The effects of resveratrol and melatonin on cardiac dysfunction in diabetic elderly female rats.

We aimed to investigate the effects of melatonin and resveratrol on diabetes-related papillary muscle dysfunction and structural heart disorders. The protective effect of resveratrol and melatonin supplementation on cardiac functions was investigated in a diabetic elderly female rat model. 16-month-old rats (n=48) were allocated into 8 groups. Group1: Control, Group2: Resveratrol Control, Group3: Melatonin Control, Group4: Resveratrol and Melatonin Control, Group5: Diabetes, Group6: Diabetes Resveratrol, Group7: Diabetes Melatonin, Group8: Diabetes Resveratrol and Melatonin. Streptozotocin was injected intraperitoneally to the rats for experimental diabetes induction. Thereafter, resveratrol (intraperitoneal) and melatonin (subcutaneous) were administered for 4 weeks. Resveratrol and melatonin had a protective effect on the contractile parameters and structural properties of the papillary muscle, which was impaired by diabetes. it has been presented that diabetes impairs the contractile function of the papillary muscle for each stimulus frequency tested and the responses obtained as a result of Ca+2 uptake and release mechanisms from the Sarcoplasmic reticulum, and it has been observed that these effects are improved with resveratrol and melatonin injection. The decrease in myocardial papillary muscle strength in the diabetic elderly female rat can be reversed with the combination of resveratrol, melatonin and resveratrol+melatonin. Melatonin+resveratrol supplementation is no different from melatonin and/or resveratrol supplementation. Resveratrol and melatonin supplementation may have a protective effect on cardiac functions in a diabetic elderly female rat model.

Immediate post-operative intravesical instillation of a single dose chemotherapy is not superior to continuous saline irrigation.

INTRODUCTION AND OBJECTIVES: To evaluate whether there is any difference between immediate postoperative instillation of intravesical chemotherapy (IPOIC) and continuous saline bladder irrigation (CSBI) in terms of bladder cancer (BC) recurrence in patients with primary low- or intermediate-risk non-muscle-invasive BC (NMIBC). MATERIALS AND METHODS: Medical records of 1482 patients who underwent transurethral resection of bladder tumor between March 1994 and August 2020 were reviewed retrospectively. Patients were divided into two groups according to IPOIC and/or CSBI administration status [Group-1 = CSBI alone; Group-2 = CSBI following IPOIC]. Low- and intermediate-risk NMIBC patients were also divided into subgroups according to IPOIC and/or CSBI administration status. RESULTS: A total of 594 patients with primary NMIBC were included. Of the patients, 86 (14.5%) were female and 508 (85.5%) were male with a median age of 69 (60-78) years. The frequency of patients in Group-1 and Group-2 were 361 (60.8%) and 233 (39.2%), respectively. Recurrent disease was observed in 213 (35.9%) patients. There was no difference between the groups when they were compared for recurrent disease frequency, median time to first recurrence and frequency of recurrence within first 12 months (P = .064, P = .671, and P = .145, respectively). Disease recurrence rates in low-risk NMIBC patients was lower when they were treated with "CSBI following IPOIC" when compared to "CSBI alone" (P = .042). However, no difference was observed in low-risk NMIBC subgroups when they were compared for pathological features of recurrent tumors such as number, size, grade, stage, and presence of carcinoma in situ (P > .05, for each). CONCLUSIONS: "CSBI following IPOIC" combination was not superior to "CSBI alone" for preventing adverse pathological outcomes in recurrent low- and intermediate-risk NMIBC.

The Effect of 2 Weeks of Naringenin on AQP4, IL-2 and DNA Damage in Brain Ischemia Reperfusion in Rats.

