Shock wave lithotripsy in the era of COVID-19.

Objective: The objective of the study y was to evaluate factors which can improve shock wave lithotripsy (SWL) results to keep up with COVID-19 pandemic. Methods: Between June 2020 and June 2021, patients with radio-opaque or faint radio-opaque upper urinary tract stones, stone attenuation value ≤1200 HU, and stones size <2.5 cm were treated by electrohydraulic SWL. Patients with respiratory tract symptoms elevated temperature, contact with COVID-19 patients, or positive COVID-19 swab 2 weeks preoperatively, skin-to-stone distance >11 cm, and body mass index >30 kg/m2 were excluded from the study. Patients were prospectively enrolled in SWL done at a rate of 40-50 SWs/min under combined ultrasound and fluoroscopy-guided, ramped into high power in the 1st 300 shocks. Success rate and complications were recorded. Results: Five hundred and ninety patients completed the study. The success rate after 1st session was 408/590 patients (69.15%) which was augmented by 2nd session to reach 527/590 patients 89.3%. The success rate was 96.2% at 3 months postoperatively. Most complications were mild (Grade 1 or 2). Conclusions: SWL results improved using slow rate high power from the start of the session under combined fluoroscopy and ultrasound guidance. SWL may be a preferred option during a pandemic.

Serum and Tissue Lipocalin-2 Expression in Chronic Kidney Disease Pruritic Patients.

BACKGROUND: Uremic pruritus is an irritating symptom for patients with end-stage kidney disease. Lipocalin-2 (LCN2) has relevant importance in several biological cellular processes and immunity. It is also a major player in the progression of many disorders, such as renal injury. AIM: To evaluate LCN2 expression in chronic kidney disease (CKD) pruritic patients in serum together with immunohistochemical expression in skin samples and further correlation of their results with the studied clinicopathologic parameters. MATERIALS AND METHODS: Serum level of LCN2 (assessed by enzyme-linked immunosorbent assay) and skin immunohistochemical expression were investigated in 25 CKD patients and 25 healthy controls. Ten patients were subjected to narrowband ultraviolet B phototherapy for 12 weeks then re-evaluated for serum and tissue LCN2 after therapy. RESULTS: LCN2 expression was increased significantly in both the epidermis and dermal adnexa in CKD patients over controls. Also, serum LCN2 level was higher in patients than in healthy subjects and was significantly associated with itching severity, grades of CKD, urea, and creatinine serum level. Tissue and serum levels of LCN2 were significantly diminished in CKD patients following narrowband therapy along with improvement of the severity of pruritus. CONCLUSIONS: The increased serum and tissue LCN2 expression in CKD pruritic patients and its pronounced decrease, in addition to the improvement of pruritus after treatment, suggest a major pathogenic role of LCN2 in uremic pruritus.

ESSM Position Statement on Surgical Treatment of Peyronie's Disease.

INTRODUCTION: Patients with Peyronie's disease may experience significat distress. The choice of treatment depends on a variety of factors, including the stage of the disease, the presence of pain, severity and direction of the curvature, penile length and the quality of erectile function. AIM: To review the evidence associated with surgical treatment of Peyronie`s Disease and provide clinical recommendations on behalf of the European Society for Sexual Medicine. 131 peer-reviewed studies and systematic reviews, which were published from 2009 to 2019 in the English language, were included. METHODS: MEDLINE, Google Scholar and EMBASE were searched for randomized clinical trials, meta-analyses, open-label prospective and retrospective studies. MAIN OUTCOME MEASURE: The panel provided statements on clinically relevant questions including patient involvement in the decision process, indications for surgery, choice of the approach, and the management of patient expectations. A comparison of the different grafts used in patients who have undergone plaque incision/excision and grafting in order to identify an ideal graft, has been carried out. The prevalence of postoperative complications has been summarized. Levels of evidence were provided according to the Oxford 2011 criteria and Oxford Centre for Evidence-Based Medicine recommendations. RESULTS: In order to allow shared decision making, a patient preoperative counselling regarding the pros and cons of each intervention is recommended. In particular, adverse effects of surgical treatments should be discussed to set realistic understanding and expectations of surgical outcomes and ultimately improve postoperative satisfaction rates. Surgical treatment should be only offered in the chronic phase of the condition, when the deformity and/or degree of erectile dysfunction, prevent patients from engaging in satisfying sexual interaction, or if the deformity is the cause of severe bother. CONCLUSIONS: Current European Society for Sexual Medicine recommendations cover several aspects of Peyronie's disease treatment. These recommendations aim both to ensure patients and partners have accurate and realistic expectations of their treatment options, as well as to formulate algorithms to guide clinician management pathways. Osmonov D, Ragheb A, Ward S et al, ESSM Position Statement on Surgical Treatment of Peyronie's Disease. Sex Med 2022;10:100459.

