The renin-angiotensin system (RAS) is recognized by its pivotal role on cardiovascular regulation and more recently also on metabolism. Angiotensin-(1-7) has been described as a new potential therapeutic tool on treating and preventing metabolic disorders by regulating several pathways in visceral white adipose tissue (vWAT). This tissue has an important role on the corporal and metabolic homeostasis. The aim of this study was to access the proteins differentially regulated by Ang-(1-7) using proteomic analysis of visceral white adipose tissue. Male FVB/N mice were divided into three groups and fed for 60 days, with each group receiving one of the following diets: standard diet+HPβCD (ST), high fat diet + HPβCD (HFD) and high fat diet+Ang-(1–7)/HPβCD (HFD+Ang-(1-7)). Body weight, fat weight and food intake were measured. At the end of treatment, Ang-(1-7) induced a decreased in body and fat weight. Differential proteomic analysis using two-dimensional electrophoresis (2-DE) combined with mass spectrometry were performed to elucidate the molecular action of Ang-(1-7) on the antiobesity effect in visceral white adipose tissue. Results of protein mapping of mesenteric adipose tissue using 2-DE revealed the presence of about 450 spots in each gel (n=3/treatment) with a great reproducibility (>70%). Image analysis and further statistical analysis allowed the detection and identification of eight proteins whose expression were modulated in response to HFD when compared to ST. Among these, two proteins showed a sensitive response to Ang-(1-7) treatment (Enolase1 protein and aldehydedehydrogenase mitochondrial precursor). Besides, three proteins were statistically different expressed between HFD+Ang-(1-7) and HFD groups and four proteins were modulated compared to standard diet. In conclusion, comparative proteomic analysis of a mice model of diet-induced obesity allowed us to outline possible pathways involved in the response to Ang-(1-7), suggesting that Ang-(1-7) may be a useful tool for treat metabolic disorders.

The increasing prevalence of obesity worldwide is of great importance since is considered a risk factor for cardiovascular diseases. The purpose of this study was to evaluate the metabolic profile, inflammatory markers and the renin-angiotensin system expression in the adipose tissue of mice subjected to different caloric restriction degrees and treated with standard and high-fat diet. Male Swiss mice were divided into eight groups and were fed for eight weeks with: G1: Standard Diet (ST) ad libitum; G2: ST+20% caloric restriction; G3: ST+40% caloric restriction; G4: ST+60% caloric restriction; G5: High-Fat Diet (HFD) ad libitum; G6: HFD+20% caloric restriction; G7: HFD+40% caloric restriction; G8: HFD+60% caloric restriction. Food intake, body weight, glycemic parameters, lipid profile and albumin were assessed. The weight of adipose tissues and the area of adipocytes from epididymal adipose tissue were analyzed. The expression of AGT, ACE, ACE-2, IL-6 e TNF-α epididymal adipose tissue was evaluated by PCR at real-time. The main findings showed a reduced body weight, improved glycemic and lipid profile, reduced albumin, decreased weights adipose tissues and reduced adipocyte size in epididymal adipose tissue. It was also noticed a reduced expression of mRNA of IL-6, TNF-α, AGT and ACE in the 20% and 40% treatment groups and an increase on its expression in the 60% caloric restriction groups. It was concluded that 20% and 40% of caloric restriction improved metabolism controlling the pro-inflammatory cytokines expression in mice, while a severe 60% caloric restriction produce a new pro-inflammatory profile with increased AGT and ACE expression.

