Oxygen Free Radical Activity Research Articles

Effects of High-Intensity Anaerobic Exercise on the Scavenging Activity of Various Reactive Oxygen Species and Free Radicals in Athletes.

High-intensity exercise in athletes results in mainly the production of excess reactive oxygen species (ROS) in skeletal muscle, and thus athletes should maintain greater ROS scavenging activity in the body. We investigated the changes in six different ROS-scavenging activities in athletes following high-intensity anaerobic exercise. A 30-s Wingate exercise test as a form of high-intensity anaerobic exercise was completed by 10 male university track and field team members. Blood samples were collected before and after the exercise, and the ROS-scavenging activities (OH•, O2•−, 1O2, RO• and ROO•, and CH3•) were evaluated by the electron spin resonance (ESR) spin-trapping method. The anaerobic exercise significantly increased RO• and ROO• scavenging activities, and the total area of the radar chart in the ROS-scavenging activities increased 178% from that in pre-exercise. A significant correlation between the mean power of the anaerobic exercise and the 1O2 scavenging activity was revealed (r = 0.72, p < 0.05). The increase ratio in OH• scavenging activity after high-intensity exercise was significantly greater in the higher mean-power group compared to the lower mean-power group (n = 5, each). These results suggest that (i) the scavenging activities of some ROS are increased immediately after high-intensity anaerobic exercise, and (ii) an individual’s OH• scavenging activity responsiveness may be related to his anaerobic exercise performance. In addition, greater pre-exercise 1O2 scavenging activity might lead to the generation of higher mean power in high-intensity anaerobic exercise.

The effect of intrauterine resuscitation by maternal hyperoxygenation on perinatal and maternal outcome: a randomized controlled trial

Maternal hyperoxygenation is widely used during labor as an intrauterine resuscitation technique. However, robust evidence regarding its beneficial effect and potential side effects is scarce, and previous studies show conflicting results. To assess the effect of maternal hyperoxygenation upon suspected fetal distress during the second stage of term labor on fetal heart rate, neonatal outcome, maternal side effects, and mode of delivery. In a single-center randomized controlled trial in a tertiary hospital in The Netherlands, participants were randomized in case of an intermediary or abnormal fetal heart rate pattern during the second stage of term labor, to receive either conventional care or 100% oxygen at 10 L/min until delivery. The primary outcome was the change in fetal heart rate pattern. Prespecified secondary outcomes were Apgar score, umbilical cord blood gas analysis, neonatal intensive care unit admission, perinatal death, free oxygen radical activity, maternal side effects, and mode of delivery. We performed subgroup analyses for intermediary and abnormal fetal heart rate, and for small for gestational age fetuses. From March 2016 through April 2018, a total of 117 women were included. Fetal heart rate patterns could be analyzed in 71 women. Changes in fetal heart rate (defined as improvement, equal, or deterioration) in favor of maternal hyperoxygenation were significant (odds ratio, 5.7; 95% confidence interval, 1.7-19.1) using ordinal logistic regression. Apgar score, umbilical cord blood gas analysis, free oxygen radicals, and mode of delivery showed no significant differences between the intervention and control group. Among women with an abnormal fetal heart rate, there were fewer episiotomies on fetal indication in the intervention group (25%) than in the control group (65%, P< .01). Maternal hyperoxygenation has a positive effect on the fetal heart rate in the presence of suspected fetal distress during the second stage of labor. There was no significant difference in the mode of delivery or neonatal outcome; however, significantly fewer episiotomies on fetal indication were performed following maternal hyperoxygenation in the subgroup with abnormal fetal heart rate pattern.

Activity of enzymatic antioxidants in periodontitis: A systematic overview of the literature.

Periodontitis is initiated by a bacterial infection and an abnormal immune response of the host resulting in the formation of dysbiotic subgingival biofilm and the progressive destruction of the attachment apparatus of the teeth. It is believed that disturbances in the local and/or general indicators of oxidative stress are one of the mechanisms in the etiopathogenesis of periodontitis. Organisms using oxygen in their metabolic processes are equipped with mechanisms that protect against the activity of oxygen-free radicals. They are commonly referred to as 'the antioxidative barrier of the system'. The main enzymatic antioxidants which have been widely studied in the gingival fluid, saliva and blood serum of patients with periodontitis are superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The aim of this systematic overview of the literature was to present the current research on the activity of these antioxidant enzymes in the gingival fluid, saliva and blood serum of patients with periodontitis. Findings on the activity of these enzymes in the gingival tissue, gingival fluid, saliva, and blood serum in the course of the types of periodontitis that have been classified so far (chronic or aggressive) are quite disparate. Their activity in the gingival tissue was usually elevated, whereas in the saliva it was reduced. These differences may have resulted from the different methods of biochemically assessing their activity, and may have not reflected the stage and/or the risk of progression of periodontitis.