Combined Blood Indexes of Systemic Inflammation as a Mirror to Admission to Intensive Care Unit in COVID-19 Patients: A Multicentric Study.

BACKGROUND: The Coronavirus 2019 is a pandemic that has spread worldwide, threatening human health. The main cause of death in patients with COVID-19 is a systemic pro-inflammatory mechanism that quickly progresses to acute respiratory distress syndrome. Hematological ratios as affordable indicators of inflammatory response were studied in COVID-19 patients. The study aimed to study the importance of the blood cell indexes of the systemic inflammatory response, as the Aggregate Index of Systemic Inflammation (AISI), neutrophils lymphocyte to platelet ratio (NLPR), systemic immune-inflammation index (SII) and, systemic inflammation response index (SIRI) in predicting intensive care unit (ICU) admission of COVID-19 patients. METHODS: 495 COVID-19 patients managed in four tertiary centers; divided into non-ICU and ICU groups. RESULTS: Total leucocyte count (TLC), AISI, NLPR, SII, and SIRI were more elevated in the ICU group (P < 0.001 for all except AMC P = 0.006), while this group had less absolute lymphocyte count (ALC) (P = 0.047). We estimated the optimal cut-off values of the hematological ratio; AISI (729), NLPR (0.0195), SII (1346), and SIRI (2.5). SII had the highest specificity (95.6%), while NLPR had the highest sensitivity (61.3%). Age, AISI, CRP, D-dimer, and oxygen aid were the independent predictors for ICU admission in COVID-19 in multivariate logistic regression. CONCLUSION: AISI is a predictor for severity and ICU admission in COVID-19 patients, SII is a predictor of survival, while NLPR and SIRI have an additive role that needs further evaluation.

Fat mass and obesity-associated gene expression and disease severity in type 2 diabetes mellitus.

Obesity and visceral adiposity are major risk factors for type 2 diabetes mellitus (T2DM). The fat mass and obesity-associated (FTO) gene is associated with increased risk of obesity and T2DM. The aim of this work was to study the association between FTO gene expression and serum FTO protein level with disease severity in T2DM patients. PATIENTS AND METHODS: One hundred T2DM patients were divided into two equal groups according to diabetes control and complications and fifty healthy controls were included in this study. FTO messenger ribonucleic acid (mRNA) expression level was analyzed by Real time polymerase chain reaction (PCR) technique and serum level of FTO protein was measured by ELISA. RESULTS: FTO gene expression and FTO protein levels were increased in the two T2DM groups compared to the control group with significant further increases in patients with severe disease. FTO gene expression and FTO protein levels were positively correlated with obesity, insulin resistance and blood glucose indices as well as the presence of diabetic complications. Regression analyses showed that FTO gene expression and FTO protein levels were risk factors for T2DM severity. CONCLUSIONS: Increased FTO gene expression and its serum protein levels are associated with increased T2DM severity.

Value of early second session shock wave lithotripsy in treatment of upper ureteric stones compared to laser ureteroscopy.

