Do penile haemodynamics change in the presence of hydrogen sulphide (H2 S) donor in metabolic syndrome-induced erectile dysfunction?

Erectile dysfunction (ED) is defined in relation to the metabolic syndrome (metS). Hydrogen sulphide (H2 S), a gasotransmitter, has been revealed to get involved in hypertension, insulin secretion and regulation of vascular tone especially in erectile physiology. This study aimed to investigate the effect of H2 S on metS-induced ED. Animals were divided into two groups as control and metS, which were fed with standard diet or 60% high-fructose diet for 10 weeks respectively. The metS model was evaluated with biochemical analyses, waist circumference/tibia length ratio and HOMA index. Penile hemodynamic parameters were evaluated by the measurement of intracavernous pressure/mean arterial pressure ratio during cavernous nerve stimulation in the presence and absence of intracavernous injection of NaHS (100 µg/50 µl) and its control 0.9%NaCl (50 µl) in both groups. H2 S levels were measured in penile tissues by methylene blue assay. H2 S levels were significantly decreased in the penile tissues of the metS group. Decreased intracavernous pressure/mean arterial pressure ratio improved after intracavernous administration of NaHS in the metS group. These results suggest the significant role of H2 S in the metS-induced erectile dysfunction that could be a new therapeutic target.

Investigation of genotoxic effects of doripenem using cytogenetic and molecular methods.

The main aim of this study was to investigate the genotoxic effects of doripenem (DRP) using both cytogenetic and molecular test systems. Although there have been some studies reporting the effects of DRP, none of them has shown the genotoxic effects of DRP. In order to achieve the main aim of the study, the human peripheral lymphocytes were treated with 100 µg/ml, 200 µg/ml, and 400 µg/ml concentrations of DRP for 24 and 48 hours, and the chromosome aberration (CA) and micronucleus (MN) methods were used as the cytogenetic tests and RAPD-PCR method was used as the molecular test to determine the genotoxic effects of DRP. DRP did not induce the chromosome aberrations and micronucleus frequencies at all concentrations and at all treatment periods. So, it was concluded that DRP did not show any cytotoxic effect. However, DRP increased the number of polymorphic bands and decreased the ratio of genomic template stability, especially at the 48-hour treatment period. In this study, according to the obtained results, it was determined that DRP failed to show any genotoxic risk at the therapeutic doses. This result also indicates that DRP could be a reliable antibiotics according to its rapid metabolism.

May argyrophilic nucleolar organizing region-associated protein synthesis be used for selecting the most reliable dose of drugs such as rhamnetin in cancer treatments?

BACKGROUND: Rhamnetin is a flavonoid that has antioxidant, anti-inflammatory and anti-cancer effects. Nucleolar-organizing regions are the ribosomal genes region. We aimed to identify whether rhamnetin has an effect on cell proliferation and whether AgNOR proteins may be used for the detection of therapeutic benefits of the drugs and new metabolites, which have the potential of being used for cancer treatments. METHODS: Twenty-four mice with Ehrlich's ascites carcinoma (EAC) were randomly assigned to three main groups as positive control, and groups 2 and 3 treated intraperitoneally with rhamnetin (100 µg/kg and 200 µg/kg, respectively). All the animals were sacrificed on day16, 24 h after the last dose; the tumors, which developed at the site of injection were removed. Then, mean AgNOR number and total AgNOR area/nuclear area (TAA/NA) were detected for each mouse. RESULTS: Significant differences were detected among all groups for mean AgNOR number (p = 0.000) and TAA/NA ratio (p = 0.000). While the difference between positive control and Rhamnetin (100 µg/kg) group was not significant (p = 0.387), there are significant differences between positive control and Rhamnetin (200 µg/kg) group (p = 0.000) and between Rhamnetin (100 µg/kg) and Rhamnetin (200 µg/kg) groups (p = 0.000) for TAA/NA ratio. CONCLUSION: Rhamnetin has an important role in preventing cancer formation. Our study showed that mean AgNOR numbers and TAA/NA values may be used also as biomarkers for evaluating the success rate of the performed therapeutic strategy and accurate dose selection for the management of the disease (Tab. 3, Fig. 3, Ref. 45).

Fryns anophthalmia-plus syndrome: two rare cases.

Fryns anophthalmia-plus syndrome is a rare syndrome with clinical diversity primarily including anophthalmia/microphthalmia, facial clefts, cleft lip/palate, ear and nasal deformities. Here we present two different cases of APS with anopthalmia/microphthalmia, cleft palate, low set ears, ventriculomegaly and one of which had intestinal non-fixation anomaly not described in the literature before.

