Effect of exercise training on antioxidant system in brain regions of rat

The purpose of this investigation was to determine whether any alterations in antioxidant enzyme activities and levels of glutathione (GSH) in brain regions occurred following exercise training. Sprague-Dawley rats were given exercise training on a treadmill for 7.5 weeks and sacrificed 18 h after the last exercise along with the sedentary control rats. Different brain regions—cerebral cortex (CC), brainstem (BS), corpus striatum (CS), and hippocampus (H)—were isolated; GSH, oxidized glutathione (GSSG), Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined. The exercise training increased SOD activity significantly (130% of sedentary control) in BS and in CS. SOD activity in H was the lowest of all four brain regions. Different brain regions showed GSH-Px activity in decreasing order for CS < BS < CC < H. GSH levels were 43% less in BS than CC and CS. The ratio of GSH/ GSSG significantly increased from 6.8 to 8.3 in CC, and from 9.4 to 13.5 in BS as a result of exercise training. Different brain regions contained different activities of antioxidant enzymes, as well as GSH and GSSG levels, which were preferentially altered as a result of exercise training to cope with oxidative stress.     

Dose response of carboplatin-induced nephrotoxicity in rats

Abstract: Carboplatin, a second-generation platinum-containing anticancer drug, is currently being used against a variety of cancers. High-dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. However, the biochemical mechanism of carboplatin-induced renal injury has not been well studied. This study investigated the dose response of carboplatin-induced changes in endogenous antioxidants, lipid peroxidation and platinum content in rat kidney. Male Wistar rats (250-300 g) were divided into five groups and treated as follows: (1) control (saline, intraperitoneally); (2) carboplatin (64 mg/kg, intraperitoneally); (3) carboplatin (128 mg/kg, intraperitoneally); (4) carboplatin (192 mg/kg, intraperitoneally); and (5) carboplatin (256 mg/kg, intraperitoneally). The animals were sacrificed four days after treatment. The blood and kidneys were isolated and analyzed. Plasma creatinine and blood urea nitrogen levels were increased significantly in response to carboplatin in a dose-dependent manner. Renal superoxide dismutase and catalase activities were decreased significantly due to carboplatin at dosages of 128 mg/kg and above. The protein expressions of renal copper/zinc-superoxide dismutase and manganese-superoxide dismutase significantly depleted after carboplatin. Carboplatin (192 and 256 mg/kg) significantly increased lipid peroxidation (malondialdehyde concentration) in rat kidneys. Carboplatin dose-dependently increased the renal platinum concentration, with significance at dosages of 128 mg/kg and above. Carboplatin (256 mg/kg) significantly increased renal xanthine oxidase activity, while ratio of reduced to oxidized glutathione depleted significantly. The data suggested that carboplatin caused dose-dependent oxidative renal injury, as evidenced by renal antioxidant depletion, enhanced lipid peroxidation, platinum content, plasma creatinine and blood urea nitrogen levels in rats.     

Prognostic factors in acute-on-chronic liver failure: A prospective study from western India

The profile of acute-on-chronic liver failure (ACLF) has not been reported from western India. This study was undertaken to analyze the etiology and clinical profile of patients with ACLF and correlate these with outcome. Fifty-four consecutive cases of ACLF were investigated for underlying chronic liver disease (CLD) and acute insult and followed up for 6 months. Mortality, Child–Pugh score, and model for end-stage liver disease (MELD) score were recorded. The most common etiologies of CLD were hepatitis B (29.6 %) and cryptogenic (27.7 %). Prognosis was worse in patients with hepatitis B or alcohol as cause of CLD (mortality 79 %). Acute viral hepatitis A or E was the commonest cause of acute insult (33.3 %) and with statistically better outcome (60 % survival) as compared to sepsis, gastrointestinal bleed, or flare of HBV (survival 5 %, p < 0.05). On univariate analysis age, past history of decompensation, leukocytosis, serum bilirubin and creatinine, international normalized ratio, presence of spontaneous bacterial peritonitis, Child–Pugh score and hepatorenal syndrome were significant predictors of mortality. Multivariate analysis revealed a MELD score of >27 and presence of encephalopathy as independent predictors of mortality. Patients with ACLF had high mortality especially when they had underlying chronic hepatitis B or alcoholic liver disease. Presence of encephalopathy and MELD score were independent baseline predictors of mortality. Child–Pugh score was helpful for prognostication.     

Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure

In vitro susceptibility testing and genotyping were done on urogenital isolates of Chlamydia trachomatis from 3 patients, 2 of whom showed evidence of clinical treatment failure with azithromycin and one of whom was the wife of a patient. All 3 isolates demonstrated multidrug resistance to doxycycline, azithromycin, and ofloxacin at concentrations >4.0 microg/mL. Recurrent disease due to relapsing infection with the same resistant isolate was documented on the basis of identical genotypes of both organisms. This first report of clinically significant multidrug-resistant C. trachomatis causing relapsing or persistent infection may portend an emerging problem to clinicians and public health officials.     

