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Even while accelerated cardiomyocyte apoptosis is one of the primary causes of cardiac damage, the underlying mechanism is still mostly unknown. In addition to examining potential protective effects of bisoprolol and diosmin against CoCl2-induced cardiac injury, the goal of this study was to identify potential mechanisms regulating the hypoxic cardiac damage caused by cobalt chloride (CoCl2). For a period of 21 days except Cocl2 14 days from the first day of the experiment, rats were split into the following groups: Normal control group, rats received vehicle only (2 ml/kg/day, p.o.), (Cocl2, 150 mg/kg/day, p.o.), bisoprolol (25 mg/kg/day, p.o.); diosmin (100 mg/kg/day, p.o.) and bisoprolol + diosmin + Cocl2 groups. At the end of the experimental period, serum was taken for estimation of cardiac function, lipid profile, and pro/anti-inflammatory cytokines. Moreover, tissue samples were collected for evaluation of oxidative stress, endothelial dysfunction, α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Diosmin and bisoprolol, either alone or in combination, enhance heart function by reducing abnormalities in the electrocardiogram and the hypotension brought on by CoCl2. Additionally, they significantly ameliorate endothelial dysfunction by downregulating the cardiac expressions of α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Bisoprolol and diosmin produced modulatory activity against inflammatory state, redox balance, and atherogenic index concurrently. Together, diosmin and bisoprolol, either alone or in combination, significantly reduced all the cardiac alterations brought on by CoCl2. The capacity to obstruct hypoxia-induced α-SMA, PKC-α, MiR-143-3P/MAPK/MCP-1, MiR-143-3P/ERK5/CXCR4, Orai-1/STIM-1 signaling activation, as well as their anti-inflammatory, antioxidant, and anti-apoptotic properties, may be responsible for these cardio-protective results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

One of the best antipsychotics for treating schizophrenia and bipolar disorders is olanzapine (OLA). However, its use is restricted owing to unfavorable adverse effects as liver damage, dyslipidemia, and weight gain. The primary objective of the present investigation was to examine the signaling mechanisms that underlie the metabolic disruption generated by OLA. Besides, the potential protective effect of sulforaphane (SFN) and β-sitosterol (βSS) against obesity and metabolic toxicity induced by OLA were inspected as well. A total of five groups of male Wistar rats were established, including the control, OLA, SFN+OLA, βSS+OLA, and the combination + OLA groups. Hepatic histopathology, biochemical analyses, ultimate body weights, liver function, oxidative stress, and pro-inflammatory cytokines were evaluated. In addition to the relative expression of FOXO, the signaling pathways for PI3K/AKT, JAK/STAT3, and MAPK were assessed as well. All biochemical and hepatic histopathological abnormalities caused by OLA were alleviated by SFN and/or βSS. A substantial decrease in systolic blood pressure (SBP), proinflammatory cytokines, serum lipid profile parameters, hepatic MDA, TBIL, AST, and ALT were reduced through SFN or/and βSS. To sum up, the detrimental effects of OLA are mediated by alterations in the Akt/FOXO3a/ATG12, Ras/SOS2/Raf-1/MEK/ERK1/2, and Smad3,4/TGF-β signaling pathways. The administration of SFN and/or βSS has the potential to mitigate the metabolic deficit, biochemical imbalances, hepatic histological abnormalities, and the overall unfavorable consequences induced by OLA by modulating the abovementioned signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plants respond to increased CO2 concentrations through stomatal closure, which can contribute to increased water use efficiency. Grasses display faster stomatal responses than eudicots due to dumbbell-shaped guard cells flanked by subsidiary cells working in opposition. However, forward genetic screening for stomatal CO2 signal transduction mutants in grasses has yet to be reported. The grass model Brachypodium distachyon is closely related to agronomically important cereal crops, sharing largely collinear genomes. To gain insights into CO2 control mechanisms of stomatal movements in grasses, we developed an unbiased forward genetic screen with an EMS-mutagenized B. distachyon M5 generation population using infrared imaging to identify plants with altered leaf temperatures at elevated CO2. Among isolated mutants, a "chill1" mutant exhibited cooler leaf temperatures than wild-type Bd21-3 parent control plants after exposure to increased CO2. chill1 plants showed strongly impaired high CO2-induced stomatal closure despite retaining a robust abscisic acid-induced stomatal closing response. Through bulked segregant whole-genome sequencing analyses followed by analyses of further backcrossed F4 generation plants and generation and characterization of sodium azide and CRISPR-cas9 mutants, chill1 was mapped to a protein kinase, Mitogen-Activated Protein Kinase 5 (BdMPK5). The chill1 mutation impaired BdMPK5 protein-mediated CO2/HCO3- sensing together with the High Temperature 1 (HT1) Raf-like kinase in vitro. Furthermore, AlphaFold2-directed structural modeling predicted that the identified BdMPK5-D90N chill1 mutant residue is located at the interface of BdMPK5 with the BdHT1 Raf-like kinase. BdMPK5 is a key signaling component that mediates CO2-induced stomatal movements and is proposed to function as a component of the primary CO2 sensor in grasses., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Welders are more likely to develop neurobehavioral disorders because of their exposure to neurotoxic metals such as manganese. This study aimed to measure the neurobehavioral performance of welders occupationally exposed to manganese at welding enterprises and its relationship with the workplace environment., Methods: It is a comparative cross-sectional study carried out on 130 welders working at 50 welding enterprises in Menoufia governorate, Egypt, compared to 130 non-occupationally exposed controls., Results: It was found that the environments of the studied welding enterprises had levels of respirable dust, manganese, and total welding fumes that exceeded internationally permissible limits. In addition, the mean blood manganese levels were significantly higher among welders (4.16 ± 0.61) than the controls (1.72 ± 0.41). Welders had a significantly higher prevalence of neurological manifestations and lower performance of neurobehavioral tests. Lower neurobehavioral performance among welders was significantly correlated with increased work duration and blood levels in some tests., Conclusion: To lessen the fumes in the breathing zone of workers, it is therefore strongly recommended to regularly wear high-quality personal protective equipment, especially masks, and to ensure proper ventilation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Occupational and environmental exposure to chromium compounds such as potassium dichromate (PDC) (K 2 Cr 2 O 7 ) has emerged as a potential aetiologic cause for renal disease through apoptotic, and inflammatory reactions. The known potent antioxidants such as nicorandil (NIC) and/or pentoxifylline (PTX) were studied for their possible nephroprotective effect in PDC-treated rats., Methods: Forty male Wistar rats were divided into five groups; control, PDC group, NIC+PDC, PTX+PDC group, and combination+PDC group. Nephrotoxicity was evaluated histopathologically and biochemically. Invasive blood pressure, renal function parameters urea, creatinine, uric acid and albumin, glomerular filtration rate markers Cys-C, Kim-1 and NGAL, inflammatory markers IL-1β, IL-6, TNF-α, TGF-β, COX-II, p38MAPK, NF-κB and TLR4, oxidative stress SOD, GSH, MDA, MPO, HO-1 and Nrf2 and apoptotic mediators Notch1 and PCNA were evaluated. Besides, renal cortical histopathology was assayed as well., Results: PDC led to a considerable increase in indicators for kidney injury, renal function parameters, invasive blood pressure, oxidative stress, and inflammatory markers. They were markedly reduced by coadministration of PDC with either/or NIC and PTX. The NIC and PTX combination regimen showed a more significant improvement than either medication used alone. Our results demonstrated the nephroprotective effect of NIC, PTX, and their combined regimen on PDC-induced kidney injury through suppression of oxidative stress, apoptosis, and inflammatory response., Conclusion: Renal recovery from PDC injury was achieved through enhanced MAPK/Nrf2/HO-1 and suppressed Notch1/TLR4/NF-κB signaling pathways. This study highlights the role of NIC and PTX as effective interventions to ameliorate nephrotoxicity in patients undergoing PDC toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

In this study, we aimed to evaluate the immunogenic profile of a chimeric DNA-based hepatitis C virus (HCV) vaccine candidate encoding the full-length viral core-E1-E2 (HCV-CE) fragment. The vaccine candidate was designed to uniformly express the HCV genotype 4 core-E1-E2 protein. The recombinant HCV-CE protein was bacterially expressed in C41 (DE3) cells, and then BALB/c mice were immunized with different combinations of DNA/DNA or DNA/protein prime/boost immunizations. The proper construction of our vaccine candidate was confirmed by specific amplification of the encoded fragments and basic local alignment search tool (BLAST) results of the nucleotide sequence, which revealed a high degree of similarity with several HCV serotypes/genotypes. The platform for bacterial expression was optimized to maximize the yield of the purified recombinant HCV-CE protein. The recombinant protein showed high specific antigenicity against the sera of HCV-infected patients according to the ELISA and western blot results. The predicted B- and T-cell epitopes showed high antigenic and interferon-γ (IFN-γ) induction potential, in addition to cross-genotype conservation and population coverage. The mice antisera further demonstrated a remarkable ability to capture 100% of the native viral antigens circulating in the sera of HCV patients, with no cross-reactivity detected in control sera. In conclusion, the proposed HCV vaccination strategy demonstrated promising potential regarding its safety, immunogenicity, and population coverage., (Copyright© by the Egyptian Association of Immunologists.)