Aim:
To evaluate the structural and functional features of the left atrium in patients with type 2 diabetes with paroxysmal (PAF) and persistent atrial fibrillation (AF).
Methods:
We studied 64 patients with type 2 diabetes with normal left ventricular ejection fraction, without severe chronic renal failure. 14 patients (66+7 years) had PAF episodes on standard or Holter ECG recording (group 1), 20 patients (54+8 years) had persistent nonvalvular AF (group 2), 30 patients (66+6 years) without verified AF (group 3). Patients undertook standard echocardiography for assess LA volumes (LA Vol), LA ejection fraction (LAEF), Tissue doppler measurements for assess signs of LV diastolic dysfunction as the evidence of high ratio (>10) of the peak E transmitral flow to peak Em of septal mitral annulus (E/Em). Interatrial septum systolic strain and strain rate (Sstr and Sstr-r), lateral wall systolic strain and strain rate (Lstr and Lstr-r) were calculated in all patients groups.
Results:
In clinical characteristics (age, sex, BMI, systolic and diastolic BP levels, duration of DM, HbA1c levels, the nature of glucose-lowering and antihypertensive therapy), LVEF, the wall thickness and volume of LV groups did not differ between themselves. All groups of patients showed signs of LV diastolic dysfunction by E/Em (group 1 17,7+2,4,, group 2 22,9+9,3,group 3 14,9+5,2). A most marked impairment was observed in patients with a persistent form of AF compared with patients without AF (p<0.05). LAEF was significantly smaller in group 1 (33,5+4,5%) and group 2 (22,6+3,7%) than in group without AF (50,1+3,4%) (p<0.05). When comparing systolic strain and strain rate of LA walls was found that the groups of patients were significantly different among themselves too. The greatest deformation of LA walls was observed in patients without AF (Sstr 33,3+1,6%, Sstr-r 2,8+0,8 s-1, Lstr 32,3+1,8%, Lstr-r 2,17+0,2 s-1), significantly more than in patients with PAF (Sstr 18,1+1,5%, Sstr-r 1,9+0,7 s-1, Lstr 21,3+1,2%, Lstr-r 1,7+0,3 s-1), and patients with a persistent form of AF (Sstr 14,3+2,0%, Sstr-r 0,8+0,8 s-1, Lstr 12,13+1,6%, Lstr-r 1,0+0,7 s-1). Also patients with a persistent form of AF had significantly smaller data of septal and lateral strain than patients with PAF (p<0.05).
Conclusion:
These results suggest that the LV diastolic dysfunction, impaired LA function may associate with risk of atrial fibrillation in patients with type 2 diabetes. The degree of reduction of LA walls deformation may be predictor of development of paroxysmal and persistent AF in patients with type 2 diabetes.

Aging is accompanied by significant changes in patterns of health and disease. Chronic conditions such as diabetes mellitus (DM) is highly prevalent in the elderly population and is responsible for high mortality rates due to complications. The present study aimed to evaluate the impact of socioeconomic variables on quality of life of elderly hypertensive patients by the Family Health Programm in the city of Montes Claros, Minas Gerais, Brazil. An analytical cross study conducted in a representative sample of 157 elderly diabetic patients. Data were collected through a questionnaire on socioeconomic characteristics and quality of life specific to diabetic patients (DQOL-Brasil). Data were analyzed using Mann-Whitney and Kuskall-Wallis test (nonparametric) and T Test and ANOVA (parametric). In relation to socioeconomic factors evaluated, we results showed that of the subjects were female (n = 102, 65.0%), aged 60-69 years (n = 82, 52.2%), married / cohabiting (n = 80, 51.0%), catholics (n = 101, 64.3), literate (n = 91, 58.0%) and family income between 330 and 660 dollars (n = 93, 59.2%). The association between socioeconomic factors and the domain - Satisfaction no present association statistically significant between the variables. For the domain - Impact, married / cohabiting individuals (79.6, SD = 12.1) (P = 0.001) and literate (78.3, SD = 11.5) (P = 0.027) present mean higher to quality of life. For the domain - Social Concerns / Vocational, subjects men have higher average quality of life (87.2, SD = 14.1) (P = 0.011). By analyzing the domain - Concerns related to diabetes, elderly married / cohabiting overall averages showed higher quality of life (78.1, SD = 10.1) (P = 0.05). Socioeconomic factors such as marital status, education and gender influence the quality of life of elderly diabetics patients.

