Increased oxidative stress and oxidative DNA damage in non-remission schizophrenia patients.

Increasing evidence shows that oxidative stress plays a role in the pathophysiology of schizophrenia. But there is not any study which examines the effects of oxidative stress on DNA in schizophrenia patients. Therefore we aimed to assess the oxidative stress levels and oxidative DNA damage in schizophrenia patients with and without symptomatic remission. A total of 64 schizophrenia patients (38 with symptomatic remission and 26 without symptomatic remission) and 80 healthy volunteers were included in the study. 8-hydroxydeoxyguanosine (8-OHdG), total oxidant status (TOS) and total antioxidant status (TAS) were measured in plasma. TOS, oxidative stress index (OSI) and 8-OHdG levels were significantly higher in non-remission schizophrenic (Non-R-Sch) patients than in the controls. TOS and OSI levels were significantly higher in remission schizophrenic (R-Sch) patients than in the controls. TAS level were significantly lower and TOS and OSI levels were significantly higher in R-Sch patients than in Non-R-Sch patients. Despite the ongoing oxidative stress in patients with both R-Sch and Non-R-Sch, oxidative DNA damage was higher in only Non-R-Sch patients compared to controls. It is suggested that oxidative stress can cause the disease via DNA damage, and oxidative stress plays a role in schizophrenia through oxidative DNA damage.

Alterations of Lipid-Lipoprotein and Leptin in Bipolar Disorder Associated with Clinic Process.

INTRODUCTION: Obesity is more common among patients with bipolar disorder as compared to normal population. There are studies showing increased leptin levels in obese patients. The aim of the present study was to investigate the alterations in leptin levels, body mass index (BMI), and lipid-lipoprotein levels during manic period, as well as during euthymic period, after one month in patients with bipolar disorder. METHODS: Thirty-one adult patients, who had been hospitalized in the psychiatry clinic because of manic period of bipolar disorder, were included in the present study. Serum leptin and lipid-lipoprotein levels and BMI of the patients were analyzed both on the first day and 30th day of hospitalization after they became euthymic. RESULTS: Total cholesterol and triglyceride levels significantly increased in male patients (p<.05). The increase in total cholesterol and LDL-C levels was not significant in female patients (p=.066 and p=.056, respectively). BMI was significantly, but slightly increased in both genders (.56±.14 kg/m2), however, such a change was not observed in serum leptin levels. CONCLUSION: Results of the present study demonstrated that clinical improvement in bipolar patients showed different association in each gender with the alterations in BMI and serum lipid and/or lipoprotein levels. Such an alteration might have resulted from direct or indirect effect of drugs, as well as from lifestyle changes.

Treatment of ureteral calculi with semirigid ureteroscopy: where should we stop?

OBJECTIVES: To evaluate the efficacy of semirigid ureteroscopy in the management of ureteral stones located in different parts of the ureter. METHODS: 1,503 patients were treated with semirigid ureteroscopy. All ureteral stones were either removed only by a basket catheter or disintegrated by pneumatic lithotripsy. Success rates, auxiliary procedures, complication rates and operation time were comparatively evaluated according to stone location. RESULTS: Overall, mean stone size and age were 12.1 +/- 3.7 mm and 43.2 +/- 9.72 years, respectively. While 1,416 patients (94.2%) were completely stone-free, the procedure was unsuccessful in 87 cases (5.8%). The success rate was relatively low in the proximal ureter (71.7%) when compared with the mid (94.8%) and distal ureter (98.9%) (p = 0.021). Mean operation time was 25.4 +/- 11.7 min. Longer duration of operation and higher complication rate were found in proximal ureteral calculi. Stone migration to the kidney and hematuria were the main reasons of failure in the proximal ureter and ureteral stenting was needed for 56.4% of patients with upper ureteral stone. CONCLUSIONS: Semirigid ureteroscopy can be the treatment of choice in lower and midureteral stones. However, it is an invasive and less successful treatment modality for proximal ureteral stones with relatively high complication rates.