Numerous efforts to manage acute kidney injury (AKI) were unsuccessful because its pathophysiology is still poorly understood. Thus, our research hotspot was to explore the possible renoprotective effects of rosuvastatin (Ros) and diosmetin (D) on macrophage polarization and the role of HSP70/TLR4/MyD88/NF-κB p65/NLRP3/STAT3 signaling in cis-induced AKI and study the activity of D against uropathogenic bacteria. Fifty-four albino male rats were randomized into 9 groups equally: Control, Ros, D20, D40, untreated Cis, and Cis groups cotreated with Ros, D20, D40 and Ros+D40 for 10 days. Our results indicated that Ros and D, in a dose-dependent manner, markedly restored body weight, systolic blood pressure, and renal histological architecture besides significantly upregulated SOD levels, expression of anti-inflammatory CD163 macrophages, arginase1levels, IL-10 levels,STAT3 and PCNA immunoreactivity. Also, they significantly downregulated renal index, serum urea, serum creatinine, serum cystatin c, inflammatory biomarkers (C reactive protein, IL1β & TNF-α), MDA levels, HSP70/TLR4/MyD88/NF-κB p65/NLRP3 expressions, proinflammatory CD68 macrophages and caspase-3 immunoreactivity, resulting in a reversal of cis-induced renal damage. These findings were further confirmed by molecular docking that showed the binding affinity of Ros and D towards TLR4 and NLRP3. Furthermore, D had antibacterial action with a minimum inhibitory concentration ranging from 128 to 256 µg/mL and caused a delay in the growth of the tested isolates, and negatively affected the membrane integrity. In conclusion, Ros and D had antioxidant, anti-inflammatory and antiapoptotic properties and switched macrophage from proinflammatory CD68 to anti-inflammatory CD163. Additionally, the targeting of HSP70/TLR4/MyD88/NF-κB p65/NLRP3/STAT3 signals are effective therapeutic strategy in AKI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

One of the most significant chemotherapeutic side effects of cisplatin (Cis) that limits its use and efficacy is testicular toxicity. Thus, the objective of the present study was to investigate the possible ameliorative effect of Fenofibrate (Fen), Diosmetin (D), and their combination against cis-mediated testicular damage. Fifty-four adult male albino rats were randomly allocated into nine groups (6 rats each): Control group, Fen (100 mg/kg), D20 (20 mg/kg), D40 (40 mg/kg), Cis group (7 mg/kg), Cis +Fen group (7 mg/kg+100 mg/kg), Cis+D20 group (7 mg/kg+20 mg/kg), Cis+D40 group (7 mg/kg+40 mg/kg), Cis+Fen+D40 treated group (7 mg/kg+100 mg/kg+40 mg/kg). Relative testicular weight, epididymal sperm count and viability, serum testosterone level, testicular oxidative stress indices, mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR-α), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), histopathological, and immunohistochemical alterations were assessed. Our results revealed that cis administration induced testicular oxidative and inflammatory damage as indicated by a substantial reduction in relative testicular weight, sperm parameters, serum testosterone levels, the antioxidant enzyme activity of catalase, and Johnson's histopathological score, PPAR-α/NRF-2/HO-1 and proliferating cell nuclear antigen (PCNA) immunoexpression with marked increment in malondialdehyde (MDA), Cosentino's score, nuclear factor kappa B (NF-κβ p65), interleukin (IL)- 1β and caspase 3 in testicular tissue. Interestingly, Fen and D diminished the harmful effects of cis on testes via upregulation of the antioxidant activities and downregulation of lipid peroxidation, apoptosis, and inflammation. Moreover, the combination therapy Fen/D40 also exhibited a more pronounced enhancement of previous markers than either treatment alone. In conclusion, because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with Fen or D or their combination could be beneficial in reducing the harmful impacts of cis on testicular tissue, particularly in patients that receive cis chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cisplatin (Cis) is a treatment for testicular germ-cell tumors (TGCTs). Unfortunately, it causes testicular toxicity due to releasing reactive oxygen species (ROS) causing damage to testicular cells and chromosomes. The current study aimed to investigate the ameliorative effect of selenium nanoparticles (SeNPs) against cisplatin testicular toxicity in male rats by assessment of body weight, testis weight, oxidative stress markers in testis homogenates as (malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione reduced (GSH), Glutathione peroxidase (GSH ∼ PX) and Catalase (CAT)), gene expression, testosterone concentration (T), sperm characteristics (count, motility and abnormality) and testicular histopathology. Methods: Thirty adult male rats divided equally into four groups; a single dose intraperitoneally injection of cisplatin (10 mg/kg) and selenium nanoparticles (2 mg/kg/day) were administrated alone or in combination. Cis group showed a decrease in body weight, testis weight, antioxidant activities (SOD, GSH, GSH ∼ PX and CAT), T concentration and steroidogenetic expression, the data recorded an increase in MDA levels and sperm abnormality, meanwhile histopathology of testis sections showed degenerative changes in the seminiferous tubules. The co-administration of selenium nanoparticles ameliorated the harmful effects of cisplatin. In conclusion; SeNPs through its antioxidant potential may be useful to prevent the testicular toxicity induced by cisplatin to the rat testis by reducing oxidative stress., Competing Interests: Declaration of competing interest All authors are declaring and signing when submitting papers for publication, and they agree for publish paper in this journal. The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Adolescent females are often environmentally exposed to pesticides by living near agricultural fields, by using pesticides at home, or by having contact with contaminated clothes and pesticide application work tools. This study assessed respiratory, hepatic, renal, and hematological health disorders that might arise due to environmental exposure to pesticides among adolescent females. A cross-sectional study was conducted with 100 adolescent females environmentally exposed to pesticides that had one or more of their family members working as seasonal pesticide applicators and 50 nonexposed (control) adolescent females from Menoufia governorate, Egypt. The studied period of pesticide application season of the cotton crop was from May 1 to September 1, 2017. Participants completed a self-administered questionnaire about pesticide exposure and respiratory, hepatic, renal, and hematological disorders. In addition, serum acetylcholinesterase (AChE), spirometry, complete blood count, and liver and kidney function tests were measured pre and post-pesticide application season. The control adolescent females had a higher AChE activity, a lower prevalence of respiratory symptoms, and higher means of spirometric measurements than the exposed group. During the pre- and postseason, the exposed group presented a prevalence of (6%, 24%) for cough, (4%, 11%) for rhinitis, and (6%, 26%) for dyspnea during the pre and postseason, respectively. In addition, there was a decrease in means of spirometric measurements (FEV 1 %, FEV 1 /FVC%, FEF 25-75 %, and PEF%) in the postseason compared to preseason among the exposed group. Also, there were significant associations between (AChE) activity and both the prevalence of respiratory manifestations and spirometric measurements among the exposed females. On the other hand, there was a statistically significant increase in red blood corpuscle (RBC) and lymphocyte counts, and a statistically significantly lower mean hemoglobin level among the exposed group (postseason) than each of their pre-season values and the control group (P < 0.05). AChE level, total protein, albumin, and albumin/globulin (A/G) ratio levels were statistically significantly lower, while SGPT, SGOT and globulin, blood urea, and serum creatinine mean levels were statistically significantly higher among the exposed group (postseason) than either of their preseason or the control group (P < 0.05). There was a positive correlation between the AChE level and all studied CBC parameters for the exposed group reaching a statistically significant level with basophils (P < 0.05). Also, there was a negative correlation between the AChE level and each of SGPT, SGOT, ALP, globulin, blood urea, and serum creatinine for the exposed group reaching a statistically significant level with each of SGPT and SGOT (P < 0.05). At the same time, a nonsignificant positive correlation was found between AChE level and each of total protein, albumin, and A/G ratio (P > 0.05). So, environmental exposure to organophosphorus pesticides has a detrimental impact on respiratory, hepatic, renal, and hematological systems of adolescent females living in rural districts at the Menoufia governorate. Educational and training intervention programs on pesticide handling and safety precautions are recommended for protecting both pesticide workers and their family members who might be exposed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pro-inflammatory cytokines and reactive oxygen species (ROS) are produced in acute spinal cord injury, leading to myelin breakdown, inflammation, mitochondrial dysfunction, and apoptosis of neurons and glial cells. The aim of the present study was to investigate possible protective effects of L-carnitine (carn) or atorvastatin (ator) on spinal cord ischemia-reperfusion injury (IRI). Rats were randomized into nine equal groups (n = 8): control and control taking carn (100 mg/kg BW), ator (2.5 mg/kg BW) or both, as well as sham-operation, IRI and IRI taking same doses of carn, ator or both. Neurological assessments were done 48 hours after IRI, and serum nitrite/nitrate was measured. Finally, lumbar segments of spinal cord were excised, and part was homogenized and prepared for measuring tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), advanced oxidation protein products (AOPP), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. The other part was sectioned for evaluation of histopathological changes and for immunostaining by glial fibrillary acidic protein (GFAP), Bax and Bcl-2. The IRI increased ROS (nitrite/nitrate, MDA, AOPP) and pro-inflammatory cytokines (TNF-α, IL-1β), and decreased antioxidants (GSH, GPx, SOD, catalase) with impaired sensory and motor functions. Astrogliosis was detected by GFAP, and increased apoptosis was demonstrated by increasing Bax and decreasing Bcl-2. Treatment with carn or ator alone decreased TNF-α, IL-1β, nitrite/nitrate, MDA and AOPP, and increased GSH, GPx, SOD, and catalase with improvement of neurological functions and histological studies. Combination of carn and ator improved most of measured IRI-affected parameters better than isolated carn or ator administration.