Introduction
Gallic acid (GA) is a trihydroxybenzoic acid present in plants worldwide. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit oral squamous cell carcinomacell viability, proliferation and invasion and suppresscell‑mediated angiogenesis. Treatment of oral squamous cell carcinoma (SCC9 and SCC4) with gallic acid decreased cell viability in a dose‑dependent manner.
Methods and Results
We first confirmed that GA decreases proliferation, invasion and migration in squamous cell carcinoma lines. Next, SCC-9 and SCC-4 cells were incubated in a well humidified incubator with 5% CO2 and 95% air at 37 °C (normoxiccondictions). For hypoxic cultures, cells were incubated 150 μM CoCl2 for 24 hours and maintained in a 5% CO2 atmosphere at 37˚C. Then, we divided cells into 4 groups including control, CoCl2, GA (10µg/mL) and CoCl2 + GA (10µg/mL). Col1A1 mRNAwas decreased in hypoxic cells after treatment with GA. Besides, GAincreased HIF-1α and e-cadherin mRNAs levels. In conclusion, our current findings suggest that GAincreased HIF-1α and e-cadherin mRNAs levels, and decreased Col1A1 mRNA levels. In addition, we found that the GAinhibit oral cancer cell migration, proliferation and invasion.

Recent studies have shown that angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas axis activation is able to improve metabolic profile, enhances glucose tolerance and insulin sensitivity, improves metabolic parameters and counteracts deleterious effects of Ang II. Thus, the aim of the present study was to evaluate the effects of endogenous ACE 2 activation in the metabolic profile of mice by compound diminazene aceturate (DIZE). Methods: Male FVB/N mice aged 12 weeks were treated with the ACE 2 activator, (DIZE, 1 mg/kg/day, gavage) or saline (control) for 30 days. Glucose tolerance and insulin sensitivity tests, and blood analysis were performed. Epididymal ACE 2, ACE, angiotensinogen, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were measured by quantitative RT-PCR. Results: ACE 2 activation treatment lowered body weight (DIZE vs control) (28.69 vs 30.28g, P < 0.001), serum cholesterol (140,0 vs 177.5; P <0.05), and serum triglyceride (75,00 vs 165,0; P <0.05), as well as the epididymal (0.008 vs 0.016; P <0.05); and retroperitoneal (0.0024 vs. 0.0068; P < 0.01) adipose tissue weights. These effects were associated with significant increase in epididymal ACE 2 and a decrease in ACE and AGT expression. Additionally, DIZE decreased adipogenesis-related genes as ACC (P<0.01) and FAS (P<0.001) mRNA expression.

Objective
In this study, we investigated the involvement of the Ang-(1-7)/Mas axis in cell migration under hypoxic condition induced by cobaltous chloride and the underlying mechanism.
Methods and Results
We first confirmed that Ang-(1-7) decreases HIF-1α signaling in a newly developed hydroxypropyl-β-cyclodextrin (HPBCD)-based Ang-(1-7) nano-formulation in a novel transgenic rat model of inducible insulin resistance and DM2. The chronic administration of this compound prevented the marked elevation of HIF-1α in diabetic rat kidney. Next, mouse embryonic fibroblasts (MEFs) and SCC-9 cells were incubated in a well humidified incubator with 5% CO2 and 95% air at 37 °C (normoxic condictions). For hypoxic cultures, cells were incubated 150 μM CoCl2 for 24 hours and maintained in a 5% CO2 atmosphere at 37˚C. Then, we divided cells into 4 groups including control, CoCl2, Ang-(1-7) and CoCl2 + Ang-(1-7). HIF-1α protein expression and AKT phosphorylation were decreased in hypoxic cells after treatment with Ang-(1-7). Besides, Ang-(1-7) decreased SCC-9 cell migration in hypoxic condition.
Conclusions
In conclusion, our current findings suggest that Ang-(1–7) attenuates HIF-1 α protein stabilization via AKT and Mas receptor-dependent mechanism. In addition, we found that the Ang-(1–7)/Mas receptor inhibit oral cancer cell migration.