Robotic Versus Laparoscopic Partial Nephrectomy: A Systematic Review and Meta-Analysis

Context

Centres worldwide have been performing partial nephrectomies laparoscopically for greater than a decade. With the increasing use of robotics, many centres have reported their early experiences using it for nephron-sparing surgery.

Objective

To review published literature comparing robotic partial nephrectomy (RPN) with laparoscopic partial nephrectomy (LPN).

Evidence acquisition

An online systematic review of the literature according to Cochrane guidelines was conducted from 2000 to 2012 including studies comparing RPN and LPN. All studies comparing RPN with LPN were included. The outcome measures were the patient demographics, tumour size, operating time, warm ischaemic time, blood loss, transfusion rates, length of hospital stay, conversion rates, and complications. A meta-analysis of the results was conducted. For continuous data, a Mantel-Haenszel chi-square test was used; for dichotomous data, an inverse variance was used. Each was expressed as a risk ratio with a 95% confidence interval p < 0.05 considered significant.

Evidence synthesis

A total of 717 patients were included, 313 patients in the robotic group and 404 patients in the laparoscopic group (seven studies). There was no significant difference between the two groups in any of the demographic parameters except for age (age: p = 0.006; sex: p = 0.54; laterality: p = 0.05; tumour size: p = 0.62, tumour location: p = 57; or confirmed malignant final pathology: p = 0.79). There was no difference between the two groups regarding operative times (p = 0.58), estimated blood loss (p = 0.76), or conversion rates (p = 0.84). The RPN group had significantly less warm ischaemic time than the LPN group (p = 0.0008). There was no difference regarding postoperative length of hospital stay (p = 0.37), complications (p = 0.86), or positive margins (p = 0.93).

Conclusions

In early experience, RPN appears to be a feasible and safe alternative to its laparoscopic counterpart with decreased warm ischaemia times noted.     

Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: validation across time and place and recommendation for benchmarking

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Staging of patients with prostate cancer is the cornerstone of treatment. However, after curative intended therapy a high portion of patients relapse with local and/or distant recurrence. Therefore, one may question whether surgical lymph node dissection (LND) is sufficiently reliable for staging of these patients. Several imaging methods for primary LN staging of patients with prostate cancer have been tested. Acceptable detection rates have not been achieved by CT or MRI or for that matter with PET/CT using the most common tracer fluoromethylcholine (FCH). Other more recent metabolic tracers like acetate and choline seem to be more sensitive for assessment of LNs in both primary staging and re‐staging. However, previous studies were small. Therefore, we assessed the value of [¹⁸F]FCH PET/CT for primary LN staging in a prospective study of a larger sample and with a ‘blinded’ review. After a study period of 3 years and >200 included patients, we concluded that [¹⁸F]FCH PET/CT did not reach an optimal detection rate compared with LND, and, therefore, it cannot replace this procedure. However, we did detect several bone metastases with [¹⁸F]FCH PET/CT that the normal bone scans had missed, and this might be worth pursuing.

OBJECTIVES

• ? To assess the value of [¹⁸F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging of prostate cancer.
• ? To evaluate if FCH PET/CT can replace LN dissection (LND) for LN staging of prostate cancer, as about one‐third of patients with prostate cancer who receive intended curative therapy will have recurrence, one reason being undetected LN involvement.

PATIENTS AND METHODS

• ? From January 2008 to December 2010, 210 intermediate‐ or high‐risk patients had a FCH PET/CT scan before regional LND.
• ? After dissection, the result of histological examination of the LNs (gold standard) was compared with the result of FCH PET/CT obtained by ‘blinded review’.
• ? Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of FCH PET/CT were measured for detection of LNe metastases.

RESULTS

• ? Of the 210 patients, 76 (36.2%) were in the intermediate‐risk group and 134 (63.8%) were in the high‐risk group. A medium (range) of 5 (1–28) LNs were removed per patient.
• ? Histological examination of removed LNs showed metastases in 41 patients. Sensitivity, specificity, PPV, and NPV of FCH PET/CT for patient‐based LN staging were 73.2%, 87.6%, 58.8% and 93.1%, respectively.
• ? Corresponding values for LN‐based analyses were 56.2%, 94.0%, 40.2%, and 96.8%, respectively.
• ? The mean diameter of the true positive LN metastases was significantly larger than that of the false negative LNs (10.3 vs 4.6 mm; P < 0.001).
• ? In addition, FCH PET/CT detected a high focal bone uptake, consistent with bone metastases, in 18 patients, 12 of which had histologically benign LNs.

CONCLUSIONS

• ? Due to a relatively low sensitivity and a correspondingly rather low PPV, FCH PET/CT is not ideal for primary LN staging in patients with prostate cancer.
• ? However, FCH PET/CT does convey important additional information otherwise not recognised, especially for bone metastases.