PURPOSE: The safety and efficacy of early second session shock wave lithotripsy (SWL) compared with laser ureteroscopy (URS) for the treatment of upper ureteric stones were evaluated. METHODS: From January to October 2019, 108 patients with upper ureteric stones (< 1.5 cm and ≤ 1000 Hounsfield unit (HU)) were randomized into SWL and laser URS groups. The second SWL session was performed within 48-72 h of the first session. Using plain abdominal X-ray and ultrasonography, patients were evaluated 48-72 h after the first SWL session and one week after the second and third SWL sessions or one week after URS. The procedure was considered a success when no additional procedures were needed to clear the stone. To determine the stone-free rate (SFR), noncontrast computed tomography of the urinary tract was performed three months postoperatively. RESULTS: In the SWL group, the success rates were 92.6% and 94.4% after the second and third sessions. The SFR was 96.2% in the laser URS group. The success rates were not significantly different between the second and third SWL sessions versus the laser URS (p = 0.418 and 0.660, respectively). Operative and fluoroscopy times were significantly longer in the SWL group (p = 0.001), and JJ stent insertions were needed after laser URS. CONCLUSION: Ultraslow full-power SWL treatment of patients with upper ureteric stones (< 1.5 cm and ≤ 1000 HU) with an early second session is safe and effective compared to laser URS. Patients who do not respond to early second SWL session should be shifted to another treatment modality.

Ultraslow full-power shock wave lithotripsy protocol in the management of high attenuation value upper ureteric stones: A randomized comparative study.

OBJECTIVES: To evaluate the efficacy and safety of ultraslow full-power shock wave lithotripsy protocol in the management of high attenuation value upper ureteric stones compared with slow-rate, power-ramping shock wave lithotripsy. METHODS: This was a randomized trial enrolling patients with a single high attenuation value (≥1000 HU) upper ureteric stones between January 2019 and July 2019. Ultraslow full-power shock wave lithotripsy (54 patients) was applied at a rate of 30 shock waves/min with power ramping from 6 to 18 kV for 100 shock waves, then a safety pause for 2 min, followed by ramping 18-22 kV for 100 shock waves, then a safety pause for 2 min. Then, full power (22 kV) was maintained until the end of the session. Slow-rate, power-ramping shock wave lithotripsy (47 patients) was applied at a rate of 60 shock waves/min with power ramping from 6 to 10 kV during the first 500 shock waves, then from 11 to 22 kV during the next 1000 shock waves, then maintained on 22 kV in the last 1500 shock waves. Up to three sessions were carried out with a follow up 3 months after the last session. The primary outcome was the stone-free rate. Perioperative data of the two protocols were compared. RESULTS: There was no significant difference in preoperative data. The stone-free rate was significantly higher in ultraslow full-power shock wave lithotripsy after single (92.6% vs 23.4%) and multiple (96.3% vs 63.8%) sessions. Most complications were mild, with no significant difference between both groups (9.3% vs 12.8%; P = 0.573). Logistic regression analysis identified ultraslow full-power shock wave lithotripsy protocol as the only significant independent factor for the stone-free rate (odds ratio 12.589, P = 0.025). CONCLUSION: Ultraslow full-power shock wave lithotripsy for high attenuation value upper ureteric stones is associated with a significantly higher stone-free rate, and with mild complications that are comparable to those of standard shock wave lithotripsy.

Relation of baseline prostate volume to improvement of lower urinary tract symptoms due to tamsulosin monotherapy in benign prostatic hyperplasia: An exploratory, multicenter, prospective study.

