Oral lactate intensifies insulin toxicity during severe insulin-induced hypoglycemia in mice

ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p < 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p < 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.

Evaluation of the impact of orally administered carbohydrates on postprandial blood glucose levels in different pre-clinical models

ABSTRACT We developed a pre-clinical model in which to evaluate the impact of orally administered carbohydrates on postprandial blood glucose levels. For this purpose, we compared the effects of different carbohydrates with well-established glycemic indexes. We orally administered (gavage) increasing amounts (0.2, 0.4, 0.6, 0.8, and 1.0 g/kg) of sucrose and lactose to rats which had been fasted for 6 h or 15 h, respectively. In part of the experiments we administered frutose (gavagem). Three different models were compared for measuring postprandial blood glucose levels: a) evaluation of interstitial glucose concentrations by using a real time continuous glucose monitoring system; b) evaluation of glucose levels in blood obtained from the rat tail; c) evaluation of serum glucose levels in blood collected after decapitation. Our results showed that blood obtained from the tails of 15-h fasted rats was the best model in which to evaluate the effect of carbohydrates on postprandial blood glucose levels.

Glutamine dipeptide supplementation improves clinical responses in patients with diabetic foot syndrome

ABSTRACT The effect of glutamine dipeptide (GDP) supplementation in patients with diabetic foot syndrome was evaluated. A total of 22 patients took part in the study. GDP was supplied in 10 g sachets, and was dissolved in water immediately before use, with ingestion once a day, after lunch or after dinner (20 g/day) over a period of 30 days. Quantification of foot insensitive areas, oxidative stress, blood cytokines, and biochemical, hematological and toxicological parameters was performed before and after GDP supplementation. We observed an increase in blood levels of interferon-α (P=0.023), interferon-γ (P=0.038), interleukin-4 (P=0.003), interleukin-6 (P=0.0025), interleukin-7 (P=0.028), interleukin-12 p40 (P=0.017), interleukin-13 (P=0.001), leukocytes (P=0.037), eosinophils (P=0.049), and typical lymphocytes (P<0.001) due to GDP administration. In addition, we observed a reduced number (P=0.048) of insensitive areas on the foot, and reduction (P=0.047) of fasting hyperglycemia. Patients also showed increased blood high density lipoprotein (P<0.01) and protein thiol groups (P=0.004). These favorable results were associated with the absence of renal and hepatic toxicity. These results are of clinical relevance, since supplementation with GDP over 30 days improved clinical responses in patients with diabetic foot syndrome.

Investigation of the Acute Effects of Dry Extract of Glycine Max on Postprandial Glycemia in Rats

The acute effects of Glycine max (GM) on post prandial glycemia (PPG) in male Wistar rats were investigated. All substances were orally administered by gavage in overnight fasted animals. The elevation of PPG promoted by starch (1g/kg) was prevented by GM (2.5 mg/kg, 5.0 mg/kg, 7.5 mg/kg, 10.0 mg/kg, and 100.0 mg/kg). In conclusion GM showed potential antidiabetic effect.

Oxidative stress parameters as biomarkers of risk factor for diabetic foot among the patients with type 2 diabetes

The aim of this study was to determine whether plasma levels of carbonylated proteins, total antioxidant capacity (TAC) and reduced protein thiols could be suitable biomarkers of risk factors for diabetic foot. Individuals with type 2 diabetes with normal protective sensation (normal foot group) vs. loss of protective sensation and/or signs of peripheral arterial disease and/or foot deformities and/or history of ulcers and/or neuropathic fractures and/or amputation (diabetic foot group) were compared. The diabetic foot group showed higher carbonylated protein levels (P = 0.0457) and lower levels of TAC (P = 0.0148) and reduced protein thiols (P = 0.0088), compared with the normal foot group. In general, several other parameters of risk of diabetes complication (blood levels of glycated hemoglobin, glucose and cholesterol, duration of diabetes, body mass index and waist circumference) showed a tendency of higher values in the diabetic foot group. The results suggest that the plasma levels of carbonylated proteins, TAC and reduced protein thiols could furnish information about the risk of diabetic foot, considering that the changes in these biomarkers were associated with the loss of sensitivity and foot ulcerations.