Zinc Deficiency Induces Oxidative Damage and Causes Spleen Fibrosis.

Zinc (Zn) is an essential trace element for animals. Zn controls the action of more than 300 enzymes and plays an important role in the regulation of gene expression. Evidence has shown that Zn has an antioxidant function, and oxidative damage can occur with Zn deficiency. To assess the effect of Zn deficiency-induced spleen fibrosis, Zn-deficient mice, normal mice, and high-Zn mice were generated and assessed. The Zn content of the spleen in each group was determined, and histopathological examination of the spleens of each group was performed. In the film, we found that the spleens of the Zn-deficient group had high levels of proteinaceous material exudation, interstitial broadening, and lymphocyte reduction, with increased collagen, α-SMA expression, antioxidants, and oxygen free radicals. Zn deficiency inhibited the expression of antioxidants in mice, and the activity of oxygen free radicals in Zn-deficient mice was increased. The detection of α-SMA, collagen 1, and TGF-β by fluorescence quantitative PCR revealed that the expression index increased in Zn-deficient mice. In addition, to verify the effect of Zn deficiency on the extracellular matrix (ECM) regulatory system, MMPs were determined by real-time PCR, and the expression in the Zn deficiency group was lower than that in the normal group and high-Zn group. The MMP-2 and MMP-13 analyses showed that the expression of the high-Zn group was significantly higher than that of the normal group, indicating that Zn plays an important role in its expression. The above experimental analysis showed that Zn deficiency induces oxygen free radical damage, which further leads to spleen fibrosis.

Dyslipidemic and Antioxidant activity ofPiper longumextract in hyperlipemic rats

The dyslipidemic and antioxidant activity of Piper longum extract has been studied in triton and high fat diet fed hyperlipemic rats. The extract lowered the serum lipids at (200 mg/kg, b.w., p.o.) in triton WR-1339 induced hyperlipidemia. Chronic feeding of this extract (100 mg/kg, b.w.) in animals simultaneously fed with high fat diet (HFD) for 30 days caused lowering of lipid and apoproteins level of lipoproteins in experimental animals. P. langum activates lipolytic enzymes in plasma and liver lipids. These extract increased faecal bile acid extraction and enhanced plasma lecithin: cholesterol acyltransferase activity. Piper langum extract showed potent inhibition of antioxidant and scavenger of oxygen free radical activity (in vitro) and it induced oxidative stress.

Extraction of Polyphenols from Porphyra and Scavenging Activity of Oxygen Free Radicals

Polyphenols from Porphyra are important biological active substances. The effects of temperature, times, ethanol concentration and liquid to solid ratio were studied for the extraction yield of polyphenols from Porphyra through a single-factor exploration.Then, through an orthogonal experiment, it was investigated to get the best extraction conditions. The content of polyphenols was determined by Folin-Ciocalteu method. Scavenging ability to oxygen free radicals was also assessed. The results show that extraction temperature is 75°C, the extraction time is 2.5 h, ethanol concentration is 70% and the ratio of liquid to solid is 25:1(mL/g).The proportion of the extraction of the polyphenols from Porphyra under these industrial process conditions is 6.263mg/g. Polyphenols from Porphyra have strong scavenging hydroxyl radical and superoxide anion radical. IC50 of polyphenols from Porphyra on hydroxyl radical and superoxide anion radical is 0.405 mg/mL, 0.539mg/mL, respectively.

Interactions of Hydroxyapatite with Proteins and Its Toxicological Effect to Zebrafish Embryos Development

The increased application of nanomaterials has raised the level of public concern regarding possible toxicities caused by exposure to nanostructures. The interactions of nanosized hydroxyapatite (HA) with cytochrome c and hemoglobin were investigated by zeta-potential, UV-vis, fluorescence and circular dichroism. The experimental results indicated that the interactions were formed via charge attraction and hydrogen bond and obeyed Langmuir adsorption isotherm. The two functional proteins bridged between HA particles to aggregate into the coralloid form, where change of the secondary structure of proteins occurred. From effects of nanosized HA, SiO2 and TiO2 particles on the zebrafish embryos development, they were adsorbed on the membrane surface confirmed by the electronic scanning microscopy. Nano-HA aggregated into the biggest particles around the membrane protein and then caused a little toxicity to development of zebrafish embryos. The SiO2 particles were distributed throughout the outer surface and caused jam of membrane passage, delay of the hatching time and axial malformation. Maybe owing to the oxygen free radical activity, TiO2 caused some serious deformity characters in the cardiovascular system.