Secondhand tobacco smoke (SHS) is a significant public health problem for all ages worldwide. Children are more vulnerable to the health effects of SHS because of the inhalation of more air per body volume compared to adults. The study aimed to assess neurobehavioral performance among SHS exposed Egyptian basic school children (10-12 years) and its relationship with urinary cotinine levels. Multistage cluster sampling was carried out, where 181 children (80 exposed and 101 non-exposed children) were recruited. A questionnaire on SHS exposure was sent to students' parents/caregivers. Urine samples were taken for assessment of cotinine levels by enzyme immunoassay. A Neurobehavioral test battery was measured. The exposed children had significantly lower performance in tests of attention (PASAT) [5.22 ± 5.10 vs. 6.98 ± 5.87, p = 0.035], visuomotor speed (Digit Symbol and Trail making A) [41.40 ± 18.01 vs. 46.53 ± 15.89 and 107.92 ± 44.34 vs. 92.44 ± 37.09; respectively] than non-exposed subjects. The neurobehavioral effects were correlated with urinary cotinine levels among children exposed to SHS compared to unexposed children. The study revealed poor performance in neurobehavioral domains of attention and visuomotor skills among children exposed to SHS. This necessitates the implementation of antismoking media awareness programs on the harmful effects of SHS and how to protect children from it.

Occupational exposure in spraying and application of non-arsenical insecticides has been classified as a probable human carcinogen. The fundamental molecular mechanisms involved the tumor-related genes. This study aimed to investigate the carcinogenesis effects related to chronic exposure to organophosphate (OP) pesticides in pesticide applicators. This was a cross-sectional study conducted on 27 pesticide applicators and 24 matched controls through the period from June to December 2018. The level of acetylcholinesterase (AChE) was determined and the effects of OPs exposure on messenger RNA (mRNA) expression of the DNA-damage responsive genes P53, P21, GADD45a, and MDM2 were determined using real-time quantitative polymerase chain reaction. A significant reduction of serum AChE enzyme activities was observed in chronically exposed subjects in comparison with the control group ( p = 0.001). The expression of P53, P21 mRNA was significantly downregulated in the exposed group compared with the healthy nonexposed control group ( p < 0.05). Conversely, the expression of MDM2 and GADD45a did not significantly differ between the exposed subjects and the control group ( p > 0.05). No significant differences were noted between the exposed and control groups regarding the genotype or allele distributions of P53 Arg72Pro polymorphism. These results suggested that chronic exposure to OP insecticides may have mitogenic and carcinogenicity activity for the exposed cases due to downregulation of P53 and P21 but did not demonstrate any DNA damage properties for the exposed cases, and finally, a regular follow-up of the exposed cases for tumor markers is recommended.

Background: Adolescent females living in agricultural areas where crops are routinely sprayed by pesticides are expected to be environmentally exposed to pesticides' health hazards partially as those occupationally exposed., Objective: to assess menstrual and neurobehavioral disorders among adolescent females environmentally exposed to pesticides., Methods: This was a cross-sectional study conducted on 100 pesticide exposed adolescent females who had one or more of family members are pesticides' seasonal applicators and 50 non- exposed adolescent females matched for age and education, served as controls at Menoufia governorate, Egypt during the period of pesticide application season of cotton crop from the first days of May to the end of September 2017. A self-administered and a series of neurobehavioral tests were administered and serum Acetylcholinesterase (AChE) activity was assessed., Results: A significant lower AChE activity levels were found in the exposed group than controls (Mean±SD=238.49± 23.83 vs 303.35±78.54 IU/L; respectively). There were significant higher mean scores of trail making test (parts 1 and 2) and significant lower mean scores of (similarities test, Benton visual retention test, block design test, Santa Ana dexterity test (dominant and non-dominant hands) and Beery visuo-motor imitation test in the exposed group than the controls (P<0.05). Also, the exposed group reported more prevalent irregular menstrual cycle (26.8%) and intermenstrual bleeding (28.2%) compared to the control participants (8.1% and 8.1%; respectively)., Conclusion: Adolescent females living in agricultural areas and from families whose one or more members are pesticides' applicators have significantly lower neurobehavioral performance, report more prevalent menstrual irregularities and have lower levels of serum AChE compared to a control group. The neurobehavioral deficits demonstrated a dose-response relationship AChE levels in the exposed participants. This necessitates the need for implementation of health education programs to prevent or reduce health effects associated with pesticide exposure to adolescent females., Competing Interests: Conflicts of Interest: None declared

Penile curvature is a common urological disease. Tunical plication for correction of penile curvature has been much popularized being simpler, adjustable to avoid overcorrection, less bleeding, and less postoperative erectile dysfunction. This study aims to assess the results of modified 16-dot plication technique for correction of congenital and acquired penile curvature and avoidance of knot-associated complications. Eighteen patients underwent correction of their penile curvature using the modified 16-dot plication technique between January 2014 and October 2015. Patients' pre and postoperative data were analyzed. The mean age of patients is 44 years old. Of the patients 15 who were available for follow-up, 8 patients had congenital penile curvature (CPC) and 7 had Peyronie's disease (PD). The angle of deviation ranged from 30° to 90°. Erectile function (EF) was assessed preoperative by IIEF score and duplex ultrasound. Postoperative follow-up at 3 and 6 months revealed straight erect penis in all patients. Longer follow-up at 1 to 2 years, 2 patients complained from slight recurrence of curve (<20°) and 2 patients complained of worsening of their erectile function. Penile shortening was noted by 6 patients. None of our patients stated any knot complication or bothersome, nor do hematomas, numbness, or painful erections. The modified 16-dot plication technique for correction if penile curvature is a safe and effective method. This modification allowed the knots to be tucked in the plicate tunical tissue avoiding knot-associated complications. More investigation on a large scale of patients or multicenter studies is recommended.