Pharmaceutical consultation as a tool to improve health outcomes for patients with type 2 diabetes

This study develops and evaluates a pharmaceutical consultation program (PCP) to improve treatment for Type 2 diabetes patients (T2DP) and reduce risk factors for diabetic complications with possible application in other chronic diseases. We recruited T2DP receiving conventional medical treatment but with fasting glycemia >140mg/dl and/or glycated hemoglobin >7%. The PCP includes strategies obtained from Dader's method, the PWDT (Pharmacist's Workup of Drug Therapy method) model of pharmaceutical care, the SOAP (Subjective data, Objective data, Assessment, and Plan of care) method, and concepts based on a nursing care model. The PCP evaluated lifestyle, pharmacotherapy and monitoring it using laboratory tests, vital signs, and anthropometry. These procedures were repeated every 4 months for 1 year. Data obtained in each consultation were used to provide patient education focusing on healthy lifestyles and medications. Fifty patients completed the PCP. There were reductions in glycemia (P<0.0001), glycated hemoglobin (P=0.0022), cholesterolemia (P=0.0072), triacylglycerolemia (P=0.0204) and blood pressure (P<0.0001). Increased concordance with drug treatment and correction of drug-related problems contributed to improved treatment. We can therefore conclude that our PCP was suitable for improving health outcomes in T2DP by reducing risk factors for diabetic complications.

Neste estudo, desenvolvemos e avaliamos um programa de consulta farmacêutica (PCF) visando melhorar o tratamento de pacientes diabéticos tipo 2 (PDT2) e reduzir os fatores de risco de complicações diabéticas com possibilidade de aplicação em outras doenças crônicas. Para alcançar este propósito, PDT2 recebendo tratamento médico convencional, apresentando glicemia de jejum > 140 mg/dl e/ou hemoglobina glicada >7% foram selecionados. O PCF inclui estratégias obtidas a partir do método de Dader, do modelo de cuidados farmacêuticos PWDT (Pharmacist's Workup of Drug Therapy method), do método SOAP (Subjective data, Objective data, Assessment, and Plan of care) e conceitos baseados em um modelo de cuidados em enfermagem. O PCF avaliou o estilo de vida, farmacoterapia e seu monitoramento através de exames laboratoriais, sinais vitais e antropometria. Estes procedimentos foram repetidos a cada 4 meses durante 1 ano. Os dados obtidos em cada consulta possibilitaram oferecer educação focada no estilo de vida e uso de medicamentos. Para os 50 pacientes que concluiram o PCF houve redução da glicemia (P < 0.0001), hemoglobina glicada (P = 0.0022), colesterolemia (P = 0.0072), triacilgliceridemia (P= 0.0204) e pressão arterial (P < 0.0001). O aumento da concordância e a correção dos problemas relacionados a medicamentos contribuíram para melhoria do tratamento. Assim, podemos concluir que o PCF foi adequado para melhorar a saúde de PDT2 ao reduzir fatores de risco de complicações diabéticas.

Infliximab treatment prevents hyperglycemia and the intensification of hepatic gluconeogenesis in an animal model of high fat diet-induced liver glucose overproduction

The effect of infliximab on gluconeogenesis in an animal model of diet-induced liver glucose overproduction was investigated. The mice were treated with standard diet (SD group) or high fat diet (HFD group). HFD group were randomly divided and treated either with saline (100 µl/dose, ip, twice a day) or infliximab (10 µg in 100 µl saline per dose, ip, twice a day, i.e., 0.5 mg/kg per day). SD group also received saline. The treatment with infliximab or saline started on the first day of the introduction of the HFD and was maintained during two weeks. After this period, the mice were fasted (15 h) and anesthetized. After laparotomy, blood was collected for glucose determination followed by liver perfusion in which L-alanine (5 mM) was used as gluconeogenic substrate. HFD group treated with saline showed higher (p < 0.05) liver glucose production from L-alanine and fasting hyperglycemia. However, these metabolic changes were prevented by infliximab treatment. Therefore, this study suggested that infliximab could prevent the glucose overproduction and hyperglycemia related with glucose intolerance and type 2 diabetes.

