Early mitochondrial adaptations in skeletal muscle to diet-induced obesity are strain dependent and determine oxidative stress and energy expenditure but not insulin sensitivity

This study sought to elucidate the relationship between skeletal muscle mitochondrial dysfunction, oxidative stress, and insulin resistance in two mouse models with differential susceptibility to diet-induced obesity. We examined the time course of mitochondrial dysfunction and insulin resistance in obesity-prone C57B and obesity-resistant FVB mouse strains in response to high-fat feeding. After 5 wk, impaired insulin-mediated glucose uptake in skeletal muscle developed in both strains in the absence of any impairment in proximal insulin signaling. Impaired mitochondrial oxidative capacity preceded the development of insulin resistant glucose uptake in C57B mice in concert with increased oxidative stress in skeletal muscle. By contrast, mitochondrial uncoupling in FVB mice, which prevented oxidative stress and increased energy expenditure, did not prevent insulin resistant glucose uptake in skeletal muscle. Preventing oxidative stress in C57B mice treated systemically with an antioxidant normalized skeletal muscle mitochondrial function but failed to normalize glucose tolerance and insulin sensitivity. Furthermore, high fat-fed uncoupling protein 3 knockout mice developed increased oxidative stress that did not worsen glucose tolerance. In the evolution of diet-induced obesity and insulin resistance, initial but divergent strain-dependent mitochondrial adaptations modulate oxidative stress and energy expenditure without influencing the onset of impaired insulin-mediated glucose uptake.     

High HIF-1α expression genotypes in oral lichen planus

Objective

The aim of this study is to assess whether C1772T and G1790A hypoxia-inducible factor-1 (HIF-1)α polymorphisms are associated with risk of oral lichen planus (OLP).

Material and methods

Restriction fragment length polymorphism analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 32 OLP and 88 individuals without OLP.

Results

The frequency of the CC, TT, GA, and AA genotypes was higher in patients with OLP. Notably, individuals carrying the C and A, and T and A haplotypes showed a significant association OLP risk.

Conclusions

Our study demonstrated that the C1772T and G1790A polymorphisms of HIF-1α gene increased the risk of OLP. C1772T and G1790A polymorphisms of HIF-1α gene had differing patterns of allelic imbalance in the normal samples and subsequent chronic lesions. Further studies are necessary to elucidate the HIF-1α pathway in OLP, which would facilitate the development of novel therapeutic strategies for the prevention and treatment of OLP.

Clinical relevance

These results, in conjunction with previous studies, suggest that HIF-1α may play important roles in the chronicity of oral mucosa lesions of OLP patients. Taken together, we suggest that HIF-1α polymorphisms enhance its target genes, thereby altering the microenvironment and supporting sequential release of inflammatory mediators or cellular events in OLP. It appears unlikely that inhibition of a single proinflammatory mediator will prove useful in clinical practice, but several ways to reprogram mediators engaged in a wide array of roles simultaneously are encouraging.     

Low expression of MSH2 DNA repair protein is associated with poor prognosis in head and neck squamous cell carcinoma

Objective

This study aimed to investigate the expression of the MSH2 DNA repair protein in head and neck squamous cell carcinoma (HNSCC) in order to analyze its association with clinicopathologic factors and overall survival of patients.

Material and Methods

Clinical data and primary lesions of HNSSC were collected from 55 patients who underwent surgical resection with postoperative radiotherapy in Montes Claros, state of Minas Gerais, Brazil, between 2000 and 2008. Immunohistochemical reactions were performed to analyze MSH2 protein expression.

Results

Bivariate analysis showed no significant correlation or association between MSH2 expression and clinicopathologic parameters by Mann-Whitney and Kruskal-Wallis tests. Patients with locoregional metastatic disease (OR=4.949, p<0.001) and lower MSH2 immunohistochemical expressions (OR=2.943, p=0.032) presented poorer survival for HNSCC by Cox regression models.

Conclusions

Our data demonstrated that lower MSH2 expression might contribute to a higher clinic aggressiveness of HNSCC by promoting an unfavorable outcome.     

