Cetoacidosis diabética como debut de diabetes mellitus inmunomediada en paciente en tratamiento con inhibidores de checkpoint / Diabetic ketoacidosis as debut of immune-mediated diabetes mellitus in a patient in treatment with immune checkpoint inhibitors

Los inhibidores de checkpoint (ICP) son anticuerpos usados en inmunoterapia contra el cáncer. Uno de sus blancos de acción es el receptor de muerte celular programada-1 (PD-1), el cual es importante para mantener la tolerancia inmunitaria. Sin embargo, este mecanismo se asocia a riesgo de eventos adversos relacionados a la inmunidad que pueden afectar a múltiples órganos incluyendo el sistema endocrino. Se describe el caso inhabitual de un paciente que a los 18 meses de terapia con ICP debutó con cetoacidosis diabética (CAD).

Immune checkpoint inhibitors consist in antibodies used in immunotherapy against cancer. One of their targets is the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, this mechanism is associated with a risk for immune-related adverse events potentially affecting multiple organs, including the endocrine system. We describe the unusual case of a patient who, after 18 months of treatment with an immune checkpoint inhibitor, debuted with diabetic ketoacidosis

Hiperglicemia y diabetes inducidas por esteroides / Hyperglycemia and steroid-induced diabetes

La hiperglicemia y/o diabetes inducida por esteroides, se define como la elevación de la glicemia, causada por la acción de los fármacos glucocorticoideos, sobre el metabolismo de los carbohidratos, y presenta una prevalencia entre un 20% al 50%, en pacientes sin diabetes previa, existiendo mayor riesgo para esta patología en pacientes con diabetes pre-existente, obesidad, uso crónico de esteroides o en dosis altas, entre otros. El diagnóstico se rige por los criterios para diabetes en la mayoría de los casos. No obstante, existen casos en donde la hiperglicemia por esteroides es sub-diagnosticada. Su manejo se basa en el tratamiento farmacológico (antidiabéticos orales, subcutáneos e insulina) y no farmacológico (dieta y ejercicio), tomando en cuenta, el patrón glicémico, peso, edad, co-morbilidades, dosis, tipo y tiempo de uso de los esteroides. La relevancia de conocer como diagnosticar y tratar dicha patología, se debe al riesgo de ingreso hospitalario, de infección, de mala cicatrización y de mortalidad en casos no tratados. En vista del aumento del uso de glucocorticoides en la actualidad, se hace una revisión del abordaje terapéutico de la hiperglicemia y diabetes inducida por esteroides.

Hyperglycemia and Steroid-induced Diabetes is defined as the elevation of glycemia caused by the action of glucocorticoid drugs on carbohydrate metabolism, with a prevalence between 20% and 50% in patients without Diabetes. Though, there is a greater risk of this pathology in patients with pre-existing Diabetes, Obesity, chronic use of steroids or in high doses, among others. In most cases, the diagnosis is governed by the criteria of Diabetes; however, there are cases where hyperglycemia Steroid-induced is under-diagnosed. Its management is based on pharmacological treatment (oral and subcutaneous hypoglycemic agents and insulin) and non-pharmacological treatment (diet and exercise), in accordance with the glycemic pattern, weight, age, co-morbidities, dose, type and the duration of the use of steroid. The relevance of knowing how to diagnose and treat this pathology is the risk of hospital admission, infection, poor healing and mortality in untreated cases. In view of the increased use of glucocorticoids nowadays, a review is made about the therapeutic approach to hyperglycemia and steroid-induced Diabetes.

La amarga realidad de los edulcorantes no nutritivos: desde una perspectiva global al contexto chileno / The bitter reality of non-nutritive sweeteners: a global perspective applied to the Chilean context

Actualmente los edulcorantes no nutritivos (ENN) son ampliamente usados para endulzar los alimentos en reemplazo de los azúcares simples, con la ventaja de no aportar energía. A pesar de que en general no presentan efectos tóxicos, los estudios epidemiológicos no han podido evidenciar que su uso contribuya a mejorar la pérdida de peso, sino por el contrario, han revelado que los ENN pueden inducir alteraciones metabólicas como intolerancia a la glucosa. Estudios in vivo e in vitro han mostrado que muchos ENN activan a receptores del sabor dulce no sólo en los botones gustativos, sino que también en los receptores presentes en tejidos como el adiposo y pancreático, interfiriendo con su función normal. Además, el consumo ENN se ha asociado a alteraciones de la composición de la microbiota intestinal que conducen a una respuesta inflamatoria de bajo grado. La nueva evidencia disponible sobre los ENN hace necesario evaluar el uso cada vez más intenso de los ENN en Chile. Debido a que el gusto exacerbado por el sabor dulce que cultivamos desde la infancia es un potente catalizador del uso de ENN, proponemos que una oportuna educación del sentido del gusto puede contribuir a mejorar las elecciones alimentarias.