Background: Work stress among nurses has increased in recent years due to the demands of clinical nursing., Objectives: To investigate psychosocial work stress among nurses using the effort-reward imbalance (ERI) model with assessment malondialdehyde (MDA) as an oxidative stress marker and total antioxidants., Methods: The present study was conducted on 204 registered nurses worked at two tertiary hospitals in Menoufia governorate, Egypt through the period from the 1st of February to the end of July 2016. Two questionnaires were applied including general demographic and occupational histories as well as effort-reward questionnaire. Blood analysis was performed to assess MDA and total antioxidant levels., Results: ERI was prevalent among the study participants (72.5%). ERI was more prevalent among young married nurses who worked more than 10 years. Nurses that worked at ICUs complained more of ERI (43.2%) while nurses that worked at operation rooms complained more of overcommitment (62.5%). MDA levels were significantly positively correlated with E/R ratios (rho = 0.350, P ≤ 0.001)., Conclusions: Work stress was prevalent among the studied nurses as revealed by the high ERI and MDA levels. Young married female nurses complained more of work stress. ICUs and operating rooms were the most stressful departments at the studied hospitals. Hence, implementing programs and strategies that eliminate stressful working conditions at hospitals is critical to the reduction and prevention of work stress among nurses.

To evaluate the cytoprotective effects of rutin, ozone and their combination on adriamycin (ADR)-induced testicular toxicity, 50 male albino rats were classified into five groups of ten animals each as follows: placebo group; ADR group; ADR + rutin group; ADR + ozone group and ADR + rutin + ozone group. Sperm functions, testosterone (T), luteinising hormone (LH), follicle stimulating hormone (FSH), testicular enzymes, oxidant/antioxidant status, C-reactive protein, monocyte chemoattractant proteins-1 and leukotriene B4 were determined. After ADR injection, a decline in sperm functions was observed. FSH and LH levels were increased, T level and testicular enzymes were decreased, significant enhancement in oxidative stress with subsequent depletion in antioxidants was detected and inflammatory markers were significantly elevated. Treatment with rutin and/or ozone, however, improved the aforementioned parameters. Ozone therapy alone almost completely reversed the toxic effects of ADR and restored all parameters to normal levels., (© 2016 Blackwell Verlag GmbH.)

Objective: To evaluate the efficacy and safety of immediate versus delayed shockwave lithotripsy (SWL) for inaccessible stones after uncomplicated percutaneous nephrolithotomy (PCNL)., Patients and Methods: Between December 2011 and June 2014, patients with residual inaccessible stones after uncomplicated PCNL were prospectively randomised into two treatment groups; Group I, immediate SWL and Group II, delayed SWL at 1 week after PCNL. Patients with residual stones of ⩾1.5 cm, a stone density of >1000 Hounsfield units and body mass index of >40 kg/m 2 were excluded from the study. The following data were reported: patients' demographics, stone characteristics after PCNL, hospital stay, perioperative complications, stent duration, and stone-free rate (SFR)., Results: In all, 84 patients (51 males and 33 females) with mean (SD) age of 39 (8.5) years were included in the study. Group I included 44 patients, whilst Group II included 40 patients. There was no statistically significant difference amongst the groups for patients' demographics, stone characteristics, and perioperative complications. The hospital stay was significantly shorter in Group I, at a mean (SD) of 34 (3.7) vs 45 (2.9) h ( P  < 0.001). The duration of ureteric stenting was significantly lower in Group I as compared to Group II, at a mean (SD) of 12 (4.2) vs 25 (3.5) days ( P  < 0.001). The SFR was 93.2% and 95% in Groups I and II, respectively ( P  = 0.9)., Conclusions: Immediate SWL after PCNL is as effective and safe as delayed SWL with a lesser hospital stay and duration of ureteric stenting.

Background: Hepatitis C virus (HCV) is a major health problem worldwide particularly in Egypt. The humoral immune response has an important function in the control of HCV infection. The aim of this study was to investigate the role of neutralizing antibodies in Hepatitis C Virus (HCV) clearance in infected individuals., Methods: This study was carried out on apparently healthy blood donors (n = 200). Detectable HCV antibodies were assessed by commercial ELISA and specific human immunoglobulins targeting peptides derived from HCV E1/E2 glycoproteins were measured in donors' blood using an in house optimized ELISA. Human IgG purification was carried out from positive HCV RNA and negative HCV RNA samples in order to evaluate its neutralizing activity in vitro using Huh 7 cells., Results: The studied cohort included 96/200 subjects who tested positive for HCV antibodies, among which 56/96 (58%) samples were positive for HCV RNA (Group 1) and 40/96 (42%) samples had undetectable HCV RNA (Group 2). ELISA results showed that Human HCV immunoglobulin (HHI) targeting HCV E1 synthetic peptide (a.a. 315 - 323) was detectable in 63/96 (66%) and HHI targeting HCV E2 (a.a. 412 - 419) tested positive in 14/96 (15%) while 19/96 (20%) were positive for HCV E2 (a.a. 517 - 531). HHI higher than the cutoff level against peptide HCV E1 (a.a. 315 - 323) was detected in 22/63 (35%) in Group 2 and positive in 41/63 (65%) in Group 1. HHI against peptide HCV E2 (a.a. 412 - 419) was positive in 7 (50%) blood donors in Group 2 and also positive in 7 (50%) of Group 1. While HHI targeting HCV E2 (a.a. 517 - 531) was positive in 11 (60%) in Group 2 compared with 8 cases (40%) in Group 1. Purified human antibodies from cases positive for HCV antibodies and negative for HCV RNA showed in vitro neutralization at concentrations 30 and 10 µg/mL while the same concentration of purified human IgG from cases positive for HCV RNA showed no viral neutralization., Conclusions: The tested epitope(s) derived from HCV envelope E1 and E2 are important for viral clearance and hence can be used for HCV vaccine development.

Objectives: To compare the efficacy of silodosin (8 mg) vs tamsulosin (0.4 mg), as a medical expulsive therapy, in the management of distal ureteric stones (DUS) in terms of stone clearance rate and stone expulsion time., Patients and Methods: A prospective randomised study was conducted on 115 patients, aged 21-55 years, who had unilateral DUS of ⩽10 mm. Patients were divided into two groups. Group 1 received silodosin (8 mg) and Group 2 received tamsulosin (0.4 mg) daily for 1 month. The patients were followed-up by ultrasonography, plain abdominal radiograph of the kidneys, ureters and bladder, and computed tomography (in some cases)., Results: There was a significantly higher stone clearance rate of 83% in Group 1 vs 57% in Group 2 (P = 0.007). Group 1 also showed a significant advantage for stone expulsion time and analgesic use. Four patients, two in each group, discontinued the treatment in first few days due to side-effects (orthostatic hypotension). No severe complications were recorded during the treatment period. Retrograde ejaculation was recorded in nine and three patients in Groups 1 and 2, respectively., Conclusion: Our data show that silodosin is more effective than tamsulosin in the management of DUS for stone clearance rates and stone expulsion times. A multicentre study on larger scale is needed to confirm the efficacy and safety of silodosin.

Physicochemical investigation of the red alga Acanthophora spicifera (Vahl) Borgesen, collected from Al-Shoaiba coast, Red Sea, Saudi Arabia, led to the isolation of a flavone from the algal tissue with acetone. Preparative chromatography on silica gel thin-layer chromatography was used for the separation of the flavone and eluted with the methanol:chloroform:ethyl acetate (1:7:2) solvent system. The physicochemical analyses infrared, mass spectra, and ultraviolet spectra in addition to shift reagents (NaOMe, NaOAc, NaOAc + H3BO3, AlCl3, and AlCl3 + HCl) were used for the identification and elucidation of the structure of the flavone compound (4,5,7-trihydroxy flavonoids). The flavone compound was identified as apigenin bycomparing its physicochemical data with those in the literature. Analgesic and anti-inflammatory activities of apigenin were evaluated. Apigenin showed promising analgesic and anti-inflammatory activities in the hot plate test and writhing test in mice as well as tail-immersion tests and carrageenan-induced paw edema and cotton pellet-induced granuloma formation in rats. It is concluded that apigenin possesses potent analgesic, anti-inflammatory, and antiproliferative activities, which might be due to the inhibition of PGE2 as well as proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α.

