Comparison of effects of cyclooxygenase inhibitors on myometrial contraction and constriction of ductus arteriosus in rats

The aim of this study was to compare the tocolytic effect of a selective cyclooxygenase-2 inhibitor, DFU (5,5-dimethyl-3(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), indomethacin and nimesulide on myometrial strips isolated from rats in both lipopolysaccharide-induced preterm labour and term labour. We also compared the constrictor effects of DFU and indomethacin on the fetal ductus arteriosus. Myometrial strips were obtained from preterm and term labour Wistar albino rats and were mounted in organ baths for the recording of isometric tension. DFU, nimesulide and indomethacin significantly inhibited KCl-, oxytocin-, prostaglandin E(2)- and prostaglandin F(2 alpha)-stimulated contractions of myometrial strips isolated from rats in preterm and term labour. The E(max) value of indomethacin was significantly lower than those for DFU and nimesulide (P<0.05), with no change-log (10) EC(50) values. There was no significant difference between in -log (10) EC(50) and E(max) values of DFU and nimesulide for any of the tissues (P>0.05). In addition, there was no significant difference between -log (10) EC(50) and E(max) values for each of these three agents in myometrial tissues isolated from rats in preterm and term labour (P>0.05). Fetal ductus arteriosus was significantly constricted by DFU (10 or 100 mg/kg) in preterm and term rats, although DFU (10 or 100 mg/kg)-induced constriction ratios were significantly lower than those for indomethacin (P<0.05). These data demonstrate that DFU, a specific cyclooxygenase-2 inhibitor, could be considered as a new therapeutic agent for preterm labour. However, careful attention should be given to constriction of the fetal ductus arteriosus.     

Catechol-O-methyltransferase gene Val108/158Met polymorphism, and susceptibility to schizophrenia: association is more significant in women

Schizophrenia is a complex disorder with a polygenic inheritance. Catechol-O-methyltransferase (COMT) plays a significant role in the regulation of dopaminergic systems. A polymorphism at COMT Val108/158Met has been identified in association with schizophrenia. We examined the allele and genotype association of the COMT Val108/158Met polymorphism of 297 unrelated schizophrenic patients who strictly met DSM-IV criteria for schizophrenia, and 341 healthy controls. We found significant difference in allele and genotype frequencies between schizophrenic patients and controls (chi2=13.030; P=0.001). The allele frequency of the COMT-L was 45.79% in the total schizophrenic patients, and 41.50% in controls. The genotype frequency of the COM-LL was 21.2% in the total schizophrenic patients, and 11.4% in controls (OR=2.085; 95% CI=1.350-3.219; chi2=11.293; P=0.001). With a separate sex analysis, the frequency of the COMT-L allele was moderately distributed in male schizophrenia (chi2=6.177; df=2; P=0.046). The COMT-LL genotype had a 1.818-fold increased risk for schizophrenia (OR=1.818; 95% CI=1.010-3.273; chi2=4.048; P=0.044). The frequency of the COMT-L allele was even more significantly distributed in women schizophrenia (chi2=7.797; df=2; P=0.020). The COMT-LL genotype had remarkably more increased risk for schizophrenia (OR=2.456; 95% CI=1.287-4.687; chi2=7.710; P=0.005). In conclusion, our results provide strong evidence for a role of the COMT-L allele and LL genotype in the etiopathophysiology of schizophrenia with a sexual difference.     