Effects of oral L-carnitine and DL-carnitine supplementation on alloxan-diabetic rats

The effect of oral L-carnitine (LC) or DL-carnitine (DLC) supplementation during one or four weeks (200 or 400 mg.kg-1.day-1) in diabetic rats was investigated. After the supplementation period, the blood was collected for the evaluation of total (TC) and free L-carnitine (FC), glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triacylglycerol. Tissues were collected for the determination of TC and FC concentrations. The carnitine supplementation did not change levels of glucose, total cholesterol, HDL-C and LDL-C in the blood. Diabetic rats showed hypertriacylglycerolemia and decreased blood and tissue levels of FC and TC. Normalization of the blood triacylglycerol and increased blood and tissue levels of FC and TC were observed with the LC or DLC supplementation. However, the hyperglycemia remained unchanged. Thus, the reduction of blood triacylglycerol obtained with carnitine supplementation in the diabetic rats did not depend on an amelioration in the glycemia and was mediated partly at least by an increment of serum and tissue concentrations of FC and TC.

Perfil de paciettes diabéticos tipo 2 usuários e insulina disponibilizada pelaa secretaria municipal de saúde de maringá, pr, Brasil / Profile of ype-22 diabetes nsulin-user patients provided by the municipal health department of maringá, pr, Braiil

Investigou-se o perfil de 80 pacientes diabéticos tipo 2 (PDT2), constituído de homens (45%) e mulheres (55%) com média de idade de 62,8 ± 8,5 anos, usuários de insulina NPH fornecida pela Secretaria Municipal de Saúde de Maringá, PR, Brasil. Obteve-se informações por meio de um questionário e pela medida do índice de massa corporal (IMC). Verificou-se que: 1) 72% apresentavam obesidade ou sobrepeso; 2) 67,5% utilizavam antihipertensivos dos quais os inibidores da enzima conversora (ECA) e os bloqueadores dos receptores de angiotensina (BRA) representavam 84%; 3) O IMC foi similar em PDT2 usuários ou não de agentes antihipertensivos; 4) 46% além da insulina utilizavam antidiabéticos orais; 5) a dose de insulina (unidades. kg-1. dia-1) foi inferior (p< 0,05) em usuários de antihipertensivos, sugerindo existir uma correlação entre terapia antihipertensiva e o uso de menores doses de insulina. Este efeito ocorreria de maneira independente do IMC ou da simultânea a terapia com antidiabéticos orais.

The profile of 80 type-2 diabetic patients (T2DP), male (45%) and female (55%), with mean age 62.8 ± 8.5 years old, receiving NPH insulin from the municipal health department of Maringa city, PR, Brazil, was investigated. Information about each volunteer was obtained using a questionnaire and an evaluation of body mass index (BMI). It was verified that: 1) 72% showed obesity or overweight; 2) 67.5% used antihypertensive drugs in which angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) were the main antihypertensive drugs (84%); 3) The BMI was similar in the T2DP with hypertension or without hypertension; 4) 46%, in addition to insulin therapy, also used antidiabetic drugs; 5) The daily dose of insulin (units. kg-1. day-1) in the group which received antihypertensive therapy was lower (p< 0.05), suggesting the presence of a relationship between antihypertensive treatment and lower doses of insulin. In addition, this relationship would occur independently of the influence of BMI or the simultaneous treatment with oral antidiabetic drugs.

Comparative performance of lab tests and blood testing device to monitor glucose, total cholesterol and triacylglycerol in type 2 diabetic patients / Desempenho comparativo de testes de laboratório e de dispositivos de teste de sangue para monitorar glicose, colesterol total e triglicérides em pacientes diabéticos tipo 2

The performance of lab tests (LT) and blood testing devices (BTD) to monitor glycemia vs. glycated hemoglobin A1c (A1c) were compared. In addition, the performance of blood glucose, total cholesterol (TC) and triacylglycerol measured by LT and BDT were compared. All parameters were measured based on the same blood samples from overnight fasted type 2 diabetic patients (T2DP). Linear regression analysis was used for all comparisons. The results showed that A1c correlated better with LT-glucose (r = 0.58) than BTD-glucose (r = 0.42). Moreover, LT vs. BTD showed r values of 0.90, 0.82 and 0.92 for glucose, TC and triacylglycerol, respectively. It was concluded that the performance of LT-glucose was better than BDT-glucose. Moreover, since triacylycerol and TC measured by BTD correlated better with LT compared to BDT-glucose vs. LT-glucose, the inclusion of BTD-TC and BTD-triacylglycerol for detecting and monitoring hyperlipidemia in T2DP should be considered.

