Possible inhibition mechanism of dobutamine hydrochloride as potent inhibitor for human glucose-6-phosphate dehydrogenase enzyme.

Glucose-6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme in the pentose phosphate pathway. One of the enzyme's most important functions is the production of a reducing agent that is essential for preserving the level of reduced glutathione (GSH). However, some chemicals, such as industrial waste and the active ingredients of several drugs, can cause reduction or blockage in this enzyme's activity. This case causes the occurrence of anemia by damaging erythrocytes. In this study, the G6PD enzyme was purified 21,981 fold with affinity chromatography and the effects of the active ingredients of some antiarrhythmic drugs on enzyme activity were investigated with in vitro and in silico methods. We found that dobutamine hydrochloride significantly decreased enzyme activity and its inhibitory constant (Ki) value was calculated as 19.02 ± 4.83 mM. The in vitro study results also show that dobutamine hydrochloride is a potent inhibitor of enzyme activity. We also found that dobutamine hydrochloride inhibits the hG6PD enzyme's activity by causing structural alterations in substrate and coenzyme binding sites.Communicated by Ramaswamy H. Sarma.

Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats.

Isoniazid (INH) is among the most important anti-tuberculosis agents widely prescribed. However, its clinical use is restricted due to its severe side effects associated with neurotoxicity. The aim of the present study was to investigate the neuroprotective effects of chrysin (CR), a natural antioxidant, against INH-induced neurotoxicity in rats. The rats were treated orally with INH (400 mg/kg body weight) alone or with CR (25 and 50 mg/kg body weight) for 7 consecutive days. INH administration significantly increased brain lipid peroxidation and resulted in a significant decrease in antioxidant biomarkers including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH). INH treatment also increased levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activities of p38α mitogen-activated protein kinase (p38α MAPK) while decreasing levels of neural cell adhesion molecule (NCAM). Double immunofluorescence expressions of c-Jun N-terminal kinase (JNK) and Bcl-2 associated X protein (Bax) in brain tissues were increased after INH administration. Furthermore, INH increased mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (Gclm), glutamate cysteine ligase catalytic subunit (Gclc), NF-κB, TNF-α, interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and GFAP in rat brain tissues. Co-treatment with CR increased anti-oxidant capacity as well as regulated inflammation and apoptosis in brain. Additionally, molecular docking results showed that CR had the potential to interact with the active sites of TNF-α and NFκ-B. In conclusion, CR improved INH-induced brain oxidative damage, inflammation and apoptosis, possibly through their antioxidant properties.

In vitro effects of standard antioxidants on lactoperoxidase enzyme-A molecular docking approach.

Lactoperoxidase (LPO), an antioxidant enzyme, is a natural antimicrobial system that eliminates the harmful effects of microorganisms in milk. It has a wide range of applications and is also preferred in cosmetic and clinical applications, as well as used in foods. The use of antioxidants is well recognized in the food and feed industries to improve the shelf life of products. This study aimed to determine the in vitro inhibition effects of Trolox, α-tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, and propyl gallate, which are commonly used as antioxidants in food and pharmaceutical products. For this purpose, LPO was first purified in a single step using sepharose-4B-l-tyrosine-sulfanilamide affinity gel chromatography. Also, some inhibition parameters, including half-maximal inhibitory concentration (IC50 ), Ki values, and inhibition types, were calculated for each antioxidant molecule. The IC50 values of these molecules, which exhibited competitive inhibition, varied between 377.7 and 3397.8 nM. Molecular docking studies were also performed for all compounds. According to the binding scores, α-tocopherol was shown to exhibit the most effective inhibitor property (IC50 : 377.7 nM and Ki : 635.8 ± 16.8 nM) among the standard antioxidants used in this study. Inhibiting the LPO activity by standard antioxidants results in the weakening of the immune system during lactation, which is important for metabolism.

Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials.