Currently, non-nutritive sweeteners (NNS) are widely used to sweeten foods instead of simple sugars, as they possess the advantage of not contributing to energy intake. Although they do not present toxic effects in general, epidemiological studies have not been able to show benefits when they are used in weight loss programs. However, they could induce metabolic alterations such as glucose intolerance. In vivo and in vitro studies have shown that many NNSs activate sweet taste receptors not only in the taste buds, but also in receptors present in adipose and pancreatic tissues, interfering with their normal function. In addition, NNS consumption has been associated with an alteration in the composition of the gut microbiota that leads to a low-grade inflammatory response. Due to the wide use of NNS in Chile, it is necessary to evaluate the potential health effects of using NNS in the Chilean population. We propose that a timely education of the sense of taste can contribute to moderating the preference for higher levels of sweet taste that humans develop in childhood, which could help to improve food choices.

Effect on hyperglycemia and pancreas cells of chaya aqueous extracts from two different regions in streptozotocin-induced diabetes rats

Cnidoscolus chayamansa is a native plant of the Mayan region, which is also cultivated in other places like northern Mexico, Tunisia and India. Many properties are attributed to Mayan Chaya, such as aid in the control of glycemia in diabetics. Thus this study aimed to evaluate the hypoglycemic effects of chaya aqueous extracts in a model of streptozotisin-induced diabetic Wistar rats. Chaya aqueous extracts were collected from plants cultivated in Quinta Roo (Mayan region) and Durango (northern Mexico), and in this study we compare their effect with metformin (as a control). Additionally, we compared the extracts mass profiles from both regions by high-resolution liquid chromatography coupled to a triple quadrupole tandem mass detector (HPLC-MS/MS QQQ). Finally, a study of the pancreatic tissue was carried out to evaluate the effects of the extracts on the Langerhans islets. Both extracts showed a good hypoglycemic effect after two weeks of treatment, and the Langerhans islets showed a partial recovery due to the effect of the treatment. Although the plants were cultivated at a distance of 2,350 km and under different weather, the compounds found in both did not show significant differences.

Evaluación de síndrome metabólico en varones hospitalizados en Unidad de Corta Estadía Psiquiátrica Marzo 2017 / Evaluation of metabolic syndrome in Hospitalized Men in the Short Stay Psychiatric Unit. March 2017

El síndrome metabólico (SM) corresponde a un conjunto de factores de riesgo derivados de la obesidad visceral e insulinoresistencia. 35.3% de la población adulta chilena presentó SM en el período 2009 - 2010, con diferencia significativa entre hombres y mujeres (41.6% vs 30.9%, respectivamente). En Estados Unidos se ha calculado que la media de años potencialmente perdidos en pacientes con enfermedades mentales va de 25 a 30, comparada con la población general. La principal causa de muerte es la enfermedad coronaria. La mayoría de los pacientes en tratamiento neuroléptico en hospitales psiquiátricos no reciben control de factores de riesgo metabólicos. La evidencia señala que los pacientes esquizofrénicos no son adecuadamente pesquisados ni tratados por Dislipidemia (hasta un 88% de estos pacientes siguen sin tratamiento) ni por hipertensión (hasta un 62%). El objetivo de este trabajo es evaluar factores de riesgo cardiovascular en varones hospitalizados en unidad de corta estadía psiquiátrica del Instituto Psiquiátrico Dr. José Horwitz Barak. Se evaluó a 35 pacientes varones, de los cuales un 37% presentó SM, un 45.3% presentó sobrepeso.

