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.     

Pinealectomy exaggerates and melatonin treatment suppresses neuroma formation of transected sciatic nerve in rats: gross morphological, histological and stereological analysis

At present, an intensive effort for prevention of neuroma formation following peripheral nerve section continues. It has been recently suggested that surgical pinealectomy (Px) induces elevation of the collagen content in the granulation tissue of a wound, while melatonin application after Px suppresses elevation of the collagen accumulation in the tissue. The aim of the present study was to assess whether melatonin had the ability to suppress collagen production and neuroma formation following peripheral nerve transection. A total of 40 male rats (four groups of 10) were left intact (intact controls) or sham operated (sham group), were Px, or were Px and given melatonin (Px + melatonin group). All animals underwent a surgical intervention consisting of right sciatic nerve neurectomy. After 4 wk, the animals were killed following intracardiac perfusion. Gross morphology of neuroma formation in the proximal nerve segment was examined and proximal neuroma evaluated. Macroscopic and microscopic findings revealed that Px caused a proliferation of connective tissue and large neuroma formation at the proximal ends of transected nerves. Stereological analysis showed that there was a statistically significant reduction in connective tissue content of the same region in Px animals treated with melatonin (P < 0.005). The results achieved in a rodent model of sciatic nerve neuroma formation showed that there was a positive correlation between macroscopic and microscopic observations, and that melatonin enhanced axonal regeneration presumably due to its inhibitory effect on neuroma formation.     

Prevalence and significance of MEFV gene mutations in patients with gouty arthritis

Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.     

Effect of weight loss on QTc dispersion in obese subjects.

OBJECTIVE: Increased QTc dispersion is a predictor for ventricular arrhythmias. The aim of this study was to investigate whether QTc dispersion decreases after weight loss program with diet and medical treatment. METHODS: Total 30 (24 women and 6 men, mean age: 44+/-8 years) obese subjects who lost at least 10% of their original weight after 12 week weight loss program were included in present study. Obesity was defined as > or =30 kg/m(2) of body mass index (BMI). Normal weight was defined as < or = 25 kg/m(2) of BMI. RESULTS: After 12 week weight loss program, BMI decreased from 42+/-5 kg/m(2) to 36+/-4 kg/m(2) (p<0.001) and mean weight of obese subjects decreased from 110+/-17 kg to 95+/-15 kg (p<0.001). The mean amount of weight loss was 14.5+/-5.0 kg (range 9-32 kg). The average percent of weight loss was 13% (10.0%-20.3%). Maximum QTc interval (from 446+/-19 ms to 433+/-27 ms, p=0.024) and QTc dispersion (from 66+/-18 ms to 52+/-25 ms, p=0.024) significantly decreased after weight loss program. A statistically significant correlation was found between decrease in level of QTc dispersion and amount of weight loss (r=0.487, p=0.007). CONCLUSION: Substantial weight loss in obese subjects is accompanied by significantly decreased QTc dispersion. The degree of QTc dispersion reduction is associated with amount of weight loss.     

Treatment of intracoronary thrombus using tirofiban in a patient with normal coronary arteries

We report a 64-year-old Turkish man who presented with unstable angina pectoris. Coronary angiography revealed massive intracoronary thrombus, which completely occluded the distal part of the left circumflex coronary artery. The thrombotic segment and the rest of the coronary tree were free of atherosclerosis. The patient was treated with intravenous tirofiban, a glycoprotein IIb/IIIa inhibitor. A control angiography was performed one week later and showed total dissolution of the thrombus with tirofiban therapy.     

HLA-DR B1 and DQ B1 polymorphisms in patients with coronary artery ectasia

OBJECTIVES: The purpose of our study was to evaluate the significance of polymorphisms in HLA class II genes in coronary artery ectasia (CAE) patients. METHODS AND RESULTS: Twenty-six patients with CAE without associated cardiac defects were enrolled in the study. CAE was defined as luminal dilation of 1.5- to 2.0-fold of normal limits. Ninety-five healthy subjects who were donors for different organ transplantations, were chosen as control group. Physical examination, electrocardiography and chest X-ray were completely normal in these cases. Both the patients and the control group were screened and compared for their HLA class II genotypes. HLA-DR B1*13, DR16, DQ2 and DQ5 genotypes were significantly more frequent in the patient group.When the known risk factors of coronary heart disease were compared in the patients carrying these genotypes with the non-carrying group, no significant differences were encountered. CONCLUSIONS: HLA-DR B1*13, DR16, DQ2 and DQ5 may be associated with the pathogenesis and increase the risk of CAE.