Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent

Advances in tenascin-C biology

Tenascin-C is an extracellular matrix glycoprotein that is specifically and transiently expressed upon tissue injury. Upon tissue damage, tenascin-C plays a multitude of different roles that mediate both inflammatory and fibrotic processes to enable effective tissue repair. In the last decade, emerging evidence has demonstrated a vital role for tenascin-C in cardiac and arterial injury, tumor angiogenesis and metastasis, as well as in modulating stem cell behavior. Here we highlight the molecular mechanisms by which tenascin-C mediates these effects and discuss the implications of mis-regulated tenascin-C expression in driving disease pathology

Three Decades of Silicosis: Disease Trends at Autopsy in South African Gold Miners

BACKGROUND: Eliminating silicosis is a priority of the International Labour Organization and the World Health Organization. Prevalence is particularly high in developing countries. OBJECTIVES: We describe trends in silicosis among South African gold miners who had had an autopsy between 1975 and 2007 and quantify the contributions of age at autopsy and employment duration to these trends. METHODS: South African miners and ex-miners are eligible for autopsy examination for occupational lung disease, regardless of the clinical cause of death, and the families of deceased mine workers may receive compensation from the government of South Africa. Miners who died from external causes and who had been employed in the gold mines for > 1 year were stratified by population group because of differences in exposure, patterns of employment, and autopsy referral patterns. We extracted data from PATHAUT (Pathology Automation System) and used Stata 10 to estimate trends in relative proportions of silicosis that were standardized for age and employment duration. RESULTS: The crude proportion of silicosis for white miners was six times that of black miners in 1975. By 2007, it was 1.5 times higher for black miners. The proportion of miners with silicosis increased from 0.03 to 0.32 for black miners and from 0.18 to 0.22 for white miners. The increase can be explained by increasing age and employment duration for white miners. For black miners, it can be only partly explained by these two factors. CONCLUSION: As miners continue to age and work for longer periods, the burden of silicosis will continue to rise. South Africa is committed to global efforts to eliminate silicosis by 2030. The autopsy database allows for disease surveillance, which is necessary to monitor the success of this initiative

Infection by cytomegalovirus in patients with neonatal cholestasis Infecção por cytomegalovirus em pacientes com colestase neonatal

Background - Neonatal cholestasis syndrome with an intra or extrahepatic origin has been associated to viral infections. The participation of the cytomegalovirus in the etiopathogenesis of neonatal hepatitis has been already known for some time, but only recently there have been indications that this virus may be one of the possible etiological factors for extrahepatic biliary atresia. Aims - To assess the prevalence of infection by cytomegalovirus in patients with intrahepatic cholestasis and extrahepatic cholestasis. To compare the clinical characteristics of the intrahepatic cholestasis and extrahepatic cholestasis groups with the cytomegalovirus serological results. Patients and Methods - This study consisted of 76 patients with neonatal cholestasis who were admitted between January 1980 and January 1999 when they underwent a cytomegalovirus serologic study using the ELISA method. A case note was kept on each patient with the following data: age of patient at admission, serologic result for cytomegalovirus, history of maternal infection, prematurity, fetal distress, birth weight, ponderal gain, choluria and fecal acholia. The final anatomic diagnosis of cholestasis was based on the results of an abdominal ultrasonography, a liver biopsy and its evolution. The patients were then divided into two groups: group I - intrahepatic cholestasis and group II - extrahepatic cholestasis. Each of these groups were then divided into two subgroups: subgroup A - positive serology (IgM) for cytomegalovirus and subgroup B - negative serology (IgM) for cytomegalovirus. Results - The frequency of positive serology (IgM) for cytomegalovirus was 29.4% in children with intrahepatic cholestasis and 28.5% in children with extrahepatic cholestasis. In comparison with group IIB, group IIA presented a higher rate of maternal infection history. The patients in group IIA demonstrated a delayed access to the service in comparison with group IA. The groups did not demonstrate any significant differences regarding the onset age of jaundice, choluria and fecal acholia, birth weight and ponderal gain. Conclusions - The positive (IgM) seroprevalence for cytomegalovirus in children with intrahepatic cholestasis and extrahepatic cholestasis is high. The history of maternal infection was more common in extrahepatic cholestasis patients with positive serology for cytomegalovirus. There was a delay in the referral of these patients which resulted in a late diagnosis and surgical treatment.<br>Racional - A síndrome colestática neonatal, de origem intra ou extra-hepática, tem sido associada à presença de infecções virais. A participação do cytomegalovirus na etiopatogênese da hepatite neonatal já é conhecida há algum tempo e só recentemente esse vírus tem sido implicado como dos possíveis fatores etiológicos da atresia de vias biliares extra-hepática. Objetivos - Calcular a prevalência da infecção pelo cytomegalovirus em pacientes com colestase intra-hepática e colestase extra-hepática e comparar algumas características clínicas entre os grupos de colestase intra-hepática e colestase extra-hepática com o resultado de sorologia para cytomegalovirus. Casuística e Métodos - Participaram do estudo 76 pacientes com colestase neonatal admitidos durante o período de janeiro de 1980 a janeiro de 1999 que realizaram pesquisa sorológica para cytomegalovirus pelo método ELISA. Para todos esses pacientes foi elaborada uma ficha contendo os seguintes dados: idade do paciente na admissão, resultado de sorologia para cytomegalovirus, história de infecção materna, prematuridade, sofrimento fetal, peso de nascimento, ganho ponderal, colúria e acolia fecal. O diagnóstico anatômico final da colestase fundamentou-se no resultado de ultra-sonografia abdominal, biopsia hepática e evolução. Dessa forma, os pacientes foram divididos em dois grupos: I - colestase intra-hepática e II - colestase extra-hepática. Cada um desses grupos foi dividido em dois subgrupos: A - com sorologia positiva (IgM) para cytomegalovirus e B - com sorologia negativa (IgM) para cytomegalovirus. Resultados - A freqüência observada de sorologia positiva (IgM) para cytomegalovirus nas crianças com colestase intra-hepática e colestase extra-hepática foi de 29,4% e 28,5%, respectivamente. O grupo IIA apresentou percentual maior de história de infecção materna quando comparado ao grupo IIB. Os pacientes do grupo IIA apresentaram acesso mais tardio ao Serviço em relação àqueles do grupo IA. Não foram observadas diferenças significativas entre os grupos em relação à idade de início da icterícia, colúria e acolia fecal, bem como em relação ao peso de nascimento e ganho ponderal. Conclusões - A prevalência de sorologia positiva (IgM) para cytomegalovirus em crianças com colestase intra-hepática e colestase extra-hepática é alta. A história de infecção materna é mais comum nos pacientes com colestase extra-hepática e sorologia positiva para cytomegalovirus. Nesses pacientes, o encaminhamento foi mais tardio com atraso no diagnóstico e no tratamento cirúrgico