The increasing prevalence of obesity worldwide is of great importance since is considered a risk factor for cardiovascular diseases. The purpose of this study was to evaluate the metabolic profile, inflammatory markers and the renin-angiotensin system expression in the adipose tissue of mice subjected to different caloric restriction degrees and treated with standard and high-fat diet. Male Swiss mice were divided into eight groups and were fed for eight weeks with: G1: Standard Diet (ST) ad libitum; G2: ST+20% caloric restriction; G3: ST+40% caloric restriction; G4: ST+60% caloric restriction; G5: High-Fat Diet (HFD) ad libitum; G6: HFD+20% caloric restriction; G7: HFD+40% caloric restriction; G8: HFD+60% caloric restriction. Food intake, body weight, glycemic parameters, lipid profile and albumin were assessed. The weight of adipose tissues and the area of adipocytes from epididymal adipose tissue were analyzed. The expression of AGT, ACE, ACE-2, IL-6 e TNF-α epididymal adipose tissue was evaluated by PCR at real-time. The main findings showed a reduced body weight, improved glycemic and lipid profile, reduced albumin, decreased weights adipose tissues and reduced adipocyte size in epididymal adipose tissue. It was also noticed a reduced expression of mRNA of IL-6, TNF-α, AGT and ACE in the 20% and 40% treatment groups and an increase on its expression in the 60% caloric restriction groups. It was concluded that 20% and 40% of caloric restriction improved metabolism controlling the proinflammatory cytokines expression in mice, while a severe 60% caloric restriction produce a new pro-inflammatory profile with increased AGT and ACE expression.

Objective: To evaluate the physical and metabolic effects in rats treated with high fat diet (HD) and standard diet (SD) and underwent sleeve gastrectomy/vertical gastrectomy (VG) with and without omentectomy. Method: Analytical experimental study, using male Wistar rats that were randomized into six groups consisting of eight animals/each: SD+laparotomy (SD+L), SD+VG, SD+VG+omentectomy (SD+VG+O), HD+laparotomy (HD+L), HD+VG and HD+VG+omentectomy (HD+VG+O). The study was divided into two stages. First phase: Treatment for eight weeks with the respective diets. The high fat diet induced obesity, insulin resistance and type 2 diabetes mellitus. Second phase: Rats were submitted to surgical treatment and fed for four weeks with their respective diets. Throughout the treatment the body weight and food intake were measured (three times/week). At the end of the second phase, the animals were subjected to the insulin sensitivity test (IST). The sacrifice was made by decapitation to collect blood and mesenteric, retroperitoneal and periepididymal adipose tissues. Serum samples were used for biochemical analyzes: Total cholesterol, HDL, triglycerides, glucose, urea and creatinine. Data were analyzed using Graph Pad Prism 5.0, using tests of Two-Way ANOVA and One-Way ANOVA and Bonferroni post-test. Results: The results showed significant decrease in body fat between the following groups: SD+L vs. HD+L, SD+VG+O vs. HD+L and SD+VG+O vs. HD+VG+O. Dietary intake was shown to be increased in the SD+L and HD+L groups and decreasing the treatment groups after surgery. The IST indicated significant improvement in insulin sensitivity in groups HD+VG and HD+VG+O compared to HD+L. Regarding plasma analyzes, the results indicated a significant decrease in total cholesterol levels between HD+L vs. HD+VG and HD+L vs. HD+VG+O. HDL levels did not differ between groups. The results also indicated a tendency of decrease in the levels of triglycerides and glucose in groups HD+VG and HD+VG+O vs. HD+L, but no statistical association. Similar results were observed for levels of urea. Statistically significant association was observed between HD+L vs. SD and HD groups submitted to surgical treatment regarding the levels of creatinine. Conclusion: The study demonstrates beneficial effects of VG with respect to loss of total adiposity and weight, total cholesterol and creatinina levels and improves insulin sensitivity in rats treated with high fat diet and can thus be considered a therapeutic option in the treatment of obesity and its comorbidities. More studies are needed to confirm whether omentectomy would have beneficial effects associated with VG.