Analysis of myeloperoxidase promotor polymorphism and enzyme activity in Turkish patients with vitiligo.

Vitiligo is an acquired depigmentary disorder characterized by white areas of the skin due to loss of epidermal melanocytes. Oxidative stress and free radicals are suggested as important phenomena in the pathogenesis of vitiligo. Myeloperoxidase is a lysosomal enzyme of polymorphonuclear leukocytes and acts as a catalyst in the production of hypochlorous acid, a powerful oxidant. In this study we analysed enzyme activity and gene polymorphism of myeloperoxidase in patients with vitiligo. Fifty-four patients with vitiligo and 58 healthy controls were enrolled to this study. Patient groups were subdivided according to localization of the lesions; generalized, acrofacial and local. Plasma myeloperoxidase enzyme activity was determined with ELISA and G-463A gene (-463) polymorphism with the PCR-RFLP (AciI) method. The plasma MPO level was significantly lower in vitiligo patients than in the healthy controls (p = 0.005), however, it was not significantly different among subtypes of vitiligo (p = 0.8). A significant difference was not observed for G-463A genotype and allele distribution in patients with vitiligo. In conclusion, the present study is the first study investigating MPO G-463A polymorphism and enzyme levels, which warrants further studies with higher patient numbers and broader polymorphism panels.

Plasmakinetic resection of the prostate versus standard transurethral resection of the prostate: a prospective randomized trial with 1-year follow-up.

The aim of this study was to compare the clinical results of plasmakinetic resection of the prostate (PRP) with standard transurethral resection (TUR) of the prostate (TURP). A total of 240 patients (mean age 63.5; age range 52-90 years), with symptomatic benign prostatic hyperplasia were randomized into two groups and treated with two different techniques (TURP and PRP). We evaluated pre-operative, per-operative and post-operative (first and 12th months) findings of all patients. The mean catheterization time was 3 and 4.5 days in the PRP and standard TURP groups, respectively (P<0.001). We observed the improvements in maximum flow rates in PRP group were significantly higher than TURP group (P<0.001). TUR of the prostate using plasmakinetic energy seems to be a promising treatment alternative to conventional TURP. It has the advantages of low intraoperative and post-operative complications, short convalescence, excellent intraoperative hemostasis, absence of fluid absorption and TUR syndrome.

Serum prolidase activity in postmenopausal osteoporosis.

AIM: Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with increased intensity of collagen degradation and may be a useful tool in diagnosis and/or monitoring osteoporosis. The study aimed to evaluate serum prolidase activity in postmenopausal osteoporosis and its relation with several metabolic bone markers. METHODS: Sixty-one postmenopausal women with menopause times = or >1 year without any hormone replacement treatment were recruited in this study. Bone mineral density (BMD) was obtained from antero-posterior spine L2-L4 and femoral neck scanning with dual energy X-ray absorptiometry (DXA). Thirty-one subjects with T scores lower than -2.5 were accepted as osteoporotic and control group consisted of 30 subjects. Urinary deoxypyridinoline (Dpd), calcium, creatinine, serum total calcium, phosphorus (Pi), alkaline phosphatase, parathyroid hormone levels and prolidase activity were analysed with colorimetric or immunochemical RESULTS: Serum prolidase activity was neither significantly different in osteoporosis nor correlate with other bone turnover markers. Urinary Dpd/creatinine and serum Pi levels of postmenopausal osteoporotic group were significantly higher than in the control group. CONCLUSION: Serum prolidase activity does not correlate with BMD in postmenopausal osteoporosis with menopause time over 1 year. However, its role during premenopausal accelerated decrease in BMD is not established yet.

Serum adenosine deaminase activity in monitoring disease activity and response to therapy in severe psoriasis.