Investigation of the effect of rhamnetin on mice injected with solid and ehrlich ascites tumor.

Rhamnetin is a flavonoid which contained in especially clove, such as apple, tea, and onion plant. Rhamnetin has been used in cancer research due to its antitumor and antioxidant properties. In this study, effects of rhamnetin administration at different doses on ascites and solid tumors were investigated in Balb/C mice bearing EAT model that originating from rat breast adenocarcinoma. Experimental procedure: Overall, 92 Balb-c mice were used in this study. EAT cells (1 × 106 cells) that harvested from stock animals were injected to all rats via intraperitoneal and subcutaneous route. Rhamnetin (100 µg/kg-200 µg/kg) were given intraperitoneally and subcutaneously during 10 and 15 days to the animals bearing ascites tumor and solid tumor, respectively. Throughout experiments, weight changes were recorded in all groups. The maximum weight increase was observed in the control group among all groups (ascites and solid tumor groups). In the treatment groups, the least weight increase were determined in 200-µg/kg rhamnetin applied. The lowest increase in tumor volume was observed in the group that received 200-µg/kg rhamnetin (2.84) when compared to tumor control group (3.67). Result and conclusion: We determined that the number of live and dead cells in the treatment groups administered with the mean rhamnetin dose (2.5 µg/ml) was found in the count made in the EAT cell line after the incubation periods. We observed that rhamnetin plays an important role against cancer formation. We have obtained important results in our study, but detailed studies on the relationship between rhamnetin and cancer are needed.

A Fournier's gangrene after transurethral resection of the prostate.

Fournier's gangrene is a rapidly progressive and potentially lethal disease that affects the perineum and mal genitalia. Predisposing factors included age, diabetes, alcoholism, malnutrition, and low socio-economic status. Herein, we present a 70-year-old patient who developed Fournier's gangrene following transurethral resection of the prostate. He had no predispositional factors to develop Fournier's gangrene.

Effects of metabolic syndrome on early mortality and morbidity in coronary artery bypass graft patients.

Metabolic syndrome is a well-known cardiovascular risk factor closely related to increased insulin resistance. This study assessed the effects of metabolic syndrome on early post-operative mortality and morbidity in 100 coronary artery bypass graft (CABG) patients: 50 patients with and 50 without metabolic syndrome. A total of 17 patients were excluded from the analysis as they did not attend follow-up, leaving 51 males (61.4%) and 32 (38.6%) females of mean +/- SD age 60.02 +/- 9.76 years for analysis. Diabetes, hypertension and a high body mass index were significantly more common in patients with metabolic syndrome. A statistically significant relationship was found between metabolic syndrome and surgical wound infection. Non-significant positive correlations were found between metabolic syndrome and post-operative atrial fibrillation, surgical revision due to haemorrhage, ventricular tachycardia and ventricular fibrillation, and prolonged intubation. In conclusion, metabolic syndrome did not affect mortality, but did increase the risk of post-operative surgical wound infection.

Recruitment of participants through community pharmacies for a pharmacogenetic study of antihypertensive drug treatment.

OBJECTIVE: To describe the design, recruitment and baseline characteristics of participants in a community pharmacy based pharmacogenetic study of antihypertensive drug treatment. SETTING: Participants enrolled from the population-based Pharmaco-Morbidity Record Linkage System. METHOD: We designed a nested case-control study in which we will assess whether specific genetic polymorphisms modify the effect of antihypertensive drugs on the risk of myocardial infarction. In this study, cases (myocardial infarction) and controls were recruited through community pharmacies that participate in PHARMO. The PHARMO database comprises drug dispensing histories of about 2,000,000 subjects from a representative sample of Dutch community pharmacies linked to the national registrations of hospital discharges. RESULTS: In total we selected 31010 patients (2777 cases and 28233 controls) from the PHARMO database, of whom 15973 (1871 cases, 14102 controls) were approached through their community pharmacy. Overall response rate was 36.3% (n = 5791, 794 cases, 4997 controls), whereas 32.1% (n = 5126, 701 cases, 4425 controls) gave informed consent to genotype their DNA. As expected, several cardiovascular risk factors such as smoking, body mass index, hypercholesterolemia, and diabetes mellitus were more common in cases than in controls. CONCLUSION: Furthermore, cases more often used beta-blockers and calcium-antagonists, whereas controls more often used thiazide diuretics, ACE-inhibitors, and angiotensin-II receptor blockers. We have demonstrated that it is feasible to select patients from a coded database for a pharmacogenetic study and to approach them through community pharmacies, achieving reasonable response rates and without violating privacy rules.

