Different patterns of pulmonary vascular disease induced by type 1 diabetes and moderate hypoxia in rats.

Although type 1 and type 2 diabetes are strongly associated with systemic cardiovascular morbidity, the relationship with pulmonary vascular disease had been almost disregarded until recent epidemiological data revealed that diabetes might be a risk factor for pulmonary hypertension. Recent experimental studies suggest that diabetes induces changes in lung function insufficient to elevate pulmonary pressure. The aim of this study was to assess the effects of diabetes on the sensitivity to other risk factors for pulmonary hypertension. We therefore analysed the effects of the combination of diabetes with exposure to moderate hypoxia on classical markers of pulmonary hypertension. Control (saline-treated) and diabetic (70 mg kg(-1) streptozotocin-treated) male Wistar-Kyoto rats were followed for 4 weeks and exposed to normoxia or moderate normobaric hypoxia (14%) for another 2 weeks. Hypoxia, but not diabetes, strongly reduced voltage-gated potassium currents, whereas diabetes, but not hypoxia, induced pulmonary artery endothelial dysfunction. Both factors independently induced pulmonary vascular remodelling and downregulated the lung bone morphogenetic protein receptor type 2. However, diabetes, but not hypoxia, induced pulmonary infiltration of macrophages, which was markedly increased when both factors were combined. Diabetes plus hypoxia induced a modest increase in diastolic and mean pulmonary artery pressure and right ventricular weight, while each of the two factors alone had no significant effect. The pattern of changes in markers of pulmonary hypertension was different for moderate hypoxia and diabetes, with no synergic effect except for macrophage recruitment, and the combination of both factors was required to induce a moderate elevation in pulmonary arterial pressure.

Type 1 diabetes-induced hyper-responsiveness to 5-hydroxytryptamine in rat pulmonary arteries via oxidative stress and induction of cyclooxygenase-2.

Recent epidemiological data suggest that diabetes is a risk factor for pulmonary arterial hypertension. The aim of the present study was to analyze the link between type 1 diabetes and pulmonary arterial dysfunction in rats. Male Sprague-Dawley rats were randomly divided into a control group (saline) and a diabetic group (70 mg/kg streptozotocin). After 6 weeks, diabetic animals showed a down-regulation of the lung bone morphogenetic protein receptor type 2, up-regulation of 5-hydroxytryptamine (5-HT) 2A receptors and cyclooxygenase-2 (COX-2) proteins as measured by Western blot analysis, and increased contractile responses to 5-HT in isolated intrapulmonary arteries. The hyper-responsiveness to 5-HT was endothelium-independent and unaffected by inhibition of nitric-oxide synthase but prevented by indomethacin, the selective COX-2 inhibitor N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methane sulfonamide (NS-398), superoxide dismutase, and the NADPH oxidase inhibitor apocynin or chronic treatment with insulin. However, diabetic rats at 6 weeks did not develop elevated right ventricular pressure or pulmonary artery muscularization, whereas a longer exposure (4 months) to diabetes induced a modest, but significant, increase in right ventricular systolic pressure. In conclusion, type 1 diabetes mellitus in rats induces a number of changes in lung protein expression and pulmonary vascular reactivity characteristic of clinical and experimental pulmonary arterial hypertension but insufficient to elevate pulmonary pressure. Our results further strengthen the link between diabetes and pulmonary arterial hypertension.

Serum resistin levels are associated with adiposity and insulin sensitivity in obese Hispanic subjects.

BACKGROUND AND AIMS: Resistin is involved in the development of obesity and insulin resistance (IR) in mice and may play a similar role in humans through mechanisms that remain unresolved. The objective of this study was to characterize the relationship between resistin levels in obese subjects with and without IR among Hispanic subjects. MATERIAL AND METHODS: A cross-sectional study was performed on 117 nondiabetic Hispanic subjects of both genders that were allocated into three study groups: A control group (n=47) of otherwise healthy individuals in metabolic balance, a group with obesity (OB) (n=36), and a group with obesity and IR (OB-IR) (n=34). Anthropometric and clinical characterization was carried out, and resistin levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that resistin levels were higher in OB and OB-IR groups when compared to the control group (1331.79±142.15 pg/mL, 1266.28±165.97 pg/mL vs. 959.21±171.43 pg/mL; P<0.05), an effect that was not confounded by age (control, 34.04±10.00 years; OB, 37.30±10.78 years; and OB-IR, 35.67±10.15 years). In addition, we observed a significant correlation (P<0.001) between resistin levels and higher adiposity and insulin sensitivity (IS) in our cohort. CONCLUSIONS: Our results suggest that higher resistin levels are associated with higher adiposity and lower IS among obese Hispanic subjects.

[Overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico]. / Sobrepeso y obesidad en indígenas nahuas de Ixtaczoquitlán, Veracruz, México.

The study was aimed at determining the prevalence of overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico. For this purpose, a cross-cut study was conducted between 2010 and 2011, in which the body mass index (BMI) was calculated. To define overweight and obesity, the categories of the World Health Organization (WHO) and the Mexican Official Standard (NOM, Spanish acronym) were used. 227 nahuas (77,5% women) were included. According to WHO’s guidelines, the rate for overweight among nahuas was 41%, and 36.5% for obesity; according to NOM, it was 11.4 and 69.2% respectively. In conclusion, the prevalence of overweight and obesity among indigenous nahuas is high. Studies should be conducted to determine the prevalence and risk factors in order to develop prevention strategies based on this information to improve the health quality of these populations.

Diabetes induces pulmonary artery endothelial dysfunction by NADPH oxidase induction.

Recent data suggest that diabetes is a risk factor for pulmonary hypertension. The aim of the present study was to analyze whether diabetes induces endothelial dysfunction in pulmonary arteries and the mechanisms involved. Male Sprague-Dawley rats were randomly divided into a control (saline) and a diabetic group (70 mg/kg(-1) streptozotocin). After 6 wk, intrapulmonary arteries were mounted for isometric tension recording, and endothelial function was tested by the relaxant response to acetylcholine. Protein expression and localization were measured by Western blot and immunohistochemistry and superoxide production by dihydroethidium staining. Pulmonary arteries from diabetic rats showed impaired relaxant response to acetylcholine and reduced vasoconstrictor response to the nitric oxide (NO) synthase inhibitor L-NAME, whereas the response to nitroprusside and the expression of endothelial NO synthase remained unchanged. Endothelial dysfunction was reversed by addition of superoxide dismutase or the NADPH oxidase inhibitor apocynin. An increase in superoxide production and increased expression of the NADPH oxidase regulatory subunit p47(phox) were also found in pulmonary arteries from diabetic rats. In conclusion, the pulmonary circulation is a target for diabetes-induced endothelial dysfunction via enhanced NADPH oxidase-derived superoxide production.

Sobrepeso y obesidad en indígenas nahuas de Ixtaczoquitlán, Veracruz, México / Overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico

El estudio tuvo como objetivo determinar la frecuencia de sobrepeso y obesidad en indígenas nahuas de Ixtaczoquitlán, Veracruz, México. Para ello, se realizó un estudio transversal entre los años 2010-2011; donde se calculó el índice de masa corporal (IMC). Para la definición de sobrepeso y obesidad se emplearon las categorías de la Organización Mundial de la Salud (OMS) y los de la Norma Oficial Mexicana (NOM). Se incluyó 227 nahuas (77,5% mujeres). Según los lineamientos de la OMS, la proporción de nahuas con sobrepeso fue de 41%, y de obesidad 36,5%; y según la NOM fue de 11,4 y 69,2% respectivamente. En conclusión, la frecuencia de sobrepeso y obesidad en indígenas nahuas es alta. Deben realizarse estudios enfocados a determinar la prevalencia y factores de riesgo y, con ello, desarrollar estrategias de prevención que mejoren la calidad de salud de estas poblaciones.

The study was aimed at determining the prevalence of overweight and obesity in indigenous nahuas from Ixtaczoquitlán, Veracruz, Mexico. For this purpose, a cross-cut study was conducted between 2010 and 2011, in which the body mass index (BMI) was calculated. To define overweight and obesity, the categories of the World Health Organization (WHO) and the Mexican Official Standard (NOM, Spanish acronym) were used. 227 nahuas (77,5% women) were included. According to WHO’s guidelines, the rate for overweight among nahuas was 41%, and 36.5% for obesity; according to NOM, it was 11.4 and 69.2% respectively. In conclusion, the prevalence of overweight and obesity among indigenous nahuas is high. Studies should be conducted to determine the prevalence and risk factors in order to develop prevention strategies based on this information to improve the health quality of these populations.

Postnatal maturation in nitric oxide-induced pulmonary artery relaxation involving cyclooxygenase-1 activity.

