Torsemide Versus Furosemide After Continuous Renal Replacement Therapy Due to Acute Renal Failure in Cardiac Surgery Patients

Acute renal failure (ARF) usually develops in 5% to 30% of patients undergoing heart surgery and is associated with a more complicated clinical evolution course and with an excessive mortality of up to 80%. The objective of this study was to verify the frequency of ARF in postoperative coronary artery bypass surgery with and without cardiopulmonary bypass, by the evaluation of renal function markers' performance [ plasma creatinine, plasma urea, urinalysis, fractional excretion of sodium, creatinine clearance and Alpha‐glutathione S‐transferase (α‐GST)], besides to verify possible relations between clinical variables involved in postoperative heart surgery and the occurrence of renal insufficiency.     

Glutathione S-transferase (GST) inhibitors

The glutathione S-transferases (GSTs; EC 2.5.1.18) comprise a family of widely distributed Phase II detoxication enzymes that catalyse the conjugation of a broad variety of reactive electrophiles to the nucleophilic sulfur atom of the major intracellular thiol, the tripeptide glutathione. The diverse functions, including catalytic GSH conjugation, passive ligandin-type binding and modulation of signal transduction, may be selectively targeted by different inhibitors. GST inhibitors are emerging as promising therapeautic agents for managing the development of resistance amongst anticancer agents. In diagnostic medicine, as well as in antiparasitic drug development, GST inhibitors are important lead molecules. In this review, the important molecules known for their GST inhibition together with potential therapeutic uses are summarised.     

Selenium and Chronic Diseases: A Nutritional Genomics Perspective

Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases. This review discusses the results from these genetic associations in the context of selenoprotein functions and epidemiological investigations and emphasises the need to assess in future studies the combined contribution of Se status, environmental stress, and multiple or individual SNPs to disease risk.     

Long‐term exogenous application of melatonin delays drought‐induced leaf senescence in apple

To examine the potential roles of melatonin in drought tolerance, we tested the effects of its long‐term exogenous application on ‘Hanfu’ apple (Malus domestica Borkh.). When 100 μm melatonin was added to soils under drought conditions, the resultant oxidative stress was eased and leaf senescence was delayed. This molecule significantly reduced chlorophyll degradation and suppressed the up‐regulation of senescence‐associated gene 12 (SAG12) and pheophorbide a oxygenase (PAO). Such treatment also alleviated the inhibition of photosynthesis brought on by drought stress. We also investigated quenching and the efficiency of Photosystem II (PSII) photochemistry under dark and light conditions and found that melatonin helped to maintain better function of PSII under drought. The addition of melatonin also controlled the burst of hydrogen peroxide, possibly through direct scavenging and by enhancing the activities of antioxidative enzymes and the capacity of the ascorbate–glutathione cycle. Thus, understanding this effect of melatonin on drought tolerance introduces new possibilities to use this compound for agricultural purposes.     

Therapeutic potential of new hydrogen sulfide-releasing hybrids

A new class of hydrogen sulfide (H₂S)-donating hybrids combined with pharmacologically active compounds is presented in this article. The pharmacological profiles of some hybrid lead compounds in the areas of inflammation, H₂S-donating diclofenac (ACS 15); cardiovascular, H₂S-donating aspirin (ACS 14); urology, H₂S-donating sildenafil (ACS 6); and neurodegenerative, H₂S-donating latanoprost (ACS 67) for glaucoma treatment and H₂S-donating levodopa (ACS 84) for Parkinson’s disease, are described. The new H₂S-releasing hybrids demonstrate remarkable improvement in activity and tolerability as compared with the related parent compounds, suggesting an active pharmacological role for H₂S. Finally the mechanism(s) of action of glutathione-dependent and independent, and of gas (H₂S) release (spontaneous or enzymatic) and its implications for clinical pharmacology perspectives will be also discussed.     

Vagal System Impairment in Human Immunodeficiency Virus-Positive Patients with Chronic Hepatitis C: Does Hepatic Glutathione Deficiency Have a Pathogenetic Role?