The Cytochrome P450 enzymes are commonly known for the major role they in metabolism of endobiotics and xenobiotics. Besides its metabolic role, CYP2E1 gene expression in peripheral lymphocytes showed association with the onset of diabetic nephropathy. CYP2E1 protein elevation has also been reported to be responsible for the production of reactive oxygen species (ROS). The objective of this study is to investigate CYP2E1 protein expression in peripheral lymphocytes at various stages of diabetes. This study is a cross sectional studies involving four groups of subjects (N=100): control (non-diabetes) pre-diabetes, early diabetes and established diabetes. We applied the targeted proteomic approach for absolute quantification of CYP2E1. YPEIEEK and GTVVVPTLYDNQEFPDPEK were the specific tryptic peptides selected for our analytical method. D3Ac-YPEIEEK and D3Ac-GTVVVPTLYDNQEFPDPEK were used as internal standards. Lymphocytes were isolated from whole blood, microsomes were prepared, followed by in-solution digestion for production of tryptic peptides. Quantification of YPEIEEK and GTVVVPTLYDNQEFPDPEK from patients’ samples was calculated from a standard curve. HbA1c and ACR were analyzed at a hospital laboratory. CYP2E1 protein levels in peripheral blood lymphocytes were not measureable in all control subjects. CYP2E1 proteins were measureable in pre-diabetes and higher elevations were observed in early diabetes and established diabetes. Elevations of CYP2E1 were observed even when gold standard clinical indicators for glycemic control (HbA1c) and kidney function (ACR) were still within normal reference limits. The interim outcome of this study shows quantitation of CYP2E1 protein using proteomic approach is applicable in clinical practice. Quantitation of CYP2E1 may be useful as an additional tool for estimation of risks for diabetic complications.

Adipose tissue is central to the regulation of energy balance. Two functionally different fat pads are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue (BAT), which is specialized in heat production. In this context, new strategies capable of modulating the development and function of white and BAT become relevant. In the present study, we analyzed the influence of resveratrol (sirtuin activator) on energy balance and the expression of thermogenesis markers. Mice were divided into two groups: standard diet (ST) and standard diet plus resveratrol (ST + RSV). After two months of treatment, ST + RSV mice presented significantly decreased fat accumulation in adipose tissue, with diminished total cholesterol and glucose plasma levels. Additionally, increased oxygen consumption was observed in ST + RSV group. Analyses of mRNA of thermogenesis-related genes showed significant increase in UCP1, SIRT1, PTEN and BMP-7 expression in BAT. Our data suggest that improved metabolism produced by oral administration of resveratrol is, at least in part, associated with increased thermogenesis followed by high expression of UCP1 and SIRT1, which can mediate higher energy expenditure and decreased fat accumulation in adipose tissue.

Painful neuropathy is the long-term and difficult to treat complication of diabetes that affects 25% of diabetic patients and interferes with the quality of life. Unfortunately, available medical treatment is relatively ineffective due to dependency and addiction. Emerging research indicates that moderate-to-vigorous physical activity provides health-related benefits. However, to date there is insufficient research to determine whether adults with diabetes engaged in regular exercise show improvements in the development of painful neuropathy. Our study demonstrates the significance of exercise in the amelioration of pain in diabetic animals with a 6 week exercise paradigm. In this study we have shown that regular exercise can alleviate or delay the pain in diabetic neuropathy in Type 1 diabetic animals by decreasing the release of inflammatory cytokines in the dorsal root ganglia (DRG), and dorsal horn of spinal cord resulting in a decrease in the voltage gated ion channels in the DRG. A growing body of evidence implicates that the release of proinflammatory cytokines plays an important role in development and persistence of pain. This study has shown that moderate exercise reduced the release of a number of proinflammatory cytokines which subsequently improved the development of neuropathy. For exercise, streptozotocin-diabetic animals were placed in motorized running wheels for sixty minutes per day, for five days a week starting at one week after diabetes for6 weeks. Behavioral tests were performed to assess the painful diabetic neuropathy in the rats. At the end of the 6 weeks of exercise, we assessed the mechanical pain response by using the Randall-Stellitto method and the Hargraves test in order to assess the thermal pain threshold. Overall, this research suggests that exercise may provide an alternate route of treatment for painful neuropathy in Type 1 diabetic animals by decreasing the use of pain medication and provide a more useful and efficient way of management of pain.

