Effects of curcumin administration on Nesfatin-1 levels in blood, brain and fat tissues of diabetic rats.

OBJECTIVE: We evaluated the efficacy of curcumin administration on blood glucose levels and its relationship with nesfatin-1 levels in blood brain and adipose tissue of streptozotocin-induced diabetic rats. MATERIALS AND METHODS: A total of 28 male rats were divided into four groups: control group, type 2 diabetes mellitus (DM) group, control plus curcumin group and type 2DM plus curcumin group. After fifteen days, blood samples were collected from sacrificed rats. Nesftain-1 levels were analysed from blood, brain, and fat tissues of rats in all groups. RESULTS: Nesfatin-1 level was found to be significantly lower in blood, brain and fat tissues of type 2 DM rats compared to the control group. A significant decrease in fasting blood glucose levels was observed in the curcumin administration group compared to type 2 DM group. Improvement of fasting blood glucose level was accompanied by improvement of nesfatin-1 levels in blood, brain, and fat tissues. CONCLUSIONS: As expected, curcumin administration caused significant improvement in fasting blood glucose levels. However, for the first time, we found marked improvements in nesfatin-1 levels in blood, brain, and fat tissues of type 2 DM rats. Thus, considering the crucial role of nesfatin-1 in regulation of glucose metabolism, it is logical to expect an interactive relationship between curcumin and nesfatin-1.

Comparative determination of ventilatory efficiency from constant load and incremental exercise testing.

The analysis of the relationships between minute ventilation (VE) to CO2 output (VCO2), referred to as ventilatory efficiency, in response to incremental exercise testing, is considered a useful index for assessing the presence and severity of cardiopulmonary and metabolic diseases. The effects of constant load exercise testing performed at work intensity associated with anaerobic threshold (AT) and respiratory compensation points (RCP), on the accurate measurements of ventilatory efficiency are not well known. The aim of this present study was to investigate the reliability of the VE/VCO2 ratio obtained from constant load exercise tests performed with two important metabolic rates (at the AT and RCP) and compare it to that of those of incremental exercise tests. A total of 20 young male (20.8±0.4 yr) subjects initially performed an incremental exercise test and then two constant load exercise tests, on different days. Respiratory and pulmonary gas exchange variables were used to estimate AT and RCP. A paired t-test was used to analyse data. AT and RCP (average) occurred the at 60% and at 71% of peak O2 uptake, respectively. The lowest VE/VCO2 ratio recorded within the first 2 minutes of constant load exercise tests with a work load of AT (26.4±0.3) and RCP (26.7±0.5) was not statistically different from the lowest ratio obtained from the incremental exercise tests (26.0±0.7). In the constant load exercise test, despite the different metabolic rates, the increase in ventilation corresponded closely with the increase in CO2 production, reflecting an optimal ventilation and perfusion ratio. Clinicians should consider the constant load exercise test work load associated with AT and RCP as it provides a meaningful lowest value for ventilatory efficiency.

Evaluation of relationship between aerobic fitness level and range of isocapnic buffering periods during incremental exercise test.

The purpose of this study is to examine the relationship between the amount of O2 uptake (VO2) in the range of isocapnic buffering (ICB) periods and aerobic fitness levels of subjects with different exercise tolerance levels. A total of 50 young male subjects (20.8±0.4 years) performed an incremental exercise test using a cycle ergometer to determinetheir anaerobic threshold (AT), respiratory compensation point (RCP) and maximal exercise capacity (Wmax). The ICB period is defined as the region between AT and RCP. Pulmonary gas exchange parameters were measured breath-by-breath using a respiratory gas analyser. The subjects' fitness levels, as indicated by peak O2 uptake to body weight ratios (VO2peak/BW), ranged from 28 ml/min/kg to 58 ml/min/kg, and Wmax capacity to body weight ratio (Wmax/BW) ranged from 1.94 W/min/kg to 3.96 W/min/kg. The VO2 in the range of ICB periodsranged from 101 ml to 793 ml (with an average of 295±157 ml). There was a positive linear correlation between VO2peak/BW, Wmax/BW and range of ICB: R=0.76542 (p<0.0001), and R=0.92135 (p<0.0001), respectively. The results of this study suggest that the range of ICB periods may be related to aerobic fitness. Importantly, aerobic fitness levels should be evaluated and considered important data, in addition toAT, VO2peak/BW and Wmax/BW.