The effect of zinc sulphate in the prevention of radiation-induced dermatitis

There is currently substantial clinical interest in zinc (Zn) as a protective agent against radiation-related normal tissue injury. To further assess this drug's potential, the effect of Zn was studied in rats using a radiation-induced skin injury model. Sprague-Dawley rats were divided into four groups. Group 1 received neither Zn nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (RT Group). Groups 3 and 4 received the same irradiation plus 5 mg/kg/day Zn (RT+5 Zn group) or 10 mg/kg/day Zn orally (RT+10 Zn group), respectively. The rats were irradiated using a cobalt-60 teletherapy unit. Acute skin reactions were assessed every three days by two independent radiation oncology experts. At the endpoint of the study, light-microscopic findings were assessed by two independent expert pathology physicians. Clinically and histopathologically, irradiation increased dermatitis when compared with the control group (p < 0.05). The severity of radiodermatitis of the rats in the RT+5 Zn and RT+10 Zn groups was significantly lower than in the RT group (p < 0.05); radiodermatitis was seen earlier in the RT group than in the other groups (p < 0.05). Zn was found to be efficacious in preventing epidermal atrophy, dermal degeneration such as edema and collagen fiber loss, and hair follicle atrophy. The most protection for radiation dermatitis was observed in the RT+10 Zn group. It would be worthwhile studying the effects of zinc sulphate supplements in radiation-treated cancer patients, in the hope of reducing radiation-induced toxicity.     

A heterozygote phenotype is present in the jvs +/- mutant mouse livers

The juvenile visceral steatosis (jvs) mouse, having a mutation in the carnitine transporter gene Octn2, is a model of primary systemic carnitine deficiency in humans (SCD, OMIM 212140). Like humans with SCD, homozygous jvs -/- mice have hepatic and cardiac steatoses, reduced plasma and tissue carnitines, and increased urinary carnitine clearance. Because symptomatic heterozygotes have been reported for some fatty acid oxidation disorders, including SCD, we compared the jvs heterozygotes to normal control mice. We measured the free and esterified carnitine, total cholesterol, and triglycerides in adult liver samples, myocardium, and skeletal muscle. Our results indicate significant differences between the livers of nonfasting adult normal (n = 8) vs jvs heterozygotes (n = 8) (means +/- SEM, p < 0.01) for the following parameters: free carnitine, 2.28 +/- 0.36 nmol/mg protein vs 0.41 +/- 0.13; total carnitine, 3.48 +/- 0.36 vs 1.27 +/- 0.25; triglycerides, 0.14 +/- 0.04 vs 0.39 +/- 0.02; and total cholesterol, 0.21 +/- 0.02 vs 0.39 +/- 0.04, but not for esterified carnitine, 1.18 +/- 0.17 vs 0.90 +/- 0.17 (p > 0.05). There is also a negative correlation between hepatic free carnitine and triglycerides from jvs heterozygotes (p < 0.05). Similar results were obtained with myocardium and skeletal muscle. We conclude that free and total carnitine levels are significantly lower in the heterozygote mouse liver and heart while triglyceride and total cholesterol levels are significantly higher. We speculate that in situations of lipolytic stress, some SCD heterozygotes might develop clinical symptoms of carnitine deficiency.     

Endothelial function,insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women

BACKGROUND: Hyperprolactinemia has been reported to be associated with abnormalities of carbohydrate metabolism. The aim of this study was to evaluate the effects of hyperprolactinemia and bromocriptine (Brc) treatment on endothelial function, insulin sensitivity and inflammatory markers in pre-menopausal women. METHODS: Sixteen hyperprolactinemic pre-menopausal women with pituitary adenomas were recruited and 20 healthy subjects were included as controls. Patients were given Brc in doses of 2.5-20 mg/dl until normal levels of prolactin were reached. Prior to treatment and 2 months after prolactin levels were normalized, the following tests were performed. Insulin sensitivity was determined by an oral glucose tolerance test based on a formula named the insulin sensitivity index (ISI composite). Endothelial function was measured as flow-mediated dilatation (FMD) on a brachial artery using high resolution ultrasound. RESULTS: Serum glucose, insulin, estrogen, highly sensitive C-reactive protein (hsCRP), fibrinogen, homocysteine and uric acid levels were measured. Calculated ISI composite and FMD were significantly lower in the hyperprolactinemic group in comparison with the controls and improved after Brc treatment. Serum homocysteine, hsCRP and uric acid levels were significantly higher in hyperprolactinemic patients than in the controls and returned to normal levels with Brc treatment. Serum prolactin concentrations were inversely correlated with FMD measurements (r=-0.68; P<0.0001), ISI composite (r=-0.48; P<0.005) and serum estrogen (r=-0.54; P<0.005), and positively correlated with serum homocysteine concentrations (r=0.55; P<0.0001) in the hyperprolactinemic group. CONCLUSIONS: The hyperprolactinemic state is associated with impaired endothelial function and decreased insulin sensitivity, which are early markers of atherosclerosis. These alterations may predispose to the development of atherosclerosis in non-treated cases. Correction of the hyperprolactinemic state is associated with improved endothelial function and insulin sensitivity.     