A Retrospective Evaluation of 728 Kidney Donors Who Applied for Organ Donation.

OBJECTIVE: The aim of this study was to determine the sociodemographic characteristics of people who applied to be kidney donors at an organ transplantation center. MATERIAL AND METHODS: A total of 728 participants in the kidney donor program were included in the study between 2015 and 2018 at Istanbul Yeniyüzyil University Gaziosmanpasa Hospital. The sociodemographic data of the participants were retrospectively analyzed through computer records, and data were analyzed. RESULTS: Two hundred thirty-nine men and 489 women were included into the study. Six hundred ten were live donors, and 118 were cadaveric donors. Of the donors included in the study, 24.9% were illiterate, 52.1% were primary school graduates, 17.3% were high school graduates, and 5.7% were university graduates. Of the living donors, 156 (25.5%) were spouses, 91 (14.9%) were mothers, 72 (11.9%) were siblings, 65 (10.5%) were fathers, 64 (10.7%) were children, 46 were (7.5%) were other relatives, and 116 (19.0%) were nonrelatives. CONCLUSIONS: In recent years, the number of live kidney transplantations has increased. Therefore, it is necessary to protect their well-being by using evidence-based donor evaluation and treatment strategies to prevent and treat negative consequences of donations.

Determination of Health Anxiety Level in Living Organ Donation.

The aim of this study was to determine the level of pre-donation health anxiety using the Short Form Health Anxiety Inventory (SHAI) questionnaire for persons who applied to donate their kidney to a relative in need, and to evaluate whether there was a difference between these donors and a control group who did not experience health problems. The study group was comprised of 30 patients who applied for kidney donation to a relative, while the control group was comprised of 30 age- and sex-adjusted healthy subjects whose relatives did not have any health problems. The SHAI, consisting of 18 questions and some sociodemographic characteristics, was administered to both groups. The study group consisted of 60 participants, 28 (46.7%) of whom were male and 32 (53.3%) of whom were female. The mean SHAI score of the case group was 10.3 ± 7.3, while the mean of the control group was 17.6 ± 8.5. The difference between the groups was statistically significant (P = .001). The mean score of those who were donating to their wife or husband was 20.0 ± 11.7, while the mean score of those who donated to other relatives was 9.2 ± 6.1. The difference was significant (P = .014). Our study found that the case group had significantly lower health anxiety than the control group. Furthermore, those who were donating to their spouse were found to have higher anxiety than those who were donating to other relatives.

Genetic variation in the renin-angiotensin system modifies the beneficial effects of ACE inhibitors on the risk of diabetes mellitus among hypertensives.

The aim of this study was to assess whether the association between angiotensin-converting enzyme (ACE) inhibitor use and the incidence of treated diabetes mellitus is modified by genetic polymorphisms in the renin-angiotensin system (RAS).In a nested case-control study, treated hypertensive patients were genotyped for ACE (insertion (I)/deletion (D)), angiotensinogen (AGT; M235T) and angiotensin II type 1 receptor (AGTR1; A1166C). Cases of newly treated diabetes were identified based on pharmacy records and controls were not yet drug treated for diabetes (case:control ratio 1:10). Self-administered questionnaires and physical examinations were used to assess risk factors for diabetes mellitus. Logistic regression was used to calculate the relative risk of diabetes associated with ACE inhibitor use relative to other antihypertensive treatment, stratified by the RAS genotypes. Among 205 cases and 2050 controls, homozygous 1166A carriers of the AGTR1 gene had a significantly decreased incidence of diabetes associated with current use of ACE inhibitors (odds ratio, OR: 0.47; 95% CI: 0.26-0.84), whereas this incidence was increased among 1166C allele carriers (OR: 1.32; 95% CI: 0.81-2.14). The interaction OR was 3.21 (95% CI: 1.53-6.75). ACE I allele carriers had a significantly reduced incidence of diabetes associated with ACE inhibitors use (OR: 0.63; 95% CI: 0.41-0.98), whereas DD homozygotes had no reduced risk (OR: 0.95; 95% CI: 0.46-1.96). The risk of diabetes associated with ACE inhibitor use was not significantly modified by the AGT-M235T polymorphism. Treatment with ACE inhibitors in hypertensive subjects significantly reduces the occurrence of diabetes in homozygous 1166A carriers of the AGTR1 gene and carriers of the ACE I allele, but not in 1166C allele carriers of the AGTR1 gene and in homozygous ACE D allele carriers.

Pyelovenous fistula: a rare cause of hematuria.