Background: Both an autonomic impairment and a systemic depletion of reduced glutathione (GSH) may be documented in patients with chronic liver diseases and in human immunodeficiency virus (HIV)-positive patients. Methods: The coefficients of electrocardiographic R-R interval variation (CVc) were assessed in 125 patients with chronic hepatitis C (CHC) (65 HIV-positive and 60 HIV-negative) and in 61 healthy controls. The CVc values were correlated with hepatic (H-GSH), plasmatic (P-GSH), lymphocyte (L-GSH), and erythrocyte (E-GSH) concentrations of GSH and with erythrocyte malonyldialdehyde (MDA) levels. Results: Compared with healthy controls, in CHC patients the concentrations of H-GSH, P-GSH, L-GSH, and E-GSH were reduced, whereas MDA levels were increased with a statistically significant difference (P < 0.001). CVc was significantly reduced in patients with CHC (especially in those who were HIV-positive) and correlated significantly with the values of H-GSH, P-GSH, L-GSH, E-GSH, and MDA (P < 0.001). Conclusions: A dysfunction of the cardiac vagal system may be detected in patients with CHC (especially in those who are HIV-positive); this abnormality may be related to a reduced response to oxidative stress because of a systemic depletion of GSH.     

Perineuronal nets protect fast-spiking interneurons against oxidative stress

A hallmark of schizophrenia pathophysiology is the dysfunction of cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements of these fast-spiking cells may render them susceptible to redox dysregulation and oxidative stress. Using mice carrying a genetic redox imbalance, we demonstrate that extracellular perineuronal nets, which constitute a specialized polyanionic matrix enwrapping most of these interneurons as they mature, play a critical role in the protection against oxidative stress. These nets limit the effect of genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between the robustness of the perineuronal nets around parvalbumin cells and the degree of intracellular oxidative stress they display. Enzymatic degradation of the perineuronal nets renders mature parvalbumin cells and fast rhythmic neuronal synchrony more susceptible to oxidative stress. In parallel, parvalbumin cells enwrapped with mature perineuronal nets are better protected than immature parvalbumin cells surrounded by less-condensed perineuronal nets. Although the perineuronal nets act as a protective shield, they are also themselves sensitive to excess oxidative stress. The protection might therefore reflect a balance between the oxidative burden on perineuronal net degradation and the capacity of the system to maintain the nets. Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia.     

Expression of muscarinic acetylcholine receptors in hepatocytes from rat fibrotic liver

The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3 ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated. Compared to the normal state, the expression levels of m1, 3, 5 in fibrotic liver tissues or hepatocytes were obviously increased, while m2, 4 decreased. 10 μM pilocarpine or 10 μM acetylcholine could increase the alanine aminotransferase (ALT), hydroxyproline (Hyp), collagen I, III in the hepatocytes, and decreased albumin (ALB). They also changed the expressions of mAchR similarly as the fibrotic hepatocytes and livers. However, atropine could ameliorate the state of fibrotic hepatocytes. These data indicate that mAchR played an important role in the regulation of hepatic fibrosis process. Targeting mAchR would have therapeutic potential for hepatic fibrosis.     

Low-level Irradiation

Purpose : To determine whether there is an association between dermal fibroblast differentiation characteristics in vitro and breast fibrosis developing in patients following radiotherapy for breast cancer. Materials and methods : Three hundred and eighty-five patients had been characterized for the degree of breast fibrosis and the level of clinical risk factors for fibrosis as established by logistic regression. Early-passage fibroblasts from 79 patients with a high (HR) or low (LR) level of risk factors were studied in vitro. The percentage differentiated cells (%DC) 7 days after 0 and 8 Gy was scored, and unirradiated colonies were scored for the ratio of early:late fibroblast differentiation stages (E:L ratio). Results : %DC: For the 0 Gy data there was a significant interpatient variation (CoV=55%, p=0.0001). HR patients with breast fibrosis had a higher %DC compared with patients without (p =0.017). E:L ratio: for HR patients there was a significant interpatient variation (82%, p =0.0030) and a lower E:L ratio for patients with fibrosis compared with those without (p =0.086), but for LR patients this relationship was reversed (p =0.079) Conclusions : There was a true interpatient variation in the in vitro parameters of fibroblast differentiation but insufficient correlation with observed fibrosis after radiotherapy for use as a predictive test.