The Salutary Effects of Diminazene, Lisinopril or Valsartan on Cisplatin - Induced Acute Kidney Injury in Rats: A Comparative Study.

Nephrotoxicity as a cause of acute kidney injury (AKI) induced by cisplatin (CP), limits its usefulness as an anticancer agent. Diminazene, an angiotensin converting enzyme 2 activator, exhibited renoprotective properties on rat models of kidney diseases. This research aims to investigate the salutary effect of diminazene in comparison with lisinopril or valsartan in CP-induced AKI. The first and second groups of rats received oral vehicle (distilled water) for 9 days, and saline injection or intraperitoneal CP (6 mg/kg) on day 6, respectively. Third, fourth, and fifth groups received intraperitoneal injections of CP on day 6 and diminazene (15 mg/kg/day, orally), lisinopril (10 mg/kg/day, orally), or valsartan (30 mg/kg/day, orally), for 9 days, respectively. 24h after the last day of treatment, blood and kidneys were removed under anesthesia for biochemical and histopathological examination. Urine during the last 24 h before sacrificing the rats was also collected. CP significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin, calcium, phosphorus, and uric acid. It also increased urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase/creatinine ratio, and reduced creatinine clearance, as well the plasma concentrations of inflammatory cytokines [plasma tumor necrosis factor-alpha, and interleukin-1beta], and significantly reduced antioxidant indices [catalase, glutathione reductase , and superoxide dismutase]. Histopathologically, CP treatment caused necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. Diminazine, lisinopril, and valsartan ameliorated CP-induced biochemical and histopathological changes to a similar extent. The salutary effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Keywords: Cisplatin, Diminazene, ACE2 activator, Lisinopril, Valsartan, Acute kidney injury.

Oxidative stress caused by Basagran® herbicide is altered by salicylic acid treatments in peanut plants.

The present work was to study a protective role of salicylic acid (SA) on oxidative stress caused by Basagran® herbicide application. Two peanut cultivars (Arachis hypogaea cv. Giza 5 and Giza 6) with different sensitivities to the herbicide were monitored for their antioxidant responses to Basagran® and/or SA treatments. Two weeks after treatment, Basagran® lowered leaf pigments (Chlorophyll a, Chlorophyll b and total Carotenoids) but increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents indicating occurrence of lipid peroxidation and oxidative stress. Salicylic acid applied prior to low dose Basagran® lowered H2O2 and MDA contents in both G5 and G6. Except for SOD which is highly stimulated, POD, CAT and APX activities showed slight changes compared to control in leaves treated with Basagran® ± SA. The extracts tested by DPPH showed increase in total antioxidant activity by 4%-7% in SA + Basagran® treated leaves compared to control. The increased total antioxidant activity was related to the accumulation of amounts of phenolics as a protective action stimulated by SA. Alterations of antioxidant enzymatic system, accumulation of phenolics, increasing the total antioxidant activity by SA provide an evidence of protective action of SA in Basagran® detoxification.

The impact of intraoperative microbreaks with exercises on surgeons: A multi-center cohort study.

Recent literature has demonstrated ergonomic risk to surgeons in the operating room. One method used in other industries to mitigate these ergonomic risks is the incorporation of microbreaks. Thus, intraoperative microbreaks with exercises in a non-crossover design were studied. Fifty-six attending surgeons from 4 Medical Centers volunteered first in a day of their regular surgeries and then second day where there were microbreaks with exercises that could be performed in the sterile field, answering questions after each case, without significantly increasing the duration of their surgeries. Surgeons self-reported improvement or no change in their mental focus (88%) and physical performance (100%) for the surgical day incorporating microbreaks with exercises. Discomfort in the shoulders was significantly reduced while distractions and flow impact was minimal. Eighty-seven percent of the surgeons wanted to incorporate the microbreaks with exercises into their OR routine. Intraoperative microbreaks with exercises may be a way to mitigate work-related musculoskeletal fatigue, pain and injury.

Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial.

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less). Induction chemotherapy consisted of three courses of cisplatin 75 mg·m⁻² and pemetrexed 500 mg·m⁻². Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy (54 Gy, 30 fractions). Our primary end-point was "success of treatment" and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects' median age was 57 yrs. The subjects' TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3-4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6-32.9) and median progression-free survival was 13.9 months (95% CI 10.9-17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36-1.00). Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary.

Dietary sodium and Na,K-ATPase activity in Dahl salt-sensitive versus salt-resistant rats.

OBJECTIVE: To investigate the effects of high dietary sodium on brain and kidney Na,K-ATPase activity in Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats. METHODS: From the age of 4 weeks Dahl-S and Dahl-R rats were fed either standard or high-sodium diet (8% sodium chloride) for 3 weeks. The hydrolysis of [gamma-32P]-ATP in the absence or presence of various concentrations of ouabain was used to determine apparent Na,K-ATPase activity and its isoform composition. To assess whether reduced Na,K-ATPase activity and its isoform composition. To assess whether reduced Na,K-ATPase activity was caused by an endogenous inhibitor, brain and kidney microsomes were pre-incubated with antibody Fab fragments (Digibind). RESULTS: The high-sodium diet increased mean arterial pressure in the Dahl-S but not in the Dahl-R rats. Two binding sites (alpha 1 and alpha 2) in several areas of the brain and one binding site in the kidneys (alpha 1) were detected. The high-sodium diet reduced Na,K-ATPase activity in the hypothalamus of the Dahl-S but not of the Dahl-R rats, but did not cause changes in the brain cortex, pons or kidney. The Na,K-ATPase isoform composition in the brain cortex, hypothalamus and pons and kidney was not changed by the high-sodium diet. In the rats fed the standard-sodium diet, Digibind increased Na,K-ATPase activity only in the hypothalamus of the Dahl-S rats. In rats fed the high-sodium diet, Na,K-ATPase activity was increased by Digibind in the hypothalamus of both strains of rats, but by more in the Dahl-S rats. CONCLUSION: The present data indicate that a high-sodium diet inhibits hypothalamic Na,K-ATPase via increased binding of an inhibitor.

Blockade of the renin-angiotensin system at different sites: effect on renin, angiotensin and aldosterone.

INHIBITION OF RENIN-ANGIOTENSIN SYSTEM: It is now possible to effectively block the renin-angiotensin system at several steps by orally active inhibitors. Blockade of renin, the angiotensin coverting enzyme (ACE) or the angiotensin II (Ang II) type 1 (AT1) receptor leads to different hormonal changes. All three modes of blockade reduce aldosterone and all cause a reactive rise in plasma renin due to removal of angiotensin II tonic inhibition on renal renin release. ASSOCIATED CHANGES IN ANG I AND ANG II: AT1 blockade by losartan is followed by rises in plasma Ang I and Ang II; ACE inhibitors are associated with an increase in plasma Ang I but a fall in Ang II, whereas both plasma Ang I and Ang II fall with renin inhibition. DIFFERENCES IN MODE OF INHIBITION: Potential differences between the mode of blockade of the renin-angiotensin system include differences in the bioavailability of compounds, the effect of ACE on other peptide substrates, particularly bradykinin, the possibility of other actions or unknown substrates for renin and the presence of unblocked AT2 angiotensin receptors in the presence of high levels of Ang II. Whether these will result in clinically important differences remains to be determined.