Diazoxide improves muscle function in association with improved dyslipidemia and decreased muscle oxidative stress in streptozotocin-induced diabetic rats.

AIM/INTRODUCTION: Diabetes Mellitus is a chronic degenerative disease, and its main biochemical characteristic is hyperglycemia due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Hyperglycemia causes dyslipidemia and stimulates oxidative damage, leading to the main symptoms, such as fatigue and culminates in diabetic complications. Previous studies have shown that ATP-sensitive potassium channels counteract muscle fatigue and metabolic stress in healthy mouse models. To determine the effect of diazoxide on muscle strength development during diabetes, we tested the effect of diazoxide in streptozotocin-diabetic rats in muscle function, lipid profile and oxidative stress biomarkers. MATERIALS AND METHODS: Wistar rats were divided into 4 groups of six animals each: (1) Control group, (2) diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). 4 weeks after rats were sacrificed, soleus and extensor digitorum longus muscles (EDL) were extracted to prepare homogenates and serum was obtained for biochemical measurements. Oxidative damage was evaluated by the thiobarbituric acid method and the fluorescent for reactive oxygen species (ROS) probe 2,4-H2DCFDA, respectively. RESULTS: Diabetic rats with diazoxide administration showed an increase in the development of muscle strength in both muscles; in turn, the onset of fatigue was longer compared to the group of diabetic rats without treatment. Regarding the lipid profile, diazoxide decreased total cholesterol levels in the group of diabetic rats treated with diazoxide (x̅46.2 mg/dL) compared to the untreated diabetic group (x̅=104.4 mg/dL); secondly, diazoxide decreased triglyceride concentrations (x̅=105.3 mg/dL) compared to the untreated diabetic rats (x̅=412.2 mg/dL) as well as the levels of very low-density lipoproteins (x̅=20.4 mg/dL vs. x̅=82.44 mg/dL). Regarding the various markers of oxidative stress, the diabetic group treated with diazoxide was able to reduce the concentrations of TBARS and total reactive oxygen species as well as preserve the concentrations of reduced glutathione. CONCLUSION: Diazoxide administration in diabetic rats increases muscle strength development in EDL and soleus muscle, decreases fatigue, reduces cholesterol and triglyceride concentrations and improves oxidative stress parameters such as TBARS, ROS, and glutathione status.

Avocado oil induces long-term alleviation of oxidative damage in kidney mitochondria from type 2 diabetic rats by improving glutathione status.

Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats.

Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis.

Diazoxide and moderate-intensity exercise improve skeletal muscle function by decreasing oxidants and enhancing antioxidant defenses in hypertensive male rats.

High sodium intake is decisive in the incidence increase and prevalence of hypertension, which has an impact on skeletal muscle functionality. Diazoxide is an antihypertensive agent that inhibits insulin secretion and is an opener of KATP channels (adosine triphosphate sensitive potasium channels). For this reason, it is hypothesized that moderate-intensity exercise and diazoxide improve skeletal muscle function by reducing the oxidants in hypertensive rats. Male Wistar rats were assigned into eight groups: control (CTRL), diazoxide (DZX), exercise (EX), exercise + diazoxide (EX + DZX), hypertension (HTN), hypertension + diazoxide (HTN + DZX), hypertension + exercise (HTN + EX), and hypertension + exercise + diazoxide (HTN + EX + DZX). To induce hypertension, the rats received 8% NaCl dissolved in water orally for 30 days; in the following 8 weeks, 4% NaCl was supplied to maintain the pathology. The treatment with physical exercise of moderate intensity lasted 8 weeks. The administration dose of diazoxide was 35 mg/kg intraperitoneally for 14 days. Tension recording was performed on the extensor digitorum longus and the soleus muscle. Muscle homogenates were used to measure oxidants using fluorescent probe and the activity of antioxidant systems. Diazoxide and moderate-intensity exercise reduced oxidants and increased antioxidant defenses.

Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria.

Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

No association between perception of family functioning and treatment modality for chronic renal disease secondary to diabetes mellitus.