Comparou-se a performance de avaliação da glicemia através de dosagens laboratoriais (DL) ou dispositivo para teste de sangue capilar (DTSC) vs. hemoglobina glicada A1c (A1c). Comparou-se ainda a performance de avaliação da glicemia, colesterol total (CT) e triacilglicerol (DL vs. DTSC). Avaliou-se estes parametros a partir das mesmas amostras de sangue coletadas em pacientes diabéticos tipo 2 (PDT2) em jejum noturno, sendo as comparações realizadas através de análise de regressão linear. A A1c correlacionou-se melhor com a glicemia-DL (r = 0,58) em relação a glicemia-DTSC (r = 0,42). Comparou-se DL vs. DTSC obtendo se r = 0,90, 0,82 e 0,92 para glicemia, CT e triacilglicerol, respectivamente. Concluiu-se que houve melhor performance da glicose-DL em relação a glicose-DTSC. Além disso, considerando que o triacilglicerol e TC avaliado através de DTSC correlaciona-se melhor com DL em comparação a DTSC-glicose vs. DL-glicose, a inclusão de DTSC-TC e DTSC-triacilglicerol visando detectar e monitorar hyperlipidemia in PDT2 deve ser considerada.

Blood glucose regulation during fasting in rats under food restriction since birth

The effect of severe food restriction since birth on regulation of fasting glycemia in male Wistar rats was investigated. The control group (CG) had free supply of chow, while the restriction group (RG) received 50 percent of the amount ingested by the CG. The experiments were done in adult (60 days) overnight fasted rats in which glycemia, liver free glucose levels and hepatic glycogen concentration were measured. In part of the experiments in situ liver perfusion was done. The results showed that livers from the RG had higher glycogenolysis rates but lower gluconeogenesis rates from L-alanine (10 mM). Since RG showed maintained glycemia during fasting, it could be concluded that livers from RG produced glucose preferentially from glycogenolysis in detriment of gluconeogenesis. These findings demonstrated that in spite of severe caloric restriction, the metabolic adaptations of the liver did exist to assure the maintenance of blood glucose for brain supply during fasting.

Pé diabético: perfil metabólico e socioeconômico de pacientes atendidos pelo laboratório de ensino e pesquisa da Universidade Estadual De Maringá / Diabetic foot: socioeconomic and metabolic profile of patients treated in the laboratory of educationand research in the University of Maringá

O pé diabético é uma das complicações crônicas mais devastadoras em pacientes diabéticos, gerando alto impacto social e econômico, além de diminuir a qualidade de vida. Neste estudo exploratório-descritivo foram avaliados 39 pacientes diabéticos tipo 2 (PDT2), atendidos pelo Laboratório de Ensino e Pesquisa da Universidade Estadual de Maringá (agosto/2009 e abril/2010). Os pacientes foram submetidos a uma entrevista para obtenção de informações sobre o perfil socioeconômico e a avaliação laboratorial da glicemia e lipidemia (perfil metabólico). Os resultados revelaram: prevalência do gênero feminino, média de idade de 60,1 ± 9,5 anos, 71,8% tinham Ensino Fundamental incompleto, 61,5% eram casados, 74,3% eram sedentários, o tempo de doença foi de 9,2 ± 7,3 anos, 53,8% desconheciam os cuidados e complicações do pé e 70,6% estavam com a hemoglobina glicada alterada. Conclui-se que a baixa escolaridade e pouco conhecimento em relação à doença comprometem o processo de autocuidado, aumentando as chances do aparecimento das complicações crônicas.

Diabetic foot is one of the most devastating chronic complications of diabetic patients, causing high social and economic impact and decreased quality of life. In this exploratory-descriptive study were evaluated 39 patients with type 2 diabetes (T2DP) attended by the Clinical Analysis Teaching and Research Laboratory of the State University of Maringá (August/2009 and April/2010). Patients underwent an interview to obtain information on the socioeconomic profile and laboratory evaluation of blood glucose and lipids (metabolic profiling) The results revealed prevalence of female, mean age was 60.1 ± 9.5 years, 71.8% had incomplete primary education, 61.5% were married, 74.3% were sedentary, disease duration was 9.2 ± 7.3 years, 53.8% were unaware of the care and foot complications and 70.6% had glycated hemoglobin altered. We conclude that low education and little knowledge about the disease decreased the process of self-care, increasing the chances of development of chronic complications.