The effects of aging on the central nervous system steroid profiles and myelin basic protein in rats

The aim of this study was to investigate the effects of aging on the central nervous system steroid and myelin basic protein (MBP) profiles. Forty-seven male Sprague-Dawley rats (newborn, 1, 6, 12 and 24-monthsold) were studied. Tissues were obtained from the cerebellum and parietal, frontal, temporal cortex of the central nervous system of the rats for steroid extraction. The estradiol, progesteron, testosterone and dehydroepiandrosterone (DHEA) levels were measured by Enzyme Linked Immunosorbent Assay (ELISA). The average levels of estradiol (pg/g), progesteron (ng/g), DHEA (ng/g) and testosterone (ng/g) in the brain tissues were respectively 24.29, 4.59, 0.27, 0.92 in the newborn-rats; 4.18 ± 1.10, 1.54 ± 0.30, 0.28 ± 0.01, 0.57 ± 0.10 in the 1 month-old-rats; 11.02 ± 1.10, 2.96 ± 0.30, 0.27 ± 0.01, 0.61 ± 0.10 in the 6 month-old-rats; 15.80 ± 1.10, 4.80 ± 0.30, 0.28 ± 0.10, 0.67 ± 0.10 in the 12 monthold- rats; 20.07 ± 1.10, 4.12 ± 0.30, 0.28 ± 0.01, 0.55±0.10 in the 24 month-old-rats. The myelin basic protein levels were determined by immunohistochemical staining and an elevation was observed in conjunction with the aging process. The results of the study indicate that the alterations in MBP, DHEA, progesterone, testosterone and estrodiol concentrations in the central nervous system of the rats during aging can be considered fundamental for future animal and human studies.     

Modulation of VEGF expression in rat bone marrow stromal cells by GDF-5

Angiogenesis is essential for bone formation and several bone morphogenetic proteins (BMPs) have been shown to induce angiogenesis through osteoblast-derived vascular endothelial growth factor (VEGF)-A. Growth differentiation factor-5 (GDF-5) is a member of the BMP family expressed in bone and known to induce angiogenesis in vivo. In this study, the effects of GDF-5 on osteogenic differentiation and expression of VEGF-related genes were determined using rat bone marrow stromal cells. GDF-5 stimulated osteogenic differentiation. It also upregulated the expression of VEGF-A after 3 hr, accompanied by a trend of decrease in its receptor VEGFR-2 at 6 and 24 hr. VEGF-D and its receptor VEGFR-3 showed peak expression at later time points. This regulation may be further controlled by neuropilin 2 that exhibited a parallel profile to VEGF-D. These observations indicate that GDF-5 stimulates osteogenic differentiation and has a potential to induce angiogenesis through osteoblast-derived VEGF-A in bone.     

Stigma towards mental illness and substance use issues in primary health care: Challenges and opportunities for Latin America

Stigma towards mental illness and addictive disorders is a global problem and one of the main obstacles in tackling this issue remains the effective integration of mental health services into primary health care (PHC). In Latin America, information has significantly increased on the existence of stigma; however, little is known about effective interventions to prevent stigma and promote recovery-oriented practices in PHC. The aim of this study is to understand the existing evidence regarding mental health stigma in PHC with a special focus on the Latin American region. A scoping review of the literature related to mental health stigma in PHC was conducted. Two hundred and seventeen articles were evaluated; 74 met inclusion criteria and 14 additional articles were selected from references of search results. Results were subdivided into five different perspectives: users, family members and significant others, health professionals, contextual factors, and potential effective interventions. Only nine studies were based in Latin America, and only one described an intervention to reduce stigma in mental health services, not specifically in PHC. We found an urgent need to develop interventions to understand and reduce stigma in PHC settings, especially in Latin America.     

A rare complication of idiopathic osteosclerosis

Idiopathic osteosclerosis (IO) is described as a localized no expansible radiopacity with unknown etiology. The IO is generally asymptomatic and could appear as round, elliptical or irregular in shape. The internal aspect is usually uniformly radiopaque. IO should be distinguished from condensing osteitis of dental origin, or other alveolar bone related radiopacities such as periapical cemental dysplasia. This condition may cause changes in tooth position or problems during orthodontic treatment. The purpose of the present study is to report a case of tooth resorption caused by ectopic eruption rote caused by IO. This condition represents a rare complication of IO.