Cengiz Pata

Serotonin transporter gene polymorphism in irritable bowel syndrome

OBJECTIVES:Serotonin is a key mediator of intestinal peristalsis, and after it is secreted, it is effectively cleansed from the neuronal gap by means of a high affinity substance called serotonin transporter (SERT), which depends on the Na+ and Cl− ions localized in the presynaptic neuronal membranes. The aim of this study was to investigate SERT polymorphism in patients with irritable bowel syndrome (IBS).METHODS:SERT gene polymorphism was assessed by polymerase chain reaction on DNA chains obtained from leukocytes in serum samples from 54 patients diagnosed with IBS and 91 healthy subjects. The polymorphism of two regions (variable number tandem repeats and the SERT gene—linked polymorphic region [5-HTTLPR]) of SERT was assessed.RESULTS:SERT polymorphisms were found to be similar in healthy subjects and IBS patients (p > 0.05). IBS patients were divided into three groups: diarrhea predominant (n = 18), constipation predominant (n = 26), and alternating diarrhea and constipation (n = 10). These groups were compared with respect to gene polymorphism, and it was found that the 5-HTTLPR allele S/S genotype occurred with greater frequency in the constipation predominant group than in the other two subgroups (p < 0.05), and L/S genotype frequency in the diarrhea predominant group was higher than those in the constipation and control groups.CONCLUSIONS:No relationship was found between IBS and SERT gene polymorphism. It is conceivable that the presence of the S/S genotype in IBS patients carries an increased risk of the constipation predominant type of IBS, whereas the presence of the 5-HTTLPR allele L/S genotype carries an increased risk of the diarrhea predominant type.

Respiratory symptoms and pulmonary functional changes in patients with irritable bowel syndrome

OBJECTIVE:Scientific evidence of functional interface between the immune and sensory motor systems of the gut and respiratory systems has been reported. In recent studies excess prevalence of bronchial hyper-responsiveness has been shown among patients with irritable bowel syndrome (IBS). The purpose of our study was to investigate the possible relationship between IBS and asthma.METHODS:One hundred thirty-three patients with IBS (108 women, 25 men) and 137 control subjects (105 women, 32 men) were included in this study. Both for IBS and the control group, the mean ages were 41.64 ± 9.45 yr and 39.94 ± 10.62 yr, respectively. Patients more than 50 yr old, with any organic GI disease, acute respiratory system infection, current or ex-smokers, and patients using drugs affecting smooth muscle and autonomic nervous system were not included in the study. Respiratory symptoms were questioned and pulmonary function tests were performed for every subject.RESULTS:There were 45 (33.8%) and eight (5.8%) subjects with respiratory symptoms in IBS and control groups, respectively (p < 0.0001). Twenty-one (15.8%) patients from the IBS group and two (1.45%) patients from the control group had the diagnosis of asthma according to history, clinical, and PFT findings. There was no statistical difference between two groups with respect to percentage of forced vital capacity and forced expiratory volume in 1 s-to-forced vital capacity. The difference between the two groups in forced expiratory volume in 1 s, flow after 50% of the vital capacity has been exhaled, peak expiratory flow rate, and maximal mid-expiratory flow rate was statistically significant (p < 0.01).Conclusion:We found that the prevalence of asthma was more common in the IBS group than in controls. Our finding supports the speculation that asthma and IBS may share common pathophysiological processes

Association of the -1438 G/A and 102 T/C polymorphism of the 5-Ht2A receptor gene with irritable bowel syndrome 5-Ht2A gene polymorphism in irritable bowel syndrome.

Goals: The aim of this study is to investigate whether there were any association between the 102 T/C and −1438 G/A polymorphisms of the 5-HT2A receptor gene and IBS, and abdominal pain, anxiety and depression. Background: Genes involved in serotonin (5-HT) metabolism are good candidates for the pathogenesis of irritable bowel syndrome (IBS). Recently, a silent polymorphism in the 5-HT2A receptor gene was identified that is defined by a T to C transition at position 102. Also, a novel G to A base change at position −1438 of the promoter region has been detected in 5-HT2A receptor gene. Study: Fifty-four patients with IBS diagnosed according to the Rome 1 criteria and 107 healthy individuals were included in the study. PCR was used to amplify a 468-bp (G→A) and 342-bp (T→C) fragment of genomic DNA containing the polymorphism. Hospital anxiety and depression scale was used to assess the risk of depression and anxiety. Severity of chronic abdominal pain was determined by visual analogue scale (VAS). Results: It was shown that there was a high incidence of homozygote C allele of the 102T/C polymorphism (%22.2; OR: 7.89, P = 0.04) and homozygote A allele of the −1438 G/A promoter region (%%37; OR: 11.14, P = 0.01) in patients with IBS. The risk of having an anxiety disorder was 83.3% in patients with C/C genotype, which was higher than other allele carrying patients, and overall mean (%52.7). (χ2 = 8.56, P = 0.014). The patients with T/T genotype had a VAS score of 54.93 ± 2.59 mm, which was significantly higher than that of the patients with other genotypes (p1 = 0.02, p2 = 0.001). Conclusion: This study suggests that the patients with homozygote C allele of the 102 T/C polymorphisms or homozygote A allele of the −1438 G/A polymorphism of the 5-HT2A receptor gene, have a high risk of IBS. On the other hand, T/T genotype of 102 T/C polymorphism may be associated with more severe pain in patient with IBS.