AIMS: The aim of the study was to investigate the relation between baseline prostate volume (PV) and the improvement of lower urinary tract symptoms (LUTS) induced by tamsulosin monotherapy after 2-year follow-up in Egyptian benign prostatic hyperplasia (BPH) patients. SETTINGS AND DESIGN: This was a prospective comparative multicenter study. SUBJECTS AND METHODS: Three hundred and eighty-one BPH patients were included in the study from January 2014 to January 2017. The patients were divided according to their PV into two groups. Group A included patients with small-sized prostate (≤40 ml) and Group B included those with PV larger than 40 ml. Full evaluation was done at presentation. The patients are followed up at 6, 12, and 24 months of continued medical treatment with tamsulosin 0.4 mg once daily. STATISTICAL ANALYSIS USED: Data were coded and entered using the Statistical Package for the Social Sciences version 24. Data were summarized using mean and standard deviation in quantitative data. Comparisons between quantitative variables were done using unpaired t-test or the nonparametric Mann-Whitney test. A comparison between paired measurements in the same person was done using paired t-test (Chan, 2003). P < 0.05 was considered as statistically significant. RESULTS: The mean age was 60.1 ± 7.2 years. The mean value of the International Prostate Symptom Score (IPSS) was recorded for the 381 patients at presentation. In Group A, the mean value of IPSS was 20.44 ± 3.18, whereas in Group B, the mean value of IPSS was 21.23 ± 3.5. There was a significant improvement in symptoms (Qmax-IPSS) in both groups, but we found that this improvement was significantly better in Group A (P = 0.017). CONCLUSIONS: PV is an important prognostic factor affecting the improvement of the LUTS by α1-blocker monotherapy. Tamsulosin monotherapy may not be enough for large prostate (>40 mg) to maintain adequate symptom relief, and it is better to start with other medical options such as combined therapy or early nonmedical therapy. Starting α1-blocker monotherapy in smaller prostates may be of benefit in symptomatic patients without considering watchful waiting.

Percutaneous nephrostomy versus JJ ureteric stent as the initial drainage method in kidney stone patients presenting with acute kidney injury: A prospective randomized study.

OBJECTIVE: To compare percutaneous nephrostomy tube versus JJ stent as an initial urinary drainage procedure in kidney stone patients presenting with acute kidney injury. METHODS: Between January 2017 and January 2019, 143 patients with acute kidney injury secondary to obstructive kidney stone were prospectively randomized into the percutaneous nephrostomy tube group (71 patients) and JJ stent group (72 patients) at Beni-Suef University Hospital, Beni-Suef, Egypt. Exclusion criteria included candidates for acute dialysis, fever (>38°C), pyonephrosis, pregnancy and uncontrolled coagulopathy. The period required for serum creatinine normalization, failure of insertion, operative and fluoroscopy time were recorded. Definitive stone management for proximal ureteral stones >1.5 cm consisted of percutaneous nephrolithotomy for the percutaneous nephrostomy group and ureteroscopic laser lithotripsy for the JJ stent group. For stone size <1.5 cm, ureteroscopy or shockwave lithotripsy was carried out for both groups. Percutaneous nephrolithotomy was carried out for renal stones >2 cm, and shockwave lithotripsy for stones <2 cm. Distal and mid ureteral stones were treated by ureteroscopy. RESULTS: The percutaneous nephrostomy group had shorter operative time (P = 0.001). There was no significant difference in the recovery period for normalization of serum creatinine between both groups (P = 0.120). Procedural failure, ureteric mucosal injury and perforations increased in the case of male sex, stone size >1.5 cm and upper ureteric stones in the JJ stent group. Procedural failure, pelvic perforations and intraoperative bleeding increased in case of male sex, mild hydronephrosis and stone size >2.5 cm in the percutaneous nephrostomy group. Suprapubic pain, urethral pain and lower urinary tract symptoms were significant in the JJ stent group. The presence of a JJ stent directed us toward ureteroscopy (P = 0.002) and the presence of a percutaneous nephrostomy directed us toward percutaneous nephrolithotomy (P = 0.001). CONCLUSIONS: Percutaneous nephrostomy facilitates subsequent percutaneous nephrolithotomy, especially when carried out by a urologist, and it has a higher insertion success rate, a shorter operative time and a lesser incidence of postoperative urinary tract infection than a JJ stent. A JJ stent facilitates subsequent ureteroscopy, but operative complications can increase in the case of proximal ureteral stones >1.5 cm.

A decade of grafting techniques as a sole treatment for Peyronie's disease.

BACKGROUND: Peyronie's disease (PD) can be a cosmetically and functionally devastating condition. Surgical approaches have been proposed in the chronic stages of PD as plication or plaque incision/excision with grafting to preserve penile size in complex cases. Although several surgeons nowadays are inclined toward the utilization of non-autologous grafts owing to the ease of their preparation and availability, synthetic graft procedures still await more technical improvements and supporting evidence before their consideration for standard care. OBJECTIVES: In this review, our goal is to facilitate an insight into the most promising grafting materials used for the management of PD and techniques associated. MATERIALS AND METHODS: A PubMed review was conducted for all the studies on our topic within the past ten years (January 2009 until December 2019). The outcome parameters we documented and compared comprised of operative time, follow-up time, postoperative penile cosmesis and function, and, finally, overall patient satisfaction related to each technique. RESULTS: Our search yielded 23 English-written original study articles in addition to a single case report on the various grafting techniques utilized as the sole treatment for PD, each demonstrating different outcomes and points of comparison. CONCLUSION: A successful grafting procedure for PD requires an appropriately tailored surgical modality and an experienced surgeon. Nevertheless, proper preoperative patient counseling on all aspects of his condition and opted treatment modality while setting clear and realistic expectations remains key for overall patient satisfaction.

Ultraslow full-power shock wave lithotripsy versus slow power-ramping shock wave lithotripsy in stones with high attenuation value: A randomized comparative study.

OBJECTIVES: To compare the efficacy and safety of ultraslow full-power versus slow rate, power-ramping shock wave lithotripsy in the management of stones with a high attenuation value. METHODS: This was a randomized comparative study enrolling patients with single high attenuation value (≥1000 Hounsfield unit) stones (≤3 cm) between September 2015 and May 2018. Patients with skin-to-stone distance >11 cm or body mass index >30 kg/m2 were excluded. Electrohydraulic shock wave lithotripsy was carried out at rate of 30 shock waves/min for group A versus 60 shock waves/min for group B. In group A, power ramping was from 6 to 18 kV for 100 shock waves, then a safety pause for 2 min, followed by ramping 18-22 kV for 100 shock waves, then a safety pause for 2 min. This full power (22 kV) was maintained until the end of the session. In group B, power ramping was carried out with an increase of 4 kV each 500 shock waves, then maintained on 22 kV in the last 1000-1500 shock waves. Follow up was carried out up to 3 months after the last session. Perioperative data were compared, including the stone free rate (as a primary outcome) and complications (secondary outcome). Predicting factors for success were analyzed using logistic regression. RESULTS: A total of 100 patients in group A and 96 patients in group B were included. The stone-free rate was significantly higher in group A (76% vs 38.5%; P < 0.001). Both groups were comparable in complication rates (20% vs 19.8%; P = 0.971). The stone-free rate remained significantly higher in group A in logistic regression analysis (odds ratio 24.011, 95% confidence interval 8.29-69.54; P < 0.001). CONCLUSIONS: Ultraslow full-power shock wave lithotripsy for high attenuation value stones is associated with an improved stone-free rate without affecting safety. Further validation studies are required using other shock wave lithotripsy machines.

Predictive value of the immediate effect of first dose of tamsulosin on lower urinary tract symptoms improvement in benign prostatic hyperplasia patients.

OBJECTIVES: The objective is to study the effect of tamsulosin within hours after the first dose and its prediction of the future improvement of LUTS. MATERIALS AND METHODS: From May 2016 until August 2017, 340 patients aged over 40 years with benign prostatic hyperplasia (BPH)-related symptoms were prospectively enrolled; 0.4 mg tamsulosin for 3 months was given. The first visit was before beginning of tamsulosin; uroflowmetry (UFM), postvoid residual urine volume (PVR), international prostate symptom score (IPSS), and quality of life (QoL) were measured. The second visit was after 6 h from the administration of tamsulosin. UFM and PVR were measured. The third visit was after 1 month and the fourth visit was after 3 months, on which UFM, PVR, IPSS, and QoL were also measured. RESULTS: The mean patients' age was 63 ± 6.18 and the mean prostate volume was 52.23 ± 24.59 cc. The mean Qmax at 1st, 2nd, 3rd, and 4th visits was 10.28 ± 3.06 s, 14.58 ± 4.84 s, 14.46 ± 4.94 s, and 14.28 ± 5.07 s, respectively, P = 0.04. The mean voiding time at 1st, 2nd, 3rd, and 4th visits was 41.24 ± 27.18 s, 33.84 ± 18.14 s, 31.96 ± 22.02 s, and 30.14 ± 17.52 s, respectively, P = 0.03. The mean PVR at 1st, 2nd, 3rd, and 4th visits was 46.40 ± 22.14 ml, 27.76 ± 26.10 ml, 25.16 ± 28.36 ml, and 25.58 ± 28.10 ml, respectively, P = 0.001. The first dose of tamsulosin significantly increases Qmax and decreases voiding time and residual urine (RU); there was no statistical significant difference between 1st dose, 1 and 3 months in Qmax, voiding time, and RU. QOL and IPSS were significantly improved after 1 and 3 months, P < 0.001. CONCLUSION: The first dose of tamsulosin improves UFM and predicts the mid-term change in UFM as well as IPSS and QoL indices in the treatment of BPH-related LUTS.