OBJECTIVES: Activity of Serum Adenosine Deaminase (ADA), a main enzyme in purine degradation and considered as a marker for non-specific T cell activation, in psoriasis has been investigated in a few studies with conflicting results. DESIGN AND METHODS: To evaluate the significance of serum ADA activity in psoriasis, and analyze whether ADA activity may be related to disease activity, we performed a prospective study with 38 cases of psoriasis and 24 healthy volunteers. Patients were divided into two groups as cases with local and stable lesions (Group i, n: 20) and severe cases with extensive involvement (Group ii, n: 18). Serum ADA activity was determined by modified Guisti procedure. RESULTS: When taken into consideration of all patients--regardless of the severity of the disease--the mean serum ADA activity of psoriatics did not differ significantly from that of controls (p > 0.05). However, it was higher in Group ii than in Group i and healthy controls (respectively p < 0.001 and p < 0.05). A significant decrease was observed also after therapy only in Group ii (p < 0.001). CONCLUSION: Serum ADA activity may be correlated to the disease activity of severe psoriasis. We suggest that it might be a serologic marker for follow-up of in such cases. It could be used in predicting relapses before clinical findings as well as in deciding to stop or decrease systemic therapies at the right time, which have potential to cause severe systemic side effects when given for a long period. Further studies with larger case populations are required to support our findings.

Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment.

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia

Renal tubular injury induced by hyperoxaluria: evaluation of apoptotic changes.

In order to evaluate the injurious effect of hyperoxaluria on renal tubular epithelium, as judged by apoptotic changes in the renal parenchyma, we performed an experimental study in 20 rabbits. In the experimental group animals (n = 10) severe hyperoxaluria was induced by continuous ethylene glycol (EG; 0.75%). Histologic alterations, including crystal formation, together with apoptotic changes were evaluated after 7 and 28 days. Control group animals (n = 10) received normal distilled drinking water. Following 7- and 28-day periods, tissue sections obtained from kidneys were examined histopathologically under light microscopy for the presence and the degree of crystal deposition in the tubular lumen. Apoptotic changes in renal tubular cells were examined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick and labeling (TUNEL) method during the same follow-up period. Crystal deposition was evident in the tubular lumen of tissue sections obtained during the 7-day examination period. During the 28-day examination period, however, these findings were found to be either limited or to have disappeared. In relation to apoptotic changes, the percentage of positive nuclei stained using the TUNEL method was from 11 to 20% in the experimental group and 5.6% in the control group. Our findings indicate that both calcium oxalate (CaOx) crystals and hyperoxaluria itself may be injurious to renal tubular cells, as indicated by apoptotic changes. These changes may be responsible for the pathologic course of urolithiasis.

Unilateral testicular torsion: evaluation of bcl-2, p-53 and PCNA expression in contralateral testes.

OBJECTIVES AND METHODS: The present study aims to evaluate the histologic as well as apoptotic changes indicated by PCNA, p-53 and bcl-2 expression in the contralateral testes after a period of unilateral testicular torsion of 4 h. RESULTS: Regarding the histologic changes, while some significant alterations such as complete or incomplete spermatocytic arrest as well as sertoli cell only formation have to some extent been noted after the detorsion procedure, reasonably better preserved histology could be demonstrated following the orchiectomy procedure both in the early and late follow-up. Thus, the orchiectomy procedure was found to be limiting enough on the severity of the histologic changes in the contralateral testes after a certain period of time following the torsion procedure. On the other hand, however, in relation to the apoptotic events indicated by the three markers, while PCNA activity was found to be significantly different depending on the procedure performed (detorsion or orchiectomy), p-53 and bcl-2 positivity did not exhibit any difference in this aspect. Increased PCNA activity (especially after the detorsion procedure) together with marked positivity of p-53 both in the early and late follow-up indicated the increased cell turnover in the contralateral testes, which in turn may be accepted as a sign of increased apoptosis in these testes. In addition to these findings, bcl-2 expression has been found to be consistently negative in all specimens evaluated both in the early and late follow-up. CONCLUSION: Taking into account the strong inhibitory effect of bcl-2 during apoptotic events, these findings again support the likelihood of increased apoptosis in the contralateral testes.

Cytochrome P4502C9 genotype in Southeast Anatolia and possible relation with some serum tumour markers and cytokines.