The effects of blood glucose regulation on tear function tests in diabetic patients.

PURPOSE: To investigate whether blood glucose regulation in patients with diabetes mellitus (DM) has an influence on the ocular surface disease index (OSDI) score and tear function tests such as tear film osmolarity (TFO), tear break-up time (TBUT) and Schirmer tests. METHODS: Fifty diabetic patients with a fasting blood glucose (FBG) level greater than 200mg/dL and HbA1c level greater than 10% were recruited for this prospective study. All of the patients underwent a detailed ophthalmic examination including OSDI questionnaire, TFO test, TBUT test and Schirmer test initially. All tests were repeated after obtaining regulation of patients' blood sugar (approximately 6 weeks later). RESULTS: The mean age of the diabetic patients in the study was 54.96±12.48 years. Initially, the mean FBG, postprandial blood glucose (PBG) and HbA1c levels were 301.40±79.11mg/dL, 431.06±74.47mg/dL and 12.31±1.67%, respectively. After blood glucose regulation; the levels of all parameters (153.78±59.32mg/dL, 252.32±88.34mg/dL and 9.67±1.60%, respectively) statistically significantly decreased (P<0.001). The mean levels of OSDI score, TFO measurement, TBUT test and Schirmer test were 28.38±16.46 points, 349.66±13.09 mOsm/L, 6.44±1.91s and 8.66±3.57mm initially, and 17.82±11.70 points, 314.14±12.80 mOsm/L, 6.62±2.03s and 9.02±3.68mm after blood glucose regulation, respectively. Although the improvements in TBUT and Schirmer test values were not statistically significant (P>0.05), statistically significant reduction was obtained in OSDI scores and TFO levels (P<0.001, for each). CONCLUSION: DM, which is a hyperosmolar disorder, appears to cause elevation in OSDI score and increase in TFO level, especially if blood glucose is poorly regulated.

Nitric oxide levels in response to the patients with different stage of diabetes.

The association between hyperglycaemia and serum nitric oxide (NO) levels has not yet been fully clarified. Thus, it was aimed to evaluate the concentration of NO metabolites (nitrate, nitrite) in diabetic patients and to find the relationship between hyperglycaemia and serum NO levels in diabetic and prediabetic patients, and control groups. In this study, 100 subjects were divided into 3 groups: healthy control (n=20), prediabetic (n=40) and diabetic (n=40). Glycemic control was assessed using glycated hemoglobin (HbA1c). Nitrate and nitrite levels were measured using the Griess reagent. NO was obtained from the sum of nitrates and nitrites. The serum NO level was higher in diabetic (53.4±2.0 µM) and prediabetic patients (51.6±1.6 µM) as compared to that in the control (45.6±1.2 µM), (p<0.05). The NO level was not significantly different in diabetic and prediabetic patients. Higher levels of serum glucose, insulin and HOMA-IR may be responsible for the activation of endothelial cells to increase NO levels. This study supports the role of insulin resistance in increased NO levels in both diabetic and prediabetic patients.

Clinical effects of probiotics containing Bacillus species on gingivitis: a pilot randomized controlled trial.

BACKGROUND AND OBJECTIVE: Lactobacillus spp. and bifidobacteria are the most frequently used probiotics in oral health research. However, although probiotic effects have been suggested for other genera, such as bacilli, no trials are available to describe the effect of bacilli probiotics on gingivitis in humans. The aim of the present study was to evaluate the clinical effects of a bacilli-containing toothpaste, a mouthrinse and a toothbrush cleaner versus a placebo in patients with generalized gingivitis. MATERIAL AND METHODS: In this double-blind placebo-controlled randomized clinical trial, nonsmoking, systemically healthy patients with generalized gingivitis were included. They used a placebo or an experimental probiotic Bacillus subtilis-, Bacillus megaterium- and Bacillus pumulus-containing toothpaste, mouthrinse and toothbrush cleaner for 8 wk. Primary outcome measures of interest were plaque and gingivitis index, and the secondary outcome measures were pocket probing depth and bleeding on probing. RESULTS: Twenty male and 20 female patients were randomized over the two groups. All participants could be included in the final analysis. Although plaque and gingivitis indices were significantly reduced after 8 wk, no intergroup differences could be found at any time point. Also, for the secondary outcome measure, intragroup but no intergroup differences could be detected. No harm or unintended effects were reported by the patients after using the study products. CONCLUSIONS: This study did not show any statistically significant differences between a placebo and a bacilli-containing toothpaste, mouthrinse and toothbrush cleaner on gingivitis parameters.

