Effects of exercise and metformin on the prevention of glucose intolerance: a comparative study

We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.

Effects of exercise and metformin on the prevention of glucose intolerance: a comparative study.

We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.

Avaliação da atividade antiinflamatória do coentro (Coriandrum sativum L. ) em roedores / Evaluation of the anti-inflammatory activity of coriander (Coriandrum sativum L. ) in rodents

Coriandrum sativum L. (Umbelliferae), conhecido popularmente por coentro, é uma planta doméstica cultivada nas diversas partes do mundo, inclusive no Brasil. As folhas e frutos do coentro são utilizados como condimento em culinária e na medicina popular como analgésica, antirreumática, carminativa e colagoga. O objetivo deste estudo foi avaliar o efeito do tratamento com o óleo essencial (OEC) e o extrato hidroalcóolico (EHC) do coentro em modelos experimentais de inflamação em roedores. A atividade antiinflamatória do coentro foi avaliada por meio dos testes de pleurisia em ratos e formação do edema de orelha em camundongos. A pleurisia foi induzida pela carragenina em animais tratados ou não com EHC. O edema de orelha induzido pela aplicação tópica de óleo de cróton e a atividade da mieloperoxidase foi avaliada em camundongos tratados ou não com OEC ou EHC. No teste da pleurisia o tratamento com EHC promoveu significativa diminuição no edema pleural, mas não sobre a migração leucocitária. Além disso, diferentemente ao observado com o tratamento com OEC, o uso tópico de EHC diminui significativamente o edema de orelha e a migração celular induzidos pela aplicação do óleo de cróton. Os dados indicam que EHC apresenta atividade antiinflamatória quando administrado pelas via oral e tópica, enquanto que OEC não apresenta atividade antiinflamatória tópica.

Commonly known as coriander, Coriandrum sativum L. (Umbelliferae) is a home plant grown in several parts of the world, including Brazil. Its leaves and fruits have been used as condiment in cooking and in folk medicine as analgesic, antirheumatic, carminative and cholagogue. The aim of this study was to evaluate the effect of essential oil (EO) and hydroalcoholic extract (HE) from coriander on experimental inflammation models in rodents. Coriander anti-inflammatory activity was evaluated by pleurisy tests in rats and ear edema formation in mice. Pleurisy was induced by carrageenan in HE-treated or non-treated animals. The ear edema was induced by topical application of croton oil and the myeloperoxidase activity was evaluated in EO-treated and HE-treated or non-treated mice. In the pleurisy test, HE treatment significantly decreased pleural edema but not the leukocyte migration. Furthermore, differently from EO, the topical use of HE significantly decreased ear edema and cell migration induced by croton oil application. The results indicate that HE had anti-inflammatory activity when orally and topically administered, whereas EO did not present topical anti-inflammatory activity.

Fatores interferentes na taxa de adesão à farmacoterapia em idosos atendidos na rede pública de saúde do Município de Salto Grande - SP, Brasil / Factors interfering with the medication adherence rate of elderly patients in the public health system in the town of Salto Grande, São Paulo State, Brazil

O objetivo deste estudo foi determinar a taxa de adesão à farmacoterapia e identificar os fatores que interferem nesta taxa em pacientes idosos atendidos em uma Unidade Básica de Saúde (UBS) no município de Salto Grande, São Paulo. Foram recrutados 120 pacientes idosos para participar de estudo transversal, desenvolvido no período de maio a setembro de 2009. Foi aplicado questionário para determinar a taxa de adesão (MMAS-8) e identificar as características sócio-econômicas, de saúde autorreferidas, da farmacoterapia utilizada e da satisfação dos pacientes com os serviços de saúde da UBS estudada. Um total de 102 pacientes completo o estudo, sendo que a maioria dos indivíduos apresentou taxa de adesão insatisfatória (14,7% alta adesão, 48,0% adesão média e 37,3% baixa adesão). Apresentaram forte correlação com adesão, satisfação com os serviços de saúde (r= 0,884; p < 0,0001) e o Índice de Complexidade da Farmacoterapia (ICFT) (r= - 0,705; p < 0,001). O número de medicamentos consumidos (r= - 0,604; p < 0,001), número de doenças relatadas (r = - 0,604; p < 0,001) e número de moradores por residência (r= 0,428; p < 0,001) apresentaram correlação intermediária com adesão. Foi encontrada uma correlação fraca entre adesão e escolaridade (r= 0,263; p < 0,001), raça (r= 0,090; p < 0,001), sexo (r= 0,080; p < 0,001), renda familiar (r= 0,054; p < 0,001) e idade (r= -0,090; p < 0,001). Esses resultados indicam que a população estudada não adere adequadamente à farmacoterapia, com forte influência da satisfação dos pacientes com os serviços de saúde e ICFT nesses resultados.