Recently, the pyridazine nucleus has been widely studied in the field of particular and new medicinal factors as drugs acting on the cardiovascular system. Additionally, a number of thienopyridazines have been claimed to possess interacting biological macromolecules and pharmacological activities such as NAD(P)H oxidase inhibitor, anticancer, and identified as a novel allosteric modulator of the adenosine A1 receptor. The literature survey demonstrates that coumarin, 1,2-pyrazole benzothiazole, and 1,3- thiazole scaffolds are the most versatile class of molecules. In this study, a series of substituted pyrazole[3,4-d]pyridazine derivatives (2a-n) were prepared, and their structures were characterized by Mass analysis, NMR, and FT-IR. These obtained pyrazole[3,4-d]pyridazine compounds were very good inhibitors of the carbonic anhydrase (hCA I and II) isoenzymes and acetylcholinesterase (AChE) with Ki values in the range of 9.03 ±â€¯3.81-55.42 ±â€¯14.77 nM for hCA I, 18.04 ±â€¯4.55-66.24 ±â€¯19.21 nM for hCA II, and 394.77 ±â€¯68.13-952.93 ±â€¯182.72 nM for AChE, respectively. The possible inhibition mechanism of the best-posed pyrazole[3,4-d]pyridazine and pyrazole-3-carboxylic acid derivatives and their interaction with catalytic active pocket residues were determined based on the calculations.

The effect of metabolic syndrome on prostate cancer final pathology.

AIM OF STUDY: Metabolic syndrome (MetS) is an abnormality that increases the risk of cardiovascular disease and diabetes. In the recent years, studies showed that MetS is associated with increased risk of incidence, aggressiveness, and mortality of prostate cancer (PCa). We examined the influence of MetS at final pathology in Turkish patients with PCa. MATERIALS AND METHODS: MetS was defined according to the American Heart Association, National Heart, Lung, Blood Institute, and International Diabetes Federation and requires any three of five components. The patients without and with MetS were in Group 1 and 2, respectively. Data were compared with independent sample t-test and Chi-squared test. RESULTS: There were 117 patients in the study. The patients' age was between 51 and 77 years with a median of 64.87 ± 5.65 and 62.29 ± 5.57, and prostate-specific antigen (PSA) level of the patients was 8.19 ± 5.35 and 8.68 ± 2.22 ng/ml in Group 1 and 2. Of these patients; Group 1 and 2 had 86 and 31 patients. High-grade PCa (Gleason >7) and advanced PCa (T3, T4) at final pathology were reported in 44.18-18.60% and 38.70-32.25% in Group 1 and 2. CONCLUSION: The patients with MetS are diagnosed significantly younger and had higher PSA levels than the other patients. Advanced disease of PCa is seen much more in patients with MetS.

Amoxicillin and gentamicin antibiotics treatment adversely influence the fertility and morphology through decreasing the Dazl gene expression level and increasing the oxidative stress.

The present study was designed to explain the impact of amoxicillin, gentamicin, and cefazolin on the oxidative stress (OS) and reproductivity in the mouse testes. Our data showed that reduced glutathione (GSH) level, which is a marker for OS, strikingly reduced and hydrogen peroxide (H2O2) level, which acts as a signaling molecule in mammalian germ cells, strikingly increased with amoxicillin, gentamicin, and cefazolin treatment. The gene expression and enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferases (GST) were significantly affected in the presence of these antibiotics. Also, spermatogenesis was adversely affected by suppressing Deleted in Azoospermia (Dazl) gene expression. Finally, oxidative stress and spermatogenesis failure distorted to sperm viability, motility, and morphology in amoxicillin and gentamicin-treated mice.

Changing the Stage, Grade and Histological Subtypes of Renal Cell Carcinomas during 10 Years Period.

Renal cell carcinomas (RCCs) account 80-85% of all primary renal neoplasms and originate from the renal cortex. The patients who underwent radical or partial nephrectomy for renal tumour in our unit between January 2005 and 2015 were evaluated retrospectively. The patients were divided into two groups; group 1 includes patients who were treated between January 2005 and December 2009, group 2 those from January 2010 to 2015. There were 103 patients in group 1. The patients were between 21 and 89 years with mean age of 61.46 year. Renal cell carcinomas account 83.4% of the patients, benign renal tumours were 8.7% and transitional cell carcinomas were 7.7% of the patients in group 1. A total of 32.5% RCCs were classified as pT1a, 24.4% as pT1b, 15.1% as pT2a, 11.6% as pT2b, 15.1% as pT3a and 1.1% as pT4. There were 202 patients in group 2 and the patients were between 27 and 81 years with mean age of 58.5 year. Renal cell carcinomas comprised the main bulk of the tumours with 182 nephrectomy specimens. According to the pathological classification of RCCs, 51 specimens were found as pT1a, 54 were pT1b, 13 were pT2a, 14 were pT2b, 48 were pT3a and 2 were pT4. Although, the incidence of small renal masses has been increasing with widespread use of imaging techniques and recent advancements, the proportion of high grade and advanced stage renal tumours increased during the study period.