Serum nesfatin-1 levels in patients with different glucose tolerance levels.

The aim of this study was to compare the levels of nesfatin-1 in healthy subjects with those in prediabetic and diabetic patients who have different glucose tolerance levels. Overall, 100 subjects were divided into 5 groups healthy control (C), impaired fasting glycemia (IFG), impaired glucose tolerance (IGT), metabolic syndrome (MS) and type 2 diabetes mellitus, (Type 2 DM). Glycated hemoglobin (HbA1c) assessed the glycemic control. Homeostasis model assessment of insulin resistance (HOMA-IR) was determined using computer analyses. Nesfatin-1 levels were measured using ELISA method. IFG and IGT (prediabetic groups) from MS and Type 2 DM (diabetic groups) differed significantly in HOMA-IR. The nesfatin-1 levels were lower, although not statistically significant, in IFG (0.937+/-0.03 ng/ml, p=0.07) and IGT (1.039+/-0.06 ng/ml, p=0.5) groups compared to healthy subjects (1.094+/-0.07 ng/ml). However, the nesfatin-1 levels were lower in patients with Type 2 DM (0.867+/-0.02 ng/ml, p=0.007) and MS (0.885+/-0.01 ng/ml, p=0.01) compared to healthy subjects. Nesfatin-1 levels were significantly lower in diabetic patients compared to healthy subjects. This study supports the role of insulin resistance in decreased nesfatin-1 levels in patients with Type 2 DM and MS.

Bone health and vitamin D status in alcoholic liver disease.

Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (<80 nmol/L). The lowest serum vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.

Effects of eight weeks of exercise training and orlistat therapy on body composition and maximal exercise capacity in obese females.

A comparative assessment was made of the short-term effects of orlistat therapy and exercise training on body composition and aerobic fitness in obese females. A total of 24 obese patients were enrolled in to the study; 12 received orlistat therapy (DO) and 12 participated in a regular aerobic exercise-training programme (DE). All patients were on hypocaloric diets. Each patient performed three incremental ramp exercise tests (one at Week 0, one at the end of Week 4 and one at the end of Week 8) to exhaustion using an electromagnetically braked cycle ergometer to determine their anaerobic threshold and maximal exercise (Wmax) capacity. Patients in the DE group performed continuous exercise at a work rate that corresponded to the anaerobic threshold. Weight loss and loss of fat mass after 8 weeks were -6.4% (P=0.002) and -13.4% (DE) vs -5.8% (P=0.002) and -6.4% (P=0.008) (DO), respectively. Wmax capacity was 90.8+/-5 W (basal) vs 92.9+/-5 W (Week 4, P=0.1) and 100.4+/-6 W (Week 8, 10.5%, P=0.04) in the DO group, and 96.2+/-6 W (basal) vs 129.1+/-4 W (Week 4, 34.1%, P=0.002) and 137.5+/-5 W(Week 8, 42.9%, P=0.002) in the DE group. Despite similar decreases in body weight in both groups, patients in the DE group achieved a markedly higher level of Wmax, reflecting a better improvement in cardiopulmonary fitness, compared with patients in the DO group. Considering the improvement of aerobic fitness in the short term, an aerobic exercise-training programme should be considered for sedentary obese patients to improve their aerobic fitness and thereby reduce the negative outcomes of obesity.

Effects of different weight loss protocols on serum leptin levels in obese females.

We investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of three 12-week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions (P<0.01) in body weight and fat mass after the 12 week period in all groups: -11.4+/-0.5 kg and -9.8+/-0.5 kg (OEWL), -8.3+/-0.8 kg and -5.7+/-0.9 kg (OWL), -8.9+/-1.2 kg and -7.4+/-1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2 % (OEWL1), -37.8 % (OWL) and -48.6 % (EWL) (P<0.01 all). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2+/-7.2 % (OEWL), -27.8+/-4.8 % (OWL) and -39.3+/-4.3 % (EWL) (P<0.01 all). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group (P=0.03). Consequently, an exercise training program in adjunct to pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment. It also seems to have further beneficial effects on leptin resistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass.