Metabolic correction in the management of diabetic peripheral neuropathy: improving clinical results beyond symptom control.

Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyl-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metformin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of developing DPN and how metabolic correction can reduce these risks.

Alpha-Lipoic Acid and Diabetic Neuropathy

Diabetic neuropathy presents a major public health problem. It is defined by the symptoms and signs of peripheral nerve dysfunction in diabetic patients, in whom other causes of neuropathy have been excluded. Pathogenetic mechanisms that have been implicated in diabetic neuropathy are: a) increased flux through the polyol pathway, leading to accumulation of sorbitol, a reduction in myo-inositol, and an associated reduced Na+-K+-ATPase activity, and b) endoneurial microvascular damage and hypoxia due to nitric oxide inactivation by increased oxygen free radical activity. Alpha-lipoic acid seems to delay or reverse peripheral diabetic neuropathy through its multiple antioxidant properties. Treatment with alpha-lipoic acid increases reduced glutathione, an important endogenous antioxidant. In clinical trials, 600 mg alpha-lipoic acid has been shown to improve neuropathic deficits. This review focuses on the relationship of alpha-lipoic acid and auto-oxidative glycosylation. It discusses the impact of alpha-lipoic acid on hyperglycemia-induced oxidative stress, and examines the role of alpha-lipoic acid in preventing glycation process and nerve hypoxia.

Intrauterine resuscitation during labor: Should maternal oxygen administration be a first-line measure?

Intrauterine resuscitation techniques are often used during labor when the fetal heart rate pattern is nonreassuring. These techniques have not been well studied; common practices are based on classic studies many years old. Models of intrauterine resuscitation using one (or more) technique as a first-line intervention and adding others in a specific series or clinical algorithm based on fetal response have not been tested. Maternal oxygen therapy is often used; however, recent evidence suggests potential risks to the mother and fetus or newborn. Even small increases in maternal and fetal pO(2) as a result of maternal oxygen administration can produce oxygen free radical activity in mothers and fetuses. The potential long-term effects are unknown. Caution should be exercised when considering maternal oxygen administration as a first-line intrauterine resuscitation measure until more data are available, reserving its use after other measures have been unsuccessful in resolving the nonreassuring fetal heart rate pattern.

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

The early anti-oxidant effect of carvedilol predicts the clinical course in congestive heart failure patients

Carvedilol, a beta1 and beta2 as well as an alpha1 adrenoreceptor antagonist with multiple hemodynamic, anti-ischemic and anti-oxidant properties, is widely accepted for the treatment of hypertension and congestive heart failure (CHF). It has been shown to improve morbidity and mortality in CHF. To assess whether the anti-oxidant effect of carvedilol has an impact on the clinical course in post-myocardial infarction (MI) CHF. Thirty-nine recent MI patients, aged 60.5 +/- 7 years, New York Heart Association functional class (FC) II-III, and left ventricular ejection fraction (LVEF) 29 +/- 3.8%, underwent oxygen free radical (OFR) assessment using the thiobarbituric acid reactive substances, thermochemoluminescence and conjugated dienes methods. OFR was determined at baseline, 1, 3, 12, and 24 h after 3.125, 6.25 and 12.5 mg carvedilol, and after 6 months of treatment. Brain natriuretic peptide (BNP), LVEF, FC change, 6-min walk test (6MW) and quality of life scores were evaluated before and after 6 months. Two patterns of OFR activity were found. In 29 patients (group 1) a significant and consistent reduction in OFR following administration of each dose of carvedilol was found, significantly correlating with each of the outcome parameters. In ten patients (group 2), no change in OFR was found, nor in any of the other outcomes. At 6 months, FC improved in 23 patients from group 1 (79.3%) and only in one (10%) from group 2 (P<0.01). 6MW increased by more than 10% in group 1 with no change in group 2 (P<0.05). BNP decreased from 397 +/- 36 pg/ml to 171 +/- 15.9 pg/ml (P<0.01) in group 1 compared to 381 +/- 32.5 pg/ml and 405 +/- 36 pg/ml, respectively (P=not significant) in group 2. One year hospital admissions and death rate were significantly higher in group 2. The early anti-oxidative effect of carvedilol correlates well with the clinical course and probably predicts it.

Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps

Neutrophil depletion has a beneficial effect on ischemic myocardium and skeletal muscle upon reperfusion. Antineoplastic agents reduce blood neutrophils effectively, and lead to neutrophil depletion. The purpose of this study was to investigate the effects of four antineoplastic agents in low doses (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) on ischemia-reperfusion injury, using an epigastric island skin-flap model in rats. Fifty male Sprague-Dawley rats, weighing 250-300 g, were randomly divided into five groups, each consisting of 10 rats: control, cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil groups. Epigastric island skin flaps (measuring 3.5 x 4 cm) were raised and subjected to 10 h of in situ ischemia, followed by 7-day reperfusion and evaluation. Treatment with antineoplastic agents (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) was used to introduce neutropenia. Complete blood counts, cutaneous bleeding time, and skin-flap survival were evaluated. Additionally, levels of malonyldialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured from extracted skin tissue. Numbers of leukocytes and platelets were decreased in all experimental groups. However, neutropenia and thrombocytopenia were not seen. Cutaneous bleeding activity was prolonged in all experimental groups, but not above the normal value. MDA and NO levels were found to be lower in all four antineoplastic agent groups than in the control group, while GSH, GSH-Px, and SOD enzyme activities were significantly higher (P < 0.05). However, MDA and NO levels were significantly decreased in the cyclophosphamide and 5-fluorouracil groups, as compared to the cisplatinum and mitomycin-C groups (P < 0.01). Also, GSH, GSH-Px, and SOD enzyme activities were significantly increased in the cyclophosphamide and 5-fluorouracil groups, compared to the other two antineoplastic agent groups (P < 0.01). We conclude that antineoplastic agents have beneficial effects on ischemia-reperfusion injuries when their doses are carefully adjusted, by decreasing the number of leukocytes and platelets, and altering the activity of free oxygen radicals.

Free radical inhibition and serial chemiluminescence in evolving experimental pancreatitis

Oxygen free radical activity and inhibition were examined in experimental pancreatitis. Twenty-five rats were randomized to five groups: controls received intravenous saline, to simulate pancreatitis one group received intravenous caerulein (5 micrograms kg-1 h-1), and three groups received sodium taurocholate via the pancreatic duct (0.2 ml, 5 per cent), either alone, following allopurinol or immediately before superoxide dismutase. Chemiluminescence (a phenomenon based on the emission of light during chemical reactions and which is dependent on oxygen free radical activity) was used as an index of oxygen free radical activity and was measured in tissue samples at 5-min intervals following induction of pancreatitis. The control mean(s.e.m.) serum amylase level 1 h after induction of pancreatitis was 635(13) units. It was significantly elevated in caerulein-induced pancreatitis, 1833(118) units (P less than 0.05) and exceeded 3000 units in all taurocholate-infused animals. Mean(s.e.m.) chemiluminescence ranged from 44 (8) mV 100 mg-1 at time zero to 404(113) mV 100 mg-1 at 1 h in controls. In caerulein-induced pancreatitis mean(s.e.m.) chemiluminescence peaked at 20 min (1399(239) mV 100 mg-1, P less than 0.02) and in taurocholate-induced pancreatitis at 15 min (2316(95) mV 100 mg-1, P less than 0.004). Superoxide dismutase significantly reduced chemiluminescence and hyperamylasaemia in taurocholate groups. Increasing oxygen free radical activity paralleled evolving pancreatitis. Superoxide dismutase may have a therapeutic role in pancreatitis.

Oxygen free radical activity in experimental colonic carcinoma.

