Ghrelin and peptide YY increase with weight loss during a 12-month intervention to reduce dietary energy density in obese women

Reducing dietary energy density (ED) promotes weight loss; however, underlying mechanisms are not well understood. The purpose of this study was to determine if low-ED diets facilitate weight loss through actions on ghrelin and peptide YY (PYY), independent of influences of psychosocial measures. Seventy-one obese women (BMI 30–40 kg/m²) ages 22–60 years received counseling to reduce ED. Fasting blood samples were analyzed for total ghrelin and total PYY by radioimmunoassay at months 0, 3, 6, and 12. Restraint, disinhibition, and hunger were assessed by the Eating Inventory. Body weight (−7.8 ± 0.5 kg), BMI (−2.9 ± 0.2 kg/m²), body fat (−3.0 ± 0.3%), and ED (−0.47 ± 0.05 kcal/g or −1.97 ± 0.21 kJ/g) decreased from months 0 to 6 (p < 0.05) after which no change occurred from months 6 to 12. Ghrelin increased in a curvilinear fashion (month 0: 973 ± 39, month 3: 1024 ± 37, month 6: 1109 ± 44, and month 12: 1063 ± 45 pg/ml, p < 0.001) and PYY increased linearly (month 0: 74.2 ± 3.1, month 3: 76.4 ± 3.2, month 6: 77.2 ± 3.0, month 12: 82.8 ± 3.2 pg/ml, p < 0.001). ED, body weight, and hunger predicted ghrelin, with ED being the strongest predictor (ghrelin = 2674.8 + 291.6 × ED − 19.2 × BW − 15 × H; p < 0.05). There was a trend toward a significant association between ED and PYY (PYY = 115.0 − 43.1 × ED; p = 0.05). Reductions in ED may promote weight loss and weight loss maintenance by opposing increases in ghrelin and promoting increases in PYY.     

Increased plasma levels of osteopontin are associated with activation of the renin–aldosterone system and with myocardial and coronary microvascular damage in dilated cardiomyopathy

In patients with dilated cardiomyopathy (DCM) abnormal myocardial blood flow (MBF) has been associated with coronary microvascular dysfunction. The aim of this study was to test the hypothesis that osteopontin (OPN) plasma levels could be associated with the activation of the renin–aldosterone system (RAS) in these patients and be involved in mediating myocardial and coronary damage. In 66 patients with idiopathic left ventricular dysfunction of variable severity the plasma levels of OPN were correlated with biomarkers of systemic metabolism, RAS activation, myocardial dysfunction and with clinical indexes of left ventricle (LV) function and perfusion obtained by 2D-echocardiography and PET. As compared to controls, patients showed a significant increase of inflammatory markers (OPN: 508 ± 30.8 ng/ml vs. 426.9 ± 16.4, p < 0.05 and interleukin (IL)-6: 1.71 ± 0.29 pg/ml vs. 0.38 ± 0.03 pg/ml, p < 0.001) and of indexes of cardiac damage. OPN levels were significantly correlated with the extent of microvascular dysfunction (MBF at rest: p = 0.01; during dipyridamole: p = 0.0003) and with plasma renin activity (PRA) (r = 0.26, p = 0.04). Both in patients with milder or more severe LV dysfunction lower MBF values were associated with higher OPN levels and PRA. These results suggest a interdependent role of RAS and vascular inflammation in cardiomyopathy.     