Adult urethral stricture: practice of Turkish urologists

ABSTRACT Objectives: To evaluate national practice patterns in the treatment of male anterior urethral strictures among Turkish urologists. Materials and Methods: A survey form including 12 questions prepared to determine active Turkish urologists' approach to diagnosis and treatment of the adult urethral stricture (US) were filled out. Based on the survey results, the institutions which 218 urologists work and their years of expertise, methods they used for diagnosis and treatment, whether or not they perform open urethroplasty and timing of open urethroplasty were investigated. Results: Optic internal urethrotomy and dilatation are the most commonly used minimal invasive procedures in treatment of US with the ratios of 93.5% and 63.3% respectively. On the other hand it was seen that urethroplasty was a less commonly used procedure, compared to minimal invasive techniques, with the ratio of 36.7%. Survey results showed us that the number of US cases observed and open urethroplasty procedures performed increases with increasing years of professional experience. Conclusions: As a method demanding special surgical experience and known as a time-consuming and challenging procedure, open urethroplasty will be able to take a greater part in current urological practice with the help of theoretical education and practical courses given by specific centers and experienced authors.

Does resectoscope size play a role in formation of urethral stricture following transurethral prostate resection?

BACKGROUND AND AIMS: To investigate the possible effect of resectoscope size on urethral stricture rate after monopolar TURP. MATERIALS AND METHODS: A retrospective study of 71 men undergoing TURP was conducted at two centers' from November 2009 to May 2013. The patients were divided into one of two groups according to the resectoscope diameter used for TURP. Resectoscope diameter was 24 F in group 1 (n=35) or 26 F in group 2 (n=36). Urethral catheter type, catheter removal time and energy type were kept constant for all patients. Urethral stricture formation in different localizations after TURP was compared between groups. RESULTS: There was no significant difference between the two groups in terms of age, pre-operative prostate gland volume (PV), prostate-specific antigen (PSA), maximal urinary flow rates (Qmax), International Prostate Symptom Score (IPSS) and post-voiding residual urine volume (PVR). The resection time and weight of resected prostate tissue were similar for both groups (p>0.05). A statistically significant higher incidence of bulbar stricture was detected in group 2 compared to group 1 (p=0.018). CONCLUSIONS: The use of small-diameter resectoscope shafts may cause a reduction in the incidence of uretral strictures in relation to urethral friction and mucosal damage.

Does resectoscope size play a role in formation of urethral stricture following transurethral prostate resection?

ABSTRACTBackground and aims:To investigate the possible effect of resectoscope size on urethral stricture rate after monopolar TURP.Materials and Methods:A retrospective study of 71 men undergoing TURP was conducted at two centers’ from November 2009 to May 2013. The patients were divided into one of two groups according to the resectoscope diameter used for TURP. Resectoscope diameter was 24 F in group 1 (n=35) or 26 F in group 2 (n=36). Urethral catheter type, catheter removal time and energy type were kept constant for all patients. Urethral stricture formation in different localizations after TURP was compared between groups.Results:There was no significant difference between the two groups in terms of age, pre-operative prostate gland volume (PV), prostate-specific antigen (PSA), maximal urinary flow rates (Qmax), International Prostate Symptom Score (IPSS) and post-voiding residual urine volume (PVR). The resection time and weight of resected prostate tissue were similar for both groups (p>0.05). A statistically significant higher incidence of bulbar stricture was detected in group 2 compared to group1 (p=0.018).Conclusions:The use of small-diameter resectoscope shafts may cause a reduction in the incidence of uretral strictures in relation to urethral friction and mucosal damage.

Clinical significance of single microscopic focus of adenocarcinoma at prostate biopsy.