Outcome of Botulinum Toxin-A intraprostatic injection for benign prostatic hyperplasia induced lower urinary tract symptoms: A prospective multicenter study.

INTRODUCTION: Our aim was to determine the factors predicting the outcome of intraprostatic injection of Botulinum Toxin-A (BTX-A) in the treatment of benign prostatic hyperplasia (BPH)-induced lower urinary tract symptoms (LUTS) and to evaluate its efficacy and safety. METHODS: Between September 2016 and May 2018, 45 Egyptian patients, with BPH-induced LUTS were included; the indication was a failure of medical treatment, unfit, or refusing surgical intervention. Measurements of prostate size by TRUS, total PSA level before and 12 weeks after injection. IPSS, uroflow, and postvoiding residual urine (PVR) were measured before injection, 2, 4, 8 and 12 weeks postinjection. 100 U BTX-A vial was diluted with 10 mL of saline then injected into the transition zone at base and midzone of the prostate by TRUS. RESULTS: The mean patients' age was 64.4 ± 6.6 years. Mean baseline IPSS 24.06 decreased to 18.75 at 2 weeks and progressively decreased to 16.37 at 12 weeks (P < 0.001), Q max of 9.08 mL/s. increased to 10.44 at 2 weeks and 11.44 at 12 weeks (P < 0.001), mean prostate volume was 67.44cc; decreased to 66.06cc (P < 0.001) at 12 weeks and mean residual urine was 82.62 mL and decreased to 57.66 mL at 12 weeks. DISCUSSION: Intraprostatic injection of BTX-A as modality treatment of LUTS/BPH significantly improve IPSS, Q max , PVR, and decrease prostate volume. We can suspect better results with this line of treatment in patients with IPSS ≤ 22 and Q max ≤ 10 mL/min and prostate volume ≤ 56.5cc.

The role of diffusion-weighted and fluid attenuated inversion recovery magnetic resonance imaging in diagnosis and timing of acute ischemic stroke

Background: Ischemic stroke causes serious long-term disability and a great number of economic losses. Thrombolytic therapy is used only if the time of stroke onset was <4.5 hours. However, new categories such as wake-up and day un-witnessed strokes, patients unable to tell exact time of last seen well. The importance of study is to use diffusion weighted/Fluid attenuated inversion recovery (DWI/FLAIR) mismatch as a radiological marker which can help to identify patients with lacunar and non-lacunar stroke within 4.5 hours of onset and use it to determine whether patients with unknown onset stroke qualify for thrombolytic therapy or not. Patients and methods: prospective cohort study was conducted on 72 patients with known time of symptoms onset, imaged within 24 hours from stroke onset. Patients underwent the admission Computed tomography CT and magnetic resonance scans (DWI and FLAIR only) with time gap was no longer than one hour. The presences of lesions in the neuroradiological modalities were assessed in correlation with the duration of the stroke.Results: The time from stroke onsetto neuroimaging was significantly shorter with ischemic lesions visible in DWI/FLAIR mismatch group when compared to other modalities. The DWI/FLAIR was characterized by global specificity 100%, sensitivity 91.9%, PPV 100% and NPV 92.1%. It succeeded to diagnose 12 patients with lacunar stroke before 4.5 hours from the stroke onset.Conclusion: The presence of acute ischemic lesions only in DWI/FLAIR mismatch group can help to identify both lacunar and non-lacunar stroke patients who are within 4.5 hours' time window for intravenous thrombolysis

Influence of the neural microenvironment on prostate cancer.