The metabolic syndrome (MS) corresponds to a set of risk factors derived from visceral obesity and insulin resistance. 35.3% of the Chilean adult population had MS in the 2009-2010 period, with a significant difference between men and women (41.6% vs 30.9%, respectively). In the United States, it has been estimated that the average number of years potentially lost in patients with mental illness ranges from 25 to 30, compared with the general population. The main cause of death is coronary heart disease. Most patients on neuroleptic treatment in psychiatric hospitals do not receive control of metabolic risk factors. The evidence indicates that schizophrenic patients are not adequately researched or treated for dyslipidemia (up to 88% of these patients remain untreated) or hypertension (up to 62%). OBJECTIVE: To evaluate cardiovascular risk factors in hospitalized men in a short stay psychiatric unit of the Psychiatric Institute Dr. José Horwitz Barak. Thirty-five male patients were evaluated, of which 37% had MS, and 45.3% were overweight.

Hypoglycemic activity of Capparis ovata desf. var. palaestina zoh. methanol extract

Caper (Capparis ovata Desf. and Capparis spinosa L.) is naturally widespread in Turkey. Traditionally, buds, fruits, seeds and roots of this plant are used as tonic, diuretic, anti-rheumatic, expectorant, antidiabetic, and antifungal. The aim of this study is to evaluate potential hypoglycemic effect of C. ovata var. palaestina extracts in alloxan-induced diabetic mice. For this purpose; diabetic mice were administered with 100, 300, 500 mg/kg (i.p.) doses of methanol extract of bud and fruit. Blood glucose levels were screened 60, 120, 240 and 360 min. after treatment. Furthermore, high resolution mass spectrometry (HRMS) analysis, ABTS and DPPH free radical scavenging activity test, and phenolic and flavonoid compounds analysis of extracts were carried out. The data obtained from in vivo study revealed that fruit-methanol 500 mg/kg (FM3), bud-methanol 300 mg/kg (BM2), bud-methanol 500 mg/kg (BM3) extracts showed significant hypoglycemic activity. All extracts indicated significant antioxidant activity, however bud-methanol (BM) extract demonstrated the most potent antioxidant activity. Moreover high levels of phenolic substances and flavonoids were involved in all extracts, but the highest levels were found in FM extract. HRMS study showed that rutin, quercetin 3-O-glucoside (isoquercitrin) and stachydrine substances had seen in BM extract. The results of this study showed that the C. ovata var. palaestina extracts which, indicate hypoglycemic, antioxidant activities, might provide additional support in diabetes.

Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model

ABSTRACT Diabetes is a metabolic disease caused by abnormal insulin secretion or action. In the present study, the effects of betulinic acid (BA, a triterpene) are evaluated on glucose, α-amylase and plasma insulin levels, insulin resistance and the histopathology of pancreatic islets in streptozotocin-nicotinamide (STZ-NA) diabetic mice. Seventy adult male NMRI mice were randomly divided into seven groups: control, sham, diabetic, diabetic treated with BA (10, 20 and 40 mg/kg) and diabetic treated with metformin (200 mg/kg). Diabetes was induced in mice by intraperitoneal injection of streptozotocin 50 mg/kg after a dose of nicotinamide 120 mg/kg. Two weeks after treatment with BA, blood samples were collected for measuring glucose, α-amylase and insulin levels, and the pancreas was isolated for histopathology evaluation. Diabetes reduced the number and diameter of pancreatic islets, and increased α-amylase and insulin resistance. BA treatment reduced blood glucose, α-amylase and improved insulin sensitivity as well as pancreas histopathology. In addition, BA showed stronger effects on the pancreatic histology and insulin resistance compared to the metformin group

Experimental model of glucocorticoid-induced insulin resistance

ABSTRACT PURPOSE: To evaluate metabolic effects in experimental model of glucocorticoid-induced insulin resistance. METHODS: Twenty Wistar male rats were randomly divided into two groups, which were treated with intraperitoneally injected dexamethasone 1mg/Kg/day for ten days consecutively (Group D; n=10) and placebo (Group C; n=10). The variables analyzed were: from the first to the 10th day - body weight (before and after treatment); food and water daily consumption; on the 10th day - glycemia, insulinemia, HOMA-beta and HOMA-IR. The blood samples for laboratory analysis were obtained by intracardiac puncture. Also on the 10th day liver fragments were taken for analyzing glycogen and fattty. RESULTS: Group D animals compared to group C had: weight reduction (g), (D=226.5±24.7 vs C=295.0±25.4; p=0.001); increased glycemia (mmol/l) (D=19.5±2.1 vs C=14.2±3.1; p=0.0001); diminished insulinemia (mU/l) (D=0.2±0.1 vs C=2.0±0.4; p=0.0001); reduced HOMA-β (D=0.2±0.1 vs C=4.2±1.7; p=0.0002); diminished HOMA-IR (D=0.2±0.1 vs C=1.3±0.4; p=0.0002). Histological examination of the liver showed that 100% of group D and none of group C had moderate fatty. (p=0.2). CONCLUSION: Animals treated with glucocorticoid, in this experimental model, expressed hyperglycemia, hypoinsulinism and decreased peripheral insulin sensitivity.