INTRODUCTION: This work was undertaken with the aim of studying the association between perception of family functioning and mode of medical treatment in Mexicans between 40 and 65 years whose suffer from chronic kidney disease. MATERIAL AND METHODS: Participants 37 patients, 22 men, 40 to 65 years of age with chronic renal disease secondary to diabetes mellitus. Patients were assigned to three groups, diet, diet + dialysis and diet + hemodialysis, they responded to four self-administered questionnaires, a demographic questionnaire and three questionnaires to assess family functioning, the Apgar family test, the family functioning perception test, and the scale of Garcia et al. RESULTS: There was no relationship between perception of family functioning of patients with chronic kidney disease secondary to diabetes mellitus and type of medical treatment. CONCLUSIONS: The perception of family functioning was not associated with the type of medical treatment of adults with chronic renal failure secondary to diabetes mellitus. The use of various instruments to explore family functioning is important to identify areas to address the psychotherapeutic management of the family. Key words: Family functioning, Diabetes mellitus type 2, Chronic renal disease, Middle adulthood.

Comparative Effect of Three Different Exercise Intensities in Combination with Diazoxide on Contraction Capacity and Oxidative Stress of Skeletal Muscle in Obese Rats.

Obesity is a chronic disease that impairs skeletal muscle function, affects the ability to contract, and promotes the development of fatigue. For this reason, the study of treatments that seek to reduce the harmful effects of obesity on muscle tissue has been deepened. Diazoxide treatment and various exercise protocols have been proposed to protect skeletal muscle against oxidative stress and its effects. However, the intensity and duration of exercise combined with diazoxide that would obtain the best results for improving skeletal muscle function in obese rats is unknown. To this end, this study evaluated the effects of three different exercise intensities combined with diazoxide on contraction capacity, resistance to fatigue, markers of oxidative stress, lipid peroxidation, ROS, and glutathione redox status of skeletal muscle. The results showed that treatments with diazoxide and exercise at different intensities improved muscle contraction capacity by reducing oxidative stress during obesity, with the best results being obtained with low-intensity exercise in combination with diazoxide. Therefore, these results suggest that diazoxide and low-intensity exercise improve muscle function during obesity by decreasing oxidative stress with the same efficiency as a moderate-intensity exercise protocol.

Apuntes sobre la institucionalización de la Medicina en Michoacán, siglo XIX.

El objetivo del estudio fue mostrar rasgos identitarios del proceso de institucionalización de la Medicina en el siglo XIX en Michoacán. Se señalan aspectos relevantes de la creación y la evolución de las instituciones relacionadas con el cuidado de la salud de los michoacanos durante el siglo XIX a partir de la revisión de material hemerográfico y textos referentes a la práctica de la Medicina en esa centuria, en el Estado de Michoacán.The objective of the study was to show identity traits of the process of institutionalization of Medicine in the 19th century in Michoacán. Relevant aspects of the creation and evolution of the institutions related to the health care of Michoacans during the 19th century are pointed out from the review of hemerographic material and texts referring to the practice of medicine in that century, in the State from Michoacan.

La higiene en la ciudad de Morelia, México, durante el régimen del porfiriato.

Este trabajo se realizó con el objetivo de documentar el estado de la higiene y los preceptos que a ella atañen en la ciudad de Morelia, México, durante el porfiriato. Para ello se consultaron documentos de la época, como periódicos, memorias de gobierno, leyes y reformas del Bando de Policía decretados por los gobiernos en turno en materia de higiene privada y pública.This work was carried out with the objective of documenting the state of hygiene and the precepts that concern it, in the city of Morelia, Mexico during the Porfiriato period. In order to do that, documents of that time were consulted such as newspapers, government reports, laws and reforms of the Police Band decreed by the governments, concerning public and private hygiene.

The object of study of hygiene in the texts published in Spain in the 19th century.

With the current COVID-19 pandemic that humanity is experiencing and the mobilization of all health systems to exercise sanitary measures such as quarantines and other measures to reduce infections, it should be remembered that these practices have been possible thanks to the experiences that in hygiene matters we have accumulated in our history. This essay aims to highlight about hygiene, the historicity of the concept, and its object of study as a medical discipline, in medical texts published in Spain during the 19th century, to help us understand the contributions of this science to current clinical practice and for these purposes, the bibliographic material was obtained from the National Library of Spain.