BACKGROUND: Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. METHOD: We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. RESULT: Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. CONCLUSION: Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer.

Modulation of hepatic drug metabolizing enzymes by dietary doses of thymoquinone in female New Zealand White rabbits.

Herbal medicines can affect drug metabolizing enzymes. Therefore the effect of thymoquinone (TQ), the active ingredient of black seeds, was examined on rabbit liver drug metabolizing enzymes. Two groups of New Zealand female rabbits received TQ at 10 and 20 mg/kg/day orally and a control group of six animals each were killed after 8 weeks. Blood and livers were harvested and the activity of cytochrome P450 (CYP) and phase II enzymes in the microsomal and cytosolic preparations were measured by HPLC and ELISA methods. The liver enzymes ALT/AST and albumin were similar in the three groups. CYP1A2, CYP3A4, but not CYP2E1, were significantly diminished by TQ treatment. Of the phase II enzymes, glutathione-S-transferase (GST) and glutathione peroxidase (GPx) were significantly induced by the high TQ dose, while the total glutathione levels were unaffected. Glutathione reductase (GR), on the other hand, was significantly induced in the two experimental groups. Thymoquinone has differential effects on CYP and phase II enzymes. Inhibition of some CYP enzyme activities may lead to a hazardous herb-drug interaction. Induction of GR activity may explain the salutatory effect of the black seeds in inhibiting the generation of bioactive metabolites known to promote carcinogenesis and oxidative cell damage.

Empirical treatment of low-level leukocytospermia with doxycycline in male infertility patients.

OBJECTIVE: To design a retrospective study in which infertile men with a seminal leukocyte count of 0.2-1 × 10(6) white blood cells [WBC]/mL were given doxycycline to examine the potential benefits of the treatment on the improvement of semen parameters and natural pregnancy outcomes. It has been reported that even low-level leukocytospermia (0.2-1.0 × 10(6) WBC/mL) could be harmful to male reproductive function and achievement of pregnancy. METHODS: The records of 223 patients were reviewed and 61 patients were identified with a leukocyte count of 0.2-1.0 × 10(6) WBC/mL. Of the 61 patients, 27 presented before 2006 and were not routinely treated for this level of leukocytospermia. These patients were our historic control population. Since 2006, 34 patients met these criteria and received empirical antibiotic therapy (treatment group). RESULTS: The treatment of low-level leukocytospermia with doxycycline did not show statistically significant differences in the semen parameters among the treated patients. Although the therapy did not alter the semen parameters, low-level leukocytospermia resolved in 56% of the treatment group, well above the spontaneous resolution rate of 25% observed in historic controls. The natural pregnancy rate among the treatment group (15 of 32 [47%]) was significantly greater than that among the controls (5 of 25 [20%]). The odds ratio for pregnancy outcome was 3.7 (95% confidence interval 1.1-11.7; P = .04). CONCLUSION: Low-level leukocytospermia might have deleterious effects on male fertility, and antibiotic therapy for such a condition might improve the natural pregnancy rate among infertile couples.

Attenuated combined action of cyclosporine a and hyperlipidemia on atherogenesis in rabbits by thymoquinone.