The influence of sex hormones on ocular blood flow in women

PURPOSE: To investigate the influence of sex hormones on ocular haemodynamics, blood flow velocities in the ophthalmic and central retinal arteries and serum levels of sex hormones were measured in pre- and postmenopausal women. METHODS: Colour Doppler imaging (CDI) was used to determine the flow velocities (peak systolic velocity [PSV] and end-diastolic velocity [EDV]) and the resistive index (RI) in the ophthalmic and central retinal arteries in 22 premenopausal and 32 postmenopausal women, who had never received hormone replacement therapy. Serum levels were measured for oestradiol, free testosterone and follicle-stimulating hormone. The CDI parameters were compared between the two groups and the influence of serum levels of oestradiol and testosterone on blood flow velocities and the resistive indices were analysed. RESULTS: After correcting for age and mean arterial blood pressure, an analysis of covariance disclosed a significantly lower EDV (p=0.02) and a significantly higher RI (p=0.01) in the central retinal artery of postmenopausal women compared with premenopausal women. Partial correlation analysis, controlling for age, revealed significant correlations between the CDI parameters and serum levels of oestradiol and testosterone. For premenopausal women, PSV (r=0.58, p=0.04) and EDV (r=0.73, p=0.006) in the ophthalmic artery correlated positively with serum oestradiol levels. The RI in the central retinal artery decreased with increasing oestradiol levels in both groups (premenopausal r= -0.40, p=0.04; postmenopausal r= -0.32, p=0.05). Peak systolic velocity in the central retinal artery correlated negatively (r= -0.49, p=0.04), whereas the RI correlated positively (r=0.53, p=0.02) with testosterone levels in the premenopausal group. Postmenopausal women with higher testosterone levels had lower EDV (r= -0.53, p=0.007) in the central retinal artery and higher RI in both vessels (ophthalmic artery r=0.48, p=0.01; central retinal artery r=0.61, p=0.002). CONCLUSION: Our data provide evidence of a relationship between serum sex hormone levels and blood flow velocities and resistive indices in retrobulbar arteries. Oestradiol appears to have beneficial effects on ocular haemodynamics, whereas testosterone may act as an antagonistic to the effects of oestrogen.     

A double-orifice atrioventricular valve case: intraoperative transesophageal echocardiography in diagnosis and treatment

We describe a 45-yr-old woman with an intermediate type atrioventricular septal defect associated with a double-orifice left atrioventricular valve (DOLAV). We diagnosed this exceptional anomaly by intraoperative transesophageal echocardiography (TEE) during surgery that was scheduled for only a primum type atrial septal defect (ASD) repair. Preoperative transthoracic echocardiography and angiography revealed the ASD but could not demonstrate the DOLAV. We were able to repair this rare and challenging abnormality successfully under the guidance of TEE imaging during the operation. TEE provides valuable information about both anatomy and functional aspect of the valvular structures. Besides its proven role in cardiac surgery, intraoperative use of TEE also serves as a useful tool for diagnosis of such unexpected and potentially missed abnormalities.     