Oxygen free radical activity has been implicated in carcinogenesis through DNA lysis. This study measured chemiluminescence and superoxide dismutase (SOD) inhibition as an index of oxygen free radical activity in azoxymethane-induced colonic carcinoma. After 3 weeks of acclimatization, ten Fisher 344 rats were injected with azoxymethane (7 mg kg-1 week-1) over 10 weeks. All animals were killed at 37 weeks and colonic mucosa (5-25 mg wet weight) was sampled from sites of histologically confirmed gross tumour and sites 3-5 cm distant from tumour as well as from ten paired normal controls. The samples were processed in buffered luminol and chemiluminescence was measured in a luminometer. Each sample was then placed in a solution of SOD for 3 min before a second chemiluminescence estimation. Mean(s.e.m.) chemiluminescence from control mucosal samples decreased from 8.1(1.0) to 3.9(1.1) mV per 100 mg tissue (P < 0.05) after incubation in SOD, suggesting that oxygen free radical activity was being measured. There was an increase to 20.2(0.9) mV per 100 mg in azoxymethane-treated colon remote from tumour and to 53.9(2.1) mV per 100 mg at tumour sites; both were reduced significantly after incubation with SOD to 6.7(0.7) and 11.0(0.8) mV per 100 mg respectively (P < 0.001). Chemiluminescence was significantly increased in azoxymethane-induced colonic carcinoma, both remote from and maximally at the tumour site, suggesting a field change in carcinogenesis associated with oxygen free radical activity.

EFFECTS OF MANGANESE SUPEROXIDE DISMUTASE NEBULIZATION ON PULMONARY FUNCTION IN AN OVINE MODEL OF ACUTE LUNG INJURY

Smoke inhalation injury is a major cause of morbidity and mortality in thermally injured individuals. There is evidence of increased oxygen free radical activity, e.g., superoxide, in association with smoke inhalation injury. Because superoxide dismutase converts the reactive superoxide radical to peroxide, we hypothesized that nebulization of manganese superoxide dismutase (Mn-SOD) into the airway might attenuate pulmonary dysfunction secondary to smoke inhalation injury. The present study was designed as a prospective, controlled, and randomized laboratory experiment to determine the effects of aerosolized Mn-SOD on lung fluid balance, as indexed by changes in pulmonary microvascular permeability, lung lymph flow (Q(L)), and gas exchange in an established and clinically relevant ovine model of smoke inhalation injury. Fifteen female Merino sheep were chronically instrumented with a femoral arterial, a Swan-Ganz, and a left atrial catheter. In addition, the right caudal mediastinal lymph node was cannulated to measure Q(L) (mL.h(-1)). Pneumatic occluders were placed around the right pulmonary veins for the determination of the reflection coefficient (sigma). After 7 days of recovery, sheep were randomly allocated to (a) an untreated control group (4 groups of 12 breaths of cotton smoke), (b) an injured group treated with nebulized Mn-SOD (5 mg/kg), and (c) an injured group that received only the vehicle (nebulized saline). Nebulization was performed 1 h and 12 h after smoke inhalation. Mn-SOD nebulization attenuated the increase in both filtration coefficient and sigma and significantly decreased lung tissue conjugated dienes. However, there were no differences in Q(L), PaO2/FiO2 ratio, and bloodless lung wet/dry weight ratio between groups. Although Mn-SOD nebulization attenuated the loss of protein, it failed to improve lung edema and pulmonary gas exchange, thereby limiting its clinical use.

Thioctic Acid for Patients with Symptomatic Diabetic Polyneuropathy

Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of life. Near-normoglycemia is now generally accepted as the primary approach to prevention of diabetic neuropathy, but is not achievable in a considerable number of patients. A growing body of evidence suggests that oxidative stress resulting from enhanced free-radical formation and/or defects in antioxidant defense is implicated in the pathogenesis of diabetic neuropathy. Markers of oxidative stress such as superoxide anion and peroxynitrite production are increased in diabetic patients in relation to the severity of polyneuropathy. In experimental diabetic neuropathy, oxygen free-radical activity in the sciatic nerve is increased, and treatment with thioctic acid, a potent lipophilic antioxidant, results in prevention or improvement of the diabetes-induced neurovascular and metabolic abnormalities in various organ systems. Pharmacodynamic studies have shown that thioctic acid favorably influences the vascular abnormalities of diabetic polyneuropathy such as impaired microcirculation, increased indices of oxidative stress, and increased levels of markers for vascular dysfunction, such as thrombomodulin, albuminuria, and nuclear factor-kappaB. Thus far, seven controlled randomized clinical trials of thioctic acid in patients with diabetic neuropathy have been completed (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN I-III], Deutsche Kardiale Autonome Neuropathie [DEKAN], Oral Pilot [ORPIL], Symptomatic Diabetic Neuropathy [SYDNEY], Neurological Assessment of Thioctic Acid in Neuropathy [NATHAN] II) using different study designs, durations of treatment, doses, sample sizes, and patient populations. Recently, a comprehensive analysis was undertaken of trials with comparable designs that met specific eligibility criteria for a meta-analysis to obtain a more precise estimate of the efficacy and safety of thioctic acid (600mg intravenously for 3 weeks) in diabetic patients with symptomatic polyneuropathy. This meta-analysis included the largest sample of diabetic patients (n = 1258) ever to have been treated with a single drug or class of drugs to reduce neuropathic symptoms, and confirmed the favorable effects of thioctic acid based on the highest level of evidence (Class Ia: evidence from meta-analyses of randomized, controlled trials). The following conclusions can be drawn from these trials: (i) short-term treatment for 3 weeks using intravenous thioctic acid 600 mg/day reduces the chief symptoms of diabetic polyneuropathy to a clinically meaningful degree; (ii) this effect on neuropathic symptoms is accompanied by an improvement of neuropathic deficits, suggesting potential for the drug to favorably influence underlying neuropathy; (iii) oral treatment for 4-7 months tends to reduce neuropathic deficits and improve cardiac autonomic neuropathy; and (iv) clinical and postmarketing surveillance studies have revealed a highly favorable safety profile of the drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with thioctic acid (NATHAN I) is being conducted in North America and Europe to investigate effects on progression of diabetic polyneuropathy, using a clinically meaningful and reliable primary outcome measure that combines clinical and neurophysiological assessment.