Environmental Heavy Metal Exposure and Chronic Kidney Disease in the General Population

Lead (Pb), mercury (Hg), and cadmium (Cd) are common heavy metal toxins and cause toxicological renal effects at high levels, but the relevance of low-level environmental exposures in the general population is controversial. A total of 1,797 adults who participated in the KNHANES (a cross-sectional nationally representative survey in Korea) were examined, and 128 of them (7.1%) had chronic kidney disease (CKD). Our study assessed the association between Pb, Hg, Cd exposure, and CKD. Blood Pb and Cd levels were correlated with CKD in univariate logistic regression model. However, these environmental heavy metals were not associated with CKD after adjustment for age, sex, BMI, smoking, hyperlipidemia, hypertension, diabetes, and these metals in multivariate logistic regression models. We stratified the analysis according to hypertension or diabetes. In the adults with hypertension or diabetes, CKD had a significant association with elevated blood Cd after adjustment, but no association was present with blood Pb and Hg. The corresponding odds ratio [OR] of Cd for CKD were 1.52 (95% confidence interval [CI], 1.05-2.19, P=0.026) in adults with hypertension and 1.92 (95% CI, 1.14-3.25, P=0.014) in adults with diabetes. Environmental low level of Pb, Hg, Cd exposure in the general population was not associated with CKD. However, Cd exposure was associated with CKD, especially in adults with hypertension or diabetes. This finding suggests that environmental low Cd exposure may be a contributor to the risk of CKD in adults with hypertension or diabetes.

Riesgo de diabetes mellitus tipo 2 asociado al uso de estatinas: evidencias y posibles mecanismos / Risk of type 2 diabetes mellitus associated with statin therapy: evidence and possible mechanisms

In the last decade, an increased number of new cases of type 2 diabetes mellitus (T2DM) among patients who use statins have been reported. The aim of the present review is to compile the most relevant information about the risk of T2DM associated with the use and dose of different statins, especially based on meta-analysis considering different studies worldwide. To explain this relationship, several studies have reported the effect of statins on insulin resistance in dyslipidemic non-diabetic patients, reporting different findings according to the types of statins. In addition, some reports -based on culture of β pancreatic cells- have evaluated the effect of these drugs in certain cellular events that are essential for insulin secretion. Clearly, further studies in humans are needed -applying more robust tests than those used up to date- in order to define more precisely the potential mechanisms explaining the higher incidence of T2DM among statin users.

Effect of moderate ethanol administration on biochemical indices in streptozotocin-diabetic Wistar rats / Efecto de la administración moderada de etanol sobre los índices bioqumicos en ratas Wistar diabéticas por estreptozotocina

OBJECTIVE: This study was designed to evaluate the effect of moderate ethanol administration on the biochemical indices in streptozotocin (STZ)-diabetic rats. METHODS: Twenty-four male Wistar rats were divided into four groups of six animals each. Groups one and two contained non-diabetic normal rats and normal rats treated with ethanol, respectively. Group three was untreated STZ-diabetic rats and group four was made up of ethanol-treated STZ-diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (35 mg/kg), while ethanol (10%v/v) was given at a dose 2 g/kg thrice per week for three weeks. After the last dose of ethanol and an overnight fasting, rats were sacrificed by cervical dislocation. Blood was collected by syringe from the heart into plain centrifuge tubes. RESULTS: Moderate ethanol administration to STZ-diabetic rats caused a significant (p < 0. 05) increase in relative weight of liver relative to normal. Ethanol intake in STZ-diabetic rats produced an insignificant (p > 0. 05) effect on the levels of fasting blood glucose (FBG) and HbA1c rrelative to the untreated-diabetic group. Moderately, ethanol administration to STZ-diabetic rats produced a marked and significant (p < 0. 05) increase in the levels of serum total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol and the activities of alanine aminotransferase relative to untreated diabetic rats. Ethanol-treated diabetic rats had significantly (p < 0. 05) lower high-density lipoprotein (HDL)-cholesterol levels, while the activities of lactate dehydrogenase and α-amylase were insignificantly (p > 0. 05) affected. There were no significant (p > 0. 05) differences in all the biochemical indices in normal rats relative to ethanol-treated normal rats. CONCLUSIONS: Moderate ethanol administration did not affect FBG and HbA1c , but altered the lipid profile of STZ-diabetic rats. Moderate ethanol intake may further increase the risk of complications in diabetes.

