Cytokines,adipocytokines and inflammatory markers in patients on continuous ambulatory peritoneal dialysis and hemodialysis

Background: Cytokines are essential mediators of immune response. Chronic renal failure patients suffer from chronic inflammation that results from factors such as impaired renal function, accumulation of uremic toxins and bio incompatibility of dialyzer membranes. These patients are also at increased risk of cardiovascular diseases. We have evaluated cytokines, adipocytokines and inflammatory markers in patients with chronic renal failure undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD).

Material and methods: We have determined serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), leptin and ghrelin levels of chronic renal failure patients treated with either HD (n?=?20) or CAPD (n?=?20). TNF-α, IL-6, ghrelin and leptin measurements were performed by commercially available kits based on enzyme-linked immunosorbent assay (ELISA) method. hsCRP levels were determined by turbidimetric methods.

Results: Serum TNF-α and IL-6 levels of patients on HD were significantly higher than those of the ones on CAPD (p?<?0.05). Ghrelin, leptin and hsCRP concentrations were similar in both groups.

Conclusions: We can conclude that cytokine production is more obvious in HD process.     

Primary hypertrophic pyloric stenosis in the adult: a case report.

A 66-year-old male was admitted with a two-month history of vomiting and weight loss. Endoscopy showed a pyloric obstruction and the patient underwent subtotal gastrectomy with gastro- jejunostomy. The histopathological study of the specimen revealed primary hypertrophic pyloric stenosis without any evidence of duodenal peptic disease. In the adult, this is a rare cause of gastric outlet obstruction of unknown etiology. It is usually recognized by histopathological examination of the specimen after a gastric resection performed to treat gastric outlet obstruction syndrome. However, some endoscopic and radiological signs, such as the cervix sign, or elongation of the pyloric channel, may give clues about the presence of the disease preoperatively. In symptomatic cases, surgery is the preferred treatment modality.     

Inflammatory status influences aromatase and steroid receptor expression in endometriosis

Aberrant up-regulation of aromatase in eutopic endometrium and implants from women with endometriosis has been reported. Aromatase induction may be mediated by increased cyclooxygenase-2 (COX-2). Recently, we demonstrated that progesterone receptor (PR)-A and PR-B serve an antiinflammatory role in the uterus by antagonizing nuclear factor kappaB activation and COX-2 expression. PR-C, which antagonizes PR-B, is up-regulated by inflammation. Although estrogen receptor alpha (ERalpha) is implicated in endometriosis, an antiinflammatory role of ERbeta has been suggested. We examined stage-specific expression of aromatase, COX-2, ER, and PR isoform expression in eutopic endometrium, implants, peritoneum, and endometrioma samples from endometriosis patients. Endometrial and peritoneal biopsies were obtained from unaffected women and those with fibroids. Aromatase expression in eutopic endometrium from endometriosis patients was significantly increased compared with controls. Aromatase expression in endometriosis implants was markedly increased compared with eutopic endometrium. Aromatase mRNA levels were increased significantly in red implants relative to black implants and endometrioma cyst capsule. Moreover, COX-2 expression was increased in implants and in eutopic endometrium of women with endometriosis as compared with control endometrium. As observed for aromatase mRNA, the highest levels of COX-2 mRNA were found in red implants. The ratio of ERbeta/ERalpha mRNA was significantly elevated in endometriomas compared with endometriosis implants and eutopic endometrium. Expression of PR-C mRNA relative to PR-A and PR-B mRNA was significantly increased in endometriomas compared with eutopic and control endometrium. PR-A protein was barely detectable in endometriomas. Thus, whereas PR-C may enhance disease progression, up-regulation of ERbeta may play an antiinflammatory and opposing role.     

Induction of apoptosis and inhibition of growth of human hepatoma HepG2 cells by heparin

BACKGROUND/AIMS: Apoptotic and anti-proliferative effects of heparin on a number of cancers have been described. There have been no studies analyzing the effect of heparin on human hepatoma cells. The aim of this study was to investigate the effect of heparin on human hepatoma cell line, HepG2. METHODOLOGY: HepG2 cell line was cultured with different concentrations of heparin. Colony count, viability assay, percentage of the apoptosis and proliferative index were assessed at the end of the 7th day. Trypan blue was used to assess viability. Apoptosis and proliferative indexes were assessed by flow-cytometry. RESULTS: Hepatoma cells were arrested at the G0/G1 phase with heparin incubation and proliferative indexes decreased significantly in 20, 40 and 80 U/mL of heparin concentrations in comparison with the control (36 +/- 1%, 30 +/- 5% and 29 +/- 8% vs. 44 +/- 1%, p < 0.01). Flow cytometry revealed a statistically significant increase in apoptosis in groups incubated with 40 and 80 U/mL of heparin in comparison with the control (39 +/- 26% and 58 +/- 18% vs. 0.83 +/- 1.3%, p < 0.01). Colony counts per well and viable cells per microL decreased significantly in 80 U/mL of heparin. CONCLUSIONS: Heparin leads to a significant anti-proliferative and an apoptotic effect on human hepatoma cells in vitro.     

