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Sci Rep ; 7: 46594, 2017 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-28436455


Myanmar offers unique opportunities for both biodiversity conservation and foreign direct investment due to projected economic growth linked to natural resource exploitation. Industrial-scale development introduces new land uses into the landscape, with unknown repercussions for local communities and biodiversity conservation. We use participatory mapping of 31 communities, focus groups in 28 communities, and analyses of forest cover change during 2000-2010 using MODIS vegetation continuous fields images, to understand the social and environmental impacts of gold mining and agricultural concessions in Myanmar's Hukaung Valley (~21,800 km2). Local communities, particularly the poorest households, benefit from work and trade opportunities offered by gold mining and agricultural companies but continue to depend on forests for house construction materials, food, and income from the sale of forest resources. However, gold mining and agricultural concessions reduce tree cover, potentially reducing access to forest resources and further marginalizing these households. Our analyses do not provide evidence that long-term resident communities contributed to forest cover loss between 2000 and 2010. We argue that landscape management, which recognizes local community rights to customary community use areas, and appropriate zoning for commercial land uses and protected areas could contribute to both local livelihoods and protect biodiversity throughout Myanmar during economic growth.

Lancet Planet Health ; 1(5): e180-e187, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29851639


BACKGROUND: Potential synergies between public health and environmental protection that offer new opportunities for achieving health and sustainable development targets have been postulated. However, empirical evidence of the effect of ecosystem degradation and protection on public health outcomes is scarce, which restricts policy makers' ability to assess the net health effects of land-use change. METHODS: We used generalised linear mixed-effects models to analyse data for 35 547 households in 1766 communities from the Cambodian Demographic Health Surveys to investigate the relation between health and protected areas across deforestation gradients in Cambodia between Feb 1, 2005, and April 30, 2014. Diarrhoea, acute respiratory infection, and fever in children younger than 5 years were used as population health indicators. Dense and mixed forest coverage were derived from Open Development Cambodia, and forest loss was calculated from 2000 to 2004, 2004 to 2009, and 2009 to 2014. The incidence of non-specific illness and injury in people older than 15 years was used as a negative control. Our analyses included rich pseudo-panel data (combining cross-sectional datasets from 2005, 2010, and 2014) that accounted for socioeconomic, demographic, and behavioural characteristics, and had a negative control, approximating a quasi-experimental study design. FINDINGS: Deforestation of dense forest was associated with an increased incidence of diarrhoea (p=0·007), fever (p=0·0495), and acute respiratory infection in children (p=0·003). For example, a 10 percentage point increase in loss of dense forest was estimated to be associated with an increase of 14·1% (95% CI 2·6-35·8) in the incidence of diarrhoea in children younger than 5 years per household in the 2 weeks before the Cambodian Demographic Health Surveys. Protected area coverage, but not type, was associated with decreased incidences of diarrhoea (p=0·028) and acute respiratory infection (p=0·030). Apart from an association between mixed forest coverage and increased incidence of diarrhoea, forest coverage was not associated with any health outcomes. INTERPRETATION: Deforestation is associated with increased risk of several major sources of global childhood morbidity and mortality. Although causal mechanisms are unclear, our findings suggest that protected areas could help to alleviate the global health burden, presenting new possibilities for simultaneous achievement of public health and conservation goals. FUNDING: Ministry of Education of Singapore.

Toxicol Pathol ; 43(7): 1004-14, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26059826


Clinical and nonclinical studies have implicated glucagon-like peptide-1 (GLP-1) receptor agonist therapy as a risk factor for acute pancreatitis in patients with type 2 diabetes. Therefore, it is critical to understand the effect that dulaglutide, an approved GLP-1 receptor agonist, has on the exocrine pancreas. Dulaglutide 8.15 mg/kg (approximately 500 times the maximum recommended human dose based on plasma exposure) was administered twice weekly for 12 months to cynomolgus monkeys. Serum amylase and lipase activities were measured and 6 sections of each pancreas were examined microscopically. Ductal epithelial cell proliferation was estimated using Ki67 labeling. Dulaglutide administration did not alter serum amylase or lipase activities measured at the end of treatment compared to control values. An extensive histologic evaluation of the pancreas revealed no changes in the acinar or endocrine portions and no evidence of pancreatitis, necrosis, or pancreatic intraepithelial neoplasia. An increase in goblet cells noted in 4 of the 19 treated monkeys was considered an effect of dulaglutide but was not associated with dilation, blockage, or accumulation of mucin in the pancreatic duct. There was no difference in cell proliferation in ductal epithelium between control and dulaglutide-treated monkeys. These data reveal that chronic dosing of nondiabetic primates with dulaglutide does not induce inflammatory or preneoplastic changes in exocrine pancreas.

Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/toxicidade , Fragmentos Fc das Imunoglobulinas/toxicidade , Pâncreas Exócrino/efeitos dos fármacos , Proteínas Recombinantes de Fusão/toxicidade , Animais , Peptídeos Semelhantes ao Glucagon/toxicidade , Macaca fascicularis , Masculino , Pâncreas Exócrino/patologia
Endocrinology ; 156(7): 2409-16, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25860028


Glucagon-like peptide-1 (GLP-1) receptor agonists, used for the treatment of type 2 diabetes, have caused hyperplasia/neoplasia of thyroid C cells in rodent carcinogenicity studies. Studies in monkeys have not identified an effect of GLP-1 receptor agonists on thyroid C cells; however, group sizes were small. Dulaglutide is a once-weekly, long-acting human GLP-1 receptor agonist recently approved in the United States and the European Union. The objective of this study was to determine whether dulaglutide altered C-cell mass in monkeys. Male cynomolgus monkeys (20 per group) were sc injected with dulaglutide 8.15 mg/kg (∼500-fold maximum human plasma exposure) or a vehicle control twice weekly for 52 weeks. Basal and calcium gluconate-stimulated serum calcitonin concentrations were obtained at 3, 6, 9, and 12 months. Thyroid glands were weighed, fixed, and sectioned at 500-µm intervals. C-cell volumes were measured using an automated image analysis. C-cell proliferation was estimated using Ki67/calcitonin colabeling and cell counting. Administration of dulaglutide 8.15 mg/kg twice weekly for 52 weeks did not increase serum calcitonin in monkeys or affect thyroid weight, histology, C-cell proliferation, or absolute/relative C-cell volume. This study represents a comprehensive evaluation of the monkey thyroid C cells after dosing with a GLP-1 receptor agonist, with a large group size, and measurement of multiple relevant parameters. The lack of effect of dulaglutide on C cells is consistent with other studies in monkeys using GLP-1 receptor agonists and suggests that nonhuman primates are less sensitive than rodents to the induction of proliferative changes in thyroid C cells by GLP-1 receptor agonists.

Calcitonina/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/farmacologia , Fragmentos Fc das Imunoglobulinas/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Glândula Tireoide/efeitos dos fármacos , Animais , Calcitonina/sangue , Gluconato de Cálcio/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon/farmacologia , Macaca fascicularis , Masculino , Tamanho do Órgão/efeitos dos fármacos , Receptores de Glucagon/agonistas , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia
Endocrinology ; 156(7): 2417-28, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25860029


The tumorigenic potential of dulaglutide was evaluated in rats and transgenic mice. Rats were injected sc twice weekly for 93 weeks with dulaglutide 0, 0.05, 0.5, 1.5, or 5 mg/kg corresponding to 0, 0.5, 7, 20, and 58 times, respectively, the maximum recommended human dose based on plasma area under the curve. Transgenic mice were dosed sc twice weekly with dulaglutide 0, 0.3, 1, or 3 mg/kg for 26 weeks. Dulaglutide effects were limited to the thyroid C-cells. In rats, diffuse C-cell hyperplasia and adenomas were statistically increased at 0.5 mg/kg or greater (P ≤ .01 at 5 mg/kg), and C-cell carcinomas were numerically increased at 5 mg/kg. Focal C-cell hyperplasia was higher compared with controls in females given 0.5, 1.5, and 5 mg/kg. In transgenic mice, no dulaglutide-related C-cell hyperplasia or neoplasia was observed at any dose; however, minimal cytoplasmic hypertrophy of C cells was observed in all dulaglutide groups. Systemic exposures decreased over time in mice, possibly due to an antidrug antibody response. In a 52-week study designed to quantitate C-cell mass and plasma calcitonin responses, rats received twice-weekly sc injections of dulaglutide 0 or 5 mg/kg. Dulaglutide increased focal C-cell hyperplasia; however, quantitative increases in C-cell mass did not occur. Consistent with the lack of morphometric changes in C-cell mass, dulaglutide did not affect the incidence of diffuse C-cell hyperplasia or basal or calcium-stimulated plasma calcitonin, suggesting that diffuse increases in C-cell mass did not occur during the initial 52 weeks of the rat carcinogenicity study.

Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/toxicidade , Fragmentos Fc das Imunoglobulinas/toxicidade , Proteínas Recombinantes de Fusão/toxicidade , Glândula Tireoide/efeitos dos fármacos , Neoplasias da Glândula Tireoide/induzido quimicamente , Animais , Calcitonina/sangue , Calcitonina/efeitos dos fármacos , Testes de Carcinogenicidade , Carcinoma Neuroendócrino , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon/toxicidade , Hiperplasia , Masculino , Camundongos , Camundongos Transgênicos , Tamanho do Órgão , Proteínas Proto-Oncogênicas p21(ras)/genética , Ratos , Receptores de Glucagon/agonistas , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia