Role Of Oxygen Free Radicals Research Articles

Study on the influence of active oxygen on the natural oxidation of arsenopyrite under different temperature conditions

Arsenic (As), a toxic element, contaminates farmlands, rivers, and groundwater, posing severe environmental and health risks. Notably, As-containing materials in tailings are affected by temperature variations during long-term storage, and this considerably impact the oxidation and migration of elements in arsenopyrite.This study focused on arsenopyrite and investigated the process of its oxidative dissolution and release of arsenic under different temperature conditions by using in-situ XRD, in-situ XPS and electron paramagnetic resonance spectroscopy(EPR), The role of oxygen free radicals in the oxidation of arsenopyrite was elucidated. It has been established that under high-temperature conditions As, iron (Fe), and sulfur (S) are primarily present As(V)/As(IV), Fe(III), and SO42−, respectively. The O2⋅− generated during the oxidation of As(III) by O2, OH⋅ produced by the Fe(II)/FeOH2+ reaction, and H2O2 formed via their interaction play a crucial role in the photochemical oxidation of arsenopyrite. These findings provide a theoretical basis for the formation of ferric arsenate precipitation, contributing in the adsorption and immobilisation of oxidatively released arsenic.

Synergistic toxicity of NiO nanoparticles and benzo[a]pyrene co-exposure in liver cells: Role of free oxygen radicals induced oxidative stress

Current attention has been given on health effects of combined exposure of nanoscale materials and organic pollutants. Nickel (II) oxide nanoparticles (NiO NPs) displays exceptional properties and is being used in various areas such as batteries, diesel–fuel additives, and biomedicals. Benzo[a]pyrene (BaP) is a ubiquitous pollutant. Cigarette smoke, diesel exhaust, and grilled foods are main sources of BaP exposure. Therefore, combined exposure of NiO NPs and BaP to humans is unavoidable. There is a dearth of knowledge on combined effects of NiO NPs and BaP in humans. This study was aimed to investigate co-exposure effects of NiO NPs and BaP in human liver cells (HepG2) and primary rat hepatocytes. We observed that individual and co-exposure of NiO NPs and BaP induced cytotoxicity, lactate dehydrogenase leakage, lipid peroxidation, depletion of mitochondrial membrane potential, and activation of caspases (-3 and -9) in both types of cells. Individual and co-exposure of NiO NPs and BaP further accelerated the generation of free oxygen radicals (reactive oxygen species and hydrogen peroxide) and depletion of antioxidants (glutathione and various antioxidant enzymes). Remarkably, NiO NPs and BaP exerted synergistic toxicity to both HepG2 cells and primary rat hepatocytes. Moreover, combined toxicity of NiO NPs and BaP in both cells was mediated through free oxygen radicals induced oxidative stress. This work warrants further research on risk assessment of co-exposure effects NiO NPs and BaP in an appropriate in vivo model.

Reaktif Hiperplazi ve Rekürrent Tonsillitlerde Lusigenin - Serbest Oksijen Radikallerinin Karşılaştırılması

Aim and Background: Today, tonsillectomy (T) used for chronic tonsillitis is among the most common surgery type that ear, nose, and throat physicians perform. The differences in the pathogenesis of chronic tonsillitis and tonsil hypertrophy are still unknown. This study aimed to compare the levels of free oxygen radicals in patients with tonsil hypertrophy and chronic tonsillitis and to investigate the role of free oxygen radicals in the pathogenesis of chronic tonsillitis.Materials and Method: The study included 40 patients who had chronic tonsillitis indications based on Paradise criteria, and T was performed. Operation materials were histopathologically examined, and their free oxygen radicals (FOR) levels were measured. Results: Based on the histopathological results, the participants were divided into two groups: one including 28 (70%) patients who had active or chronic tonsillitis, the other including 12 (30%) patients with reactive follicular hyperplasia. Lucigenin - free oxygen radicals (Luc-FOR) levels of the group with chronic tonsillitis and that of the group with reactive follicular hyperplasia were 82.29±32.3 Auc and 50.76±7.95 Auc, respectively. Luc-FOR values were found to be significantly higher in the group with chronic tonsillitis (p=0.001). Conclusion: Free oxygen radicals play an essential role in tonsillar pathologies. Differences in the Luc-FOR levels measured from tonsillar tissue in patients with tonsil hypertrophy and chronic tonsillitis demonstrate that the pathogenesis of these two diseases is different.

The Role of Free Oxygen Radicals in Lasting Hyperexcitability of Rat Subicular Neurons After Exposure to General Anesthesia During Brain Development.

A large number of preclinical studies have established that general anesthetics (GAs) may cause neurodevelopmental toxicity in rodents and nonhuman primates, which is followed by long-term cognitive deficits. The subiculum, the main output structure of hippocampal formation, is one of the brain regions most sensitive to exposure to GAs at the peak of synaptogenesis (i.e., postnatal day (PND) 7). We have previously shown that subicular neurons exposed to GAs produce excessive amounts of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), which is a known modulator of neuronal excitability. To further explore the association between GA-mediated increase in ROS levels and long-term functional changes within subicular neurons, we sought to investigate the effects of ROS on excitability of these neurons using patch-clamp electrophysiology in acute rat brain slices. We hypothesized that both acute application of H2O2 and an early exposure (at PND 7) to GA consisting of midazolam (9mg/kg), 70% nitrous oxide, and 0.75% isoflurane can affect excitability of subicular neurons and that superoxide dismutase and catalase mimetic, EUK-134, may reverse GA-mediated hyperexcitability in the subiculum. Our results using whole-cell recordings demonstrate that acute application of H2O2 has bidirectional effects on neuronal excitability: lower concentrations (0.001%, 0.3mM) cause an excitatory effect, whereas higher concentrations (0.01%, 3mM) inhibited neuronal firing. Furthermore, 0.3mM H2O2 increased the average action potential frequency of subicular neurons by almost twofold, as assessed using cell-attach configuration. Finally, we found that preemptive in vivo administration of EUK-134 reduced GA-induced long-lasting hyperexcitability of subicular neurons ex vivo when studied in neonatal and juvenile rats. This finding suggests that the increase in ROS after GA exposure may play an important role in regulating neuronal excitability, thus making it an attractive therapeutic target for GA-induced neurotoxicity in neonates.