Strychnos henningsii Gilg (SH) is a plant commonly used in southern African traditional medicine for the management of diabetes mellitus. The present study investigated beneficial effect of the herbal extract on some biochemical and haematological parameters in streptozotocin-nicotinamide induced diabetic animal model. Diverse in vitro models known to target glucose homeostasis and its direct complications were also evaluated to elucidate its mechanism of action. Significant decrease of blood glucose levels between 6 and 10 mmolL-1 was observed after oral administration of the extract at the tested dose. The level of triglyceride, urea, calcium, AST and ALP was drastically reduced whereas the level of Hb , PCV, MCV, RBC, MCH and ALT was significantly improved. Moreover, the folklore medicine appreciably increased the white blood count and its differentials but had no significant effect on the cholesterol and uric acid. The plant extract was found to stimulate both basal and insulin stimulated glucose uptake in differentiated 3T3-L1 cells but not in Chang liver cells. The effect on 3T3-L1 cells appears independent of PPARγ as the extract did not stimulate adipogenesis. Although, SH extract was inhibitory toward intestinal alpha glucosidase, the physiological relevance is doubtful based on the recommended dosages. The extract strongly inhibited protein glycation which, at least in part, may be explained by the antioxidant and phenolic content of this plant. Cytotoxicity in Chang liver cells yielded an IC50 value of 130.0 μg/mL raising concern that continual exposure to this herbal remedy may initiate hepatotoxicity. The finding from this study suggests that SH extract may attenuate hyperglycemia through enhanced peripheral tissue glucose utilization. The extract also has the capability of regularising some abnormalities associated with pathophysiologic condition of diabetes mellitus.

Elaine Christine Dantas Moisés has completed her PhD in 2008 from the Ribeirão Preto Medical School, University of São Paulo. She is a professor in the Department of Gynecology and Obstetrics of this institution. Her work has an emphasis on the following themes: Pharmacokinetics of drugs in pregnant women, placental transfer of drugs, Diabetes Mellitus in pregnant women.

Brief Introduction
Diabetes mellitus complicated with severe diabetic nephropathy significantly increase the risk of adverse events for maternal and fetal health.
History and clinical findings
A 24 year-old pregnant woman, first pregnancy, with Type 1 Diabetes Mellitus diagnosed since childhood and with complications such as chronic renal failure associated to hypertension, diabetic retinopathy, anemia and dyslipidemia.
Investigation and diagnosis
The laboratory evaluation of patient showed decompensation of glucose levels (glycated haemoglobin of 7.1%), accompanied by chronic renal failure (creatinine 7.2mg/dl and urea of 203mg/dl), and anemia (hemoglobin of 8.1g/dl). The evaluation of ocular funduscopic examination showed diabetic retinopathy with retinal detachment on left eye and retinal ischemia on right eye.
Treatment and course
During pregnancy, the patient developed acute exacerbation of chronic renal failure, which required daily hemodialysis. Also presented difficult to control glucose levels, which required four hospitalizations for better control. The management was carried out through nutritional support, accompanied by daily glucose monitoring and insulin prescription. In order to control the complications, was prescribed subcutaneous erythropoietin and alpha -methyldopa , furosemide and nifedipine orally. At 29 weeks of gestation age, the patient developed severe hypoglycemia, breast engorgement, placental insufficiency and abnormal fetal hemodynamics, represented by ultrasound Doppler velocimetry changes in the umbilical artery (Resistance Index of 0.78) and ductus venosus (Pulsatility Index of 1.2), respectively. At this time, it was indicated the resolution of pregnancy by cesarean section. The female newborn presented birth weight of 1145 g, Apgar scores of 6 and 9 in one minute and five minutes of life, respectively, showing no significant adverse neonatal events. In the postpartum period, the patient developed acute pulmonary edema which required admission to the intensive care unit and intensification of the dialysis treatment. Patient keeps in clinical follow-up to management of the Type 1 Diabetes Mellitus and associated complications.
Conclusion
The association of daily dialysis to drug management in pregnant women with Type 1 Diabetes Mellitus complicated with end-stage renal failure is beneficial and can improve maternal and perinatal prognosis.