Serum lipid and leptin concentrations in hypopituitary patients with growth hormone deficiency

OBJECTIVE: To investigate the effects of growth hormone (GH) deficiency on serum lipid and leptin concentrations in hypopituitary patients taking conventional replacement therapy and to determine the relations between leptin and gender and anthropometric and metabolic variables. SUBJECTS: Twenty-one GH deficient adult hypopituitary patients (15 women, six men) and 21 (14 women, seven men) age, sex and body mass index (BMI) matched healthy controls. MEASUREMENTS: After an overnight fast, anthropometric parameters were measured and body composition was determined by a bioelectrical impedance analyser. Venous blood samples were obtained for the measurements of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, intact insulin, insulin-like growth factor 1 (IGF-1) and leptin concentrations. Serum leptin and hormones were analysed by radioimmunoassay. RESULTS: Hypopituitary patients with GH deficiency showed significantly higher triglyceride, total and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The unfavourable lipid profile was particularly evident in women. Significantly higher leptin concentrations were found in patients compared with healthy controls with similar body fat content (23. 5+/-11.8 ng/ml vs 11.7+/-6.9 ng/ml, P=0.01). This difference remained significant even when leptin values were expressed in relation to fat mass percentage (0.79+/-0.40 vs. 0.42+/-0.17 ng/ml%, P<0.05) and fat mass kg (1.32+/-0.81 vs 0.66+/-0.30 ng/ml kg, P<0. 05). Significant positive correlations were observed between leptin concentrations and body fat percentage and age in the control group. In patients the sole significant relation between leptin and study parameters was the positive correlation observed between leptin and total cholesterol concentrations. Serum leptin concentrations were significantly higher in women than men in the control group, but not in the patients. No significant gender difference was observed when leptin concentrations were expressed in relation to fat mass (percentage and kg). CONCLUSION: Growth hormone deficient hypopituitary patients (particularly women) on conventional replacement therapy have a more atherogenic lipid profile. Leptin concentrations are increased in GH deficient adults even after adjustment for percentage body fat and body fat mass (kg). Although the nature of our data does not allow us to draw any conclusions on the mechanism(s) of increased leptin concentrations in GH deficiency, decreased central sensitivity to leptin and increased leptin production from per unit fat mass, or alterations in leptin clearance, might be operative.     

Effects of octreotide and propranolol on colonic mucosa in rats with portal hypertensive colopathy

BACKGROUND/AIMS: The aim of the study is to clarify the effects of octreotide and propranolol, agents used in the treatment of portal hypertension, on mucosal changes in portal hypertensive colopathy. METHODOLOGY: Portal hypertension was induced in all rats by partial portal vein ligation, and after the operation all rats were caged for a 10-week period. Then, animals were divided into three groups and for two weeks medical treatment were administered to the individual groups as follows: Control group, saline 0.5 mL/day, intraperitoneally. Octreotide group, octreotide 100 micrograms/kg/12 hours, subcutaneously. Propranolol group, propranolol 20 mg/kg/day, intraperitoneally. In order to assess the portal hypertensive colopathy, criteria such as mean diameters of dilated vessels in colonic mucosa, and the existence of mucosal edema, capillary ectasia, hyperemia and hemorrhage, inflammation were used. RESULTS: When parameters were compared for the control versus propranolol groups, mucosal edema and hyperemia and hemorrhage criteria were found to be significant for the propranolol group; control versus octreotide groups, mucosal edema, capillary ectasia, and hyperemia and hemorrhage criteria were found to be significant for the octreotide group; octreotide versus propranolol groups, capillary ectasia and mucosal edema criteria were found to be significant for the octreotide group. CONCLUSIONS: The mucosal changes in portal hypertensive colopathy could be corrected by drugs modifying portal blood flow, octreotide may find a place in the treatment of portal hypertensive colopathy.     

Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect

Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 G--> A) in the TSHbeta gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHbeta locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHbeta mutation is among the more common TSHbeta gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal.     

Myocardial ischemia-reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin

Myocardial ischemia-reperfusion (I/R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. I/R injury is believed to be a consequence of free radical generation in the heart especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and pharmacological concentrations have been shown to reduce the I/R-induced cardiac damage in isolated rat hearts. However, the physiological role of melatonin in the prevention of this damage is unknown. Rats were pinealectomized or sham-operated (control) 2 months before the I/R studies. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Infarct size, expressed as the percentage of the risk zone, was found significantly higher in pinealectomized rats (49+/-3.4%) than in the control group (34+/-3.6%). Melatonin administration (4 mg/kg, either before ischemia or reperfusion) to pinealectomized rats significantly reduced the infarct size values and returned them to the control values. On the other hand, melatonin administration (4 mg/kg) to sham-operated rats failed to attenuate significantly the I/R-induced infarct size. These results suggest that physiological melatonin concentrations are important in reducing the I/R-induced myocyte damage, while pharmacological concentrations of melatonin did not add to the beneficial effect. As melatonin levels have been reported to decrease with age, melatonin replacement therapy may attenuate I/R-induced myocardial injury, especially in older patients.     

A rare cause of hydrops fetalis in two Gaucher disease type 2 patients with a novel mutation

Metabolic Brain Disease - Gaucher disease type 2 is the most progressive and the rarest form of Gaucher disease, defined as the acute neuronopathic type. We presented two GD2 patients who died...