Serum zinc levels of cord blood: Relation to birth weight and gestational period

BackgroundZn-deficiency has been associated with numerous alterations during pregnancy including low birth weight; however, the research relating neonatal zinc status and birth weight has not produced reliable results.ObjectiveTo compare the serum Zn-levels of cord blood in healthy newborns and low birth weight newborns, and to assess a possible relationship between zinc concentration and neonatal birth weight and gestational age.Material and methods123 newborns divided in “study group” (n = 50) with <2500 g birth weight neonates and “control group” (n = 73) with ≥2500 g birth weight neonates were enrolled. Study group was subdivided according to gestational age in preterm (<37 weeks) and full-term (≥37 weeks). Serum cord blood samples were collected and the Zn-levels were analyzed using flame Atomic Absorption Spectrophotometry method and the result was expressed in μmol/L. The Zn-levels were compared between the groups (Mann–Whitney-U test) and the Zn-levels were correlated with the birth weight and gestational age (Spearman's rank correlations).ResultsStatistically significant low positive correlation between Zn-levels and birth weight (ρ = 0.283; p = 0.005) was found. No statistically significant difference between Zn-levels of study and control groups [17.00 ± 0.43 vs. 18.16 ± 0.32 (p = 0.053)] was found. Statistically significant low positive correlation between Zn-levels and gestational age (ρ = 0.351; p = 0.001) was found. No statistically significant difference between Zn-levels of preterm as compare to full-term newborns [16.33 ± 0.42 vs. 18.43 ± 0.93 (p = 0.079)] was found. Zn-level of preterm subgroup was significantly lower compared to control group (p = 0.001).ConclusionsDespite low birth weight preterm neonates had significantly lower serum zinc levels of cord blood than healthy term neonates, the correlation between cord blood zinc levels and birth weight and gestational age was lower. The results are not enough to relate the change in cord blood zinc concentration to the birth weight values or gestational period. In relation to complicated pregnancies, further studies regarding zinc levels in blood in our population are required.     

The relationship between interleukin-6 in saliva,venous and capillary plasma,at rest and in response to exercise

IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise. The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma. Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA). In Trial A venous plasma IL-6 increased significantly from 0.4 ± 0.14 pg/ml to 0.99 ± 0.29 pg/ml (P < 0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change. In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22 ± 0.18 to 0.74 ± 0.28 pg/ml (P ⩽ 0.01); capillary: 0.37 ± 0.22 to 1.08 ± 0.30 pg/ml (P < 0.01). Venous and capillary plasma responses did not correlate at rest (r = 0.59, P = 0.07) but did correlate post exercise (r = 0.79, P ⩾ 0.001) and when expressed as an exercise induced change (r = 0.71, P = 0.02). Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise.     

Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard exposure

Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used against Iranian soldiers during the period from 1983 to 1988. We have investigated serum cytokines profiles of Khorasan veterans who were exposed to SM >23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due to delayed complications of SM poisoning and had disabilities were investigated. A total of 30 healthy male volunteers (relatives of the veterans) were selected as the control group. Cytokine levels were measured in the serum of case and control subjects using commercial ELISA kits. Hematologic parameters (white/red blood cell counts, hemoglobin levels, immune cell differentials) were also performed on blood samples from the study subjects. The results indicated that serum levels of ICAM-1 were significantly higher in the samples from SM-exposed veterans (772.8 [±15.1] ng/ml [p = 0.014] vs. control values of 710.2 [±20.0] ng/ml). On the other hand, serum IL-1β, IL-8 levels and TNFα, were significantly lower for the veterans than the controls (IL-1β: 3.8 [±0.1] vs. 4.3 [±0.2] pg/ml, p = 0.037; IL-8: 21.0 [±6.1] vs. 84.6 [±20.3] pg/ml, p = 0.002; TNFα: 4.5 [±0.1] vs. 5.5 [± 0.1] pg/ml, p = 0.027). Levels of other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNγ, TNFβ, and sVCAM-1 were not significantly different between the study populations. None of the assayed hematologic parameters appeared to differ as well. It seems possible that dysfunctions could have been induced in the innate immune functions of the SM-exposed veterans as a result of these changes in cytokine expression and that these, in turn, may have contributed to the increased incidence of a myriad of diseases that have been documented in these veterans, including cancers. Future studies must focus on examining the significance of these changes in circulating cytokines and their potential contribution to the development of different diseases in veterans exposed to SM.     

Serum sialic acid changes in non-insulin-dependant diabetes mellitus (NIDDM) patients following bitter melon (Momordica charantia) and rosiglitazone (Avandia) treatment

