Effects of limited food intake and vitamin C supplementation on pancreatic glucagon and insulin in guinea pigs.

The aim of this study was to investigate the effects of limited food intake (LFI) (24, 48 and 120 h) and a single i.p. dose of vitamin C supplementation (500 mg/kg) on serum glucose and C-peptide levels, and pancreatic insulin and glucagon levels in guinea pigs. The highest serum glucose levels were found after vitamin C supplementation plus LFI for 48 h (LFI 48). Serum C-peptide levels were not significantly affected by food limitation (LFI 24, LFI 48, or LFI 120) as compared with controls, but when vitamin C was supplemented, the C-peptide levels were moderately enhanced. Immunohistochemical findings on pancreatic islets showed increased staining intensity for both insulin and glucagon when vitamin C was supplemented. In addition, the alpha and beta cells were stimulated, particularly by vitamin C supplementation plus LFI 120. Based on these findings, vitamin C supplementation may have a beneficial effect on the alpha and beta cells.

Serum levels of sL-selectin and tumour necrosis factor-alpha in children with type 1 diabetes mellitus.

Type 1 diabetes mellitus (DM) is a result of inflammation and destruction of alpha-cells in the pancreatic islet cells. The aim of this study is to evaluate the associations of diabetes with soluble L-selectin (sL-selectin) and tumour necrosis factor-alpha (TNF-alpha) in children with type 1 DM; and also to evaluate the associations of these parameters with the disease period, glycaemic control state and puberty stage. Serum sL-selectin and TNF-alpha levels were measured in 44 children with type 1 DM and 44 healthy children. Neither the patients nor the control group showed significant difference between the levels of sL-selectin and TNF-alpha (sequence mean 12.17+/-1.62 ng/ml vs. 12.62+/-1.56 ng/ml and 7.27+/-3.1 pg/ml vs. 7.88+/-2.7 pg/ml). There was no statistically significant difference between children with duration of diabetes longer than 5 years and children with duration of diabetes shorter than 1 year. There was also no statistically significant difference between poor glycaemic control and good-acceptable glycaemic control patients. The present results indicate that sL-selectin and TNF-alpha serum levels are not increased and cannot be used as prognostic predictors in type 1 DM; and also sL-selectin and TNF-alpha do not change with the disease period, glycaemic control state and puberty stage.

Sequential cytokine levels in the diagnosis of appendicitis.

OBJECTIVE: To determine the diagnostic value of sequential white blood cell count (WBC), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in patients with abdominal pain. MATERIAL AND METHODS: Tests were determined at hospital admission and 6 h later in 105 children. Patients who were non-operatively followed and had a normal histopathology were classified as the non-appendicitis (NA) group. Patients with symptoms consistent with appendicitis were classified as the appendicitis group (A). Data were analyzed as positive/negative predictive value, sensitivity, specificity and accuracy rate (AR). The global power of the variables in discriminating the patients between the two groups and advanced/simple appendicitis was assessed from the area under the receiver operating characteristic (ROC). RESULTS: Initial measurements showed WBC to be a valuable diagnostic tool in acute appendicitis (AR = 74 %), whereas IL-6 and TNF-alpha were found not to be valuable. The second measurements revealed higher values, and IL-6 reached its highest AR (89 %). When initial values were evaluated in combination, the highest AR of 73 % was observed with TNF-alpha + WBC. The highest AR (90 %) was seen with IL-6 + TNF-alpha in the second measurements. ROC analysis showed WBC to be the most valuable parameter of the three. The area under the curve (AUC) was 0.750 for the initial measurement and 0.779 for the repeat measurement of WBC (p = 0.001). The most useful diagnostic parameter in discriminating between the simple and the advanced cases was IL-6 as assessed with the ROC curve (p<0.01). CONCLUSIONS: WBC elevation in patients with suspected acute appendicitis is an important parameter supporting the diagnosis at initial admission, whereas IL-6 is a more valuable tool in diagnosing advanced appendicitis.

Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats.

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.

Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer.