Introduction: Laparoscopic hernia repairs have been proven to be efficient and safe for children, despite the slightly higher recurrence rate compared with the classic surgical repair. They have the advantage of easy and precise identification of the type of defect and its correction, both in ipsilateral and contralateral sides., Objectives: The objectives of this study were to evaluate the efficacy, safety and outcome of the laparoscopically assisted piecemeal high ligation of a patent processus vaginalis (PPV) in children., Methods: A total of 40 children were enrolled into this prospective study; they were aged ≥ 6 months and had an inguinal hernia. The peritoneal cavity, including the contralateral side, was inspected for the possibility of bilateral hernias using a 3-mm 30° telescope. Another 3-mm port was introduced through the same infra-umbilical incision. The hernia was manually reduced or with the aid of a working infra-umbilical grasper. A prolene or vicryl 2/0 or 3/0 suture on a curved semicircle round-bodied taper-ended 25-30 mm needle was introduced through a very small inguinal skin-crease incision. It was passed through the abdominal wall layers to the peritoneum and was manipulated by the laparoscopic grasper to pick up the peritoneum in piecemeal all around the internal ring. The needle was then pushed to the outside near to the entrance site, thus forming a semicircle around the internal ring. The suture was then tied and the knot was subcutaneously buried. The primary outcome of the procedure was the incidence of intraoperative diagnosis and surgical repair of contralateral hernias in pre-operatively diagnosed unilateral cases. The secondary outcomes were defined as the incidence of complications and hernia recurrence., Discussion: The exploratory laparoscopy found contralateral patent processus vaginalis (CPPV) with a detection rate of 28.1%. Chan et al., Esposito et al., Toufique et al. and Niyogi et al. reported similar figures for laparoscopic contralateral hernia detection rates of 28%, 39%, 39.7% and 29.2%, respectively. The limitations of this study were the small sample size, plus the risk factors and clinical significance for CPPV., Conclusion: Laparascopically assisted piecemeal closure of the internal inguinal ring in children is a safe and effective procedure. It helps in detecting a contralateral hernia without prolonging the operative time., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate whether the immunohistochemical expression of p53, p63 and her2/neu is correlated with the prognosis of tumour recurrence and progression in patients with non-muscle invasive (NMI) bladder cancer., Patients and Methods: In all, 88 patients diagnosed with NMI transitional cell carcinoma of the bladder in a Urology Department from May 2009 to April 2014 were included in the study. Paraffin-embedded specimens were obtained by transurethral resection of the bladder tumours. Sections on haematoxylin and eosin-stained slides were examined histologically and tumour grade was classified according to the World Health Organisation system (2004) Mostofi classification. The sections were evaluated using p63, p53 and her2/neu immunohistochemical staining before and after immunotherapy with bacille Calmette-Guerin (BCG), and patients were followed up for 36 months in the Urology Department., Results: For tumour grade there was a significant relationship with the overexpression of p53 (P = 0.010), her2 (P = 0.025) and negativity of p63 (P = 0.025). There was no significant relationship between p53 or her2/neu overexpression and tumour stage. However, there was a significant correlation (P = 0.005) between p63 negativity and tumour stage. There was a significant relationship between p53 (P = 0.01), her2/neu (P = 0.025) overexpression and p63 negativity (P = 0.005) and tumour recurrence and progression., Conclusion: Patients with transitional cell carcinoma who are selected for BCG treatment should preferably be positively immunoreactive for p63, but negative for both p53 and her2/neu. These patients were less susceptible to recurrence and/or progression after BCG adjuvant therapy. Further studies are needed to investigate the relationship between these three markers and treatment with anti-her2/neu therapies.

Objective: To evaluate of efficacy of transgluteal (supine) approach for shock wave lithotripsy (SWL) in treatment of distal ureteric stones., Patients and Methods: This prospective, randomized, comparative study was conducted on 98 patients. Patients were randomly assigned into 2 groups: group A (n = 49; prone position) and group B (n = 49; supine position, transgluteal). Inclusion criteria included patients with radiopaque lower ureteric stones ≤10 mm. Exclusion criteria included radiolucent stones, stones >10 mm, the need for any auxiliary procedure, and any contraindication for SWL. Post-SWL evaluation included plain x-ray of kidney, ureter, and bladder at 2 weeks after treatment and then at monthly intervals after treatment for 3 months. Stone-free status was defined as no residual stone fragments visible on plain x-ray. Treatment failure was defined as persistence of stone fragments at 3 months or the need for ureteroscopy., Results: Stone-free rate after 1 treatment session was achieved in 44.9% and 75.5% for prone and supine positions, respectively. Proceeding to ureteroscopy, after failure of the second SWL session to clear the stones, was done in 34.7% and 8.2% for prone and supine positions, respectively. The overall success rate for SWL treatment in prone and supine groups was 65.3% and 91.8%, respectively (P <.001)., Conclusion: Transgluteal SWL while patient in supine position proved efficacy for treatment of distal ureteric stones. Larger group studies comparing the results of SWL in supine position with those of prone position and also with those of ureteroscopy may enrich our data to reach a consensus for the ideal management of distal ureteric stones., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the use of lingual mucosal graft (LMG) as a substitute for tunica albuginea in the treatment of Peyronie disease (PD)., Patients and Methods: Seventeen patients, reporting normal erectile function, with PD interfering with sexual function were operated on by plaque excision and grafting with LMG. Preoperative assessment included: the International Index of Erectile Function-5 score, penile duplex, and penile curvature angle measurement. Postoperative erectile function and penile deformity were assessed every 3 months for 9-18 months., Results: Mean age of the patients was 52 (± 4.7) years and mean angle of deformity was 60° (± 5.1). Donor site complications occurred in the form of mild transient swelling, numbness, and pain. Postoperative assessment showed complete penile straightening in 15 patients with mild curvature recurrence (<20°) in 2 patients at the third month. De novo mild erectile dysfunction was reported by 1 patient who responded to low-dose phosphodiesterase type 5 inhibitor. Patients' and partners' satisfaction was reported in 16 (94%) patients. These results remained stable until the end of the follow-up period., Conclusion: LMG seems to be a valuable substitute for tunica albuginea in cases of PD. It is readily available and shows early graft take. It also proved safety, reliability, feasibility, and a satisfactory short-term outcome for the treatment of PD., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In view of the widespread use of pesticides in Egypt and the increasing incidence of leukaemia and lymphoma we aimed to assess pesticide exposure and other selected variables as risk factors for lymphoproliferative disorders (leukaemia and non-Hodgkin lymphoma). In a hospital-based, retrospective, case-control study in 2011-2012, adult cases of lymphoproliferative disorders (n = 130) were recruited from outpatient clinics in Menoufia, Egypt, while controls (n = 130) were age- and sex-matched fracture patients. Family history of cancer, exposure to X-rays, smoking and use of hair dyes were not risk factors for lymphoproliferative disorders in univariate analysis. History of exposure to pesticides and HCV infection were significant risk factors for lymphoproliferative disorders in multivariate analysis (OR = 2.24; 95% CI: 1.22-4.11 and OR = 2.67; 95% CI: 1.50-4.80 respectively). The risk was significant for cases of non-Hodgkin lymphoma but not chronic lymphocytic leukaemia.

Isolated pump erosion is a rare complication in patients with inflatable penile prosthesis. We describe a case of a diabetic patient who underwent inflatable penile prosthesis implantation with subsequent isolated pump erosion. Repeated attempts of conservative repair of the erosion failed. Finally, the inflatable penile prosthesis was replaced with a malleable one to avoid new pump erosion. In case of isolated pump erosion, replacement of the inflatable penile prosthesis with a malleable one looks to be a good alternative salvage treatment for the patient.

Objective: To compare the technical aspects, operative time, safety and effectiveness of percutaneous nephrolithotomy (PCNL) in the free-flank modified supine position (FFMSP) vs. the standard prone position (SPP)., Patients and Methods: Seventy-seven patients (47 men and 30 women) with renal stones were enrolled and systematically randomised into two groups, A (39 patients) treated using the FFMSP, and B (38 patients) in the SPP. The outcome was considered as a cure (successful procedure) if the patient became stone-free or had residual fragments of <4 mm in diameter. The operative time (from the induction of anaesthesia to the removal of the endotracheal tube) was measured and any operative complications or conflicts were recorded. The different variables were compared and analysed between the groups., Results: Patients in both groups had comparable preoperative clinical data and there were no significant differences in the preoperative clinical characteristics. The procedure was successful in 84.6% and 84% of group A and B, respectively. The operative time was significantly longer in group B (SPP) than A (FFMSP). There was no significant difference between the groups in fluoroscopy time and patients' outcome., Conclusions: The FFMSP (with a cushion under the ipsilateral shoulder) has similar efficacy and safety as the SPP for PCNL and is associated with a significantly quicker operation.

Purpose: To evaluate tailored polypropylene (prolene) mesh, anterior rectus sheath, and vaginal wall slings positioned under the mid-urethra, to treat stress urinary incontinence (SUI) in women, as SUI is a common pathological condition causing considerable distress and compromising social, physical, psychological, and sexual health, and for which surgical treatment remains controversial., Patients and Methods: This prospective randomised study included 32 patients with SUI, evaluated by SEAPI (Stress, Emptying, Anatomy, Protection, and Instability) symptom score and urodynamics. According to sling material, 12 patients had tailored prolene mesh, 12 had anterior rectus sheath and eight had anterior vaginal wall slings. Operative variables (intraoperative bleeding, duration, complications and hospital stay) were documented, and postoperative complications and continence status were assessed. The follow-up was 12-18 months., Results: Patients who received tailored prolene mesh slings had a lower operative duration and hospital stay, and less intraoperative bleeding. Postoperative complications, e.g. urinary retention and urgency, were <12%, with no significant differences. There was no significant difference among the three studied groups in the success rate (75%, 67% and 75%)., Conclusions: Tailored prolene mesh, anterior rectus sheath and the vaginal wall sling are good alternatives to treat SUI in women, with comparable results in a short-term follow up. The surgeon's experience and the patient's clinical circumstances should be considered when choosing a sling material, as success rates are comparable, being slightly better for the prolene sling in operative duration, bleeding and hospital stay.

Introduction: Infection is the worst complication seen with inflatable penile prosthesis (IPP). Both the American Medical Systems (AMS) and Coloplast IPP have infection retardant coatings. AMS is coated at the factory with rifampicin and minocycline (InhibiZone). The Coloplast IPP has a hydrophilic coating covalently bonded to its components that will absorb any aqueous solution before implantation and provides increased surface lubricity to decrease bacterial adherence., Aim: We tested several antibiotic dips comparing zones of inhibition (ZOI) against five commonly infecting bacteria with coated Coloplast implants. Results were compared with those ZOI created with strips of an AMS IPP precoated with InhibiZone., Methods:   Pieces of sterile Coloplast Titan IPP were dipped in (i) trimethoprim/polymixin B ophthalmic solution; (ii) trimethoprim/sulfamethoxazole infusion solution; (iii) bacitracin; (iv) rifampicin/minocycline; and (v) rifampin/trimehtoprim/sulfamethoxazole. ZOI for the Titan strips and for AMS InhibiZone coated strips were tested against Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus aureus, Pseudomonas, and Enterococcus., Main Outcome Measure: ZOIs of the Coloplast Titan for each of the medicated solutions were compared with ZOI created by undipped strips of a sterile InhibiZone coated IPP placed on plates of the identical bacteria., Results: All dips except bacitracin showed ZOI≥InhibiZone (P≥0.005) for most organisms. Because of broad-spectrum effectiveness, ease of handling, and cost, infusion vial of trimehtoprim/sulfamethoxazole seemed optimal at this time. If trimehtoprim/sulfamethoxazole is unavailable; the ZOI with Polytrim ophthalmic solution zones were almost as good., Conclusions: The Coloplast strips when dipped in several solutions showed equal or significantly larger ZOI against commonly infecting organisms than the InhibiZone coated strips. At the present time using off the shelf trimethoprim sulfamethoxazole infusion solution seems optimum. The flexibility of choosing the drug eluting from the Coloplast device seems promising in the changing bacterial environment., (© 2011 International Society for Sexual Medicine.)

Objective: • To evaluate the efficacy of a bladder preservation multimodality protocol for patients with operable carcinoma invading bladder muscle., Materials and Methods: • In this prospective study, we included 33 patients with transitional cell carcinoma (TCC) (T2 and T3, Nx, M0) who were amenable to complete transurethral resection. • These patients refused radical cystectomy as their first treatment option. After maximum transurethral resection of bladder tumour (TURBT), all patients received three cycles of adjuvant chemotherapy in the form of methotrexate, vinblastin, adriamycin and cisplatin (MVAC) followed by radical radiotherapy. • Four weeks later, all cases had radiological and cystoscopical re-evaluation. • Complete responders were considered to be those patients who had no evidence of residual tumour. All patients were subjected to a regular follow-up by cystoscopy and tumour site biopsy conducted every 3 months. Abdomino-pelvic computed tomography and chest X-ray were conducted every 6 months. • The study endpoint was the response to treatment after completion of the first year of follow-up after therapy., Results: • Out of 33 eligible patients, a total of 28 patients completed the study treatment protocol. Their mean ± SD age was 56.7 ± 6 years. Trimodal therapy was well tolerated in most of cases, with no severe acute toxicities. After 12 months of follow-up, a complete response was achieved in 39.3% and a partial response in 7.1%, with an overall response rate of 46.4%. • By the end of the first year, disease-free survival was reported in 39.3%, whereas 25% were still alive with their disease, giving an overall survival of 64.3% for all patients who maintained their intact, well functioning bladders. • Tumour stage and completeness of transurethral resection of bladder tumour were the most important predictors of response and survival. T2 lesions had complete and partial response rates of 69.2% and 23%, respectively, whereas T3 lesions had rates of 40% and 13.3%, respectively (P = 0.001). • The response rate in patients who had complete TURBT was 82.6% vs 20% in those with cystoscopic biopsy only (P = 0.001). In addition, disease-free survival was 72.7% in T2 patients and 27.3% in T3 patients (P = 0.001)., Conclusion: • In the present study, bladder preservation protocol with MVAC and radical radiotherapy achieved suboptimal response rates at 1 year in patients with localized TCC invading bladder muscle. Patients with solitary T2 lesions that are amenable to complete TURBT achieved the best response rates. Longer follow-up is needed to verify these results. Patients with localized disease should be encouraged for radical cystectomy, which achieved better results., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Rationale: Kidneys are dynamic organs and represent one of the major systems maintaining the body homeostasis; they are affected by many chemicals and drugs. Grape seed extract (GSE) has been targeted to prevent drug-induced renal toxicity., Objectives: This study investigates the possible renoprotective effect of GSE against oxidative stress, renal impairment, and hypercholesterolemia (HC) induced by gentamicin (GM) and cholesterol-enriched diet. Seventy adult male Wistar rats (160 ± 10 g) were divided into seven groups: (1) served as control, (2) GSE, (3) GM, (4) GSE + GM, (5) hypercholesterolemic (HC) group, (6) GM + HC group, and (7) GM + HC + GSE. Kidney functions, inflammatory mediators, cytokines, lipid profile, nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and oxidative and antioxidative stress parameters were assessed in all groups., Main Findings: GM induced renal dysfunction, which was exacerbated by the presence of HC as confirmed by laboratory determinations. Administration of GSE attenuated the renal toxicity evidenced in significant reduction in elevated kidney function, inflammatory cytokines as well as lipid profile, NO, cGMP, enzymatic, and nonenzymatic antioxidants., Conclusion: Administration of GSE simultaneously with GM attenuated oxidative stress, diminished renal toxicity, and improved lipid profile induced by GM and HC.

Introduction: Urinary incontinence impairs sexual functioning and sexual satisfaction. Traditional artificial urinary sphincter (AUS) implantation requires perineal incision for cuff placement and a second inguinal incision for reservoir and pump placement. We believed AUS could be placed easier and quicker through one scrotal incision. Aim.  In an effort to effect more proximal placement of the cuff while keeping the advantages of the one scrotal incision technique, we report enhancements to the original surgical technique., Methods: Thirty patients have been operated upon using the enhanced technique. A modification of the SKW retractor system (AMS) facilitates deep bulbar exposure. Twenty patients were first time implantations and 10 were revisions with five of the revisions having had the original AUS placed by traditional two-incision technique. Two of the first time AUS patients received an inflatable penile prosthesis through the same incision., Main Outcome Measures: We evaluated site of cuff placement, sizes of cuffs used, postoperative continence status., Results: All of the virgin AUS required dissection of the bulbocavernosus muscle prior to cuff placement. In scrotally placed revisions, replacement cuffs were situated considerably proximal (4.5-7.5 cm) to the original cuff site. The perineal placed revisions were accomplished through a scrotal incision with replacement of two cuffs in the same site and the three other patients immediately distal. No intraoperative complications were seen. One patient developed scrotal hematoma requiring drainage. Only 15 patients are available for follow-up and all are socially continent (one pad or less)., Conclusions: Transscrotal approach is used safely and efficiently for penile implants and AUS implantation. The new enhancements to the one-scrotal incision technique allow more proximal cuff placement as evidenced by the bulbocavernosus muscle dissection and use of larger cuffs. Continence rate is similar to rates achieved with perineal placement of cuff found in the literature., (© 2010 International Society for Sexual Medicine.)

Purpose: Refractory ischemic priapism results in cavernous smooth muscle necrosis, fibrosis and eventual penile shortening. Immediate penile implant insertion for acute ischemic priapism is done to avoid consequent fibrosis and shortening but ineffective shunt surgery trials may lead to potential weakness and erosion at the corporeal tip. We evaluate nonabsorbable sling sutures to fix the implant cylinder in place and prevent protrusion through the weak corporeal tip., Materials and Methods: We prospectively evaluated 12 men who presented with prolonged refractory ischemic priapism a median of 120 hours (range 60 to 168) in duration. All patients were unresponsive to conventional treatment and 11 had undergone unsuccessful shunt surgery. Early malleable penile prosthesis implantation had been done in all cases. To avoid possible distal protrusion a nonabsorbable sling suture was taken through the cylinder and the edges of the opened tunicae albuginea to fix the cylinder to the corporotomy edges., Results: Penile implants were successfully inserted in all patients. No intraoperative or early postoperative complications were noted except in 1 with sickle cell priapism, in whom dilation led to unilateral corporeal perforation, which was managed intraoperatively. All patients were satisfied with the surgical results. No distal erosion was noted through the weak corporeal tip. No postoperative infection was reported at a median followup of 15 months (range 6 to 36). All patients successfully achieved sexual intercourse., Conclusions: Early penile prosthesis insertion for acute ischemic priapism is simple and successful. Distal cylinder protrusion through the defective corpora due to previous shunt surgery remains to confound surgical success. Nonabsorbable sling suture of the cylinder to the tunica albuginea is effective, simple and safe treatment for this formidable complication., (Copyright 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale: Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. This study investigates whether green tea extract (GTE), an antioxidant, could ameliorate the nephrotoxic effect of GM in uninephrectomized rats., Objectives: The right kidneys of 40 rats were surgically removed and 1 week later the animals were divided into four groups (n = 10). Group 1 served as control, Group 2 as GTE group, Group 3 as GM group, and Group 4 as GM+GTE group. Kidney function, inflammatory cytokine TNF-α, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed., Main Findings: Injecting uninephrectomized rats with GM induced renal dysfunction as shown by significant elevations in serum creatinine and urea. Serum TNF-α and oxidative stress parameters (superoxide anion and lipid peroxides) were also significantly increased. On the contrary, antioxidative parameters [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)] were significantly decreased. Histopathological examination of renal tissue illustrated features of degeneration, marked cellular infiltration, tubular dilatation, and varying degrees of necrosis. GTE given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and TNF-α were almost normalized in the GM+GTE group. The oxidative stress parameters were significantly decreased and the antioxidative parameters were significantly increased., Conclusion: GTE ameliorates GM-induced nephrotoxicity and oxidative damage by improving antioxidant defense and tissue integrity. Further human studies are necessary to demonstrate the antioxidant effects of GTE on renal diseases. Nevertheless, green tea (GT) may offer an inexpensive, nontoxic, and effective intervention strategy in subjects with a risk for GM-induced nephrotoxicity.

Rationale: Cyclosporine A (CsA) leads to renal and liver injury, production of free radicals and nitric oxide (NO) deficiency. This study investigates the possible protective effects of trapidil and L-arginine against CsA-induced tissue injury., Objectives: Forty adult male Wistar rats (180 +/- 20 g) were divided into five groups, eight animals in each. The first group served as control, second group served as CsA group, third group served as CsA + trapidil group, fourth group served as CsA + L-arginine group, and fifth group served as CsA + trapidil + L-arginine group. Kidney and liver functions, inflammatory mediators, cytokines, oxidant and antioxidant parameters as well as histopathological studies of renal and liver tissue were assessed in all groups., Main Findings: CsA induced renal and hepatic dysfunction, which was confirmed by laboratory and histopathological examination. Administration of trapidil diminished the renal and liver injury and significantly attenuated the levels of serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and oxidative stress, while it significantly elevated the level of serum nitric oxide and the activity of antioxidative stress. L-Arginine gave the same trend as trapidil, but trapidil effect was more pronounced. Coadministration of trapidil + L-arginine significantly ameliorated the toxic effect of CsA, but did not differ significantly from the effect of trapidil alone., Conclusions: Treatment with trapidil or L-arginine diminished the renal and hepatic CsA-induced toxicity. However, the effect of trapidil was more pronounced. Therefore, treatment with trapidil alone may be the most economic and effective as a potential therapeutic agent in CsA injury.

Introduction: Parylene coating was added to the silicone layers of the American Medical Systems (AMS) 700 controlled expansion (CX) penile prosthesis cylinders in January 2001. The coating was placed on non-tissue contacting silicone surfaces to increase lubricity, reduce friction, and silicone wear, Aim: We compared mechanical reliability of the original and Parylene-enhanced AMS 700 CX in a large single surgical group series., Methods: Seven hundred seventy-five consecutive patients receiving the AMS 700CX prosthesis (596 first time [virgin] and 179 revisions) were followed for 3 years. Four hundred fourteen received the non-coated model and 361 received the Parylene-coated device. Revision-free survival was estimated using the Kaplan-Meier product limit method and compared using the log-rank test., Main Outcome Measures: We calculated overall survival from revision for any reason and survival from mechanical problems such as fluid leakage, cylinder, connector or tubing breakage, pump or reservoir defects., Results: For the entire series (virgin + revised) the 3-year revision free survival for any cause improved from 78.6% for non-coated to 87.4% for the Parylene-coated implants. Freedom from mechanical breakage showed similar improvement from 89.2% for the non-coated to 97.5% for enhanced models., Conclusions: This study documents that short-term mechanical reliability and survival from revision for any cause is significantly increased with Parylene-coated AMS 700CX cylinders compared with the earlier AMS 700CX model with non-coated cylinders.

Introduction: Premature ejaculation (PE) is a worldwide problem without an approved treatment. Selective serotonin reuptake inhibitors (SSRIs) are widely used "off label" as pharmacotherapeutic agents in the treatment of PE., Aim: This study investigates Tramadol efficacy for on-demand treatment of PE., Main Outcomes Measures: Intravaginal ejaculation latency time (IELT) was used as an objective tool to assess the efficacy of the investigated treatments., Materials and Methods: Single-blind, placebo-controlled, crossover, stopwatch monitored two-period study was conducted, on 60 patients with lifelong PE. PE was defined as IELT of <2 minutes in 80% of intercourse episodes. A total of 25 mg of Tramadol hydrochloride was given to one group (30) prior to intercourse and placebo was supplied for the other group (30) for 8 weeks. Drugs were taken 1-2 hours before sexual activity and sexual intercourse was required at least once per week. After the initial treatment period, the two groups took the alternate medication for another 2 months. The two 8-week treatment periods were separated by 1 week washout period. IELT was timed by a stopwatch at each intercourse and was reported by patients or partners., Results: The baseline (mean +/- SD) IELT for patients before treatment was 1.17 +/- 0.39 minutes. At the end of the treatment period utilizing the active drug, the mean IELT was increased significantly in patients on Tramadol treatment to 7.37 +/- 2.53 minutes. The same patients on placebo medication had mean IELT of only 2.01 +/- 0.71 minutes. Patients uniformly reported satisfaction with their resulting control over ejaculation., Conclusions: Tramadol, a drug with a proven safety record as an anti-inflammatory agent, shows promise as a drug for treating rapid ejaculation.

Objectives: Inflatable penile prosthesis (IPP) infection remains a devastating surgical complication. American Medical Systems recently introduced an IPP with a coating of minocycline HCL and rifampin (InhibiZone). We report our experience with this coating and compare the rate of infection with our historical rate., Methods: A total of 467 patients receiving InhibiZone-coated IPPs were followed up for infection. The patients were stratified into four groups: nondiabetic, first-time (virgin) implants; diabetic, virgin implants; revision without washout; and revision with antiseptic solution washout. All patients were observed for longer than 1 year. The infection rates were compared with our published data of noncoated IPPs., Results: No infections developed among the 223 virgin implants in nondiabetic patients. Of the 83 diabetic patients with virgin implants, 1 developed an infection (1%). Of the 39 revision patients without washout, 4 (10%) had infections. When an antiseptic washout was used in patients requiring revision, the infection rate dropped to 3% (4 of 123). Compared with our previous publications of infection rates with noncoated implants, InhibiZone-coated IPPs showed a statistically significant reduction in infection in virgin nondiabetic, virgin diabetic, and revision with washout implants. No reduction in the infection rate occurred among revision patients without washout., Conclusions: Antibiotic-coated implants become infected less often in virgin, nondiabetic and virgin, diabetic patients than in our historical experience with noncoated implants. However, antibiotic-coated implants used in revision surgery did not reduce the infection rate unless adjunctive antiseptic solution washout was also used.

Introduction: Long-term revision-free survival, greater than 10 years has never been reported for inflatable penile prostheses. We conducted a historical prospective study to estimate 10 and 15 years survival of first time (virgin) implantations in 2,384 patients with four different models., Aim: Evaluation of 10- and 15-year mechanical and overall revision-free survival of inflatable penile prostheses., Main Outcome Measures: Kaplan-Meier product limit method, and comparison using the log rank test, were used to estimate the 10- and 15-year revision-free survival., Methods: Data were obtained from medical records and patient interviews, entered into a computerized database, and analyzed by a third party. Information included implant type, date, revision history with date, and reason. Fourteen different inflatables were examined. Mentor Alpha 1, Mentor Alpha NB, AMS 700 CX, and AMS 700 Ultrex had usage for an extended period of time. Because of failure times being confounded as a result of prior implants, only virgin implants were examined., Results: For the entire series, estimated 10-year revision-free survival for all reasons was 68.5% and the 15-year revision-free survival was 59.7%. Freedom from mechanical breakage at 10 years was 79.4%; 15 years was 71.2%. Recent mechanically enhanced models did even better. In 1992, Mentor Alpha added pump reinforcement to forestall mechanical breakage. This improved 10-year survival from 65.3% to 88.6% (P = 0.0001). In January 2001, AMS CX added a parylene coating to the cylinders that increased 3-year mechanical survival from 88.4 to 97.9% (P = 0.0002)., Conclusions: This is the first report on long-term reliability of inflatable penile prostheses. We estimated 60% of these virgin implants would survive 15 or more years without revision or extraction. Newer enhanced models are currently available, and our tracking predicts even better long-term survival for these devices.

Udenafil is an oral PDE5 inhibitor that is currently available in South Korea for the treatment of erectile dysfunction (ED). Phase II clinical data presented at the 11th World Congress of the International Society for the Sexual and Impotence Research showed that in men with mild-to-severe ED, the drug produced a significant improvement in erectile function after 12 weeks of treatment. Udenafil has been reported as being well tolerated, although in August 2005, the Korean Food & Drug Administration had demanded further details regarding the presence of carcinogenic substances in the drug. A phase IIa clinical trial for ED is currently underway in the US, and phase III trials are planned for 2006.

Introduction: Placement of an inflatable penile prosthesis in a patient with scarred corporal bodies secondary to priapism or removal of a previously infected implant is a formidable surgical challenge; use of downsized implants has improved chances of successful reimplantation. Nevertheless, patients are frequently dissatisfied with the resulting short penises., Aim: This study investigates the use of downsized inflatable penile prosthesis cylinders as tissue expanders in patients with corporal fibrosis., Main Outcomes Measures: Corporal length and width were calibrated before implantation of downsized prostheses and after 1 year of their use as tissue expanders., Methods: Thirty-seven patients had insertion of Mentor Narrow Base (18), AMS CXM (9), or AMS CXR (10) into scarred corporal bodies. Etiology was previously infected and removed implant (29) or priapism (8). In each of these cases it was not possible to dilate to 12 mm in order to place standard-sized cylinders. Patients were encouraged to inflate their implant for up to 3 hours daily. After several months intracorporal stretching occurred. The patients were reoperated; corporal length and width were recalibrated., Results: Upon reoperation, it was possible to pass dilators of 12 mm width proximally allowing the substitution of standard-sized AMS 700 CX (23), Mentor Alpha 1 (10), or Mentor Titan (2). Additionally, corporal length measurements in the previously infected patients increased an average of 2.2 cm allowing placement of longer cylinders. Although priapism patients did not show this phenomenon of corporal lengthening, the implant space widened enough to permit replacement with standard-size cylinders improving girth, rigidity, and appearance., Conclusions: Wider and sometimes longer cylinders can be substituted in patients with corporal fibrosis that required implantation with downsized cylinders because of fibrotic corpora. Prolonged inflation over an 8- to 12-month period results in expansion of the cylinder cavity, permitting standard-sized cylinders in all patients.

The formation of unique vacuoles in tenotomized rat soleus muscle fibers was examined by light and electron microscopy. After tenotomy at both proximal and distal tendons, virtually all muscle fibers underwent characteristic degenerative changes with a disorganization of myofibrils called the central core lesion, but eventually recovered. At 3 days after tenotomy, some muscle fibers showed small vacuoles in the sarcoplasm of the end segments, which were larger in diameter and paler in staining than those of the control fibers in light microscopy. At 5 days, more fibers formed larger vacuoles together with the extensive disorganization of myofibrils. Such vacuole formation was more conspicuous in the distal end than in the proximal end. At 1 week the myofibrillar disorganization was most extensive in the central areas, and vacuoles were considerably enlarged in some fibers to occupy most of the sarcoplasm near the fiber ends. Vacuoles decreased in number and size with time and could rarely be seen at 4 weeks postoperative. In thin-section electron microscopy, the early forms of vacuoles were often connected with the T-system tubules. The limiting membrane of such vacuoles possessed many caveolae, some of which appeared to be continuous with the T-system networks. The vacuole membrane was closely associated with the sarcoplasmic reticulum to form dyadic connections. In later stages, the vacuole membrane was lined in part with the basal lamina. From these findings, it can be concluded that the vacuoles are sarcolemmal in nature and derived from the T-system. The significances of the vacuole formation are discussed with special reference to the mechanism and fate of the vacuoles and their clinical implications.

Tenotomized soleus muscles of adult rats were analyzed morphologically and biochemically with special reference to the recovery process. Light microscopic observations of semi-thin sections showed that the characteristic central core lesion was most extensive at 1 week after tenotomy and began to diminish in extent at 2 weeks until no trace of lesion could be seen by 6th week, as confirmed by thin-section electron microscopy. Three phases of changes in the cross-sectional area of muscle fibers after tenotomy were demonstrated by morphometry: phase I designated as the initial increase up to the 3rd day, phase II as the progressive decrease until the 4th week, and phase III as the recovery to normal or even hypertrophy. In electron microscopy, the earliest alteration of myofibrils was recognized at 3 days after tenotomy. The Z discs showed a wavy or zigzag profile with frequent longitudinal splitting of myofibrils. From the 2nd week on, muscle fibers underwent a process of recovery, replacing the central core lesion with new myofibrils in which a reassembly of thick filaments into bundles of thin filaments took place, with Z discs being aligned adjacent to the peripheral complete myofibrils. In SDS-polyacrylamide gel electrophoresis, the molar ratio of myosin to actin diminished markedly as the central core lesion developed and gradually returned to normal with time, correlating well with the loss and subsequent reassembly of thick filaments.