OBJETIVO: Este estudio se diseñó con el propósito de evaluar el efecto del uso de etanol moderado sobre los índices bioquímicos en ratas Wistar diabéticas por estreptozotocina (STZ). MÉTODOS: Veinticuatro ratas Wistar machos fueron divididas en cuatro grupos de seis animales cada uno. Dos de los grupos tenían ratas normales no diabéticas y ratas normales tratadas con etanol, respectivamente. El tercer grupo estaba formado por ratas diabéticas por STZ no tratadas, y el cuarto por ratas diabéticas por STZ tratadas con etanol. La diabetes fue inducida mediante una inyección intraperitoneal de STZ (35 mg/kg), mientras que el etanol (10% v/v) fue administrado en dosis de 2 g/kg tres veces por semana durante tres semanas. Tras la última dosis de etanol y un ayuno de una noche, las ratas fueron sacrificadas mediante dislocación cervical. La sangre fue recogida del corazón con jeringuillas e introducida en tubos para centrífuga sin graduación. RESULTADOS: La administración moderada de etanol a ratas diabéticas por STZ, causó un aumento significativo (p < 0.05) en el peso relativo del hígado con relación al normal. La ingestión de etanol en ratas diabéticas por STZ tuvo un efecto insignificante (p > 0.05) en los niveles de glucosa en sangre en ayuno (GSA) y HbA1c en relación con grupos diabéticos no tratados. En medida moderada, la administración de etanol a ratas diabéticas por STZ produjo un aumento marcado y significativo (p < 0.05) en los niveles de colesterol total en suero, triglicéridos, el colesterol asociado con las lipoproteínas de baja densidad, o colesterol LDL, y la actividad de la aminotransferasa alanina en relación con las ratas diabéticas no tratadas. Las ratas diabéticas tratadas con etanol tuvieron niveles significativamente disminuidos de colesterol asociado con las lipoproteínas de alta densidad, o colesterol HDL, en tanto que la actividad del lactato deshidrogenasa y la α-amilasa no fue afectada significativamente (p > 0.05). No hubo diferencias significativas (p > 0.05) en todos los índices bioquímicos en las ratas normales con respecto a las ratas normales tratadas con etanol. CONCLUSIONES: El suministro moderado de etanol no afectó el GSA ni el HbA1c , pero alteró el perfil lípido de las ratas diabéticas por STZ. La ingestión moderada de etanol puede aumentar a un más el riesgo de las complicaciones de la diabetes.

Influência do exercício físico sobre a remodelaçao cardíaca e a atividade oxidativa em ratos diabético / Influence of physical exercise on cardiac remodeling and oxidative stress in diabetic rats

O Diabetes mellitus (DM) é um distúrbio caracterizado por resposta secretória inadequada de insulina, que se manifesta pela utilização inapropriada de glicose pelos tecidos com consequente hiperglicemia. Além das alterações cardíacas e vasculares, o DM pode acarretar doença miocárdica não aterogênica, denominada miocardiopatia diabética. Um dos principais mecanismos desencadeadores de alterações miocárdicas é o aumento na produção de espécies reativas de oxigênio (ERO). Na prevenção das complicações crônicas do DM, o exercício físico (EF) regular tem papel fundamental. Em estudos experimentais, ratos com DM induzido por estreptozotocina (STZ) e submetidos à EF têm apresentado melhora na homeostase miocárdica de glicose e da função cardíaca. O objetivo do presente trabalho foi avaliar a influência do EF sobre remodelação cardíaca, variáveis bioquímicas e atividade oxidativa em ratos diabéticos. Foram utilizados ratos Wistar divididos em quatro grupos: 1) controle sedentário (CS, n=14); 2) controle treinado (CT, n=13); 3) diabético sedentário (DS, n=19); e 4) diabético treinado (DT, n=18). O diabetes foi induzido por STZ e o protocolo de EF foi aplicado durante nove semanas. A avaliação estrutural e funcional in vivo do ventrículo esquerdo (VE) foi realizada por ecocardiograma. O estudo funcional in vitro foi realizado pela avaliação do músculo papilar do VE. Para análise de variáveis anatômicas foram medidos os pesos úmidos e secos do VE, ventrículo direito, átrios e amostras de fígado e pulmão. Amostras do VE foram utilizadas para medidas do diâmetro dos miócitos, do colágeno miocárdico e da concentração de hidroxiprolina...