Martins is a Fellow at the Centre for Ageing and Alzheimer’s disease, Edith Cowan University and UWA. Prevention of overeating by food restriction improves liver lipid and xenobiotic metabolism with the nature of fat consumed improves brain health. Contribution to biology is related to sterol side chain length indicating cholesterol as a metabolic control of liver lipoprotein and xenobiotic metabolism. Publications, patents, books and chapters have been filed for evaluation of education for obesity, diabetes and AD. Martin is the Chief Editor for Scientific and Academic Publishing (2013/2014) and a reviewer for international journals and Grant agencies.

Molecular mechanisms involved with neuroendocrine diseases such as obesity and diabetes are closely linked to insulin resistance and require attention since metabolic dysfunction has also been associated with neurodegeneration. The global increase in these chronic diseases supports a role for lipids, such as ceramide and its metabolites in the pathogenesis of these diseases. The link between the ceramide and its pathogenesis of diabetes has been an important discovery that may assist with the role of ceramide in the pathogenesis of Alzheimer’s disease (AD) also referred to as Type 3 diabetes. Lipids such as cholesterol and ceramide have been connected to processing of the amyloid precursor protein with generation or regulation of beta-amyloid production that is central to the amyloid hypothesis in AD. The cholesterol-ceramide connection has been previously linked with aging and AD. Lipidomic analysis using mass spectrometry of fasting plasma from an ageing cohort (AIBL) that includes mild cognitively impaired individuals, cognitively healthy controls and AD patients at baseline have been provided in this study. The plasma lipid ceramide was elevated in AD patients and this study provides potential for early therapeutic targets that reduce ceramide levels to manage hypercholesterolemia and insulin resistance in both diabetes and AD.

Objective
Obesity appears to be the most critical risk factor for metabolic complications. However, no direct relationship between body weight and metabolic abnormalities exist. The present study was designed to investigate aimpact of body mass index (BMI) and the presence of metabolic syndrome (MS) on early vascular atherosclerotic changes, as determined by AI and PWV. Design and Methods
The 285study participantswere divided into four groups according to BMI and MSGroup 1 included 71 metabolically normal, normal-weight subjects (MNNW); Group 2 included 69 metabolically obese, normal-weight subjects (MONW); Group 3 included of 66 metabolically obese, overweight subjects (MOOW) and Group 4 consisted of 79 metabolically obese, obese subjects (MOOB). Results
AI and PWV differed significantly between groups, such that increased from Group 1 to Group 4 in a continuous fashion. AI was significantly lower in normal weight subjects without MS than in normal weight subjects with MS (p<0.001).In Univariate GLM analysis, significant by-group differences in AI persisted even after adjustmentfor age, sex and blood pressure. Conclusions
AI was significantly higher in normal weight subjects with MS compared to normal weight metabolically benign individuals. Thus, even in patients with normal weight (BMI<=25), presence of metabolic syndrome was associated with significant deterioration in terms of arterial stiffness.

S O Adewole completed his Ph.D at the age of 46 years from Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria, Postdoctoral fellowship studies from University of KwaZulu-Natal, Durban, South Africa. He is the Chief Medical Director, Jim-Steve Medical Centre, Ipetumodu, Nigeria, Head of Anatomy, Obafemi Awolowo University. He has Published 44 papers in reputable journals and is serving as reviewer for many repute journals. His research focus has been in markers of oxidative stress, evaluating the ameliorative effects of herbal extracts and drugs on various tissues in diabetic states. As Anatomist we have better understanding of effects of diabetes mellitus on the microanatomy of various organs in the body and we are able to monitor the ameliorative effects of some of the herbal products in diabetic rats.