Ophthalmic artery color Doppler ultrasonography in mild-to-moderate preeclampsia

OBJECTIVE: To evaluate the hemodynamic changes in mild-moderate preeclampsia using ophthalmic artery Doppler ultrasonography technique. METHODS: Ophthalmic artery pulsatility and resistivity indices were calculated in 30 mild-moderate preeclamptic women and 30 normotensive gravid women of matched gestational age. Student's t-test was performed to test the significance of difference. RESULTS: Both indices of peripheral resistance were found to be significantly lower in the ophthalmic arteries of mild-moderately preeclamptic women than those measured in normotensive gravid women at similar stage of pregnancy. In a small number patients whose disease progressed to severe preeclampsia, both indices increased. CONCLUSION: In patients with mild-moderate preeclampsia, ophthalmic artery color Doppler ultrasonography detects hemodynamic changes that are not present in normotensive gravid women. Reversal of Doppler patterns in a small number of patients with progressive disease supports the hypotheses suggesting the presence of early vasodilation and late vasospasm in the etiology of preeclampsia.     

Evaluation of the mastoid air cell system by high resolution computed tomography: three-dimensional multiplanar volume rendering technique

The mastoid air cell system is an important contributor to the pathophysiology of middle-ear inflammatory disease. The mastoid cavity is not only an air reservoir, but also an active space for gas exchange. Various methods of temporal bone imaging have been designed to investigate mastoid pneumatization. In this study, we examined 100 normal temporal bones for the evaluation of mastoid pneumatization. Mastoid air cell systems were measured by reconstructed axial and coronal high resolution computed tomography (HRCT) images. The reconstructions were made by a three-dimensional multiplanar volume rendering (3D MPVR) technique. The mean volume of the mastoid air cell pneumatization was 7.9 cm(3) (4.0-14.0 cm(3), SD = 2.3 cm(3)). The ears were allocated to the groups with respect to measured mastoid air cell pneumatization. Twenty-eight per cent of the ears have small pneumatization with an air cell system not exceeding 6 cm(3). Fifty-two per cent had an air cell system between six and 10 cm(3), and 20 per cent had an air cell system exceeding 10 cm(3). With its excellent imaging quality and the ability to eliminate bone and soft tissue, HRCT is the best method for evaluating the mastoid air cell system. The 3D MPVR technique must be used to measure the temporal bone/mastoid pneumatization for the best results.     

Ileal orthotopic neobladder in women: The first experiences from Turkey and our modifications

The lower urinary tract reconstruction with an ileal neobladder in woman is not very often but has been recently introduced centers. We report 8 female patients with ileal orthotopic neobladders after cystectomy. Patients and methods: Between 1995 to 1999, 7 female patients with organ confined invasive bladder cancer and 1 female patient with severely contracted bladder secondary to tuberculosis were operated. While standard radical cystectomy was done in 7 patients with bladder cancer, only simple cystectomy was performed in patient with contracted bladder. Detubularized ileal W-neobladder with antirefluxive ureteroileal reimplantation were used as a procedure and reservoirs are connected to the proximal urethra in all patients. Cystoscopy and biopsy was done routinly in the bladder neck and there were no tumour and CIS in any patient. Results: The mean age was 65.4 years (53–70) and the mean postoperative follow-up time was 31.8 months (6–48). There was no perioperative or early postoperative (first one month) mortality. Early postoperative complications included acute renal failure in 1 patient (12.5%), deep vein thrombosis in 1 patient (12.5%) and leakage from the pouch in 2 patients (25%). In one patient (12.5%), ileo-pouchal fistula was seen in sixth month and reoperated. Although there was not hypercontinence, one patient (12.5%) had totally incontinence. All other patients had normal micturition and no residual urine. Urethral recurrence was not seen in this postoperative follow-up period but pelvic recurrence and then distant metastases were found in one case (12.5%). Conclusions: The results of ileal orthtopic neobladder after radical or simple cystectomy in appropriate female patients are satisfactory. But certainly, we need the more experiences and studies about this subject. This revised version was published online in September 2006 with corrections to the Cover Date.