Total intravenous anaesthesia in ponies using detomidine, ketamine and guaiphenesin: Pharmacokinetics, cardiopulmonary and endocrine effects

Pharmacokinetics and some pharmacological effects of anaesthesia induced by a combination of detomidine, ketamine and guaiphenesin were investigated in eight ponies. Cardiopulmonary function was studied and plasma met-enkephalin, dynorphin, β-endorphin; arginine vasopressin, adrenocorticotrophin, cortisol, 11-deoxycortisol and catecholamine concentrations were measured. The combination produced slight cardiorespiratory depression, hyperglycaemia and a reduction in haematocrit. There were no changes in plasma opioids, pituitary peptides or catecholamines. Plasma cortisol concentration decreased and plasma 11-deoxycortisol increased indicating a suppression of steroidogenesis. Steady state ketamine and guaiphenesin concentrations were attained during the infusion period, and ketamine concentrations likely to provide adequate analgesia for surgical operations were achieved (more than 2.2 μg ml-1). Steady state detomidine concentration was not attained. The ponies took on average 68 minutes to recover to standing and the recovery was uneventful.

Cardiorespiratory, endocrine and metabolic changes in ponies undergoing intravenous or inhalation anaesthesia

Six Welsh gelding ponies (weight 246 ± 6 kg) were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v. Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2 h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1 month later using the same induction regime and anaesthesia was maintained with a combination of detomidine, ketamine and guaiphenesin, while the ponies breathed oxygen-enriched air. Electrocardiogram, heart rate, mean arterial blood pressure, cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose, lactate and cortisol were measured and cardiac index and systemic vascular resistance were calculated in both groups. Beta-endorphin, met-enkephalin, dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and catecholamines were measured in the halothane anaesthesia group only and 11-deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory depression was more marked during halothane anaesthesia. Hyperglycaemia developed in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol increased during halothane and decreased during TIVA. There were no changes in the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA produced better cardiorespiratory performance and suppressed the endocrine stress response observed during halothane anaesthesia.

Improvement of biochemical parameters in type 1 diabetic rats after the roots aqueous extract of yacon [Smallanthus sonchifolius (Poepp.& Endl.)] treatment

The aim of this study was to evaluate the effect of yacon (Smallanthus sonchifolius) (Poepp.& Endl.) on clinical parameters under diabetic conditions. The aqueous extract of yacon tuberous roots (YRAE; 0.76gfructankg-1 body weight) was prepared at the moment of each administration. Thirty-two male rats were divided into four groups (n=8): control group (C); group that received YRAE (Y); untreated diabetic group (DM1); and diabetic group treated with YRAE (Y-DM1). The diabetes mellitus was induced by streptozotocin (60mgkg-1 body weight). The animals from Y2 and Y-DM1 received YRAE by gavage, at 7-day intervals, for 30days. The aqueous extract of yacon roots decreased (p<0.05) the water and food intake in diabetic rats (Y-DM1). YRAE treatment reduced (p<0.05) glycaemia, total cholesterol, VLDL-c, LDL-c and triacylglycerol levels in diabetic rats (YRAE). HDL, urea and creatinine levels did not differ (p>0.05) between the Y and Y-DM1 groups. YRAE normalised alanine aminotransferase (ALT) activity, when comparing DM1 and Y-DM1 rats, but had no effect on lactate dehydrogenase activity (LDH). In conclusion, YRAE was sufficient for controlling water and food consumption, hyperglycaemia and dyslipidaemia, and promote the reduction of the ALT, suggesting a hepatoprotective effect in rats with STZ-induced DM1. © 2013 Elsevier Ltd.

Bacille Calmette-Guérin/DNAhsp65 prime-boost is protective against diabetes in non-obese diabetic mice but not in the streptozotocin model of type 1 diabetes

Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases. © 2013 British Society for Immunology.