The aim of this study was to determine the effect of different doses of naringenin (NAR) administration for 2 weeks in rats on brain Aquaporin-4 (AQP4), interleukin-2 (IL-2) and 8-Hydroxydeoxyguanosine (8-OhdG) levels in brain ischemia-reperfusion. Experimental groups were formed as follows; 1-Control; 2-Sham Control; 3 Ischemia/ Reperfusion (I/R); 4-Naringenin (Naringenin 50) + I/R; 5-Naringenin (naringenin 100) + I/R. I/R was performed as 1 hour occlusion of the carotid arteries (ischemia) followed by 1 hour reperfusion. Naringenin was supplied for 2 weeks by intraperitoneal. At the end of the experiment, AQP4, IL-2 and 8-OHdG levels were determined in the brain frontal cortex tissue taken from animals killed under anesthesia. AQP4, IL-2 and 8-OHdG levels increased significantly in I/R group. However, both 50 mg/kg and 100 mg/kg two-week administration of naringenin significantly decreased these increased parameters (P 0.001).The results of the study show that intraperitoneal administration of naringenin for two weeks in rats may prevent the damage caused by brain ischemia-reperfusion.

Zinc and melatonin supplementation ameliorates brain cortex tissue damage in DMBA-induced breast cancer in rats.

BACKGROUND: This study aims to investigate the effects of zinc and melatonin supplementation on lipid peroxidation in the brain cortex in DMBA-induced breast cancer in female rats. METHODS: A total of 42 recently weaned Wistar rats were divided into 5 groups as follows: Control (Group 1), DMBA Control (Group 2), DMBA+Zinc (Group 3), DMBA+Melatonin (Group 4), DMBA+Melatonin et Zinc (Group 5). At the end of the study, all animals were sacrificed by decapitation and Malondialdehyde (MDA) and glutathione (GSH) levels in brain cortex tissue samples were determined via spectrophotometric methods. RESULTS: The highest MDA levels were in the DMBA-treated group (Group 2) (p<0.05). MDA levels in Group 3, Group 4, and Group 5 were significantly lower than in group 2 (p<0.05). Also, GSH levels in group 3, 4, and 5 were significantly higher than in group 2 (p<0.05). CONCLUSION: There are no reports on whether DMBA-induced experimental breast cancer affects oxidative stress in brain tissue. In this respect, our study revealed that the increased brain cortex tissue damage in DMBA-induced breast cancer is alleviated by Zinc, melatonin, or combined zinc and melatonin treatment (Fig. 3, Ref. 26).

The effects of resveratrol administration on lipid oxidation in experimental renal ischemia-reperfusion injury in rats.

We investigated how resveratrol affects lipid oxidation during experimental renal ischemia-reperfusion injury in rats. We used 48 adult male rats assigned to five groups: group 1, control; group 2, renal ischemia; group 3, renal ischemia + reperfusion; group 4, resveratrol + renal ischemia; group 5, resveratrol + renal ischemia + reperfusion. Plasma and renal tissue malondialdehyde (MDA), and erythrocyte and renal tissue glutathione (GSH) levels were measured and histologic changes in the renal tissue were examined. Ischemia-reperfusion affected the MDA-GSH balance adversely and caused histopathological changes in the renal tissue of the ischemia and ischemia + reperfusion groups. Resveratrol treatment normalized MDA and GSH levels as well as the histopathology that occurred in the renal tissue of the ischemia and ischemia + reperfusion groups.

Preliminary results of a new tool to evaluate cavernous body fibrosis following radical prostatectomy: penile elastography.

Development of cavernous tissue fibrosis due to neurovascular bundle damage during radical prostatectomy has been shown in many trials with invasive methods. In this study, we evaluated the changes in cavernous tissue elasticity by elastography in patients who underwent radical prostatectomy with or without neurovascular bundle preservation. Data from 65 patients underwent open retropubic radical prostatectomy between April 2014 and December 2015 was collected prospectively. Patients were grouped with respect to nerve-sparing status (non-, unilateral, and bilateral nerve sparing). International Index of Erectile Function scores, penile lengths, and elasticity scores were recorded at preoperative and postoperative follow-up visits (at 3rd and 6th months). The primary endpoint of the study was to evaluate the changes of the elasticity scores in all groups. Elasticity scores were measured with real-time elastography by a single experienced radiologist. Mean age, baseline total testosterone level, IIEF-5 score, elasticity scores of the cavernous body, and penile length were comparable in all groups. At postoperative 3rd and 6th months, statistically significant higher (in favor for fibrosis) mean cavernous body elasticity scores (p = 0.0001), lower mean IIEF-5 scores (p = 0.0001), and shorter penile lengths (p < 0.05) were observed in non-nerve-sparing group compared to other groups while there were no statistically significant differences between unilateral and bilateral nerve-sparing groups. Very strong negative correlation was detected between IIEF-5 and elasticity scores (p = 0.0001). According to our results, preservation of the neurovascular bundle in at least one side mediates lower elasticity scores, better International Index of Erectile Function scores, and penile lengths. Preliminary results of the penile elastography studies are promising for prediction of erectile functions and cavernous tissue fibrosis.