Effects of acute hypoxia on the estimation of lactate threshold from ventilatory gas exchange indices during an incremental exercise test.

The purpose of this study was to investigate the validity of non-invasive lactate threshold estimation using ventilatory and pulmonary gas exchange indices under condition of acute hypoxia. Seven untrained males (21.4+/-1.2 years) performed two incremental exercise tests using an electromagnetically braked cycle ergometer: one breathing room air and other breathing 12 % O2. The lactate threshold was estimated using the following parameters: increase of ventilatory equivalent for O2 (VE/VO2) without increase of ventilatory equivalent for CO2 (VE/VCO2). It was also determined from the increase in blood lactate and decrease in standard bicarbonate. The VE/VO2 and lactate increase methods yielded the respective values for lactate threshold: 1.91+/-0.10 l/min (for the VE/VO2) vs. 1.89+/-0.1 l/min (for the lactate). However, in hypoxic condition, VE/VO2 started to increase prior to the actual threshold as determined from blood lactate response: 1.67+/-0.1 l/min (for the lactate) vs. 1.37+/-0.09 l/min (for the VE/VO2) (P=0.0001), i.e. resulted in pseudo-threshold behavior. In conclusion, the ventilatory and gas exchange indices provide an accurate lactate threshold. Although the potential for pseudo-threshold behavior of the standard ventilatory and gas exchange indices of the lactate threshold must be concerned if an incremental test is performed under hypoxic conditions in which carotid body chemosensitivity is increased.

Effects of body mass index on maximal work production capacity and aerobic fitness during incremental exercise.

The aim of this study was to investigate the relationship between cardiopulmonary fitness as indicated by maximal work rate (Wmax) production and aerobic capacities (WAT), body mass index (BMI) and heart rate reserve. A total of 60 sedentary subjects (30 males, 30 females, aged 18-25 years) were enrolled in the study. Each subject performed an incremental exercise test (15 W/min) to the limit of tolerance on an electromagnetically-braked cycle ergometer. There was a negative correlation between increased BMI to Wmax capacity per kilogram body weight in male (r=-0.846, P=0.0001) and in female (r=-0.896, P=0.0001) subjects. In addition, W(AT) for each kilogram body weight also negatively correlated with increased BMI in male (r=-0.870, P=0.0001) and in females (r=-0.807, P=0.0001). The heart rate reserve correlated negatively with increasing BMI: r=-0.699, P=0.0001 (males) and r=-0.655, P=0.0001 (females). The results of the present study have suggested that, due to the inverse correlation between BMI, Wmax capacity, aerobic fitness and heart rate reserve, it may be useful to consider BMI in establishing cardiopulmonary fitness in various subjects.

Effects of acute hypoxia on the determination of anaerobic threshold using the heart rate-work rate relationships during incremental exercise tests.

Anaerobic threshold which describes the onset of systematic increase in blood lactate concentration is a widely used concept in clinical and sports medicine. A deflection point between heart rate-work rate has been introduced to determine the anaerobic threshold non-invasively. However, some researchers have consistently reported a heart rate deflection at higher work rates, while others have not. The present study was designed to investigate whether the heart rate deflection point accurately predicts the anaerobic threshold under the condition of acute hypoxia. Eight untrained males performed two incremental exercise tests using an electromagnetically braked cycle ergometer: one breathing room air and one breathing 12 % O2. The anaerobic threshold was estimated using the V-slope method and determined from the increase in blood lactate and the decrease in standard bicarbonate concentration. This threshold was also estimated by in the heart rate-work rate relationship. Not all subjects exhibited a heart rate deflection. Only two subjects in the control and four subjects in the hypoxia groups showed a heart rate deflection. Additionally, the heart rate deflection point overestimated the anaerobic threshold. In conclusion, the heart rate deflection point was not an accurate predictor of anaerobic threshold and acute hypoxia did not systematically affect the heart rate-work rate relationships.

Effects of short-period exercise training and orlistat therapy on body composition and maximal power production capacity in obese patients.