Tratamento neonatal com aloxana em ratos: efeitos do exercício

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterações histoquímicas e ultraestruturas do fígado e intestino grosso de ratos diabéticos tipo I e os efeitos do treinamento físico

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Comparação entre o volume renal em fetos de gestantes hiperglicêmicas e o volume renal em fetos de gestantes normoglicêmicas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Flavonóides de Cissus verticillata e a atividade hipoglicemiante do chá de suas folhas

Cissus verticillata, a Vitaceae very used in the traditional medicine in Pará and Minas Gerais State – Brazil, was investigated in order to validate its indication for the hyperglycaemia control. The aqueous extract reduces the normal glycaemia of male white Wistar rats in about 19.5 %. The hypoglycaemic effect of this extract could be related to the flavonoids found in the preparation. Luteolin, Kaempferol and Luteolin-3'-sulphate could be isolated from the aqueous extract after acid hydrolysis. Cissus

Estudo da isquemia e reperfusão renal associados à hiperglicemia transitória e a ciclosporina A em ratos anestesiados com isoflurano ou com propofol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of maternal diabetes on male offspring: high cell proliferation and increased activity of MMP-2 in the ventral prostate

This study presents a comprehensive view of the histological and functional status of the prostate of adult rat offspring of mothers subjected to gestational diabetes induced by alloxan. The ventral prostate of male adult offspring of diabetic (DP) or normal (CP) mothers was evaluated for collagen fibres, cell death, fibroblasts, smooth muscle cells, cell proliferation, matrix metalloproteinases (MMPs), androgen receptors (AR), transforming growth factor beta 1 (TGF beta-1), catalase and total antioxidant activity. The prostates of DP animals were lower in weight than those of the CP group. The DP group also exhibited hyperglycaemia and hypotestosteronemia, higher cell proliferation and AR expression, a reduction in alpha-actin (possibly interfering with the reproductive function of the prostate), and enhanced activity of MMP-2, although the absolute content of MMP-2 was lower in this group. These findings were associated with increased TGF beta-1 and decreased collagen distribution. The prostates of DP rats additionally exhibited reductions in catalase and total antioxidant activity. Thus, rats developing in a diabetic intrauterine environment have glycaemic and hormonal changes that impact on the structure and physiology of the prostate in adulthood. The increased AR expression possibly leads to elevated cell proliferation. Stromal remodelling was characterized by enhanced activity of MMP-2 and collagen degradation, even with increased TGF beta-1 activation. These changes associated with increased oxidative stress might interfere with tissue architecture and glandular homeostasis.

Assessment of structural cardiac abnormalities and diastolic function in women with gestational diabetes mellitus

Background: The main manifestation of hyperglycaemia during pregnancy is gestational diabetes mellitus. It can herald diabetes mellitus type 2 and its deleterious long-term effects, such as hypertension and cardiovascular disease. The aim of this study was to assess diastolic function in women with gestational diabetes mellitus, one of the first signs of future cardiovascular disease.Methods: A total of 21 women with gestational diabetes mellitus and 23 healthy pregnant women (control group) between 34 and 37weeks of gestation underwent echocardiographic assessment. The diagnosis of gestational diabetes mellitus was made in agreement with the American Diabetes Association criteria. Echocardiographic images obtained were analysed according to the criteria of the American Society of Echocardiography. Data were analysed using Pearson correlation coefficient, analysis of variance and Student's t-test.Results: Women with gestational diabetes mellitus had higher posterior wall and interventricular septum thickness, increased left ventricular mass and left ventricular mass index, lower early diastolic annular velocity and early diastolic annular velocity/late diastolic annular velocity ratio. There was a positive correlation between left ventricular mass index and fasting glucose and pregnancy body mass index.Conclusion: Patients with gestational diabetes mellitus seem to have a different diastolic profile as well as a mildly dysfunctional pattern on echocardiogram, which may show a need for greater glycaemic control.