Surgical repair of a giant renal artery aneurysm: a case report.

A case of a giant renal artery aneurysm and multiple small branch aneurysms in a 48-year old man is presented. The largest aneurysm was repaired successfully with kidney preservation. Small branch aneurysms were left alone. Subsequent CT scans 6, 12 and 20 months after the operation revealed the same aneurysms without any increase in size and shape.

DNA ploidy and S-phase fraction as predictive factors of response and outcome following neoadjuvant methotrexate, vinblastine, epirubicin and cisplatin (M-VEC) chemotherapy for invasive bladder cancer.

OBJECTIVE: To investigate the value of DNA ploidy and S-phase fraction (SPF) as factors that could predict response and outcome of invasive transitional cell carcinoma (TCC) of the bladder to neoadjuvant methotrexate, vinblastine, epirubicin and cisplatin (MVEC) chemotherapy. MATERIALS AND METHODS: Twenty-four patients with localized invasive TCC of the bladder (stages T3 to T4a, NoMo) were treated with neoadjuvant MVEC chemotherapy. DNA flow cytometry was performed in paraffin-embedded tissue obtained by transurethral resection before chemotherapy. Radical cystectomy specimens were utilized for complete pathologic staging. The tumors were subdivided into high- and low-SPF tumors according to their SPF value. DNA ploidy status was evaluated into two groups (diploidy and nondiploidy). RESULTS: DNA ploidy was not correlated to the response to chemotherapy (p = 0.67), and overall or disease-free survival (p = 0.27 and p = 0.69, respectively). Major response (pathologic complete response and partial response) was more often found in the high SPF group than among tumors with low SPF (p = 0.02). High SPF tumors were significantly associated with increased overall and disease-free survival (p = 0.0056 and p = 0.0059, respectively). CONCLUSION: A high SPF, but not DNA ploidy, may be helpful to identify patient likely to respond and survive longer following neoadjuvant MVEC chemotherapy in the treatment of invasive bladder cancer.

A nonrefluxing, serous lined extramural tunnel for ureteroileal anastomosis in ileal conduit urinary diversion: first clinical experience in 10 patients.

PURPOSE: We report the surgical technique and functional outcome of a new application for serous lined, anti-refluxing ureteroileal anastomosis in ileal conduit urinary diversion. Reflux prevention relies on the construction of a serous lined extramural ileal tunnel. MATERIALS AND METHODS: A 25 cm. distal ileal segment was isolated. The proximal 7 cm. of the ileal segment was folded and the 2 proximal 7 cm. segments were joined by seromuscular sutures. The antimesenteric borders of these 7 cm. segments were incised and the medial edges of each ureter were joined. A mesenteric window was opened at the level of ileal folding and the ureters were passed through it. They were inlaid within the trough and the conjoined ureteral end were anastomosed to the intestinal mucosa. The tunnel was then closed over the implanted ureters. The lateral limbs of the detubularized ileal segment were then joined. The technique was performed in 10 patients with a mean followup of 9.9 months (range 3 to 19). The patients were evaluated clinically and radiologically. RESULTS: None of the 10 patients had reflux on x-ray of the loop. One patient had previously undergone unilateral nephrectomy. Excretory urography showed a stabilized or improved upper tract in 18 renal units. Left ureterohydronephrosis was present in 1 renal unit because of ureteroileal stenosis. CONCLUSIONS: The initial clinical results of the serous lined extramural ileal tunnel technique for ureteroileal anastomosis in ileal conduit cases are promising. The technique appears effective and reliable.

Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low- and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma.

OBJECTIVE: To elucidate the incidence of inducible nitric oxide synthase (iNOS) expression in benign prostatic hyperplasia (BPH), low- and high-grade prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma lesions, and to explore the role of iNOS in prostate tumorigenesis. MATERIALS AND METHODS: Immunoreactivity for iNOS was examined in 20 samples each of BPH, high-grade PIN, low-grade PIN and prostatic carcinoma. RESULTS: Positive iNOS immunostaining was detected in all samples from all patients; iNOS was detected in both basal epithelial cells and secretory cells of the glandular epithelium. High-grade PIN and prostatic carcinoma samples had more intense iNOS immunostaining than low-grade PIN and BPH samples. In all samples, smooth muscle cells showed weak or moderate iNOS immunoreactivity and endothelial cells showed moderate immunostaining. CONCLUSIONS: Nitric oxide generated by iNOS may be involved in prostate tumorigenesis and further studies with immunohistochemical and molecular biology are needed to determine the exact role of iNOS in the pathogenesis of prostatic carcinoma.

Collecting duct carcinoma.

Collecting duct carcinoma of the kidney is a rare variant of renal cell carcinoma. Hematuria is the most common presenting symptom. This tubulopapillary tumor arises from or differentiates forward to medullary collecting tubules. It is typically centered on the medulla of the kidney and extends into the cortex with a desmoplastic reaction. There are few reports documenting the clinical presentation and long-term prognosis. We describe a case of this uncommon tumor with clinical, histological and immunohistochemical features and review the literature.

P53, bcl-2 and bax immunoreactivity as predictors of response and outcome after chemotherapy for metastatic germ cell testicular tumours.

OBJECTIVE: To evaluate the roles of p53, bcl-2 and bax as determinants of chemosensitivity in testicular cancers and to assess whether immunohistochemical expression of these proteins in testicular germ cell tumours (GCTs) could be used to predict the outcome in patients with metastatic testicular GCTs. PATIENTS AND METHODS: Immunoreactivity for p53, bcl-2 and bax were examined in primary testicular tumours from 24 patients with metastatic GCTs who were treated with bleomycin, etoposide and cisplatin chemotherapy. All immunostaining results were scored for the appropriate percentage of positive tumour cells and relative immunostaining intensity (score range 0-15) and compared with the response of the patients to chemotherapy. RESULTS: Overall, 20 (83%), 13 (54%) and 24 of the 24 GCTs showed > or = 1% immunoreactivity with p53, bcl-2 and bax, respectively. Only the bax immunostaining intensity and score had statistically higher mean values in the nonseminoma than in seminoma GCTs (P = 0.047 and P = 0.027, respectively). Only p53 immunostaining intensity, percentage of p53 immunopositive cells and p53 staining score were sig-nificantly different among the response groups. The median survival after chemotherapy was 30.5 months; however, taking the median values of the immunostaining scores as threshold values for the survival analysis, none of the three proteins were associated with significant differences in survival. CONCLUSIONS: The incidence of p53 and bax immuno-reactivity in testicular GCTs is higher than that of bcl-2 immunoreactivity. However, only p53 immuno-reactivity could be used to predict the response to chemotherapy. P53, bcl-2 and bax scores were not significant prognostic factors for survival after chemotherapy.

Combined interferon alpha with levamisole in patients with metastatic renal cell carcinoma.