Diabetes mellitus is associated with an increase in sialic acid concentration along with other complications. Sialic acid changes in NIDDM patients were investigated following bitter melon (55 ml/24 h) and rosiglitazone (4 mg/24 h) treatment. A total of 25 patients of both sexes were used in each experimental group. Patients following bitter melon treatment showed no significant difference of serum sialic acid (57.95±4.90 vs. 57.6±5.56 mg/dl, p=0.17) and serum glucose concentration (93.7±9.63 vs. 88.35±6.31 mg/dl, p=0.78) as compared to control subjects. However, the concentration of total cholesterol was significantly high in these patients as compared to control subjects (192±14.23 vs. 170.6±15.1 mg/dl, p<0.03) but within normal range (160–200 mg/dl), suggesting the significant hypoglycemic and lipid-lowering properties of bitter melon. The patients following rosiglitazone treatment showed a significant increase of serum sialic acid concentration (60.2±5.80 vs. 57.6±5.56 mg/dl, p=0.01) along with glucose (112±6.2 vs. 88.35±6.31 mg/dl, p<0.04) and total cholesterol concentration (216.45±20.2 vs. 170.6±15.1 mg/dl, p<0.01) as compared to control subjects. In addition six of the patients had retinopathy, two of whom were suffering also from myocardial infarction and they still had a higher serum sialic acid (61.05±1.20 mg/dl), glucose (187±2.11 mg/dl), total cholesterol (239.10±5.04 mg/dl) and triglyceride (183±4.14 mg/dl) concentration, indicating a poor response of these patients to rosiglitazone. Comparison of serum sialic acid concentration of patients, following bitter melon and rosiglitazone treatment revealed no significant difference but the study showed that bitter melon could be more effective in the management of diabetes and its related complications as compared to rosiglitazone.     

Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: A randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice

Inadequate intake of the recommended five-a-day fruit and vegetable portions might contribute to increased cardiovascular disease risk. We assessed the effects of dietary intake of a blackcurrant juice drink, rich in vitamin C and polyphenols, on oxidative stress and vascular function. This was a double-blind, placebo-controlled, parallel group study of 66 healthy adults who habitually consume <2 portions of fruit and vegetables per day. Participants were randomly allocated to consume 250 ml of placebo (flavored water) or low or high blackcurrant juice drink four times a day for 6 weeks. Flow-mediated dilation (FMD) and plasma concentrations of F₂-isoprostanes and vitamin C were measured. In the high blackcurrant juice drink group FMD increased significantly (5.8±3.1 to 6.9±3.1%, P=0.022) compared with the placebo group (6.0±2.2 to 5.1±2.4%). Plasma vitamin C concentration increased significantly in the low (38.6±17.6 to 49.4±21.0 µmol/L, P<0.001) and high (34.6±20.4 to 73.8±23.3 µmol/L, P<0.001) blackcurrant juice drink groups compared with the placebo group (38.1±21.0 to 29.0±17.6 µmol/L). F₂-isoprostane concentrations were significantly lower in the high blackcurrant juice drink group (225±64 pg/ml) compared with the low blackcurrant juice drink (257±69 pg/ml, P=0.002) and placebo group (254±59 pg/ml, P=0.003). At follow-up, changes in plasma vitamin C correlated significantly with changes in FMD (r=0.308, P=0.044). Consumption of blackcurrant juice drink high in vitamin C and polyphenols can decrease oxidative stress and improve vascular health in individuals with habitually low dietary fruit and vegetable intake.     

Chronic central ghrelin infusion reduces blood pressure and heart rate despite increasing appetite and promoting weight gain in normotensive and hypertensive rats

Acute studies showed that ghrelin acts on the central nervous system (CNS) to reduce blood pressure (BP), heart rate (HR) and sympathetic activity. However, the long-term CNS cardiovascular actions of ghrelin are still unclear. We tested whether chronic intracerebroventricular (ICV) infusion of ghrelin causes sustained reductions in BP, HR and whether it alters baroreceptor sensitivity (BRS) and autonomic input to the heart. A cannula was placed in the lateral ventricle of male Sprague–Dawley (SD) rats for ICV infusions via osmotic minipump (0.5 μl/h). BP and HR were measured 24-h/day by telemetry. After 5 days of control measurements, ghrelin (0.21 nmol/h) or saline vehicle were infused ICV for 10 days followed by a 5-day post-treatment period. Chronic ICV ghrelin infusion increased food intake (22 ± 3 to 26 ± 1 g/day) leading to ∼50 g body weight gain. BP fell slightly during ghrelin infusion while HR decreased by ∼26 bpm. In control animals BP and HR increased modestly. ICV Ghrelin infusion caused a 50% reduction in sympathetic tone to the heart but did not alter BRS. We also tested if the depressor responses to ICV ghrelin infusion were enhanced in spontaneously hypertensive rats (SHR) due to their high basal sympathetic tone. However, we observed similar BP and HR responses compared to normotensive rats. These results indicate that ghrelin, acting via direct actions on the CNS, has a sustained effect to lower HR and a modest impact to reduce BP in normotensive and hypertensive animals despite increasing appetite and body weight.     