OBJECTIVE: Prostate cancer (PC) is one of the most common cancer and an important reason of cancer specific death. The incidence of patients who diagnosed at low stage increased because of widespread using Prostate Specific Antigen (PSA) testing. We evaluated the patients who were diagnosed single microscopic focus of adenocarcinoma and treated radical prostatectomy at final pathology. METHODS: The patients who underwent transrectal ultrasound guided prostate biopsy between January 2004 and January 2012 were enrolled retrospectively. We extracted the patients who were diagnosed single microscopic focus of adenocarcinoma and treated with RP. Single microscopic adenocarcinoma was defined as one single focus measuring 3 mm or less, well differentiated (Gleason ≤6) adenocarcinoma. 37 patients were included at the study. Clinical data; including age, serum PSA levels, PSA density and prior biopsy and prostatectomy specimen results were recorded. In pathological examination; high molecular weight cytokeratin (HMW-CK), p63, and alpha-methylacyl-CoA racemase (AMACR) were used for differential diagnosis. RESULTS: The patients' ages were between 42 and 77 with a mean age of 64.9 ± 7.57 years. Mean PSA levels and prostate volumes were 8.03 ± 5.21 ng/ml and 54 ± 25.51 cc. T0, T2a, T2c and T3a were reported in 2 patients, 17 patients, 17 patients and 1 patient after pathological evaluation. According to the Gleason grading system; 6 patients were 7 (3 + 4), one patient was 7 (4 + 3), one patient was 5 (3 + 2) and 27 patients were 6 (3 + 3). CONCLUSION: Small volume of cancer at prostate biopsy is not necessarily small cancer in radical prostatectomy. The treatment choice may be over or under treatment for some patients, so the patients must be informed when choosing the treatment.

Evaluation of depression and self-esteem in children with monosymptomatic nocturnal enuresis: A controlled trial.

OBJECTIVES: Nocturnal enuresis (NE) is very common and is one of the most common causes for patients to be admitted to urology, pediatrics, child psychiatry and child surgery departments. We aimed to investigate the effect on depression and self-esteem of this disorder that can cause problems on person's social development and human relations. MATERIAL AND METHODS: 90 patients who were admitted to our clinic with complaints of nocturnal enuresis were enrolled. Investigations to rule out organic causes were performed in this group of patients. Out of them 38 children and adolescents (age range 8-18 years) with primary monosymptomatic nocturnal enuresis (PMNE) agreed to participate in the study In the same period 46 healthy children and adolescents with a similar age range without bed wetting complaint were included in the study as a control group. The age of the family, educational and socioeconomic level were questioned and Piers-Harris Children's Self-Concept Scale (PHCSCS) and Children's Depression Inventory (CDI) forms were filled out. RESULTS: Mean age of the cases (18 females or 47.4% and 20 males or 52.6%) was 10.76 ± 3.82 years whereas mean age of controls (26 females or 56.5% and 20 males or 43.5%) was 10.89 ± 3.11 years. Depression scale was significantly higher (p = 0.001) in the case group than in the control group (10.42 ± 4.31 vs 7.09 ± 4.35). In both groups there was no statistically significant difference by age and sex in terms of depression scale (p > 0.05). CONCLUSION: NE is widely seen as in the community and is a source of stresses either for children and for their families. When patients were admitted to physicians for treatment, a multidisciplinary approach should be offered and the necessary psychological support should be provided jointly by child psychiatrists and psychologists.

A new problem in inflammatory bladder diseases: use of mobile phones!

PURPOSE: Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. MATERIALS AND METHODS: Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. RESULTS: Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). CONCLUSION: Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor.

A new problem in inflammatory bladder diseases: Use of mobile phones!

Purpose Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Materials and Methods Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Results Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). Conclusion Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor. .

The use of primary and secondary doxazosin XL (8 mg) in the treatment of benign prostate hyperplasia: Is there a new approach in the event of alpha-blocker failure?

OBJECTIVE: Lower urinary tract symptoms (LUTS), which are related to benign prostate hyperplasia (BPH), are the most commonly encountered diseases in urological practice. In our study, we compared responses to (doxazosin mesylate extended release tablets) treatment. MATERIAL AND METHODS: In our study, we included one hundred patients with LUTS who did not receive any medical treatment, and one hundred patients with LUTS who did not respond to alpha-blocker drugs other than doxazosin XL (8 mg). The inclusion criteria for the study were as follows: international prostate symptom score (IPSS)>7, prostate volume >20 cc, Q-max <15 mL/sn, lack of any previous pelvic or prostatic surgery, and /or urethral catheterization. RESULTS: The mean age of the patients was 62.2±7.9 years. No statistically significant differences were detected between the groups with respect to age, prostate volume, and total prostate-specific antigen (PSA) levels. The duration of the follow-up period was calculated as 3-26 (mean 11) months. Significant differences were detected in post-voiding residual urine, IPSS, quality of life and Qmax between pre- and post-treatment values. Similar decreases in the IPSS scores, and increases in Qmax values were detected in both groups. CONCLUSION: Doxazosin XL (8 mg) treatment was found to be efficient and reliable in primary patients and in patients with severe LUTS who did not respond to medical treatment. Trial of doxazosin XL (8 mg) therapy, before surgery in patients who respond inadequately to other alpha-blocker drugs is a rational approach.