Occurrence of socransky red complex in pregnant women with and without periodontal disease

Purpose: To verify the presence of Socransky Red Complex (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) and P. intermedia using polymerase chain reaction (PCR) in periodontally healthy pregnant women and pregnant women with periodontal disease, as well as its relation to arterial blood pressure and capillary glycaemia.Materials and Methods: This case control study included 86 pregnant women, including 50 pregnant women with healthy periodontium, 27 with gingivitis and 9 with periodontitis. Arterial blood pressure and glycaemia were evaluated and recorded. Clinical specimens from the gingival crevice or periodontal pockets were gathered with sterile absorbent paper cones. DNA extraction was accomplished using the Easy-DNA Kit test and the presence of bacteria was detected by PCR with primers and specific probes for each microorganism.Results: The arterial pressure of all pregnant women was found to be within normal levels and 51% presented with hyperglycaemia, these two variables were not associated with periodontal conditions and/or presence of microorganisms. Socransky Red Complex was not present in pregnant women with healthy periodontium; however, it was present in pregnant women with gingivitis (3.7%) and in a higher percentage of pregnant women with periodontitis (33.3%).Conclusion: Socransky Red Complex was found only in cases of periodontal diseases and is not related to blood pressure and/or high levels of blood glucose.

Diabetes reduces mesenchymal stem cells in fracture healing through a TNF alpha-mediated mechanism

Diabetes interferes with bone formation and impairs fracture healing, an important complication in humans and animal models. The aim of this study was to examine the impact of diabetes on mesenchymal stem cells (MSCs) during fracture repair.Fracture of the long bones was induced in a streptozotocin-induced type 1 diabetic mouse model with or without insulin or a specific TNF alpha inhibitor, pegsunercept. MSCs were detected with cluster designation-271 (also known as p75 neurotrophin receptor) or stem cell antigen-1 (Sca-1) antibodies in areas of new endochondral bone formation in the calluses. MSC apoptosis was measured by TUNEL assay and proliferation was measured by Ki67 antibody. In vitro apoptosis and proliferation were examined in C3H10T1/2 and human-bone-marrow-derived MSCs following transfection with FOXO1 small interfering (si)RNA.Diabetes significantly increased TNF alpha levels and reduced MSC numbers in new bone area. MSC numbers were restored to normal levels with insulin or pegsunercept treatment. Inhibition of TNF alpha significantly reduced MSC loss by increasing MSC proliferation and decreasing MSC apoptosis in diabetic animals, but had no effect on MSCs in normoglycaemic animals. In vitro experiments established that TNF alpha alone was sufficient to induce apoptosis and inhibit proliferation of MSCs. Furthermore, silencing forkhead box protein O1 (FOXO1) prevented TNF alpha-induced MSC apoptosis and reduced proliferation by regulating apoptotic and cell cycle genes.Diabetes-enhanced TNF alpha significantly reduced MSC numbers in new bone areas during fracture healing. Mechanistically, diabetes-enhanced TNF alpha reduced MSC proliferation and increased MSC apoptosis. Reducing the activity of TNF alpha in vivo may help to preserve endogenous MSCs and maximise regenerative potential in diabetic patients.

In-hospital death in acute coronary syndrome was related to admission glucose in men but not in women

Background: Admission hyperglycaemia is associated with mortality in patients with acute coronary syndrome (ACS), but controversy exists whether hyperglycaemia uniformly affects both genders. We evaluated coronary risk factors, gender, hyperglycaemia and their effect on hospital mortality. Methods: 959 ACS patients (363 women and 596 men) were grouped based on glycaemia >= or < 200 mg/dL and gender: men with glucose < 200 mg/dL (menG-); women with glucose < 200 mg/dL (womenG-); men with glucose >= 200 mg/dL (menG+); and women with glucose >= 200 mg/dL (womenG+). A logistic regression analysis compared the relation between gender and glycaemia groups and death, adjusted for coronary risk factors and laboratory data. Results group: menG- had lower mortality than menG+ (OR = 0.172, IC95% 0.062-0.478), and womenG+ (OR = 0.275, IC95% 0.090-0.841); womenG- mortality was lower than menG+ (OR = 0.230, IC95% 0.074-0.717). No difference was found between menG+ vs womenG+ (p = 0.461), or womenG- vs womenG+ (p = 0.110). Age (OR = 1.067, IC95% 1.031-1.104), EF (OR = 0.942, IC95% 0.915-0.968), and serum creatinine (OR = 1.329, IC95% 1.128-1.566) were other independent factors related to in-hospital death. Conclusions: Death was greater in hyperglycemic men compared to lower blood glucose men and women groups, but there was no differences between women groups in respect to glycaemia after adjustment for coronary risk factors.