To evaluate the efficacy and toxicity of interferon alpha-2b (IFN-alpha2b) and levamisole treatment regimen in patients with metastatic renal cell carcinoma (RCC). Seventeen patients with metastatic RCC were treated using recombinant IFN-alpha2b at a dose of 10 MU/m2 body surface subcutaneously three times in a week, for 3 months, with levamisole 50 mg t.d.s orally on days 1-3 on alternate weeks. The mean follow-up period was 10.7 (range 2-23) months. We achieved 1 complete response (lasting for 12+ months) and 1 partial response (lasting for 15 months), for an objective response rate of 11.7%. A further 7 patients (41%) had a stabilization of disease. The overall toxicity was moderate, with mainly grade I or II side effects. Grade III toxicities reported among 3 patients including vomiting (2 patients) and anorexia (1 patient). There was no treatment related death. Although additions of levamisole to IFN-alpha do not result in any significant increase in treatment toxicity, the response rate appears to be no better than IFN-alpha monotherapy reported in the literature.

Conformal radiotherapy in primary non-Hodgkin's lymphoma of the male urethra.

Primary malignant lymphoma of the urethra is very rare. Fifteen cases are reported in the literature and only four of them belong to the male urethra. We present the fifth case of primary Non-Hodgkin's lymphoma of the male urethra that is managed by conformal radiotherapy.

Leiomyoma of the epididymis.

Tumours of the epididymis, both primary and secondary, whether benign or malignant are very rare. We report a case of leiomyoma of the epididymis and discuss the treatment of this tumour.

Palliative analgesic effect of Re-186 HEDP in various cancer patients with bone metastases.

UNLABELLED: The clinical picture of bone metastases is manifested by pain and loss of mechanical stability. Standard treatment options for bone metastases include external beam radiotherapy and the use of analgesics. Due to a large number of lesions in many patients, the use of radionuclide therapy with beta emitters may be preferable. Re-186 hydroxyethylidene diphosphonate (Re-186 HEDP) is one of the radiopharmaceuticals suitable for palliative treatment of metastatic bone pain. The aim of this study was to investigate palliative and side effects of Re-186 HEDP in patients with different types of cancers. MATERIAL & METHOD: Thirty one (17 male, 14 female) patients with various cancers (10 prostate, 10 breast, 4 rectum, 5 lung, 2 nasopharynx) and bone metastases were included in the study. Therapy was started with a fixed dose of 1295 MBq of Re-186 HEDP. If necessary, the same dose was repeated at least 3 times after an interval of 10-12 weeks; A total of 40 standard doses were given; 6 patients received repeated doses (3 doses in 3 patients, 2 doses in 3 patients). The patients with bone marrow suppression were excluded from the study. The pain relief was assessed the Eastern Cooperative Oncologic Group (ECOG) and the Karnofsky status index. All patients were evaluated with standard evaluation forms filled in daily for a maximum of 10 weeks. RESULTS: The mean response rate was 87.5% in patients with breast and prostate cancer, 75% in patients with rectum cancer and 20% in patients with lung cancer. The overall response rate was 67.5%. The palliation period varied between 6 and 10 weeks, with a mean of 8.1+/-1.3 weeks. The maximal palliation effect was observed between the 3rd and 7th weeks. No serious side effects were seen except mild hematologic toxicity. DISCUSSION & CONCLUSION: It is concluded that Re-186 HEDP is a highly effective agent in the palliation of metastatic bone pain in patients with prostate, breast and rectum cancer, but not effective in lung cancer. On the other hand, Re-186 seems to be a good alternative to Sr-89 because of its preferable physical characteristics (such as short half life and gamma energy emission), low side effect profile, early response and repeatability.

Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma.

PURPOSE: We assessed the influence of clinical and pathological factors on multifocality of renal cell carcinoma. MATERIALS AND METHODS: Between June 1995 and September 1999 radical nephrectomy was performed in 71 men and 32 women with a mean age of 56.5 years. The 103 removed kidneys with renal cell carcinoma were sectioned at 3 mm. intervals and inspected microscopically for satellite carcinomas. We evaluated pathological stage, grade, cell type, histological pattern, vascular involvement, tumor size and the incidence of multifocality. To determine cell type we used several classification systems. RESULTS: The primary tumor was 2 to 20 cm. (mean plus or minus standard deviation 7.10 +/- 3.48). Overall satellite carcinomas were present in 22 of the 103 cases (21.4%). When the predominant lesion was 5 cm. or smaller, the incidence of multifocality was 19%. The incidence of multifocality was statistically higher in patients with stage pT3 than in those with stage pT1 or pT2 disease (p = 0.022). Multiple logistic regression analysis demonstrated that only primary tumor pathological stage was a significant predictor of renal cell carcinoma multifocality in stages T3 versus T1 and T3 versus T2 cancer (odds ratio 3.45, 95% confidence interval 1.15 to 10.39 and 5.75, 1.31 to 25.29, respectively). Other parameters, such as tumor size, grade, vascular invasion, cell type and histological pattern, did not correlate with multifocality. CONCLUSIONS: Our results imply that primary tumor stage is a significant factor for multifocal disease. Therefore, more precise preoperative staging of the primary lesion is required if nephron sparing surgery is indicated.