Substrates for CYP2C9 include fluoxetine, phenytoin, warfarin, losartam and numerous nonsteroidal anti-inflammatory drugs. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino-acid residues 144 Arg/Cys and 359 Ile/Leu of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, the frequency of this allele is, however, rather low. Consistently with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. The polymorphic enzyme CYP2C9 takes part in the metabolism of alkylating agents and polycyclic aromatic hydrocarbons like benzo(a)pyrene, a carcinogen present in tobacco smoke. Although the impact of impaired enzyme activity in metabolism of carcinogens and procarcinogens has not been fully defined, an association of CYP2C9 variant alleles to DNA adduct levels in lung tissues as well as to lung cancer risk have been reported. In this study 64 healthy subjects (44M/22F) were analysed for CYP2C9 genotype with PCR-RFLP and for serum carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), CA 19-9, CA 15-3, ferritin, IL-6, IL-8 concentrations by chemiluminescence or electrochemiluminescence methods. CYP2C9*1 was found to be the most prevalent allele and CYP2C9*1/CYP2C9*1 was the most frequent genotype represented in 64% of the population in southeastern Anatolia (Gaziantep). Although slight differences in serum tumour marker and cytokine concentrations were observed for CYP2C9 genotypes the differences were statistically insignificant (P > 0.05). This could be due to the complexity of the role of CYP2C9 in benzo(a)pyrene metabolism as well as from other contributing factors like interindividual variability of diverse enzymes participating in the same metabolic pathway, unequal expression of the variant alleles and differences in exposure to carcinogens. However, determination of CYP2C9 phenotypes in a larger group of subjects might clarify these slight differences.

Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children.

OBJECTIVES: Recent evidence favors primary role of cellular autoimmunity and its humoral mediators in pathogenesis and following Type I diabetes mellitus (DM). The present study was carried out to investigate serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in children with type I DM. Potential role of lipid metabolism, glycemic control, body mass index (BMI) and disease duration were evaluated. DESIGN AND METHODS: Thirty-five children with type I DM and 30 age and gender matched nondiabetic controls were recruited for this study. RESULTS: Circulating IL-8 levels were elevated in children with type I DM (12.7 +/- 1.7 pg/mL) compared with nondiabetic controls (5.5 +/- 0.3 pg/mL) and the difference remained significant after adjustment for cofactors and covariates (p: 0.033). Although statistically insignificant serum CRP concentrations were slightly higher in diabetic children (p: 0.075). Serum TNF-alpha and IL-6 levels were comparable in diabetic and nondiabetic groups. However newly diagnosed (<1 yr) cases had higher TNF-alpha and IL-6 levels compared to cases with longer standing DM. In diabetic children BMI was independently associated with an increase in serum IL-8 levels. Serum CRP, lipids, apolipoproteins and glycemic control were not significant predictors of cytokine concentrations in children with type I DM. CONCLUSION: Circulating levels of IL-8 were elevated and were correlated with BMI in children with type I DM, hinting perhaps at adipose tissue as a site of production. Elevated systemic IL-6 and TNF-alpha were limited to newly diagnosed cases suggesting activation of the inflammatory immune response system at early stages of the disease.

Unilateral testicular torsion: protective effect of verapamil on contralateral testicular histology.

In this experimental study, it was our aim to reduce the effects of ischemic insults to the contralateral testicle after unilateral testicular torsion. The protective effect of a calcium channel blocking agent (verapamil) on the histology and the tubular diameter of contralateral testicle was evaluated. Following a definite period of unilateral testicular torsion (i.e., 4 h), the protective effect of this specific medication was evaluated both after detorsion and orchiectomy procedures. The results of our study demonstrated the protective effect of verapamil on both parameters, especially in animals undergoing orchiectomy. The majority of the specimens demonstrated normal histologic findings together with preserved tubular structures after a 1-week period under verapamil medication.

Diagnostic value of biochemical markers of bone turnover and postmenopausal osteoporosis.