The aim of this study was to determine the rate of adherence to pharmacotherapy and to identify the factors that interfere with this adherence in elderly patients attended at a local Health Center (BHU) in Salto Grande, a country town in Sao Paulo. One hundred and twenty patients were recruited to participate in a cross-sectional study, conducted from May to September 2009. A questionnaire was used to determine the adherence rate (MMAS-8) and to identify the socio-economic factors, health condition (self-reported), medication used and satisfaction of the patients with the health services provided at the BHU. A total of 102 patients completed the study, most of whom showed unsatisfactory adherence rates (14.7% high adherence, 48.0% mean adherence and 37.3% poor adherence). Adherence was strongly correlated with patient satisfaction with health services (r= 0.884; p < 0.0001) and the Medication Regimen Complexity Index (MRCI) (r= - 0.705; p < 0.001). The number of drugs consumed (r = - 0.604, p <0.001), number of reported diseases (r = - 0.604, p <0.001) and number of residents per house (r = 0.428, p <0.001) showed intermediate correlation with intermediate adherence. Weak correlation was found between adherence and education level (r = 0.263, p <0.001), race (r = 0.090, p <0.001), sex (r = 0.080, p <0.001), family income (r = 0.054, p <0.001 ) and age (r = -0.090, p <0.001). These results indicate that the population does not adhere adequately to medication prescribed at the BHU and that patients? satisfaction with health services and the MRCI influence these results strongly.

Avaliação dos efeitos da suplementação com farinha de linhaça (Linum usitatissimum L. ) marrom e dourada sobre o perfil lipídico e a evolução ponderal em ratos Wistar / Evaluation of the effects of supplementation with brown and golden flax (Linum usitatissimum L. ) flour on lipid profile and weight gain in Wistar rats

Neste trabalho foram comparados os efeitos da farinha de linhaça dourada e farinha de linhaça marrom sobre o perfil lipídico e evolução ponderal em ratos Wistar. Os animais foram divididos aleatoriamente em três grupos, Grupo Controle (GC); Grupo suplementado com Farinha de Linhaça Marrom (LM) e Grupo Suplementado com Farinha de Linhaça Dourada (LD). Os animais foram submetidos à avaliação ponderal em dias alternados até o dia do sacrifício, no 36º dia, quando amostras de sangue foram coletadas para avaliação do perfil lipídico. O uso da farinha de linhaça como suplemento dietético de ratos Wistar, no período de 35 dias, promoveu redução significativa dos níveis de triglicérides séricos e da razão CT/HDL-c, com concomitante aumento dos níveis séricos de HDL-c, demonstrando assim efeito cardioprotetor. Os efeitos sobre o incremento de massa corporal dos animais durante o período do experimento sugerem importante ação preventiva no desenvolvimento da obesidade para a farinha de linhaça.

In this work, the effects of brown and golden flax flour were compared based on lipid profile and weight gain in Wistar rats. The animals were randomly divided into three groups: control group (CG); group supplemented with brown flax flour (BF); and group supplemented with golden flax flour (GF). The animals were subjected to weight assessment on alternate days until sacrifice at the 36th day, when blood samples were collected for lipid profile evaluation. The use of flax flour as dietary supplement to Wistar rats, in a 35-day period, led to a significant decrease in the serum levels of triglycerides and TC:HDL-C ratio, with concomitant increase in HDL-C serum levels, demonstrating thus a cardioprotective effect. The effects on rat weight gain over the experimental period suggest an important preventive action of flax flour on the obesity development.