Fire service instructor's undergarment choice to reduce Interleukin-6 and minimise physiological and perceptual strain

Fire Service Instructors frequently experience high levels of physiological and perceptual strain during live fire exposures. Instructors are also at risk of cardiovascular illnesses, with cardiac death being the greatest cause of fire fighter death. Current practice for UK instructors is to select undergarment type based on personal preference, between a boiler suit (BOILER) and a wicking base layer (WBL). Research suggests that shorts and t-shirt (SHORTS) may also be a beneficial alternative undergarment choice. The UK South East Fire Service requested an investigation to identify if undergarment selection can lessen the strain experienced by instructors, and reduce the acute inflammatory response to fire exposures. Eight males completed three 45 min sessions in a heat chamber (49.5±1.4 °C and 16.9±4.3% RH) whilst performing intermittent walking. At the end of heat exposure change in heart rate was not effected by garment type (p=0.061, ηp²=0.373). Change in rectal temperature was different between garments (p=0.009, η_p²=0.271), with trends suggesting that BOILER resulted in a greater change (1.03±0.60 °C) than SHORTS (0.76±0.37 °C, p=0.589, d=0.21) and WBL (0.72±0.33 °C, p=0.545, d=0.25). Interleukin-6 post exposure was greater for BOILER (6.96±0.28 pg mL⁻¹) than both SHORTS (6.59±0.30 pg mL⁻¹, p=0.043, d=0.42) and WBL (6.45±0.43 pg mL⁻¹, p=0.031, d=0.51). Overall, undergarment type had little impact on physiological or perceptual strain. However, wearing WBL or SHORTS may reduce the inflammatory response, and consequently decrease the risk of cardiovascular events.     

Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity – Correlation with body mass index

Irisin was recently identified as cleavage product of fibronectin type III domain containing 5 (FNDC5) and shown to increase energy expenditure in mice and humans and therefore was discussed as potential treatment option in obesity. However, the regulation of irisin under conditions of severely altered body weight such as anorexia nervosa and obesity remains to be investigated. We analyzed circulating irisin levels over a broad spectrum of body weight in 40 patients with anorexia nervosa (mean body mass index, BMI 12.6 ± 0.7 kg/m²), normal weight controls (22.6 ± 0.9 kg/m²) and obese patients with BMI of 30–40 (36.9 ± 1.2 kg/m²), 40–50 (44.9 ± 1.1 kg/m²) and >50 (70.1 ± 2.7 kg/m², n = 8/group). Correlation analyses were performed between irisin and different body indices, parameters of body composition and hormones involved in various homeostatic processes. Obese patients showed higher circulating irisin levels compared to normal weight and anorexic patients (p < 0.05) resulting in a correlation of irisin with body weight (r = 0.47, p < 0.01) and BMI (r = 0.50, p < 0.001). Plasma irisin was also positively correlated with fat mass (r = 0.48, p < 0.01), body cell mass (r = 0.45, p < 0.01) and fat free mass (r = 0.40, p < 0.05). Insulin levels were positively correlated with irisin (r = 0.45, p < 0.01), whereas circulating ghrelin, cortisol, thyroid-stimulating hormone or C-reactive protein were not (p > 0.05). These data indicate that circulating irisin is affected under conditions of altered BMI with highest levels in severely obese patients. The increase of irisin under conditions of obesity may indicate a physiological function to improve glucose tolerance which is often impaired in obese subjects.     

High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study

The aim of our investigation was to find out if ghrelin concentrations or polymorphisms predict the future risk for cardiovascular diseases and cancer in a population-based cohort initiated in 1991 (491 hypertensive and 513 control subjects). Total mortality and hospital events were followed up for 19 years. Fasting total ghrelin concentrations were determined and Arg51Gln, Leu72Met and −501A > C polymorphisms identified. Cox regression analysis was performed. The mean value in the control cohort was 674 pg/ml whereas in the hypertensive cohort it was 661 pg/ml. The associations found suggest that in the controls the highest ghrelin quartile protected from CHD (coronary heart disease). The results were significant without or with adjustments for age, sex, smoking, systolic blood pressure and LDL cholesterol, BMI, type 2 diabetes or QUICK index. C/C variant of the promoter associated with the prevention of IHD (ischemic heart disease) in the hypertensive group (p < 0.05). The controls with the Leu72Leu genotype had less cancer (p < 0.05). In conclusion, high plasma ghrelin concentration was related to protection from CHD and Leu72Leu genotype to prevention of cancer in healthy adults during the 19 years follow-up. C/C promoter protects from IHD in the hypertensive subjects.     

The ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) is present in human plasma and expressed dependent on body mass index

Ghrelin is the only known peripherally produced and centrally acting peptide hormone stimulating food intake. The acylation of ghrelin is essential for binding to its receptor. Recently, the ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) was identified in mice, rats and humans. In addition to gastric mucosal expression, GOAT was also detected in the circulation of rodents and its expression was dependent on metabolic status. We investigated whether GOAT is also present in human plasma and whether expression levels are affected under different conditions of body weight. Normal weight, anorexic and obese subjects with body mass index (BMI) 30–40, 40–50 and >50 were recruited (n = 9/group). In overnight fasted subjects GOAT protein expression was assessed by Western blot and ghrelin measured by ELISA. GOAT protein was detectable in human plasma. Anorexic patients showed reduced GOAT protein levels (−42%, p < 0.01) whereas obese patients with BMI > 50 had increased concentrations (+34%) compared to normal weight controls. Ghrelin levels were higher in anorexic patients compared to all other groups (+62–78%, p < 0.001). Plasma GOAT protein expression showed a positive correlation with BMI (r = 0.71, p < 0.001) and a negative correlation with ghrelin (r = −0.60, p < 0.001). Summarized, GOAT is also present in human plasma and GOAT protein levels depend on the metabolic environment with decreased levels in anorexic and increased levels in morbidly obese patients. These data may indicate that GOAT counteracts the adaptive changes of ghrelin observed under these conditions and ultimately contributes to the development or maintenance of anorexia and obesity as it is the only enzyme acylating ghrelin.     

Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: A randomized clinical trial

The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n = 30) or pioglitazone (Group B; n = 30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (p < 0.01), hemoglobin A1c (p < 0.01 in Group A and p < 0.05 in Group B), and insulin resistance (p < 0.01). The effect of metformin on preprandial ghrelin and its response to glucose challenge was not significant, while the pioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (p < 0.05). The effect of pioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.     

A randomized cross-over study of the effects of macronutrient composition and meal frequency on GLP-1, ghrelin and energy expenditure in humans

ObjectiveLittle is known about human postprandial increase of energy expenditure and satiety-associated hormones in relation to both meal frequency and macronutrient composition.DesignRandomized cross-over study with four conditions for each participant.MethodsSeven men and seven women (mean age 23 ± 1.5 years) were randomly assigned to the order of intake of a 750 kcal drink with the same protein content while having either 20 energy-percent (E%) or 55 E% from carbohydrates and the remaining energy from fat. Participants were also randomized to consume the drinks as one large beverage or as five 150 kcal portions every 30 min, starting in the fasting state in the morning. Energy expenditure (EE) was determined every 30 min by indirect calorimetry. Hormonal responses and suppression of hunger (by visual-analogue scales) were also studied. A p < 0.013 was considered statistically significant following Bonferroni-correction.ResultsThe area under the curve (AUC) for EE was higher during the 2.5 h after the high-carbohydrate drinks (p = 0.005 by Wilcoxon) and also after ingesting one drink compared with five (p = 0.004). AUC for serum active GLP-1 was higher after single drinks compared with five beverages (p = 0.002). Although GLP-1 levels remained particularly high at the end of the test during the low-carbohydrate meals, the AUC did not differ compared with the high-carbohydrate occasions (low-carbohydrate: 58.9 ± 18 pg/ml/h, high-carbohydrate: 45.2 ± 16 pg/ml/h, p = 0.028). Hunger sensations were suppressed more after single beverages compared with five small drinks (p = 0.009).ConclusionsWe found higher EE during 2.5 h following one large drink compared with five smaller beverages. Since hunger was also suppressed more efficiently, and serum GLP-1 levels were higher after one compared with five smaller drinks, our findings do not support nibbling to avoid hunger or to keep up EE from morning to noon.     