Diabetes mellitus (DM) is a disorder characterized by inadequate insulin secretory response, manifested by inappropriate use of glucose by tissues with consequent hyperglycemia. In addition to cardiac and vascular changes, DM can cause a non-atherogenic myocardial disease, named diabetic cardiomyopathy. One of the main mechanisms responsible for myocardial changes is the increased production of reactive oxygen species (ROS). Physical exercise (PE) plays an important role in preventing diabetes chronic complications. In experimental studies, rats with streptozotocin (STZ)-induced diabetes subjected to PE have shown improved myocardial glucose homeostasis and cardiac function. The aim of this study was to evaluate the influence of PE on cardiac remodeling, biochemical variables, and oxidative stress in diabetic rats. Wistar rats were divided into four groups: 1) sedentary control (SC, n=14); 2) trained control (TC, n=13); 3) sedentary diabetic (SD, n=19); and 4) trained diabetic (TD, n=18). Diabetes was induced by STZ and PE protocol was applied for nine weeks. The in vivo cardiac structures and left ventricular (LV) function were assessed by echocardiography. The in vitro myocardial function was evaluated in LV papillary muscle preparation. For anatomical variables analysis, wet and dry weights of LV, right ventricle, atria, and samples of liver and lung were measured. LV samples were used for myocytes diameter, myocardial collagen and hydroxyproline measurements. The myocardial oxidative stress was assessed by measuring lipid hydroperoxide (LOOH), superoxide dismutase (SOD), glutathione peroxidase (GPH-Px), and catalase...

Efeito do composto "mais vida" na ativação de macrófagos de ratos diabéticos / Effects of "mais vida", a commercial natural mix, on the activation of macrophages from diabetic rats

O objetivo deste trabalho foi avaliar a atividade funcional de macrófagos de ratos diabéticos, através da liberação do ânion superóxido, na presença do composto "mais vida". Os animais foram divididos em dois grupos, controle (N=20) e diabético (N=20). Avaliou-se a glicemia, massa corpórea e a liberação de superóxido pelos macrófagos de baço de ratos. O composto "mais vida" foi obtido através da mistura de extratos de sete plantas, sendo Orbignia martiana Rodr., Tabebuia avellanedae L.G., Arctium lappa L., Rosa centifolia L., Maytenus ilicifolia Mart., Vernonia condensata Baker e Thuja occidentalis L. Observou-se que glicemia foi maior no grupo diabético. A liberação espontânea do ânion superóxido pelos macrófagos foi menor no grupo diabético. O composto "mais vida", independente dos níveis glicêmicos, aumentou a liberação de superóxido dos macrófagos. Quando as células foram estimuladas pelos extratos vegetais isolados, também houve aumento na liberação do ânion superóxido pelos macrófagos em ambos os grupos. As maiores liberações de superóxido ocorreram quando os macrófagos foram estimulados pela Thuja occidentalis L., Rosa centifolia L., Tabebuia avellanedae L.G. e Maytenus ilicifolia Mart. Estes dados sugerem que a ativação de macrófagos pelo composto "mais vida" pode representar um mecanismo alternativo de defesa para infecções em indivíduos diabéticos.

This study investigated the effects of "mais vida", a commercial natural mix, on macrophages functional activity as evaluated by the superoxide release in diabetic rats. The animals were divided into two groups, control (N = 20) and diabetic (N = 20). This was achieved by determining blood glucose weight and the superoxide released by spleen macrophages. The "mais vida" mix was obtained by the combination of extracts from seven medicinal species, which were: Orbignia martiana Rodr., Tabebuia avellanedae L.G., Arctium lappa L., Rosa centifolia L., Maytenus ilicifolia Mart., Vernonia condensata Baker and Thuja occidentalis L. Blood glucose levels were significantly higher (p<0.05) in the diabetic group, as compared to blood glucose levels in the control group. Superoxide levels in macrophages isolated from normoglycemic rats were higher than those obtained from diabetic animals. The "mais vida" mix, independently of glycemic status, increased significantly the superoxide release in the macrophages. Each extract by itself also increased the superoxide release by phagocytes in the macrophages in both groups. The largest superoxide release occurred when the phagocytes were stimulated by Thuja occidentalis L., Rosa centifolia L., Tabebuia avellanedae L.G. and Maytenus ilicifolia Mart. In addition, the activation of macrophages by the "mais vida" mix may represent an additional protection mechanism for diabetic individuals against infections.