We studied 77 women divided into postmenopausal osteoporotic and premenopausal and postmenopausal non-osteoporotic groups in order to evaluate bone metabolism and diagnostic value of biochemical markers of bone turnover in postmenopausal osteoporosis. Postmenopausal osteoporotic (n: 40), postmenopausal non-osteoporotic (n: 24) and premenopausal non-osteoporotic (n: 13) groups were defined according to bone mineral density (BMD) scores obtained with dual energy X-ray absorptiometry (DEXA). Urinary deoxy-pyridinoline (Dpd), pyridinoline (Pyd), serum total alkaline phosphatase (ALP), bone specific alkaline phosphatase (BALP), osteocalcin (BGP), total calcium, phosphorus, and creatinine levels were determined. Urinary Dpd and Pyd levels of postmenopausal osteoporotic group (8.7 and 18.7 mumol/mg creatinine) were significantly higher than postmenopausal control (5.1 and 11.7 mumol/mg creatinine, p < 0.0001) and premenopausal control (6.0 and 13.0 mumol/mg creatinine, p < 0.0005 and p < 0.001) groups. Bone formation markers were not significantly different between groups, although BGP correlated with Dpd and Pyd (r: 0.26 and r: 0.31, p < 0.05) in osteoporotic subjects. From receiver operating curve (ROC) analysis Dpd had the best diagnostic value (0.846), followed by Pyd (0.802) in evaluation of osteoporosis, whereas BALP (0.570) and BGP (0.528) were relatively inefficient in the discrimination of postmenopausal osteoporosis. This study suggests that bone resorption markers are more efficient than bone formation markers in the diagnosis of postmenopausal osteoporosis. Urinary Dpd/creatinine ratio has the highest diagnostic value.

Menstrual cycle dependent variability for serum tumor markers CEA, AFP, CA 19-9, CA 125 and CA 15-3 in healthy women.

Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19-9, CA 125, CA 15-3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase-dependent difference was observed for CA 15-3, midluteal concentrations (mean +/- SEM; 26.33 +/- 1.56 U/ml) higher than the midfollicular (mean +/- SEM; 19.27 +/- 1.49 U/ml) concentrations (p < 0.001). But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively). CA 15-3 antigen is a product of the MUC-1 gene which is expressed in abundance by endometrial epithelial cells in the secretory phase of the menstrual cycle which may be the potential source of variability. The association of CA 125 levels with obesity suggests a possible role of adipose tissue in CA 125 metabolism. In conclusion our data suggest that in healthy women serum CA 15-3 levels are significantly elevated in the midluteal phase of the menstrual cycle compared to midfollicular phase. Therefore, consideration of menstrual cycle dependent variability for CA 15-3 appears indicated in interpretation of individual results.

The place of diuretic enhanced Doppler sonography in distinguishing between obstructive and non-obstructive hydronephrosis in children.

OBJECTIVE: In an attempt to differentiate obstructive from non-obstructive dilation of the renal collecting system in children, a prospective clinical study was carried out. MATERIAL AND METHODS: During duplex Doppler sonography examination in 23 children resistive index (RI) and pulsatility index (PI) and RI ratio values before and after intraverous furasemide administration were compared with the findings obtained with diuretic renogram examination (t(1/2)). RESULTS: Evaluation of the results demonstrated that diuresis RI and PI determination may aid differentiation of severely obstructed renal units from those with slight (equivocal) or no obstruction. CONCLUSION: Kidneys with severe UPJ obstruction tended to have more elevated RI and PI values than the non-obstructed or equivocally obstructed ones. Again, determination of RIR values for each kidney showed the same elevation in severely obstructed kidneys, while non-obstructive or indeterminately obstructed ones demonstrated statistically insignificant changes.

Xanthogranulomatous pyelonephritis: report of four cases.

We report 4 patients with xanthogranulomatous pyelonephritis (diagnosed and treated between 1992 and 1996), aged 16 to 55 years (mean age 37 years). All had urolithiasis, pyonephrosis and nonfunctioning kidneys prior to surgical intervention, and underwent total nephrectomy. Clinical, laboratory and radiologic findings are discussed in the light of the cases reported in the literature.