The effects of hormone replacement therapy type on pulmonary functions in postmenopausal women

OBJECTIVE To study whether hormone replacement therapy (HRT) or Tibolone has an effect on pulmonary function in postmenopausal women. METHODS Seventy-five postmenopausal women without any risk factor for pulmonary disease were included in this randomized, prospective study. Fifty women had undergone natural menopause and 25 had had a hysterectomy/ooforectomy. Twenty-five natural menopause women were randomly allocated to two groups: 25 patients (Group I) were treated with Tibolone 2.5 mg/day, 25 patients (group II) with Estradiol Hemihidrate 2 mg+Norethindron Asetate 1 mg/day. Twenty-five induced menopause women were treated with 17 beta-estradiol 2 mg/day. Lung function tests including forced vital capacity (FVC), forced expiratory volume (FEV(1)), FEV(1)/FVC, forced expiratory flow rate over the 25-75% of the forced vital capacity volume (FEF(25-75%)), and peak expiratory flow rate (PEF) were evaluated at the beginning and 3 months after the treatment to assess the effects of HRT and Tibolone on respiratory function. RESULTS Regardless of HRT types a significant difference was observed in FVC and FEV(1) after 3 months of the therapy (P=0.001, 0.0001, respectively). No significant difference was found between pre and post therapy values in the other parameters (P>0.05). CONCLUSIONS We determined a significant increase in FVC and FEV(1) parameters of pulmonary functions after 3 months of the therapy regardless of HRT types. Therefore, we think that HRT regimens have modifying effects on pulmonary function in postmenopausal women.

Effect of N-Acetylcysteine on Blood and Tissue Lipid Peroxidation in Lipopolysaccharide-Induced Obstructive Jaundice

In obstructive jaundice, free radical production is increased and antioxidative activity is reduced. N-Acetylcysteine (NAC) has a beneficial effect with anti-inflammatory and antioxidant activity, acting as a free radical scavenger. NAC inhibits inducible nitric oxide synthase, suppresses cytokine expression/release, and inhibits adhesion molecule expression and nuclear factor kappa B. The aim of this study was to investigate the effects of NAC on liver/renal tissue and serum lipid peroxidation in lipopolysaccharide (LPS)-induced obstructive jaundice. We randomized 60 rats into 6 groups: group 1, Sham; group 2, obstructive jaundice (OJ) induced after bile-duct ligation; group 3, OJ + NAC (100 mg kg− 1 subcutaneously); group 4, OJ + LPS (10 mg kg-1); group 5, OJ + NAC + LPS; and group 6, OJ + LPS + NAC. For each group, the biochemical markers of lipid peroxidation and the antioxidant products were measured in serum and liver/renal tissue after sacrifice. Almost all lipid peroxidation products levels were increased and antioxidant products levels were decreased in groups who received LPS (groups 4, 5, and 6), but the effect was less remarkable when NAC was administered before LPS (group 5). The same trend was seen for groups with OJ ± LPS who did not received NAC or received it after induced toxemia (groups 2, 4, and 6) as compared to groups 1 and 3. Moreover, in the case of OJ + LPS, rats treated with NAC before LPS (group 5) had lower lipid peroxidation products levels and higher antioxidant products levels as compared to those who did not received NAC (group 4). This phenomenon was not reproducible with NAC administered after LPS (group 6). Thus, results of this study showed that NAC prevents the deleterious effects of LPS in obstructive jaundice by reducing lipid peroxidation in serum and liver/renal tissue if administered before LPS. Nonetheless, NAC failed to prevent the lipid peroxidation in the case of established endotoxemia in obstructive jaundice.

A case of ochronosis: upper extremity involvement

Abstract. We present an ochronotic patient with spondylosis and upper extremity involvement. We also evaluated radiologic findings of joints that were involved and MRI features of the lumbar spine.

The urinary 5-hydroxyindole acetic acid and plasma nitric oxide levels in irritable bowel syndrome: a preliminary study.