Hipoglicemia induzida por insulina como fator desencadeador de déficit cognitivo em crianças portadoras de diabetes mellitus tipo 1 / Insulin-induced hypoglycemia as a triggering factor of cognitive impairment in children with type 1 diabetes mellitus

O Diabetes mellitus tipo 1 (DM1) surge mais frequentemente em crianças e caracteriza-se pela deficiência total de insulina, o que torna a insulinoterapia necessária. Durante a insulinoterapia a hipoglicemia é uma reação adversa comum e poderia acarretar dano cerebral associado ao déficit cognitivo (DC). Porém, o assunto é controverso, já que existem estudos nos quais a associação DC e hipoglicemia induzida por insulina (HII) não foi comprovada. Desse modo, com o objetivo de esclarecer esta questão utilizou-se o PubMed (www.ncbi.nlm.nih.gov/pubmed), um banco de dados que possui mais de 20 milhões de trabalhos científicos disponíveis on line. Utilizou-se as palavras-chave: ?hypoglycemia and cognitive function and children? ou ?diabetes and cognitive deficit and children?. Selecionou-se publicações do período entre 1960 e 2010. Excluiu-se estudos em animais experimentais, investigações restrita a adultos e estudos nos quais a avaliação do DC ocorreu durante o episódio de HII. Assim, investigações que associaram DC com HII e dano cerebral (estrutural e funcional) foram analisados. Desta maneira, após uma cuidadosa avaliação dos estudos selecionados concluiu-se que existe uma forte correlação entre dano cerebral causado pela hipoglicemia e DC envolvendo múltiplos fatores: duração, intensidade e frequência dos episódios de HII, precocidade no surgimento do DM e duração da doença. Conclui-se que é relevante o contínuo e intensivo cuidado e educação da criança portadora de DM1 submetida à insulinoterapia, com vistas a reduzir a possibilidade do dano cerebral e DC.

Type 1 diabetes (T1D) starts frequently in children and and it is characterized by total insulin deficiency and for this reason insulin therapy is necessary. During insulin therapy, hypoglycemia is a very common side effect and could bring brain damage associated with cognitive deficit (CD). However, there are controversies considering that there are studies in which the association of insulin induced hypoglycemia (IIH) and CD were not comproved. Therefore, to clarify this question it was used PubMed (www.ncbi.nlm.nih.gov/pubmed), with more than 20 millions of on line available publications. The key words ?hypoglycemia and cognitive function and children? or ?diabetes and cognitive deficit and children? were employed. The publications between 1960 and 2010 were selected. Studies from experimental animals, investigations restrict to adult people and studies in which the evaluation of CD occurred during the episode of IIH were excluded. Therefore, investigations that associated CD with IIH and brain damage (structural and functional) were analyzed. Consequently, after a care full evaluation from selected studies it was concluded that there is a strong relationship between brain damage caused by hypoglycemia and CD involving several factors: duration, intensity and frequency of IIH episodes, precocity of T1D and duration of the disease. It was concluded that the intensive care and education of children with T1D submitted to insulinoterapy is very important to reduce the possibility of brain damage and CD.

Aspectos clínicos e farmacológicos do emprego do exenatide na terapêutica do diabetes mellitus tipo 2 / Clinical and pharmacological aspects of the use of exenatide for the treatment of type II diabetes mellitus

O papel do exenatide no tratamento do diabetes mellitus tipo 2 tem sido foco de intensa pesquisa. Este fármaco age como um agonista do glucagon-like peptide 1 (GLP-1), interagindo com o receptor GLP-1, estimulando a secreção de insulina pelas células ß. O exenatide também tem se mostrado altamente eficaz na redução da secreção do glucagon, esvaziamento gástrico e ingestão alimentar. Esta revisão apresenta os principais aspectos clínicos e farmacológicos do uso do exenatide em pacientes diabéticos tipo 2. Assim, concluiu-se que o exenatide representa um novo fármaco antidiabético, uma vez que estimula a secreção de insulina por um mecanismo diferente do apresentado pelas sulfoniluréias e metiglinidas (bloqueadores de canais de potássio). Além disso, enquanto todos secretagogos de insulina (incluindo os inibidores da dipepdil peptidase-4) promovem ganho de peso, o exenatide, ao contrário, favorece a perda de peso, por sua ação inibidora do apetite.