Predictive values for extracapsular extension in prostate cancer patients with PSA values below 10 ng/mL.

OBJECTIVE: We aimed to determine predictive values of extracapsular extension (ECE) in patients who had undergone radical retropubic prostatectomy (RRP) with prostate-specific antigen (PSA) values below 10 ng/mL. MATERIAL AND METHODS: We retrospectively scanned data of 167 patients with PSA values below 10 ng/mL who had undergone radical retropubic prostatectomy (RRP) between April 2004 and August 2011 in our clinic. Age, PSA, PSA ratio, PSA density, digital rectal examination (DRE) findings, biopsy total Gleason score, perineural invasion (PNI), and lymphovascular invasion (LVI) were analyzed. Parameters of the groups with or without extracapsular extension in RRP pathology specimens were compared. RESULTS: The mean age of patients was 66.4±12.3 years. According to histopathological analysis of the specimens of RRP of 167 patients, 45 (26.9%) had extracapsular extension (pT3-4) (Group 1); 122 (73.1%) were confined to the prostate (pT2) (Group 2). The mean PSA level was high in Group 1 (p= 0.114), PSA ratio was higher in Group 2 (p=0.09). PSA density was 0.17 in Group 1 and 0.24 in Group 2 (p=0.03). DRE positivity was 53.3% and 57.1%, respectively (p=0.71). Biopsy total Gleason score was higher in Group 1 than Group 2 with a statistically significant difference (p=0.04). A statistically significant difference was found between the rates of PNI and LVI (28.9% and 1.63%, respectively) (p=0.002). There was no statistically significant difference between both groups as for surgical margin positivity (p=0.18). CONCLUSION: In PCa patients with PSA values below 10 ng/mL, PSA density, lymphovascular invasion and biopsy Gleason total score were statistically significant in predicting extracapsular invasion. Therefore, these results must be considered in preoperative evaluation.

Acute effects of sildenafil on uroflowmetric parameters in erectile dysfunction patients with and without lower urinary tract symptoms.

Using phosphodiesterase type 5 (PDE5) inhibitors in patients with lower urinary tract symptoms continues to draw attention. Despite clinical improvements in patients, it is still debatable whether urinary flow rates are increased or not. The aim of this study was to evaluate the acute effects of sildenafil, a PDE5 inhibitor, on uroflowmetry parameters. A total of 110 men who had applied to our outpatient clinics and who had had no history of alpha blocker and PDE5 inhibitor use were included in our study. Two uroflowmetries were performed within 24-72 hours without any treatment. Participants received 50 mg of sildenafil at their third visit, and uroflowmetry was repeated after 2 hours. A total of 102 men were included in the analysis, and baseline uroflowmetry values were compared with values obtained after sildenafil use. The mean age of the 102 participants who had attended all three visits (92.7%) was 52.1 ± 12.2 years. Mean of baseline maximal flow rate values were 17.1 ± 5.1 mL/s, mean of baseline maximal flow rate after sildenafil was 18.2 ± 5.1 mL/s; average flow rate values at the baseline and after sildenafil were 9.5 ± 3.5 and 9.9 ± 3.5 mL/s, respectively. Means of postvoid residual urine volume for baseline and after sildenafil were 31.2 ± 20.1 and 27.7 ± 18.4 mL, respectively. Statistically significant difference is determined between baseline and postsildenafil values in terms of average flow rates at baseline and postvoid residual urine values. Results of this study suggest that sildenafil has an effect on uroflowmetric parameters during an acute period.

Gunshot injury to the penis in a patient with penile prosthesis: a case report.

Civilian penetrating injuries to the penis are quite rare. We present the case of a 48-year-old man with prosthetic implant surgery who referred to the emergency department of our clinic with penetrating gunshot injury to the penis. The damaged implant was removed and the defect on the anterior urethra was repaired primarily. To the best of our knowledge, there is no such report in the literature regarding penile gunshot injury in a patient with penile prosthesis.