Lead, renal disease and hypertension

Lead, renal disease and hypertension

Effects of high inspired oxygen fraction during elective Caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation

Oxygen supplementation is given routinely to parturients undergoing Caesarean section under regional anaesthesia. While the aim is to improve fetal oxygenation, inspiring a high oxygen fraction (FIO2) can also increase free radical activity and lipid peroxidation in both the mother and baby. In this prospective, randomized, double-blind study, we investigated the effect of high inspired oxygen fraction (FIO2) on maternal and fetal oxygenation and oxygen free radical activity in parturients having Caesarean section under spinal anaesthesia. Forty-four healthy parturients were randomized to breathe either 21% (air group) or 60% oxygen (oxygen group) intraoperatively via a ventimask. Maternal arterial blood was collected at 5-min intervals from baseline until delivery, and umbilical arterial and venous blood was collected at delivery. We measured blood gases and the products of lipid peroxidation (8-isoprostane, malondialdehyde (MDA), hydroperoxide (OHP)) and purine metabolites. At delivery, the oxygen group had greater maternal arterial PO2 [mean 30.0 (SD 6.3) vs 14.2 (1.9) kPa; mean difference 15.8 kPa, 95% confidence interval 12.9-18.7 kPa, P<0.001] and greater umbilical venous PO2 [4.8 (1.0) vs 4.0 (1.4) kPa; mean difference 0.8 kPa, 95% confidence interval 0.0-1.5 kPa, P=0.04] compared with the air group. Maternal and umbilical plasma concentrations of lipid peroxides (8-isoprostane, MDA, OHP) were greater in the oxygen group than in the air group (P<0.05). We conclude that breathing high FIO2 modestly increased fetal oxygenation but caused a concomitant increase in oxygen free radical activity in both mother and fetus.

DNA damage of lymphocytes in experimental chronic renal failure: Beneficial effects of losartan

Kidney diseases are associated with the accumulation of various uremic toxins increasing the oxygen free radical (OFR) activity with a number of serious consequences. One of them could be the impairment of DNA stability with the increased formation of DNA breaks. The study was performed in 4/6 kidney ablation rat nephropathy lasting for three months. The results of sham-operated (Sham), remnant kidney (Nx), and Nx treated by losartan (NxL) were compared. Nx significantly increased blood pressure, plasma creatinine, urea, hippurate, malondialdehyde (MDA), lipofuscin (LF), and the number of DNA breaks of lymphocytes. Losartan decreased the rise of blood pressure and inhibited the rise of creatinine plasma concentration but not of other variables, while it markedly inhibited the number of DNA breaks (Sham 15.9 +/- 1.1, Nx 54.5 +/- 1.7, P < 0.001; Nx/Sham, NxL 23.3 +/- 2.6 P < 0.001, NxL/Sham and P < 0.001 NxL/Nx). The 4/6 kidney ablation nephropathy increases the susceptibility of lymphocyte DNA to breaks, and losartan inhibits the number of breaks by a mechanism independent on glomerular filtration, accumulation of MDA or LF (markers of oxidative stress), and hippurate (marker of the accumulation of middle molecular substances). An independent mechanism, probably the interference with proliferation, is suggested.