Incidence and Risk Factors of Steroid-induced Diabetes in Patients with Respiratory Disease

Glucocorticoids are effective for treating several respiratory diseases. However, they can cause hyperglycemia. This study determined the incidence and risk factors of steroidinduced diabetes mellitus (S-DM) in patients treated with glucocorticoid for respiratory diseases. A retrospective study examined patients with respiratory diseases treated with a prednisolone-equivalent glucocorticoid dose exceeding 20 mg/day for at least 4 weeks between January 2003 and December 2008. Patients whose initial random glucose level exceeded 200 mg/dL or who had pre-existing diabetes were excluded. S-DM was defined as a fasting glucose concentration exceeding 126 mg/dL or a random glucose concentration exceeding 200 mg/dL at least twice after beginning steroid treatment. A total of 231 patients with respiratory diseases met the inclusion criteria. Their median age was 55 yr, and 139 were female. The median cumulative prednisolone-equivalent glucocorticoid dose was 4,965 mg, and the median duration of steroid treatment was 193 days. S-DM was diagnosed in 34 (14.7%) of 231 patients. Multivariate logistic regression identified older age (odds ratio 1.05, 95% confidence interval 1.02-1.09) as a risk factor for S-DM. S-DM is frequent among patients with respiratory diseases treated with glucocorticoid. Clinicians should be aware of the possibility of S-DM, especially among elderly patients.

Side effects of cyclosporine-A treatment in rats: gingival overgrowth and early hyperglycemia

Gingival overgrowth is an adverse side effect of cyclosporine A (CsA) in the treatment of transplanted patients. The purpose of this study was to evaluate the effects of CsA on new-onset diabetes mellitus and gingival overgrowth in rats, by measuring collagen, nitric oxide and microvascular permeability. Blood glucose level, collagen, nitric oxide level and vascular permeability were determined. Blood glucose level increased significantly from 6.5 +/- 0.9 for the control group to 15+/- 1.2, 17 +/- 1.2 and 21.6+/- 1.6 mM/L at 1, 4 or 8 weeks of CsA treatment, respectively. Collagen (ug HO Proline/mg p) increased significantly from 2.5+/- 0.5 for the control group to 4.2+/- 0.8, 5.9+/- 0.6 and 7.3 +/- 0.8 at 1, 4 or 8 weeks of CsA treatment, respectively. Vascular permeability was 10.3+/- 1.2 for the control group and 15+/-1; 17.2 +/- 1.3, and 22.1+/- 2.1 ug EB/g T; at 1, 4 or 8 weeks of CsA treatment, respectively. Nitric oxide level was 3.5 +/- .9 umol/mg P for the control group and 4+/- 0.2, 8.2+/- 0.9 and 11+/-1 for 1, 2 or 8 weeks of CsA treatment, respectively. These findings appear to indicate that the development of significant gingival changes induced by CsA is related to new-onset of diabetes mellitus during the immunosuppressive treatment.

La hiperplasia gingival es un efecto colateral adverso del tratamiento con ciclosporina A (CsA) en pacientes transplantados. El proposito de este estudio fue evaluar el efecto de CsA en el inicio de diabetes mellitus, la concentracion de colageno, y de oxido nitrico y la permeabilidad capilar gingival. El nivel de glucosa en sangre de los animales controles fue: 6.5+/- 0.9, en tanto que los tratados con CsA fue: 15+/-1.2; 17+/- 1.1 y 21.6+/- 1.6 mM/L a las 1, 4 y 8 semanas respectivamente. El colageno (ug OH prolina/mg p) mostro un aumento significativo en los animales tratados con CsA respecto de los controles: 2.5+/- 0.5; 4.2+/- 0.8; 5.9+/- 0.6; 7.3+/- 0.8 respectivamente a las 1,4 y 8 semanas de tratamiento. Los valores de permeabilidad capilar (ug AE/ g T) fueron: en los animales control 10.3+./- 1.2; en los animales tratados con CsA, a las 1, 4 y 8 semanas 15+/- 1.0; 17.2 +/- 1.3 y 22.1+/- 2.1 respectivamente. Los valores de oxido nitrico (umol/mg p) en los animales control: 3.5+/-0.9; y en los animales tratados con CsA 4+/- 0.2; 8.2+/- 0.9 y 11.2 +/- 1.0 respectivamente. Estos resultados parecen indicar que el desarrollo de los significativos cambios gingivales inducidos por la administracion de CsA esta relacionado con la hiperglucemia temprana que se asocia al tratamiento con inmunosupresores.