Hair cortisol determination in sows in two consecutive reproductive cycles

Hair analysis has been proposed as a minimally invasive technique capable of furnishing information regarding the stress response during medium- and long-term periods. Bristle samples were collected from the rump region of sows at three key physiological phases (before delivery – BD; weaning time – WT; pregnancy diagnosis – PD) during consecutive reproductive cycles in order to test swine hair as a reliable matrix of cortisol evaluation. Cortisol was extracted from the bristles and assayed using radioimmunoassay. The highest mean hair cortisol concentrations were demonstrated (p < 0.001) at the PD time points (20.1 ± .95 and 16.29 ± 2.15 pg/mg). Moreover, cortisol was significantly higher (p < 0.001) at BD2 (10.48 ± 0.96 pg/mg) as compared to BD1 (5.17 ± 0.51 pg/mg) and WT1 (6.01 ± 0.47 pg/mg). The various physiological phases had a significant effect on cortisol concentration (p < 0.00001) with a higher cortisol concentration found during late pregnancy and lactation than in early-mid pregnancy. This could be due not only to the physiological hormonal status, but also to the different housing conditions (single crates vs. group housing). The season of the year was also observed to have an effect (p < 0.005), with the lowest cortisol concentration recorded during the hot season.     

Short-term glutamate administration positively affects the number of antral follicles and the ovulation rate in cyclic adult goats

The acute effects of short-term glutamate administration on the number of antral follicles and ovulation rate were examined in adult goats. Neither live weight (44.5 ± 1.3 kg) nor body condition (3.3 ± 0.8 units) differed between the control (untreated) and glutamate-treated (0.175 mg/kg) animals (p > 0.05). However, the number of antral follicles (3.4 vs. 2.1, p = 0.05) and ovulation rate (2.5 vs. 1.5, p = 0.05) was higher in the glutamate-administered group than in the controls.     

Comparison of NT-proCNP and CNP plasma levels in heart failure,diabetes and cirrhosis patients

C-type natriuretic peptide (CNP) plasma levels are extremely low and a pre-analytical phase is necessary to assay plasma CNP concentrations. Amino-terminal CNP (NT-proCNP) circulates at higher concentrations than CNP, allowing a direct assay and the use of smaller amounts of plasma.Aim of this study was to evaluate the analytical performance of a direct NT-proCNP assay and to measure its plasma levels in heart failure (CHF), diabetes and chirrosis patients.NT-proCNP and CNP were measured in 130 CHF, 19 patients with diabetes, 24 with hepatic cirrhosis and 73 controls.Plasma NT-proCNP was higher in all the clinical conditions studied (controls:45.5 ± 1.84 pg/ml, CHF:67.09 ± 7.36, diabetes:51.5 ± 5.75 cirrhosis:78.4 ± 19.9; p = 0.034, p = 0.04 controls vs. CHF and cirrhosis, respectively) and in CHF NT-proCNP concentration showed a significant increase as a function of clinical severity.By comparison of ROC curves, CNP assay resulted better associated with disease than NT-proCNP assay in all the different clinical conditions probably due to different release and clearance.The determination of NT-proCNP adds a piece of information to better understanding the molecular mechanisms at the basis of CNP action in different diseases.Due to its higher analytical feasibility, this determination could become widespread in clinical biochemistry laboratories and serve as a complementary marker of disease conditions.     

Resistance exercise modulates lipid plasma profile and cytokine content in the adipose tissue of tumour-bearing rats