Background and Aims: Postprandial increase of 3-hydroxytryptamine (5-HT) has been implicated in irritable bowel syndrome (IBS). There is evidence that nitric oxide (NO) may act as a mediator of 5-HT-evoked secretions in the colon. Our aim is to investigate the role of urinary 5-hydroxyindole acetic acid (5-HIAA) and plasma NO levels (with diarrhoea) in IBS patients. Methods: Nineteen (with constipation) IBS patients (group 1), 22 IBS patients (group 2) and 18 healthy controls (group 3) were included in the study. The diagnosis of IBS was made according to the Rome I Criteria. The urine was collected for determination of 5-HIAA and venous blood was collected from each subject for the measurement of plasma NO levels. Results: The levels of urinary 5-HIAA mmol/day and plasma NO mmol/l of group 1 (22,4±2,2 and 29,4±2 respectively) were significantly higher than group 3(14,2 ± 2,3 and 21,3 ± 2,1 respectively) (p =0,036 and p =0,019 respectively). The NO level of group 1 was also significantly higher than group 2(21,8 ± 1,9) (p = 0,021). The 5-HIAA level of group 1 was higher than group 2 (15,2, ± 2,1) and the difference was marginally significant (p = 0,055). There was no difference between group 2 and group 3 with respect to 5-HIAA and NO levels. Conclusions: The results of this preliminary study lend support to the involvement of 5-HT in some symptomatology of diarrhoea predominant IBS. Furthermore, NO may be one of the effector mediators of the 5-HT-induced symptoms in these patients.

The effects of antithrombin-III on inducible nitric oxide synthesis in experimental obstructive jaundice. An immunohistochemical study.

The absence of bile in the gastrointestinal tract stimulates bacterial overgrowth and bacterial translocation. In the response to endotoxin and LPS-induced endotoxemia which may be prevented by antithrombin-III (AT-III); endothelial cells; and various cells release cytokines, nitric oxide (NO) and other mediators. The purpose of this study was to examine blood NO levels and renal inducible NO synthase (iNOS) expression and determine whether AT-III has an inhibiting effect on renal injury and iNOS expression in obstructive jaundice (OJ). Forty rats were randomized into four groups: group A (Sham), group B (Sham+AT-III, 250 IU kg(-1)), group C (OJ), group D (OJ+AT-III, 250 IU kg(-1)). All animals were sacrificed on the 10th day and blood samples were taken for bilirubin and NO level determination. In addition, iNOS expression of the renal tissues was evaluated immunohistochemically. Blood NO levels were found to be 32.99 micromol l(-1) in group A, 32.26 micromol l(-1) in group B, 46.33 micromol l(-1) in group C, and 34.71 micromol l(-1) in group D. The intensity of iNOS staining in the OJ+AT-III group was less than the intensity of iNOS staining in the OJ group in the renal tissue. This study shows that OJ causes increased production of NO in blood and increased iNOS expression in the kidney. AT-III inhibits iNOS expression and reduces the level of blood NO. Thus, our findings indicate that under conditions of OJ, AT-III limits renal cellular injury by inhibiting LPS-induced iNOS expression.

Cytological Correlation in Patients Who Have a Pre‐diagnosis of Thyroiditis Ultrasonographically

Objective. Radiological—cytopathological correlation in patients who are pre‐diagnosed ultrasonographically as thyroiditis. Study Design. Fourty five patients with hypoechogenic, heterogeneous, and/or pseudolobulated thyroid gland sonographically were included in this prospective study. Except for the patients with subacute thyroiditis, none of the patients had a prediagnosis of thyroiditis clinically. All patients were evaluated for their thyroid gland functions and intraglandular vascularity and ultrasonography‐guided fine needle aspiration biopsy (US–FNAB) was performed. Results. The diagnosis of thyroiditis was confirmed in 36 patients (16 lymphocytic thyroiditis, 20 Hashimoto thyroiditis, two subacute granulomatous thyroiditis) in sonographically suspected patients. In six patients, FNAB was thyroiditis negative. The true diagnosis ratio of thyroiditis was increased up to 81.8% (%95 Confidence Interval: 0.70–0.92) by performing US–FNAB, while it was 4.5% with only clinical and laboratory findings (p = 0.0001). Conclusion. Hypoechogenic, heterogeneous thyroid gland may be strongly related to thyroiditis, which does not have any specific radiological findings. The sonographic finding of generalized parenchymal abnormality should alert the clinician to consider diffuse thyroid disease as the underlying cause and FNAB should be performed and a follow‐up examination of these patients must be continued due to the risk of neoplastic disease of thyroid.

The effect of PARS inhibition on ileal histopathology, apoptosis and lipid peroxidation in LPS-induced obstructive jaundice.

In our experimental study, we investigated the protective effect of 3-aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4: OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In Group 3; 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and then after 6h the rats were sacrificed. In Group 4; 10 mg kg(-1) 3-AB was administrated intraperitoneally at the fifth day and repeated daily for 3 days and at the eighth day, 10 mg kg(-1) LPS was injected intraperitoneally. In Group 5, 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and after 6h 10 mg kg(-1) 3-AB was administrated intraperitoneally and repeated daily for 3 days. At the eighth day, rats were sacrificed. Blood samples were taken for detection of serum MDA levels. Ileum samples were taken after relaparotomy for histopathological examination to evaluate the endotoxin-related intestinal injury and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities. There was marked destruction of villous and crypt epithelial cells and extensive apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the scores of intestinal mucosal damage and apoptotic cells were reduced significantly (P<0.05). On the other hand, the scores of intestinal mucosal damage and apoptotic cells were not improved in Group 5. After the administration of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if it was administrated before LPS. However, 3-AB failed to prevent the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if there was established endotoxemia in OJ.