Determination of transition zone volume by transrectal ultrasound in patients with clinically benign prostatic hyperplasia: agreement with enucleated prostate adenoma weight.

PURPOSE: Accurately estimating transition zone volume is important for the medical or surgical management of symptomatic benign prostatic hyperplasia and determination of prostate specific antigen density of the transition zone. We evaluated whether preoperative transrectal ultrasound measurements of the transition zone predict enucleated adenoma weight. MATERIALS AND METHODS: We measured transition zone volume preoperatively using transrectal ultrasound and the prolate ellipsoid method in 50 patients with presumed benign prostatic hyperplasia who underwent suprapubic prostatectomy. Transition zone volume corresponds to the adenoma. Enucleated adenoma weight was then correlated with preoperatively determined transition zone volume. RESULTS: As measured by transrectal ultrasound, mean transition zone volume plus or minus standard deviation was 80.88 +/- 37.42 cc (range 31 to 200). Mean enucleated adenoma weight was 68.70 +/- 36.26 gm. (range 18 to 180). There was a statistically significant correlation of estimated transrectal ultrasound volume of the transition zone with enucleated prostate adenoma weight (r = 0.95, p <0.001). However, when prostate adenoma weight was determined using the formula, prostate adenoma weight = -6.00 + 0.92 x transition zone volume, we noted a significant difference in mean prostate adenoma weight and mean transition zone volume (p <0.001). Since the regression coefficient of transition zone volume was significantly different from 1, we identified no agreement of prostate adenoma weight with estimated transrectal ultrasound volume of the transition zone. CONCLUSIONS: These data reveal a significant difference in mean prostatic adenoma weight and mean transition zone volume. Although transition zone volume measurements are well described, clear agreements on such measurements should be obtained to determine transition zone volume more precisely.

Bcl-2 proto-oncogene expression in low- and high-grade prostatic intraepithelial neoplasia.

OBJECTIVE: To determine the incidence of bcl-2 protein expression in low- and high-grade prostatic intra-epithelial neoplasia (PIN) lesions, and to explore the role of bcl-2 in prostatic tumorigenesis. Materials and methods Immunoreactivity for bcl-2 was examined in 10 samples of benign prostatic hyperplasia (BPH), 13 of primary prostatic adenocarcinoma, 15 of high-grade PIN and 18 of low-grade PIN. All immunostaining results were scored for the approximate percentage of positive tumour cells and relative immunostaining intensity (score range 0-12). RESULTS: In all BPH samples, bcl-2 staining was detected consistently in the basal cell layer of the ducts and acini, but no staining was ever apparent in luminal cells. The immunoreactivity for bcl-2 was heterogeneous in the prostatic carcinomas and bcl-2 protein expression was present in six samples. In these six bcl-2-positive tumours, the mean (range) staining score was 1.15 (1-6). There was detectable expression of bcl-2 in low- and high-grade PIN in all cell layers; immunoreactivity was present in 10 of 15 high-grade PIN lesions, with a mean (range) score of 1.14 (1-4), and in 12 of 18 samples of low-grade PIN, with a mean (range) score of 1.77 (1-6). CONCLUSIONS: The high incidence of bcl-2 protein expression in low- and high-grade PIN lesions suggests that bcl-2 protein expression is associated with early prostate tumorigenesis.