This descriptive study investigates in a rabbit model of atherosclerosis (i) the extent of atherogenesis induced by cyclosporine A (CsA) or hyperlipidemia alone or in combination and (ii) whether thymoquinone (TQ), a known herbal antioxidant, offers protection against these effects. New Zealand White female rabbits were assigned to five groups of six animals each: Group I, control; Group II, CsA [25 mg kg(-1) day(-1) orally (PO)]; Group III, 1% cholesterol; Group IV, 1% cholesterol + CsA (25 mg kg(-1) day(-1) PO); and Group V, 1% cholesterol + CsA (25 mg kg(-1) day(-1) PO) + TQ (10 mg kg(-1) day(-1) PO). Lipids and oxidative stress parameters [Malondialdehyde (MDA) and protein carbonyl] and aortic atherosclerosis were compared. CsA alone did not show a significant effect on either serum lipids and did not induce atherosclerosis. High-cholesterol diet induced atherosclerosis (45 ± 11% of the intimal surface of aorta was covered with atherosclerotic plaques). CsA and high-cholesterol diet increased atherosclerosis severity as measured from intimal and media lesions, but did not affect the extent of atherosclerosis. TQ decreased aortic MDA by 83%. It was also associated with reduced aortic atherosclerosis extend by 52% compared with Group IV. We concluded that (i) CsA aggravates hyperlipidemia-induced atherosclerosis and (ii) TQ attenuates the oxidative stress and atherogenesis induced by the combined effect of CsA and hyperlipidemia.

Cyclosporine-induced changes in drug metabolizing enzymes in hyperlipemic rabbit kidneys could explain its toxicity.

This study investigates the mechanism of cyclosporine A (CsA)-mediated nephrotoxicity by examining the hypothesis that CsA toxicity is mediated through its effect on the kidney drug metabolizing enzymes in a hyperlipemic rabbit model. Twenty-four female New Zealand white rabbits divided into four groups. Group 1 received regular diet. Group 2 received 1% cholesterol diet. Group 3 received CsA (25 mg/kg, orally once daily) and group 4 received 1% cholesterol diet and CsA (25 mg/kg, orally once daily). Cytochrome P450 2E1 (CYP2E1) activity in kidney microsomes was assessed by measuring p-nitrophenol hydroxylase activity. Generation of reactive oxygen species (ROS) was assessed by measuring malondialdehyde (MDA) and the protein carbonyl. Effect of CsA and hyperlipidemia on the antioxidant proteins were also assessed using standard techniques. CsA but not the high-cholesterol diet induced significant elevation in MDA, protein carbonyl and CYP2E1 activities in the kidney. The addition of cholesterol to CsA normalized ROS markers without affecting the CsA-enhanced CYP2E1 activity. Alone, CsA caused characteristic tubular injury, whereas the addition of high-cholesterol diet to CsA nearly abolished the tubular damage. CsA-enhanced rabbit kidney ROS and CYP2E1 activities. Hyperlipidemia attenuates CsA tubular injury, most probably due to normalization of renal ROS, but not CYP2E1 activity.

Attenuation of high cholesterol-induced oxidative stress in rabbit liver by thymoquinone.

BACKGROUND/AIMS: This study examines the modifying effects of thymoquinone (TQ), an agent with antioxidant and hypolipidemic properties, on reactive oxygen species, antioxidant activity, and steatosis in livers of hyperlipidemic rabbit. METHODS: Oxidative stress was induced in New Zealand White rabbit by a high-cholesterol diet for 8 weeks. Four groups of six animals each were divided into a control group; a high cholesterol group (received 1% cholesterol diet); a high cholesterol/low TQ group (received 1% cholesterol diet plus TQ 10 mg/kg/day), and a high cholesterol/high TQ (20 mg/kg/day) group. Blood samples were taken at the end of the study and examined for fasting serum glucose, insulin, and aminotransaminases. Hepatic tissue samples were examined for malondialdehyde, protein carbonyls, antioxidant enzymes, and steatosis. RESULTS: There was severe hepatic steatosis and elevated serum alanine aminotransferase in the high cholesterol group (group II) but not in the high cholesterol and low or high TQ groups (groups III, IV). The hepatic reactive oxygen species activity in the high cholesterol group was significantly higher while the antioxidant enzymes were lower (P<0.05) when compared with the control (group I) or either of the high cholesterol and TQ groups. CONCLUSION: TQ attenuates hepatic oxidative stress in fatty liver injury induced by high-cholesterol diet in rabbits.