The hypotensive and hypoglycaemic effects of Ficus exasperata (Vahl) (family: Moraceae) leaf aqueous extract (FEE) were investigated in experimental rat models. In this study, spontaneously-hypertensive rats (SHR) (type 1 diabetes), obese Zucker (type 2 diabetes) and Wistar rats were used. Three (A, B and C) groups of rats, each group consisting of 10 rats, were used. Group A Wistar rats received distilled water in quantities equivalent to the volume of streptozotocin (STZ) and FEE administered intraperitoneally to treated rats. Diabetes mellitus was induced in the SHR group B rats by multiple low-dose (MLD) intraperitoneal injections of STZ (40 mg/kg body weight) to induce type 1 diabetes. The animals in group C were the obese Zucker rats with non-insulin-independent diabetes mellitus (NDDM) (type 2 diabetes) on genetic basis. F. exasperata leaf aqueous extract (FEE, 100 mg/kg/day p.o.) was administered orally by orogastric intubation to fasted Groups B and C rats. In groups B and C rats, administration of FEE commenced 4 weeks post STZ injection, and continued for the next 4 consecutive weeks. Group A rats gave normal biochemical and morphological findings. Group B rats exhibited pronounced polyuria, hypoinsulinaemia, hyperlipidaemia and hyperglycaemia. These findings were also observed in group C rats, except that there was hyperinsilinaemia. Histopathological study of the aortic blood vessels showed extensive collagen fiber formation as well as perivascular fibrosis in both groups B and C rats. Four weeks of oral administration of F. exasperata leaf aqueous extract to diabetic groups of rats decreased blood glucose, blood pressure and lipid profiles. Administration of FEE (100 mg/kg p.o.) also restored the microanatomy of the blood vessels to almost normal levels. The findings of this study suggest that F. exasperata leaf aqueous extract possesses hypoglycaemic, hypotensive and hypolipidaemic properties. These findings lend biomedical and pharmacological support to the folkloric, ethnomedical uses of the plant in the management and/or control of diabetes and hypertension among the Yoruba-speaking people of Western Nigeria.

Elaine Christine Dantas Moisés has completed her PhD in 2008 from the Ribeirão Preto Medical School, University of São Paulo. She is a professor in the Department of Gynecology and Obstetrics of this institution. Her work has an emphasis on the following themes: Pharmacokinetics of drugs in pregnant women, placental transfer of drugs, Diabetes Mellitus in pregnant women.

Brief Introduction
Recurrent hyperinsulinemic hypoglycemia is an unusual metabolic disorder which can result in adverse perinatal outcome when it affects pregnant women.
History and clinical findings
A 21 year-old pregnant woman, first pregnancy, forwarded to prenatal follow-up in tertiary center due to frequent episodes of hypoglycemia history since she was three months old, with worsening during the first half of pregnancy.
Investigation and diagnosis
Clinical research showed frequent episodes of hypoglycemia, reaching levels corresponding to 18mg%, accompanied by hyperinsulinemia. The image analysis using ultrasound and nuclear magnetic resonance were negative, suggesting the diagnosis of hyperplasia of pancreatic betacells.
Treatment and course
The management was carried out through nutritional support, accompanied by glucose monitoring and daily analysis of fetal vitality, plus daily prescription of Diazoxide 75 mg and 15 mg prednisone, both orally. Patient evolved with satisfactory glycemic control until 35 weeks of gestational age, when it was indicated resolution of pregnancy by a progressive decrease in plasma glucose levels. The male newborn presented birth weight of 2330 grams, Apgar Score of 9 and 10 at one minute and five minutes of life, respectively. He was discharged from the University General Hospital, Medical School of Ribeirão Preto of University of São Paulo together with her mother with ten days of life. Patient refused pancreatic surgery as definitive treatment, opting for long-term clinical follow-up.
Conclusion
Hypoglycemia secondary to hyperinsulinemia by pancreatic cell hyperplasia is a rare entity, which requires careful maternal and fetal monitoring, because of its complications. Drug management during pregnancy is possible, improving perinatal outcomes.