Avaliação da farmacoterapia anti-hipertensiva em pacientes diabéticos atendidos no Sistema Único de Saúde (SUS) na rede municipal de saúde de Salto Grande, SP / Assessment of anti-hypertensive pharmacotherapy given to diabetic patients attended by the Brazilian National Health Service at the municipal health care center of Salto Grande, SP

Este trabalho objetivou avaliar o padrão de prescrição de medicamentos anti-hipertensivos e os níveis pressóricos de pacientes diabéticos hipertensos atendidos na Unidade Básica de Saúde "Cidinha Leite" do município de Salto Grande, interior do Estado de São Paulo. Trata-se de um estudo de caráter descritivo, transversal utilizando cópias das receitas e prontuários dos pacientes com idade > 40 anos atendidos na UBS estudada, com pressão arterial >130/80mmHg e/ou utilizando medicamentos anti-hipertensivos concomitantemente com medicamentos antidiabéticos (antidiabéticos orais e parenterais), tendo sido excluídos todos os indivíduos com queixas associadas ao aparelho cardiovascular, com encaminhamentos para serviços de cardiologia, que pudessem influenciar no padrão de prescrição de medicamentos anti-hipertensivos. Duzentos e quatorze (67,5%) indivíduos atenderam aos critérios de inclusão do estudo, sendo 143 (66,8%) pessoas do sexo feminino; com idade média de 59,44 anos, com 45 (21,0%) destes pacientes apresentando valores de PA <130/80mmHg. O padrão de prescrição de anti-hipertensivos para estes pacientes segue parcialmente as recomendações baseadas em evidências existentes, ocorrendo algumas escolhas de monoterapia, posologia de medicamentos e terapias medicamentosas em associação irracionais, sendo extremamente importante a adoção de estratégias educativas junto aos clínicos gerais para melhorar o tratamento medicamentoso dos diabéticos hipertensos atendidos na UBS "Cidinha Leite".

This article reviews critically the prescription patterns of antihypertensive drugs and the recorded blood pressure levels in diabetic hypertensive patients treated at the "Cidinha Leite" Primary Healthcare Center in the city of Salto Grande, in upstate Sao Paulo, Brazil. This is a descriptive, cross-sectional survey based on copies of medical records of patients aged > 40 years treated at this public health clinic, with blood pressure levels > 130/80 mmHg and/or taking antihypertensive drugs concomitantly with (oral and parenteral) antidiabetic drugs. All individuals with complaints associated with the cardiovascular system, with referrals to cardiology services, which could influence the pattern of prescription of antihypertensive drugs, were excluded. Two hundred and fourteen (67.5%) individuals met the inclusion criteria of the survey, 143 (66.8%) of whom were female; the average age of the patients was 59.44 years and 45 (21.0%) had BP values < 130/80mmHg. The prescription patterns of antihypertensive drugs for these patients partially followed the recommendations based on available evidence, but some choices of monotherapy, drug doses and drug combinations were irrational, making it extremely important to introduce educational programs for the general practitioners, so as to improve the drug treatment of diabetic hypertensive patients at the "Cidinha Leite" clinic.

The allergic inflammatory reaction in neonatal streptozotocininduced diabetic rats: evidence of insulin resistance and microvascular dysfunction.

OBJECTIVE: To investigate the allergic reaction in neonatal streptozotocin (nSTZ)-induced diabetes mellitus. MATERIAL: Male newborn Wistar rats were made diabetic by the injection of streptozotocin (160 mg/kg, i. p.) and used 8 weeks thereafter. TREATMENT: Animals were sensitized against ovalbumin (OA, 50 microg and Al(OH)3, 5 mg, s. c.) and challenged 14 or 21 days thereafter. METHODS: OA-induced airway inflammation and OA-induced pleurisy models were used to investigate leukocyte migration (total and differential leukocyte counts) and lung vascular permeability (Evans blue dye extravasation). RESULTS: nSTZ-diabetic rats presented glucose intolerance and insulin resistance. Relative to controls, nSTZ rats exhibited a 30% to 50% reduction in lung vascular permeability. Leukocyte infiltration in both models of allergen-induced inflammation, and number of pleural mast cells did not differ between groups. CONCLUSIONS: Data suggest that the reduction of allergic inflammatory reactions in nSTZ rats is restricted to microvascular dysfunctions and associated, probably, with insulin resistance in lung microvascular endothelium.

Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models.