We examined the effects of weight loss induced by diet-orlistat (DO) and diet-orlistat combined with exercise (DOE) on maximal work rate production (Wmax) capacity in obese patients. Total of 24 obese patients were involved in this study. Twelve of them were subjected to DO therapy only and the remaining 12 patients participated in a regular aerobic exercise-training program in addition to DO therapy (DOE). Each patient performed two incremental ramp exercise tests up to exhaustion using an electromagnetically-braked cycle ergometer: one at the onset and one at the end of the 4th week. DOE therapy caused a significant decrease in total body weight: 101.5+/-17.4 kg (basal) vs 96.3+/-17.3 kg (4 wk) associated with a significant decrease in body fat mass: 45.0+/-10.5 kg (basal) vs 40.9+/-9.8 kg (4 wk). DO therapy also resulted in a significant decrease of total body weight 94.9+/-14.9 kg (basal) vs 91.6+/-13.5 kg (4 wk) associated with small but significant decreases in body fat mass: 37.7+/-5.6 kg (basal) to 36.0+/-6.2 kg (4 wk). Weight reduction achieved during DO therapy was not associated with increased Wmax capacity: 106+/-32 W (basal) vs 106+/-33 W (4 wk), while DOE therapy resulted in a markedly increased Wmax capacity: 109+/-39 W (basal) vs 138+/-30 W (4 wk). DO therapy combined with aerobic exercise training resulted in a significant reduction of fat mass tissue and markedly improved the aerobic fitness and Wmax capacities of obese patients. Considering this improvement within such a short period, physicians should consider applying an aerobic exercise-training program to sedentary obese patients for improving their physical fitness and thereby reduce the negative outcomes of obesity.

Effect of altered body CO2 stores on pulmonary gas exchange dynamics during incremental exercise in humans.

The lactate threshold is a widely used and, at times, controversial construct in exercise physiology and pathophysiology. Its non-invasive estimation during incremental exercise depends upon CO2 output increasing as a function of O2 uptake, i.e. 'V-slope', as a result of bicarbonate buffering during the lactic acidosis. However, we hypothesised that the V-slope deflection could also occur as a consequence of metabolic CO2 being diverted proportionally more into the CO2 stores in the early phase of exercise. Eight healthy males performed two incremental exercise tests on a cycle ergometer, with and without controlled prior hyperventilation; the hyperventilation caused end-tidal PCO2 to decline by 10 mmHg, with the clearance of a CO2 volume averaging 2547 ml. This corresponded to an 'effective' CO2 capacitance of some 3.12 ml mmHg-1 kg-1. Gas exchange was determined breath-by-breath, and blood was sampled from the dorsum of the heated hand. Our results demonstrate that the early dynamics of CO2 wash-in to the previously depleted body stores can result in a 'pseudo-threshold', i.e. significantly before the onset of the actual lactic acidosis. Precautions should therefore be taken to avoid hyperventilation prior to non-invasive estimation of the lactate threshold.

Engineered mutants of HGF/SF with reduced binding to heparan sulphate proteoglycans, decreased clearance and enhanced activity in vivo.

BACKGROUND: Although a number of growth factors bind cell-surface heparan sulphate proteoglycans (HSPGs), the role of this interaction is unclear except for fibroblast growth factor which requires HSPG binding for signalling. Hepatocyte growth factor/scatter factor (HGF/SF) plays important roles in mammalian development and tissue regeneration and acts on target cells through a specific receptor tyrosine kinase encoded by the c-met proto-oncogene. This factor also binds HSPGs with high affinity, but conflicting data have been reported on the role of HSPG binding in HGF/SF signalling. RESULTS: To map the binding sites for HSPG and the Met receptor in HGF/SF, we have engineered a number of HGF/SF mutants in which several clusters of solvent-accessible residues in the hairpin structure of the amino-terminal domain or in kringle 2 have been replaced. Two of the mutants (HP1 and HP2) showed greatly decreased (more than 50-fold) affinity for heparin and HSPGs but retained full mitogenic and motogenic activities on target cells in culture. Furthermore, when compared with wild-type HGF/SF, the HP1 mutant exhibited a delayed clearance from the blood, higher tissue levels and a higher induction of DNA synthesis in normal, adult murine liver. CONCLUSIONS: These results establish the following: the binding sites in HGF/SF for Met and for HSPGs can be dissociated by protein engineering; high-affinity binding of HGF/SF to HSPGs is not essential for signalling; one role of HSPG binding in the HGF/SF system appears to be sequestration and degradation of the growth factor; and HGF/SF mutants with decreased affinity for HSPGs exhibit enhanced activity in vivo.