Angiogenesis plays an important role in tumor growth and metastasis in solid tumors. VEGF is an important regulator of tumor angiogenesis. Both leptin and prolactin have also been suggested to have roles in the regulation of angiogenic process. In our study, we measured serum leptin, prolactin and VEGF levels in 30 metastatic, 55 non-metastatic breast cancer patients and 25 control subjects. Serum leptin levels were found to be similar in non-metastatic (38.1+/-19.5 ng/ml), metastatic patients (39.6+/-16.3 ng/ml) and control subjects (35.6+/-13.9 ng/ml) (p>0.05). There was no statistically significant difference between patients with visceral metastasis (44.0+/-16.8 ng/ml) and patients with bone metastasis (35.2+/-15.0 ng/ml) (p>0.05). Serum prolactin levels were found to be similar in non-metastatic (12.2+/-10.7 ng/ml), metastatic patients (11.6+/-8.2 ng/ml) and control subjects (12.3+/-8.1 ng/ml), (p>0.05). Moreover, serum prolactin levels were not different in patients with visceral (11.4+/-8.8 ng/ml) and bone metastasis (11.8+/-8.0 ng/ml), (p>0.05). Metastatic patients had higher serum VEGF levels (249.8+/-154.9 pg/ml), when compared to the non-metastatic patients (138.7+/-59.3 pg/ml) and control subjects (108.4+/-47.7 pg/ml), (p<0.05). There was no difference in serum VEGF levels in non-metastatic patients and control subjects (p>0.05). Patients with visceral metastasis (337.0+/-168.0 pg/ml) had higher serum VEGF levels, when compared to patients with bone metastasis (162.6+71.8 pg/ml), (p<0.05). Serum VEGF activity may be used to evaluate angiogenic and metastatic activity in breast cancer patients. However, serum leptin and prolactin levels does not seem to be related with angiogenic activity and metastasis in breast cancer patients.

Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes.

The present study investigated the effects of alpha-lipoic acid treatment (50 mg/kg/day) on the metabolism and vascular condition already damaged by streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism, oxidative stress and antioxidant status were assessed in non-diabetic controls, 12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks and then treated with alpha-lipoic acid for the last 6 weeks) rats. Blood pressures of rats were measured by tail-cuff method. Vascular reactivity was evaluated in isolated aortic rings. Morphology of aorta was examined by electron microscopy technique. Alpha-lipoic acid treatment effectively reversed body weight, blood glucose, plasma insulin, cholesterol, triglycerides and lipid peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood pressure, which was partially improved by alpha-lipoic acid treatment. Although the superoxide dismutase (SOD) activity in aortic homogenates was not changed by diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx) activity significantly increased in untreated diabetic rats. Alpha-lipoic acid treatment improved catalase activity in diabetic aorta. The contractile effect of phenylephrine markedly increased in diabetic rings, which was completely reversed by alpha-lipoic acid treatment. The maximum vasorelaxant response of pre-contracted aortic rings exposed to cumulatively increased concentrations of acetylcholine was unaffected by diabetes or antioxidant treatment. Sodium nitroprusside-induced endothelium-independent relaxations were similar in all experimental groups. Various alterations caused by STZ-diabetes in aorta structure were partially ameliorated by alpha-lipoic acid treatment. The potency of alpha-lipoic acid on the reversal of hypertension by affecting vascular reactivity and morphology as well as general metabolism of diabetic rats confirms the importance of hyperglycemia-induced oxidative stress in the development of diabetes-induced vascular complications and suggests a potential therapeutic approach.

Effect of vitamin E on adriamycin- induced nephrotoxicity at the ultrastructural level in guinea pigs.

It is known that Adriamycin, which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in several organs. In this study, we have established that vitamin E has some beneficial effects on the kidney by protecting it from some of the toxicity induced by Adriamycin. A study was carried out which comprised one control group and two experimental groups of guinea pigs. In the experiment Adriamycin was administered either alone (group II) or together with vitamin E (group III). The results of groups II and III were compared with controls (group I). The kidneys were subsequently removed and examined by routine electron microscopic techniques. We found that vitamin E administered together with Adriamycin could reverse some of the degenerative changes caused by Adriamycin.

Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in obese children.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) metabolism may be disturbed in obese children. We investigated serum GH, IGF-I, IGF-binding protein-3 (IGFBP-3) levels in 42 obese and 40 non-obese healthy children aged 6-14 years. GH stimulation tests with L-dopa and insulin were performed. Serum IGF-I levels were studied by immunoradiometric assay (IRMA) and IGFBP-3 levels by radioimmunoassay (RIA). IGF-I levels were significantly higher in the obese group (p < 0.05), but IGFBP-3 levels were not different from the control group. IGF-I and IGFBP-3 levels were significantly higher in the obese pubertal children than in the obese prepubertal ones (p < 0.05). A positive linear correlation was found between body mass index (BMI) and IGF-I levels (r = 0.51, p < 0.05). These results suggest that obesity may have a considerable effect on IGF-I.

Effects of inhaled steroid treatment on serum eosinophilic cationic protein (ECP) and low affinity receptor for IgE (Fc epsilon RII/sCD23) in childhood bronchial asthma.

Serum eosinophilic cationic protein (ECP) and soluble low affinity receptor for IgE (Fc epsilon RII/sCD23) concentrations were measured in relation to symptom-medication scores, pulmonary function, and total IgE levels in 27 chronic allergic asthmatic children (17 boys, 10 girls), mean age 10.8 years, before and at the end of a three month inhaled corticosteroid (budesonide) treatment period. Serum ECP and sCD23 concentrations were also measured in age matched non-asthmatic controls with allergic rhinitis. All asthma patients had significantly higher serum ECP and sCD23 than the controls, whereas the mean serum IgE was not different. No correlation between total IgE concentrations and serum sCD23 could be detected in either group. At the end of the treatment period, symptom-medication scores and pulmonary function improved. Serum ECP and sCD23 concentrations were reduced; however, total IgE values did not change significantly. A significant relation was found between the improvement of symptom-medication scores and fall in both sCD23 and ECP concentrations. Although there was a significant correlation of pulmonary function values with serum ECP, no such relation was observed for sCD23. It appears that serum sCD23 and ECP concentrations could be good disease markers, particularly in asthma. Monitoring of serum inflammation markers, especially ECP, may be useful in the follow up of asthmatic children on anti-inflammatory treatment.

Changes in serum type I and III procollagen levels in children with chronic renal failure.

Serum levels of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) can be used as markers of bone formation and the evaluation of children with growth disorders. We measured the serum levels of these collagens with radioimmunoassay in 24 children aged between 4 and 14 years with chronic renal failure (CRF; n = 12 dialysis, n = 12 nondialysis) and 12 age-matched healthy controls, to find out whether these parameters have a prognostic or therapeutic value in monitoring the growth retardation in CRF. Mean serum PIIINP levels in the dialysis patients were higher than in the control group; the difference between the groups was statistically significant (p < 0.05). It seemed that the pubertal stage of the patients did not affect the levels of PICP and PIIINP. There was no significant correlation between PICP and PIIINP in any patients. Neither PICP nor PIIINP correlated with the height z-score or bone age. It was concluded that the increased serum PIIINP levels in renal patients might be accepted as a poor prognostic factor leading to progressive renal failure and end-stage renal disease. Further investigations into the effects of these collagens on growth failure associated with CRF are needed.

Tumor necrosis factor-alpha (TNF-alpha) in pleural fluids.

Our study was undertaken to investigate the role of tumor necrosis factor-alpha (TNF-alpha) at the site of disease activity in tuberculous pleuritis (TP). Concentrations of TNF-alpha were measured directly by radioimmunoassay (RIA) in the pleural fluid (PF) and plasma (P) of patients with TP (n = 14), malignant effusions (n = 18) and transudates (n = 7). Among these three groups mean plasma levels of TNF-alpha were not statistically significant (P > 0.05), but in the TP group mean levels of TNF-alpha in PF were significantly higher than in the cancer and transudate groups (P < 0.001), and there was no significant difference between the cancer and transudate groups (P > 0.05). These results may indicate a local synthesis of TNF-alpha by cells within the pleural cavity in this disease.