A 72-year-old female who was admitted to our urology clinic with painless intermittent macroscopic hematuria existing for 3 months with no other voiding symptom was diagnosed with left pyelovenous fistula. Although a rare condition, pyelovenous fistula should be kept in mind when the cause of macroscopic hematuria cannot be diagnosed with routine radiological examinations, and retrograde pyelography should be the method of choice for the diagnosis in this rare condition.

Predictive ability of Guy's stone score in pediatric patients undergoing percutaneous nephrolithotomy.

BACKGROUND: Several authors have evaluated, in a number of external validation and predominantly adult studies, Guy's stone score (GSS) as a predictive tool for the assessment of stone clearance after percutaneous nephrolithotomy (PCNL). However, there are limited and conflicting data investigating whether GSS could be a potential independent factor associated with residual stone rates and complications of PCNL for children. OBJECTIVE: The aim of the current study was to evaluate the ability of GSS, as an independent factor, to predict residual stone rates and complications in pediatric patients undergoing PCNL. STUDY DESIGN: The records of the pediatric patients who had undergone PCNL for stone disease at the current department were retrospectively reviewed. Variables included patient, stone, and treatment parameters. The GSS was used for assessment of stone complexity. Univariate and multivariate analyses were performed to evaluate factors associated with residual stone rates and complications of pediatric PCNL. RESULTS: The study group consisted of 114 children (63 boys and 51 girls) with a median (interquartile range) age of 6 (3-11) years and who had undergone 122 PCNLs (eight bilateral). Multivariate logistic regression analysis (Summary Table) demonstrated that the independent risk factors for increased residual stone rate following pediatric PCNL monotherapy were GSS (OR 3.14, 95% CI 1.31-7.49, P = 0.01) and number of calyces involved (OR 4.02, 95% CI 1.11-14.53, P = 0.033). Multivariate logistic regression analysis demonstrated that the independent risk factors for complications following pediatric PCNL were surgical experience (OR 2.72, 95% CI 1.09-6.82, P = 0.032), and operation time (OR 1.01, 95% CI 1.00-1.03, P = 0.040). DISCUSSION: A prediction model is needed to pre-operatively counsel patients and evaluate outcomes for measuring treatment success of PCNL. The GSS provides a simple, reliable and reproducible tool for describing the complexity of PCNL while predicting postoperative stone-free status, despite its limitations. However, little research has been conducted on the applicability of GSS in pediatric patients undergoing PCNL. In addition, conflicting results have been reported about its association with complications of pediatric PCNL. CONCLUSIONS: The current study found that although GSS had a significant predictive ability for residual stone rates after pediatric PCNL revealed by multivariate logistic regression, the results did not conclude that complexity of GSS was directly proportional to complications of pediatric PCNL. The factors, including calyceal involvement and surgeon experience, may need to be incorporated in GSS to further improve its ability to predict outcomes of pediatric PCNL. IRB APPROVED PROTOCOL NUMBER: 1422.

Evaluation of ureteral jet dynamics in pediatric kidney stone formers: A cross-sectional study.

INTRODUCTION: The risk of kidney stone formation increases with urinary stasis, which is associated with decreased peristaltism. The relationship between nonobstructive kidney stone formation and ureteral jet dynamics, which can be measured with Doppler ultrasonography (US) and provide information about ureteral peristaltism, has been demonstrated in adults. OBJECTIVE: To investigate the relationship between ureteral jet dynamics, which provide information about ureteral peristaltism, and stone formation in children. STUDY DESIGN: Children admitted to Dokuz Eylul University Hospital with flank pain, and asymptomatic age-matched children for the control group, were prospectively enrolled and underwent Doppler US for diagnostic reasons and bilateral ureteral jet flow measurements. Children diagnosed with unilateral nonobstructive lower pole kidney stones formed Group 1, and the control group, without any evidence of stone disease, formed Group 2. Ureteral jet dynamics were compared between the affected renal units in Group 1, and healthy renal units in Group 1 and Group 2. RESULTS: A total of 32 children were included for each group. The mean average jet flow-rate (JETave (cm/second)) in affected renal units in Group 1 was found to be significantly lower than in the healthy renal units in Group 1 and left and right healthy renal units in Group 2 (P < 0.05). The continuous JETpattern rate in affected renal units in Group 1 was found to be significantly higher compared with healthy renal units in Groups 1 and 2 (P = 0.012) (Table). The odds ratio for kidney stone formation was 5.6 for renal units with JETave <9.5 cm/s when compared with renal units with JETave ≥9.5 cm/s. DISCUSSION: In a recent study, it was demonstrated in adults that low ureteral jet flow-rate and continuous JETpattern were significantly higher in affected renal units. The findings in children were also similar to adults: the mean JETave was significantly lower and determination rate of continuous flow pattern was significantly higher in affected renal units. CONCLUSIONS: Children with low JETave and continuous JETpattern as a sign of decreased ureteral peristaltism are at an increased risk of kidney stone formation. However, it is vital that further studies are conducted to elaborate on this topic.