Cancer cachexia is a multifactorial syndrome characterised by progressive weight loss, frequently accompanied by anorexia, sarcopenia, and chronic systemic inflammation. The white adipose tissue is markedly affected by cachexia and contributes to this syndrome throught the secretion of pro-inflammatory factors which reach the adjacent tissues and the circulation. A nonpharmacologic intervention that may attenuate cancer cachexia is chronic physical activity, but the effect of resistance training upon adipose tissue inflammation in cachexia has never been examined. For that purpose we designed a protocol in which animals were randomly assigned to a control group (CT, n = 7), a Tumour bearing group (TB, n = 7), a Resistance Trained group (RT, n = 7) and a Resistance Trained tumour bearing group (RTTB, n = 7). Trained rats climbed a vertical ladder with an extra load attached to the tail, representing 75–90% of total body mass, 3 times per week, for 8 weeks. In the 6th week of resistance training, tumour cells (3 × 10⁷ Walker 256 carcinosarcoma) were inoculated in the tumour groups. Body, adipose tissue, muscle and tumour mass was determined, as well a blood biochemical parameters, and the hormone and cytokine profile assessed. The glycogen content of the liver and muscle was measured. IL-10, IL-6 and TNF-α protein expression was evaluated in the mesenteric adipose tissue (MEAT) examined. Resistance training increased by 9% body weight gain in RTTB (final weight 310.8 ± 9.8 g), when compared with TB (final weight 288.3 ± 4.9 g). LDL-c levels were decreased in RTTB (0.28 ± 0.9 mmol/L) by 43% when compared with TB (0.57 ± 0.1 mmol/L). HDL-c levels were increased in RTTB (1.31 ± 0.12 mmol/L) by 15% in regard to CT (1.13 ± 0.7 mmol/L) and 22% as compared with TB (1.07 ± 0.07 mmol/L). RTTB testosterone levels (577 ± 131 ng/mL) were 55% higher when compared with CT (254 ± 41.3 ng/mL) and 63% higher when compared with TB (221 ± 23.1 ng/mL). Adiponectin levels were augmented in RT (23 μg/mL) by 43% when compared with TB (11 μg/mL). Protein expression of IL-6 was increased 38% in TB MEAT (5.95 pg/μg), as compared with CT (3.64 pg/μg) and 50% compared with RTTB (2.91 pg/μg). Similar results with respect to TNF-α TB (7.18 pg/μg) were observed: 39% and 46%, higher protein expression in comparison with CT (4.63 pg/μg) and RTTB (3.8 pg/μg), respectively. IL-10 protein expression was found to be increased in TB (4.4 pg/μg) and RTTB (3.2 pg/μg) 50% and 47%, respectively, in comparison with CT (1.2 pu/μg). The IL-10/TNF-α ratio was higher in RTTB in relation to all others experimental groups. The results show a robust effect of resistance exercise training in preventing important symptoms of cancer cachexia, thus strongly suggesting it may appear as an alternative to endurance exercise as a non-pharmacological therapy in the management of this syndrome.     

Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats

AimsAngiotensin-converting enzyme (ACE) inhibitors are used in diabetic kidney disease to reduce systemic/intra-glomerular pressure. The objective of this study was to investigate whether reducing blood pressure (BP) could modulate renal glucose transporter expression, and urinary markers of diabetic nephropathy in diabetic hypertensive rats treated with ramipril or amlodipine.Main methodsDiabetes was induced in spontaneously-hypertensive rats (~ 210 g) by streptozotocin (50 mg/kg). Thirty days later, animals received ramipril 15 μg/kg/day (R, n = 10), or amlodipine 10 mg/kg/day (A, n = 8,) or water (C, n = 10) by gavage. After 30-day treatment, body weight, glycaemia, urinary albumin and TGF-β1 (enzyme-linked immunosorbent assay) and BP (tail-cuff pressure method) were evaluated. Kidneys were removed for evaluation of renal cortex glucose transporters (Western blotting) and renal tissue ACE activity (fluorometric assay).Key findingsAfter treatments, body weight (p = 0.77) and glycaemia (p = 0.22) were similar among the groups. Systolic BP was similarly reduced (p < 0.001) in A and R vs. C (172.4 ± 3.2; 186.7 ± 3.7 and 202.2 ± 4.3 mm Hg; respectively). ACE activity (C: 0.903 ± 0.086; A: 0.654 ± 0.025, and R: 0.389 ± 0.057 mU/mg), albuminuria (C: 264.8 ± 15.4; A: 140.8 ± 13.5 and R: 102.8 ± 6.7 mg/24 h), and renal cortex GLUT1 content (C: 46.81 ± 4.54; A: 40.30 ± 5.39 and R: 26.89 ± 0.79 AU) decreased only in R (p < 0.001, p < 0.05 and p < 0.001; respectively).SignificanceWe concluded that the blockade of the renin–angiotensin system with ramipril reduced early markers of diabetic nephropathy, a phenomenon that cannot be specifically related to decreased BP levels.     

C-type natriuretic peptide plasma levels are reduced in obese adolescents

The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8 ± 0.4 years; BMI: 29.8 ± 0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4 ± 0.2 vs 13.6 ± 2.3 pg/ml, p < 0.0001; BNP: 18.8 ± 2.6 vs 36.9 ± 5.5 pg/ml, p = 0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.