The maturation in the vasodilator response to nitric oxide (NO) in isolated intrapulmonary arteries was analyzed in newborns and 15- to 20-day-old piglets. The vasodilator responses to NO gas but not to the NO donor sodium nitroprusside increased with age. The inhibitory effects of the superoxide dismutase inhibitor diethyldithiocarbamate and xanthine oxidase plus hypoxanthine and the potentiation induced by superoxide dismutase and MnCl(2) of NO-induced vasodilatation were similar in the two age groups. Diphenyleneiodonium (NADPH oxidase inhibitor) potentiated the response to NO, and this effect was more pronounced in the older animals. The nonselective cyclooxygenase inhibitors indomethacin and meclofenamate and the preferential cyclooxygenase-1 inhibitor aspirin augmented NO-induced relaxation specifically in newborns, whereas the selective cycloxygenase-2 inhibitor NS-398 had no effect. The expressions of alpha-actin, cycloxygenase-1, and cycloxygenase-2 proteins were similar, whereas Cu,Zn-superoxide dismutase decreased with age. Therefore, the present data suggest that the maturational increase in the vasodilatation of NO in the pulmonary arteries during the first days of extrauterine life involves a cycloxygenase-dependent inhibition of neonatal NO activity.

Pharmaceutical services in a Mexican pain relief and palliative care institute

Neither the purchase nor the distribution of pharmaceuticals in hospitals and community pharmacies in Mexico is under the care of pharmacists. Some are under control of physicians. This report presents the results of the implementation of some of pharmaceutical services for the Jalisco Pain Relief, and Palliative Care Institute (Palia Institute), under the direction of the Secretary of Health, Government of Jalisco. The services implemented were drug distribution system, Drug Information Service, Pharmacovigilance Program , and home pharmacotherapy follow-up pilot program for patients with advanced illness, with the ultimate using the appropriate medication. The drug distribution system included dispensing of opioid pain medications, antidepressants, anticonvulsants, NSAIDs, anxiolytic drugs, steroid drugs, laxatives, and anti-emetics. The frequently used drugs were morphine sulfate (62%), amitriptyline (6.4%), and dextropropoxyphene (5.8%). The Drug Information Service answered 114 consultations, mainly asked by a physician (71%) concerned with adverse drug reactions and contraindications (21%). The pharmacovigilance program identified 146 suspected adverse drug reactions and classified them reasonably as possible (27%), probable (69%), and certain (4%). These were attributed mainly to pregabalin and tramadol. The home pharmacotherapy follow-up pilot program cared patients with different cancer diagnoses and drug-related problems (DRP), which were identified and classified (according to second Granada Consensus) for pharmaceutical intervention as DRP 1 (5%), DRP 2 (10%), DRP 3 (14%), DRP 4 (19%), DRP 5 (24%), or DRP 6 (28%). This report provides information concerning the accurate use of medication and, above all, an opportunity for Mexican pharmacists to become an part of health teams seeking to resolve drug-related problems (AU)

En México, ni la compra ni la distribución de medicamentos en hospitales y farmacias comunitarias están bajo el cuidado de farmacéuticos. Unos cuantos están a cargo de médicos. Este artículo presenta los resultados de la implementación de algunos servicios farmacéuticos en el Instituto Jaliscience de Alivio al Dolor y Cuidados Paliativos (Instituto Palia), bajo la dirección de la Secretaría de Salud del Gobierno de Jalisco. Los servicios implementados fueron un sistema de distribución de medicamentos, un Servicio de Información de Medicamentos, un programa de Farmacovigilancia, y un programa piloto de seguimiento farmacoterapéutico domiciliario para pacientes con enfermedad avanzada, con el objetivo de utilizar la medicación apropiada. El sistema de distribución de medicamentos incluyó la dispensación de analgésicos opiáceos, antidepresivos, anticonvulsivantes, AINEs, ansiolíticos, esteroides, laxantes y antieméticos. Los más utilizados fueron sulfato de morfina (62%), amitriptilina (6,4%) y dextropropoxifeno (5,8%). El Servicio de Información de Medicamentos respondió a 114 consultas realizadas principalmente por un médico, concernientes a reacciones adversas (71%) y contraindicaciones (21%). El programa de Farmacovigilancia identificó 146 sospechas de reacciones adversas y las clasificó como posible (27%), probable (69%), y seguras (4%). Se atribuyeron principalmente a pregabalina y tramadol. El programa piloto de seguimiento farmacoterapéutico domiciliario atendió pacientes con diferentes diagnósticos de cáncer y se identificaron problemas relacionados con medicamentos que se clasificaron (según el Segundo Consenso de Granada) como PRM 1(5%), PRM 2 (10%), PRM 3 (14%), PRM 4 (19%), PRM 5 (24%), o PRM 6 (28%). Este artículo proporciona información relacionada al uso adecuado de medicamentos y, sobre todo ofrece una oportunidad para que los farmacéuticos mexicanos lleguen a ser parte del equipo de salud tratando de resolver los problemas relacionados con medicamentos (AU)