Rosmarinus officinalis L. (Family Lamiaceae), popularly named rosemary, is a common household plant grown in many parts of the world, including Brazil. Rosemary leaves are used for food flavoring and have been used in folk medicine for many conditions; they have antispasmodic, analgesic, antirheumatic, carminative, cholagogue, diuretic, expectorant, and antiepileptic effects. The objective of this study was to evaluate the effects of rosemary essential oil (REO) on experimental models of nociception and inflammation in animals. The anti-inflammatory effect of REO was evaluated by inflammatory exudate volume and leukocyte migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. Antinociception was evaluated using the acetic acid-induced writhing and hot plate tests in mice. REO (500 mg/kg) significantly reduced the volume of pleural exudate and slightly decreased the number of cells that had migrated compared with the control animals. At doses of 250, 500, and 750 mg/kg, REO significantly inhibited carrageenan-induced edema 1-4 hours after injection of the phlogistic agent. In the hot plate test, REO administration (125, 250, and 500 mg/kg) showed unremarkable effects on response latency, whereas control injection of meperidine induced significant antinociceptive effects. REO at doses of 70, 125, and 250 mg/kg had a significant antinociceptive effect in the acetic acid-induced abdominal writhing test compared with control animals. These data suggest that REO possesses anti-inflammatory and peripheral antinociceptive activity.

Chlorpropamide treatment restores the reduced carrageenan-induced paw edema and pleural exudate volume in diabetic rats.

OBJECTIVE AND DESIGN: Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. MATERIALS: Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. TREATMENT: n-STZ diabetic rats were treated with chlorpropamide (200mg/kg, 15d, by gavage) 8 weeks after STZ injection. METHODS: Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. RESULTS: Chlorpropamide treatment improved glucose tolerance, beta-cell function (assessed by HOMA-beta), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. CONCLUSION: Chlorpropamide treatment by restoring beta-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats.

Acute immune and non-immune inflammatory response in spontaneously hypertensive rats and normotensive rats. Role of endogenous nitric oxide.

UNLABELLED: The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated. RESULTS: The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR. CONCLUSION: The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.

The influence of improved glycaemic control with chlorpropamide on microvascular reactivity and nitric oxide synthase activity in diabetic rats.

Hyperglycaemia is a primary cause of vascular complications in diabetes. A hallmark of these vascular complications is endothelial cell dysfunction, which is partly due to reduced production of nitric oxide. The aim of this study was to verify the influence of improved glycaemic control with chlorpropamide on microvascular reactivity, endothelial nitric oxide synthase (e-NOS) expression, and NOS activity in neonatal streptozotocin-induced diabetic rats (n-STZ). Diabetes was induced by STZ injection into neonates Wistar rats. n-STZ diabetic rats were treated with chlorpropamide (200 mg kg(-1), 15 days, by gavage). The changes in mesenteric arteriolar and venular diameters were determined in anaesthetized control and n-STZ diabetic rats, before and after topical application of acetylcholine, bradykinin and sodium nitroprusside (SNP). We also assessed e-NOS expression (using polymerase chain reaction after reverse transcription of mRNAs into cDNAs) and NOS activity (conversion of L-arginine to citrulline) in the mesenteric vascular bed of chlorpropamide-treated n-STZ, vehicle-treated n-STZ, and control rats. In n-STZ, chlorpropamide treatment reduced high glycaemic levels, improved glucose tolerance and homoeostatic model assessment (HOMA-beta), and restored NOS activity. Impaired vasodilator responses of arterioles and venules to acetylcholine, bradykinin and SNP were partially corrected by chlorpropamide treatment in n-STZ. We concluded that improved metabolic control and restored NOS activity might be collaborating with improved microvascular reactivity found in chlorpropamide-treated n-STZ.

The role of adrenal corticosteroids in the anti-inflammatory effect of the whole extract of Harpagophytum procumbens in rats.

This study was carried out to evaluate whether the anti-inflammatory response in rats to the whole extract of Harpagophytum procumbens is a consequence of adrenal corticosteroid release. Carrageenan-induced inflammatory responses in the hindpaws were evaluated in control, sham-operated and adrenalectomized rats. The extract was administered orally (by gavage) or intraperitoneally, 30min prior to injury stimulus. Blood samples were then collected, and the number of circulating leukocytes was estimated. Pretreatment with the whole extract of H. procumbens reduced the intensity of inflammatory response in normal, sham-operated and adrenalectomized animals. When administered orally, the extract was ineffective. The reduced number of circulating leukocytes observed following intraperitoneal injection of the extract characterized adrenal hyperactivity. The inhibitory effect of the whole extract of H. procumbens on acute inflammatory response in the rat, when administered intraperitoneally, does not depend on the release of adrenal corticosteroids.