Effectiveness and safety of cabazitaxel chemotherapy for metastatic castration-resistant prostatic carcinoma on Turkish patients (The Anatolian Society of Medical Oncology).

OBJECTIVE: Prostate cancer is among the most common cancers in males. Prostate cancer is androgen dependent in the beginning, but as time progresses, it becomes refractory to androgen deprivation treatment. At this stage, docetaxel has been used as standard treatment for years. Cabazitaxel has become the first chemotherapeutic agent which has been shown to increase survival for patients with metastatic Castrate Resistant Prostate Cancer (mCRPC) that progresses after docetaxel. Phase 3 TROPIC study demonstrated that cabazitaxel prolongs survival. PATIENTS AND METHODS: In this study, we evaluated a total of 103 patients who took cabazitaxel chemotherapy for mCRPC diagnosis in 21 centers of Turkey, retrospectively. This study included patients who progressed despite docetaxel treatments, had ECOG performance score between 0-2, and used cabazitaxel treatment. Patients received cabazitaxel 25 mg/m2 at every 3 weeks, and prednisolone 5 mg twice a day. RESULTS: Median number of cabazitaxel cures was 5.03 (range: 1-17). Cabazitaxel response evaluation detected that 34% of the patients had a partial response, 22.3% had stable disease and 32% had a progressive disease. Grade 3-4 hematological toxicities were neutropenia (28.2%), neutropenic fever (14.5%), anemia (6.7%), and thrombocytopenia (3.8%). In our study, median progression-free survival (PFS) was 7.7 months and overall survival (OS) was 10.6 months. CONCLUSIONS: This study reflects toxicity profile of Turkish patients as a Caucasian race. We suggest that cabazitaxel is a safe and effective treatment option for mCRPC patients who progress after docetaxel. Moreover, ethnicity may play important roles both in treatment response and in toxicity profile.

Antioxidant and triglyceride-lowering effects of vitamin E associated with the prevention of abnormalities in the reactivity and morphology of aorta from streptozotocin-diabetic rats. Antioxidants in Diabetes-Induced Complications (ADIC) Study Group.

In this study, we evaluated the effects of vitamin E on the vascular reactivity and structure of thoracic aorta from streptozotocin (STZ)-diabetic rats. Plasma glucose, cholesterol, and triglyceride concentrations in rats were increased markedly by STZ-diabetes. The thiobarbituric acid (TBA) reactivity level as an index of lipid peroxidation was higher in both plasma and aorta of STZ-diabetic rats compared with controls. The rings of thoracic aorta with or without endothelium were mounted in organ chambers for measurement of isometric tension and were contracted by a single dose (10-5 mol/L) and then cumulative doses of noradrenaline ([NA] 10(-9) to 10(-5) mol/L). Pretreatment with methylene blue (MB) or removal of the endothelium resulted in a similar degree of enhancement in NA-induced contraction of control rings. STZ-diabetes increased the fast and slow components of NA-induced contraction in all experiments. The maximal contractile response of aorta to NA was also augmented by STZ-diabetes, whereas the sensitivity (pD2) remained unaltered. STZ-diabetes resulted in significant increases in the maximum contractile response and sensitivity of aorta to KCl. STZ-diabetic rats showed a significant reduction in the percentage of endothelial response (PER). A group of diabetic rats was treated from the time of diabetes induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned plasma triglycerides toward normal levels. Diabetes-induced abnormal contractility and endothelial dysfunction were significantly but not completely prevented by vitamin E treatment. The endothelium-independent relaxation response to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E treatment. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E treatment can protect the morphological integrity of aorta against STZ-diabetes. The results suggest the following: (1) The increased triglycerides/lipid peroxides may be an important reason for morphological or functional disruption of endothelium and enhanced activation of contractile mechanisms of vascular smooth muscle in STZ-diabetic rats. Both contribute to an increased responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E treatment of STZ-diabetic rats can prevent the development of abnormal contractility and structure and endothelial dysfunction in aorta. (3) The triglyceride- and/or lipid peroxidation-lowering effect of vitamin E may be crucial for the protective effect of this vitamin on the vasculature.