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats / Relação entre o estresse oxidativo ea osteopenia diabética em ratos pré-menopausa

The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acid-reactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes was induced by alloxan and confirmed by glycemia >250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to control animals. However, the antioxidant parameter measured by GSH content, was significantly lower (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness, and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significantly lower (p<0.05) in the diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats.

A relação entre peroxidação lipídica, defesa antioxidante e osteopenia diabética permanece obscura. Este estudo avaliou a associação entre índice de peroxidação lipídica, parâmetro de defesa antioxidante e metabolismo ósseo em um modelo diabético pré-menopausa através de medidas como a concentração de substâncias reativas ao ácido tiobarbitúrico (SRAT) e conteúdo de glutationa reduzida (GSH) no homogenato cerebral, análises histomorfométricas, teste biomecânico e densidade mineral óssea (DMO). Ratos Wistar fêmeas com ciclo estral regular foram distribuídos em dois grupos: Grupo 1 - ratas controle (n = 15) e Grupo 2 - ratas diabéticas (n = 15). O diabetes foi induzido pela aloxana e confirmado pela glicemia >250 mg/dL. O índice de peroxidação lipídica, medido pela concentração de SRAT, demonstrou um aumento significativo (p<0.05) nos animais diabéticos, em relação aos animais controle. Entretanto, o parâmetro de defesa antioxidante, mensurado pelo conteúdo de GSH, foi reduzido significativamente (p<0.05) nos animais diabéticos. As análises histomorfométricas mostraram um aumento significativo (p<0.05) da separação trabecular do fêmur, associado à diminuição significativa da espessura trabecular (p<0.05) e volume ósseo trabecular reduzido nas ratas diabéticas. Além disso, o teste biomecânico, medido pela força máxima, e valores de DMO foram reduzidos significativamente (p<0.05) no grupo diabético. Dessa maneira, nossos resultados demonstraram que a peroxidação lipídica aumentada e defesa antioxidante modificada podem estar relacionadas ao desenvolvimento do estresse oxidativo e osteopenia diabética em ratas pré-menopausadas.

Polyherbal preparation for anti-diabetic activity: A screening study.

Objective: To screen the Polyherbal preparation for anti-diabetic activity in rats. Materials and Methods: The blood glucose lowering activity of the Polyherbal preparation-I (1:1:1 of Wheat germ oil, Coriandrum sativum and Aloe vera) was studied in normal rats after oral administration at doses of 1.0 and 2.0 ml/kg and Polyherbal preparation-I, II (Wheat germ oil, fresh juice of C. sativum and Aloe vera in the ratio of 2:2:1), and III (Wheat germ oil, fresh juice of C. sativum and Aloe vera in the ratio of 1:2:2) on alloxan-induced diabetic rats, after oral administration at doses of 1.0 and 2.0 ml/kg. Blood samples were collected from the tail vein method at 0, 0.5, 1, 2, 4, 8, 12, and 24 h in normal rats and in diabetic rats at 0, 1, 3, 7, 15, and 30 days. Blood plasma glucose was estimated by the GOD/POD (glucose oxidase and peroxidase) method. The data was compared statistically using the one-way ANOVA method followed by the Dunnett multiple component test. Statistical significance was set at P<0.05. Results: The Polyherbal preparation-I produced significant (P<0.05) reduction in the blood glucose level of normal rats and Polyherbal preparation-I, II, and III produced significant (P<0.01) reduction in the blood glucose level of diabetic rats during 30 days study and compared with that of control and Glibenclamide. Conclusion: The Polyherbal preparation-I showed a significant glucose lowering effect in normal rats and Polyherbal preparation-I, II, and III in diabetic rats. This preparation is going to be promising anti-diabetic preparation for masses; however, it requires further extensive studies in human beings.