Immunomodulatory effect of Canova medication on experimental Leishmania amazonensis infection.

This study investigates the action of Canova medication (CM) on experimental infection by Leishmania (Leishmania) amazonensis, utilizing in vitro and in vivo assays. For the in vitro tests, Balb/c mouse peritoneal macrophages (5x10(5) cells in 500 microl of culture medium, supplemented with 10% fetal calf serum, penicillin (100 U/ml) and streptomycin (0.1 mg/ml) (were distributed in 24-well plates and CM was added at concentrations of 20 or 40%. Twenty-four hours later, the macrophages were infected with Leishmania amastigotes in culture medium. The effect of CM on macrophages leishmanicidal activity in 24 and 48 h cultures was evaluated by determining infection index and measuring nitric oxide (NO) production. The in vivo tests were performed in mice infected with 10(7)L. (L.) amazonensis promastigotes injected in to the right hind footpad (25 microl in phosphate buffered saline). The progression of the lesions was examined over a 9-week period by measuring footpad swelling, and the parasite load in regional lymph nodes and spleen. The in vitro results showed that at 40% CM reduced the infection index, and induced NO production in the elicited macrophages, which suggests that the inhibitory effect on infection index may be mediated by NO. In the in vivo infection, when administered, orally or subcutaneously in mice, CM reduced infection by L. (L.) amazonensis in the paws, resulting in smaller lesions. CM treatment also decreased parasite load in the regional popliteal lymph nodes and in the spleen. These results suggest that CM modulates experimental infection by L. (L.) amazonensis, controlling infection progression and limiting dissemination.

Efficiency of combined methotrexate/chloroquine therapy in adjuvant-induced arthritis.

The present study evaluates the effects of methotrexate (MTX) and chloroquine (CQ), and of combined MTX + CQ treatment, on the inflammatory response and on plasma and liver phosphatase and transaminase activities, employing an adjuvant-induced arthritis model in rats. Arthritis was induced by the intradermal injection of a suspension of Mycobacterium tuberculosis in mineral oil into the plantar surface of the hind paws. Development of the inflammatory response was assessed over a 21-day period. Animal groups received either: (i) MTX, administered i.p., weekly, in 0.15, 1.5, 3, 6 or 12 mg/kg doses; (ii) CQ, given intragastrically, in daily 25 or 50 mg/kg doses; or (iii) MTX + CQ, administered in two combinations (MTX1.5 mg/kg + CQ50 mg/kg, or MTX6 mg/kg + CQ50 mg/kg). At the end of the experimental period, the animals were anesthetized and killed, blood and liver samples were collected and prepared for measurement of acid and alkaline phosphatase (AP, ALP), and aspartate (AST) and alanine aminotransferase (ALT) activities. MTX at 6 and 12 mg/kg reduced the inflammatory response while CQ had no effect. MTX6 mg/kg + CQ50 mg/kg reduced the inflammatory response similar to MTX12 mg/kg, without affecting the bone marrow. Plasma AP and liver ALP activities were very elevated in the arthritic rats. While MTX treatment partially reduced both plasma AP and liver ALP activities at all doses used in the arthritic rats, CQ treatment reduced plasma AP, but increased liver AP activity. MTX + CQ treatment decreased plasma AP and liver ALP activities in the arthritic rats to control values. Plasma and liver AST activities were unaltered in the arthritic rats, and were unaffected by treatment. However, plasma and liver ALT activities were significantly reduced in the arthritic rats. While MTX or CQ treatment did not alter plasma transaminase activity in the arthritic rats, after MTX + CQ treatment, plasma ALT activity returned to normal values. In conclusion, the present data suggest that MTX + CQ treatment provides more effective anti-inflammatory protection against adjuvant-induced arthritis than does MTX alone, reverting the alterations in enzyme activities induced by this inflammatory disease in rats.

Participation of endogenous corticosteroids in inflammatory response in type 2 streptozotocin diabetic rats.

The inflammatory response is decreased in diabetic animals. After adrenals removal this impaired response in type 2 diabetic rats evaluated by pleurisy and vascular permeability tests was restored. Our studies demonstrate that endogenous corticosteroids play a partial role in the impaired inflammatory response in type 2 streptozotocin diabetic rats.