Con la actual pandemia de COVID-19 que la humanidad vive y la movilización de todos los sistemas de salud para ejercer medidas sanitarias, como los confinamientos, las cuarentenas y otras medidas para disminuir los contagios, vale la pena recordar que estas prácticas han sido posibles por las experiencias que en materia de higiene hemos acumulado en nuestra historia. Este ensayo tiene como objetivo destacar la higiene, la historicidad del concepto y su objeto de estudio como disciplina médica, en textos publicados en España en el siglo XIX, para ayudarnos a entender los aportes de esta ciencia a la práctica clínica actual. Con tales fines se obtuvo el material bibliográfico en la Biblioteca Nacional de España.

Family psychotherapy in patients with uncontrolled hypertension. Preliminary study.

BACKGROUND: Family psychotherapy has been shown to have a positive impact on the evolution of patients with psychosomatic disorders, and in those with arterial hypertension it could improve the level of control of the disease. OBJECTIVE: To evaluate the impact of an intervention in family psychotherapy in patients with uncontrolled systemic arterial hypertension. METHOD: Study with comparative groups. 15 uncontrolled hypertensive patients, assigned to 2 groups: an intervention group of 10 patients who received family psychotherapy and a control group of 5 patients. In both groups, the pharmacological treatment indicated by experts was continued. Both groups were compared before and after the intervention regarding quality of life (InCaViSa), family functioning (Family Functioning Scale), systolic and diastolic blood pressure, body mass index and glucose, cholesterol, triglycerides, uric acid and creatinine. RESULTS: There was qualitative improvement in the domains of the InCaViSa scale to estimate quality of life in the intervention group and there were no statistically significant changes between the groups in family functioning or in body weight. Among the biochemical variables, only cholesterol showed a significant reduction (p = 0.47). Greater mobility of the family towards more functional behaviors was found in the group that received the intervention, and also in this group, systolic and diastolic blood pressure values decreased (p < 0.001), and the use of antihypertensive, anxiolytic and antidepressant drugs, as well. CONCLUSIONS: Family psychotherapeutic intervention can favor the control of blood pressure, reduce the doses of antihypertensive, anxiolytic and antidepressant drugs and it can help to transition to better functionally family states.

ANTECEDENTES: La psicoterapia familiar ha demostrado tener un impacto positivo en la evolución de enfermos con trastornos psicosomáticos, y en aquellos con hipertensión arterial arterial pudiera mejorar el nivel de control de la enfermedad. OBJETIVO: Evaluar el impacto de una intervención en psicoterapia familiar en pacientes con hipertensión arterial sistémica no controlada. MÉTODO: Estudio con grupos comparados. 15 pacientes hipertensos no controlados, asignados a dos grupos: un de intervención, con 10 pacientes que recibieron psicoterapia familiar, y otro de control con 5 pacientes. En ambos grupos se continuó con el tratamiento farmacológico indicado por expertos. Se compararon ambos grupos antes y después de la intervención respecto a calidad de vida (InCaViSa), funcionamiento familiar (Escala de Funcionamiento Familiar), presión arterial sistólica y diastólica, índice de masa corporal, glucosa, colesterol, triglicéridos, ácido úrico y creatinina. RESULTADOS: Hubo una mejoría cualitativa en los dominios de la escala InCaViSa para estimar la calidad de vida en el grupo de intervención y no hubo cambios estadísticamente significativos entre los grupos en cuanto a funcionamiento familiar y peso corporal. Entre las variables bioquímicas, solo el colesterol mostró una reducción significativa (p = 0.47). Se encontró una mayor movilidad de la familia hacia comportamientos más funcionales en el grupo que recibió la intervención, y también en este grupo disminuyeron las cifras de presión sistólica y diastólica (p < 0.001), así como el uso de antihipertensivos, ansiolíticos y antidepresivos. CONCLUSIONES: La intervención psicoterapéutica familiar puede favorecer el control de la presión arterial, reducir las dosis de antihipertensivos, ansiolíticos y antidepresivos, y ayudar en la transición a estados de mejor funcionalidad familiar.