The role of exenatide in the treatment of type II Diabetes Mellitus has become the focus of intense research. This drug works as a glucagon-like peptide 1 (GLP-1) agonist as it interacts with GLP-1 receptor through the stimulation of the insulin secretion in ß cells. The exenatide also has presented to be highly effective to reduce glucagon secretion, gastric emptiness, and food intake. This review shows the major clinical and pharmacological aspects of using exenatide in type II Diabetes Mellitus patients. Thus, it was concluded that exenatide is a new antidiabetic drug; since exenatide stimulates insulin secretion by a different mechanism of sulfonylureas and metiglinides (potassium channels blockers). Moreover, in spite of the fact that all insulin secretagogues (including the dipeptidyl peptidase-4 inhibitors) in contrast exenatide promotes weight gain mediated by its inhibitory appetite action.

Aspectos clínicos e farmacológicos da associação sinvastatina-ezetimiba / Clinical and pharmacological aspects of the combination of simvastatin and ezetimibe

O objetivo do tratamento de pacientes hipercolesterolemicos deve ser o de alcançar concentração sangüínea de colesterol e LDL próximos ao de pacientes normais. Uma série de estratégias terapêuticas tem sido usada para obter um adequado controle da hipercolesterolemia. Dentre elas, destaca-se o emprego da sinvastatina que inibe a síntese hepática de colesterol e o ezetimiba que inibe a absorção intestinal de colesterol. A ausência de um adequado controle da colesterolemia com sinvastatina ou ezetimiba isoladamente abre a possibilidade de associação destes fármacos. Assim, a associação de sinvastatina e ezetimiba reduz com mais efi ciência a concentração sangüínea de colesterol e LDL do que o emprego separado de cada um destes fármacos. Portanto, podemos concluir que esta associação constitui a melhor opção terapêutica para pacientes nos quais a estatina isoladamente não alcança perfi l lipídico satisfatório.

The goal of hypercholesterolemic patient treatment should be obtaining both LDL and cholesterol blood level concentrations close to those of normal individuals. A number of therapeutic strategies have been carried out in order to achieve hypercholesterolemia proper control. Simvastatin stands out by preventing cholesterol synthesis in the liver as Ezetimibe prevents intestinal cholesterol absorption. The lack of proper cholesterolemia control regarding the single use of Simvastatin and Ezetimibe enables the possibility of combining such drugs. Thus, the combination of Simvastatin and Ezetimibe remarkably decreases the concentrations of both cholesterol blood level and LDL. Therefore, we conclude that such combination represents the best therapeutic choice for patients who isolated estatine does not reach a proper lipid profile.

Investigation of the tolerability of oral stevioside in Brazilian hyperlipidemic patients

The tolerability of stevioside (2.75 mg/kg/day) obtained from leaves of Stevia rebaudiana (Bert) Bertoni (Compositae) was investigated in hyperlipidemic patients. For this purpose a placebo controlled double blind study was performed. The patients were randomized in two groups: the first group received capsules containing placebo and the second group received capsules containing stevioside (50 mg) during 90 days. All capsules were ingested twice daily, i.e., 2 capsules before lunch and 2 capsules before dinner. After the selection of the patients and each 30 days body mass index and laboratory tests (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, total cholesterol, high density lipoprotein, low density lipoprotein, very low density lipoprotein, triglycerides and glucose) were performed. Stevioside did not show any clinical relevant modification in all parameters investigated. Moreover the patients did not report severe adverse effect. Thus, we can concluded that stevioside, at least in the doses employed in this study was safe.

A tolerabilidade do esteviosideo (2.75 mg/kg/dia) obtido a partir de folhas de Stevia rebaudiana (Bert) Bertoni (Compositae) foi investigada em pacientes hiperlipidêmicos. Para alcançar este objetivo realizamos estudo clínico do tipo duplo cego. Os pacientes foram randomizados em 2 grupos: o primeiro recebeu cápsulas contendo placebo e o segundo recebeu cápsulas contendo esteviosídeo (50 mg). Foram ingeridas duas cápsulas antes do almoço e duas cápsulas antes do jantar durante 90 dias. Após a seleção dos pacientes e a cada 30 dias o índice de massa corpórea e exames laboratoriais (alanina aminotransferase, aspartato aminotransferase, gama-glutamiltransferase, colesterol total, lipoproteína de alta densidade, lipoproteína de baixa densidade, lipoproteína de muito baixa densidade, trigliceridemia e glicemia) foram realizados. O esteviosídeo não acarretou qualquer alteração clinicamente relevante nos parâmetros investigados. Além disso, os pacientes não relataram efeitos adversos severos. Assim, podemos concluir que o esteviosídeo, na dose empregada neste estudo é seguro, embora não apresente efeito hipolipemiante.

