | And 5 more authors.
European Respiratory Journal | Year: 2015

African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (-0.13 L, 95% CI -0.23- -0.03 L) and FVC (-0.21 L, 95% CI -0.32- -0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. Copyright ©ERS 2015.

Sanchez-Jimenez R.,National Polytechnic Institute of Mexico | Alvarado-Vasquez N.,National Institute of Respiratory Diseases
Medical Hypotheses | Year: 2013

Diabetes mellitus type 2 (DM2), obesity, and the metabolic syndrome are considered that a low-grade chronic inflammatory condition. Although synthesis of different pro- and anti-inflammatory cytokines has been implicated in this process, this low-grade inflammatory condition is characterized especially by an increase in Tumor Necrosis Factor alpha (TNF-α), a cytokine that has been associated to the development of insulin resistance and muscle wasting in the diabetic patients. In consequence, mechanisms implicated in attenuating the deleterious effects of TNF-α are activated. One of these mechanisms may involve interleukin 15 (IL-15), which has proven effect on intermediate metabolisms, regulating blood glucose and lipid levels, and diminishing proteolysis in striated muscle. This suggests that the induction of endogenous IL-15 production by a simple event as physical activity may aid in decreasing or even inhibiting the negative effects of TNF-α in patient with DM2 or obesity, in which a low grade chronic inflammatory condition is present. © 2013 Elsevier Ltd.

Menezes A.M.B.,Federal University of Pelotas | De Oca M.M.,Central University of Venezuela | Perez-Padilla R.,National Institute of Respiratory Diseases | Nadeau G.,Glaxosmithkline | And 6 more authors.
Chest | Year: 2014

Background: Several COPD phenotypes have been described; the COPD-asthma overlap is one of the most recognized. The aim of this study was to evaluate the prevalence of three subgroups (asthma, COPD, and COPD-asthma overlap) in the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study population, to describe their main characteristics, and to determine the association of the COPD-asthma overlap group with exacerbations, hospitalizations, limitations due to physical health, and perception of general health status (GHS ). Methods: The PLATINO study is a multicenter population-based survey carried out in fi ve Latin American cities. Outcomes were self-reported exacerbations (defi ned by deterioration of breathing symptoms that affected usual daily activities or caused missed work), hospitalizations due to exacerbations, physical health limitations, and patients' perception of their GHS obtained by questionnaire. Subjects were classifi ed in three specifi c groups: COPD-a postbronchodilator (post-BD) FEV 1 /FVC ratio of , 0.70; asthma-presence of wheezing in the last year and a minimum post-BD increase in FEV 1 or FVC of 12% and 200 mL; and overlap COPD-asthma-the combination of the two. Results: Out of 5,044 subjects, 767 were classifi ed as having COPD (12%), asthma (1.7%), and COPD-asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory symptoms, had worse lung function, used more respiratory medication, had more hospitalization and exacerbations, and had worse GHS. After adjusting for confounders, the COPD-asthma overlap was associated with higher risks for exacerbations (prevalence ratio [PR], 2.11; 95% CI, 1.08-4.12), hospitalizations (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85) compared with those with COPD. Conclusions: The coexisting COPD-asthma phenotype is possibly associated with increased disease severity. © 2014 American College of Chest Physicians.

Alcazar-Leyva S.,San Luis Potosi Institute of Scientific Research and Technology | Alvarado-Vasquez N.,National Institute of Respiratory Diseases
Medical Hypotheses | Year: 2011

Thiamine (Vitamin B1) is considered an essential micronutrient for humans; its deficient intake brings about the Wernicke-Korsakoff syndrome (encephalopathy and psychosis) or beriberi (a neurological and cardiovascular disease). Once thiamine enters the cells it is phosphorylated by thiamine pyrophosphokinase (TPPK), and converted into the coenzyme thiamine pyrophosphate (TPP), the active form of thiamine. TPP is a relevant cofactor for transketolase (TK), α-ketoglutarate dehydrogenase (αKDH), and pyruvate dehydrogenase (PDH), all these enzymes are fundamental for glucose metabolism. Diabetes mellitus (DM), however, is considered both a deficient thiamine and deficient energy state, as a consequence of the limited TPP synthesis. Recent evidences have shown that the administration of thiamine or lipid-soluble derivatives, such as benfotiamine (developed to improve the bioavailability of thiamine), has positive effects in the diabetic patient (after thiamine is transformed into TPP). For this reason, administration of supplements with TPP in the diabetic patients is recommended to avoid complications, like neuropathy and nephropathy. It has been suggested that these beneficial effects are a consequence of the activation of TK (pentose pathway) or the PDH complex in mitochondria. Nitric oxide (NO) is synthesized by the endothelial cell and is also an important element for the viability and functionality of this cell type. However, in the DM patient, a deficient synthesis of NO has been reported. It is relevant to mention that recent evidences have led to propose mitochondrial activity as an important regulator of nitric oxide synthesis (ON). We consider that the exogenous administration of TPP facilitates the utilization of this molecule, regulating some metabolic processes such as phosphorylation of thiamine by TPPK, energy consumption (ATP), as well as mitochondrial activity, inducing eventually NO synthesis. If this is confirmed, the administration of TPP to the diabetic patient would provide additional protection to endothelial cells, reducing the risk of vascular damage, to which the diabetic patient is highly susceptible. © 2011 Elsevier Ltd.

Sada-Ovalle I.,Harvard University | Sada-Ovalle I.,National Institute of Respiratory Diseases | Skold M.,Harvard University | Skold M.,Karolinska Institutet | And 3 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Rationale: Invariant natural killer T (iNKT) cells are a unique subset of T cells that recognize lipid antigens presented by CD1d molecules. Recent studies have shown that iNKT cells can protect mice against Mycobacterium tuberculosis (Mtb) infection. We sought to determine whether pharmacological activation of iNKT cells by α-galactosylceramide (α-GalCer) could be used to treat tuberculosis (TB). Objectives: We hypothesized that α-GalCer, either alone or in combination with isoniazid, could be used to treat pulmonary TB. Methods: The ability of α-GalCer-activated iNKT cells to suppress Mtb replication was evaluated using an in vitro coculture system. To test its potency in vivo, mice infected with virulent Mtb were treated with α-GalCer alone or in combination with isoniazid. Measurements and Main Results: Quantitative colony-forming unit counts were compared for both experimental systems. Our results show that α-GalCer plus isoniazid controls bacterial growth better than α-GalCer or INH alone, and single or multiple α-GalCer administrations prolong the survival of the mice infected via the aerosol route. Conclusions: Our results demonstrate that α-GalCer administration can improve the outcome of Mtb infection, even when transmitted by the aerosol route. However, a combination of isoniazid and α-GalCer treatment has a synergistic effect on infection control. We conclude that more efficient treatment of TB will be achieved through a combination of classic chemotherapy and modulation of the host immune response.

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