[Macronutrients consumption and lifestyle in patients whose received transplant of kidney in The Mexican Institute for Social Security]. / Consumo de macronutrientes y estilo de vida en pacientes con trasplante renal que acudieron a un evento deportivo nacional.

The transplant offer the best quality of life to patients whose suffer from advanced chronic renal failure. This work was undertaken to know the lifestyle and macronutrients consume patterns in patients from the Mexican Institute for Social Security whose received a transplanted kidney . Demographic and anthropometric information were obtained from 119 transplanted patients and consume patterns were obtained from them through the recall of 24 hours. The IMEVID questionnaire was used to assess the lifestyle in this population. This instrument was previously validated for its reliability, its showed a value of 0.681 for alpha of Cronbach and 0.685 for Spearman-Brown test. The 70% of the patients showed less favourable lifestyles and there were no differences between genders. There were significative differences among states of the country where the subjects lived; attending the following domains of the IMEVID questionnaire. Information, physical activity and adjustment to the treatment (p < 0.001). In those States near the american border the BMI was superior to the 25 kg/m(2), there were significatives differences attending ideal and real ingestion among States of the country, (p < 0.05). The protein consumption was higher in patients living in Michoacan to those reported from patients living in other states of the country (p < 0.05)and the lipids consumption was higher in Nuevo Leon in comparison with those reported from patients living in other states of the country (p < 0.05). It is frequent to find non favourable lifestyles in patients with transplant of the kidney, even when they practices physical exercise. The promotion of healthy lifestyles via educative strategies of high impact, in patients with transplant is necessary to avoid highly cost complications and rejection of the graft.

Diazoxide and Exercise Enhance Muscle Contraction during Obesity by Decreasing ROS Levels, Lipid Peroxidation, and Improving Glutathione Redox Status.

Obesity causes insulin resistance and hyperinsulinemia which causes skeletal muscle dysfunction resulting in a decrease in contraction force and a reduced capacity to avoid fatigue, which overall, causes an increase in oxidative stress. KATP channel openers such as diazoxide and the implementation of exercise protocols have been reported to be actively involved in protecting skeletal muscle against metabolic stress; however, the effects of diazoxide and exercise on muscle contraction and oxidative stress during obesity have not been explored. This study aimed to determine the effect of diazoxide in the contraction of skeletal muscle of obese male Wistar rats (35 mg/kg), and with an exercise protocol (five weeks) and the combination from both. Results showed that the treatment with diazoxide and exercise improved muscular contraction, showing an increase in maximum tension and total tension due to decreased ROS and lipid peroxidation levels and improved glutathione redox state. Therefore, these results suggest that diazoxide and exercise improve muscle function during obesity, possibly through its effects as KATP channel openers.

[Effect of pentoxifylline on the evolution of diabetic nephropathy]. / Efecto de la pentoxifilina sobre la evolución de la nefropatía diabética.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy (DN) is the principal cause of end-chronic kidney disease. Metabolic and hemodynamic components are directly involved. However, convincing data have shown that inflammation participates in the diabetic complications. The aim of this study was to investigate whether the inhibition of the inflammation and pro-inflammatory cytokines with pentoxifylline (PXF) attenuate the progression of the DN. SUBJECTS AND METHOD: In a prospective, randomized, double-blind, placebo- controlled study, we evaluated the effect of PXF (1200 mg daily) during 12 months, in 34 patients with incipient or established DN. Evaluated parameters were inflammation, pro-inflammatory cytokines and urinary albumin excretion (UAE). RESULTS: PXF treatment had a reno-protective effect determined by a significant reduction in the UAE in both incipient and established (p<0,01) DN patient. This effect was attributed to a reduction in the C-reactive protein, interleukin-6, tumor necrosis factor-alpha and leptin serum levels (p<0,01). CONCLUSIONS: PXF treatment caused regression and prevented the progression of renal damage. Thus, PXF should be used in the preventive treatment of DN. These results showed that inflammation and pro-inflammatory cytokines are related to the progression of diabetic nephropathy.