Pharmacological studies of Cordia salicifolia Cham in normal and diabetic rats

O efeito anti-obesidade, anorexigeno, diurético e anti-hiperlipêmico de folhas secas pulverizadas de Cordia salicifolia Cham (CS) foi investigado. CS foi dissolvida em água e administrada (20 mg.Kg-1.dia-1) por gavagem durante 13 dias. A dose utilizada correspondente à empregada no Brasil. Contrariamente ao uso popular, o efeito anti-obesidade, anorexigeno e diurético não foi observado. Porém, observamos efeito hipolipidêmico em ratos normais e portadores de diabetes induzidos por aloxana.

Efeito do extrato bruto hidroalcoólico e de frações de folhas da Averrhoa carambola L. (Oxalidaceae) no metabolismo glicêmico de ratos Wistar / Effect of Hydroalcoholic extract and fractions of Averrhoa carambola L. (Oxalidaceae) leaves on the glycemic metabolism of Wistar rats

As folhas de carambola (Averrhoa carambola L.) são utilizadas na fabricação do fitoterápico Glico-Vitae®, indicado no tratamento do diabetes melittus tipo 2. Em nossos estudos, ratos machos Wistar que receberam, por via intragástrica, o extrato bruto liofilizado (EC) e as frações de EC (20 mg/kg), durante duas semanas, apresentaram redução da glicemia. Mas, diferentemente da insulina, o EC e suas frações não estimularam a síntese de glicogênio e a produção de lactato em músculo sóleo isolado. Da fração mais ativa, empregando métodos espectroscópicos de EM, RMN1H e RMN13C, foram isoladas três frações semipurificadas majoritárias e, por comparação com os dados da literatura, foram identificadas como misturas complexas de açúcares

Aspectos farmacológicos e clínicos de um novo contraceptivo oral contendo drospirenona como componente progestínico / Pharmacological and clinical aspects of a new oral contraceptive containing drospirenone as progestinic component

Este artigo de revisão avalia os primeiros aspectos clínicos e farmacológicos de um novo contraceptivo oral, contendo drospirenona como componente progestínico. Para alcançar esse propósito os principais estudos clínicos e farmacológicos publicados em revistas científicas internacionais nos últimos anos foram analisados e as principais informações em relação a esse novo contraceptivo foram selecionadas e incluídas neste artigo de revisão. Considerando que a combinação drospirenona (3000 µg) + etinilestradiol (30 µg) apresenta eficácia semelhante aos contraceptivos orais combinados tradicionais, com a vantagem de apresentar menor retenção de líquidos, poderíamos concluir que o emprego desse novo contraceptivo é relevante, particularmente em mulheres com predisposição à hipertensão, obesidade e síndrome pré-menstrual

Absence of antidiabetic and hypolipidemic effect of Gymnema sylvestre in non-diabetic and alloxan-diabetic rats

Neste estudo foi investigado o potencial antidiabético e hipolipemiante da Gymnema sylvestre (GS). O efeito agudo da GS administrada via oral sobre a glicemia e lipidemia foi avaliado em ratos Wistar sob as seguintes condições: a) após refeição balanceada; b) após ingestão de 1000 mg de amylose ou 1000 mg/kg de glicose; c) após ingestão de uma mistura de 12 mL/kg de óleo de soja + 1% de colesterol (OSC). Foi avaliado também o efeito do tratamento com GS durante duas (sub-agudo) ou quatro semanas (crônico) sobre o peso corporal, ingestão de água e alimento, glicemia e lipidemia em ratos não diabéticos e diabéticos induzidos com aloxana. A dose de GS utilizada na maioria dos experimentos (30 mg/kg) corresponde a dose empregada para tratar diabetes no Brasil. A administração aguda de GS não influenciou a elevação da glicemia durante a refeição balanceada, administração de amilose ou glicose; mas intensificou a elevação da concentração sérica de lipídeos após a administração de OSC. Além disso, o tratamento sub-agudo e crônico com GS em ratos não diabéticos e diabéticos induzidos com aloxana não alterou: a) o ganho de peso corporal; b) a ingestão de água e alimento; c) os níveis de glicose e lipídios. Assim sendo, a Gymnema sylvestre pelo menos na forma comercializada no Brasil (folhas secas em pó) requer mais ensaios experimentais e clínicos antes de ser recomendada para tratamento do diabetes e hiperlipidemia.