Aedes aegypti HPX8C modulates immune responses against viral infection.

Mosquitoes act as vectors of numerous pathogens that cause human diseases. Dengue virus (DENV) transmitted by mosquito, Aedes aegypti, is responsible for dengue fever epidemics worldwide with a serious impact on human health. Currently, disease control mainly relies on vector targeted intervention strategies. Therefore, it is imperative to understand the molecular mechanisms underlying the innate immune response of mosquitoes against pathogens. In the present study, the expression profiles of immunity-related genes in the midgut responding to DENV infection by feeding were analyzed by transcriptome and quantitative real-time PCR. The level of Antimicrobial peptides (AMPs) increased seven days post-infection (d.p.i.), which could be induced by the Toll immune pathway. The expression of reactive oxygen species (ROS) genes, including antioxidant genes, such as HPX7, HPX8A, HPX8B, HPX8C were induced at one d.p.i. and peaked again at ten d.p.i. in the midgut. Interestingly, down-regulation of the antioxidant gene HPX8C by RNA interference led to reduction in the virus titer in the mosquito, probably due to the elevated levels of ROS. Application of a ROS inhibitor and scavenger molecules further established the role of oxygen free radicals in the modulation of the immune response to DENV infection. Overall, our comparative transcriptome analyses provide valuable information about the regulation of immunity related genes in the transmission vector in response to DENV infection. It further allows us to identify novel molecular mechanisms underlying the host-virus interaction, which might aid in the development of novel strategies to control mosquito-borne diseases.

Advances in prevention and treatment of traditional Chinese medicine in myocardial injury after coronary heart disease surgery

Percutaneous coronary artery intervention(PCI)is an important method for revascularization in patients with coronary heart disease(CHD), however the clinical observation showed that postoperative PCI often appeared slow blood flow, reperfusion arrhythmia, or no reflux. Therefore, reducing myocardial injury after PCI is the key to improve the prognosis of patients with coronary heart disease after PCI. Studies have shown that Chinese medicine could restrain the role of oxygen free radicals, reduce the overload of intracellular Ca2+ , improve the energy metabolism of myocardial cells, repair microvascular injury, recover the patient's body function, and provide protection for myocardial injury after PCI surgery through multi-targets and multi-levels. Key words: Percutaneous coronary intervention; Postoperative complications; Myocardial ischemia; Traditional Chinese medicine; Review

Role of Oxygen Free Radicals, Nitric Oxide and Mitochondria in Mediating Cardiac Alterations During Liver Cirrhosis Induced by Thioacetamide

Thioacetamide (TAA) administration is widely used for induction of liver cirrhosis in rats, where reactive oxygen radicals (ROS) and nitric oxide (NO) participate in development of liver damage. Cardiac dysfunction is an important complication of liver cirrhosis, but the role of ROS or NO in cardiac abnormalities during liver cirrhosis is not well understood. This was investigated in animals after TAA-induced liver cirrhosis and temporal changes in oxidative stress, NO and mitochondrial function in the heart evaluated. TAA induced elevation in cardiac levels of nitrate before development of frank liver cirrhosis, without gross histological alterations. This was accompanied by an early induction of P38 MAP kinase, which is influenced by ROS and plays an important signaling role for induction of iNOS. Increased nitrotyrosine, protein oxidation and lipid peroxidation in the heart and cardiac mitochondria, suggestive of oxidative stress, also preceded frank liver cirrhosis. However, compromised cardiac mitochondrial function with a decrease in respiratory control ratio and increased mitochondrial swelling was seen later, when cirrhosis was evident. In conclusion, TAA induces elevations in ROS and NO in the heart in parallel to early liver damage. This leads to later development of functional deficits in cardiac mitochondria after development of liver cirrhosis.

Malondialdehyde and SOD-induced changes of gastric tissues in acute gastric mucosal injury under positive acceleration.

The aim of this study was to investigate the impacts of positive acceleration (+Gz) on the gastric mucosal tissues in cases of acute gastric mucosal injury and to explore the role of oxygen free radicals. Thirty Sprague Dawley rats were randomly divided into the absolute ethanol control group (A group), absolute ethanol +5Gz group (B group), absolute ethanol +10Gz group (C group). Following centrifugation, the gastric tissues of each group were studied for the presence of gastric mucosal injuries and morphological changes. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) contents were simultaneously investigated. Degree of gastric mucosal injuries were as follows: C group (visually 49.080 ± 10.254, under light microscopy 9.400 ± 2.011) > B group (visually 23.654 ± 9.678, under light microscopy 5.000 ± 1.054) > A group (visually 11.410 ± 3.742, under light microscopy 3.800 ± 1.399). The gastric mucosal MDA content (0.376 ± 0.084 vs 0.235 ± 0.044) was significantly higher in the C group than in the A group, whereas the SOD content (8.852 ± 1.001 vs 10.694 ± 0.965) was lower than that in the A group. However, the MDA and SOD contents did not change much in the B group. Our results suggest that the +Gz exposure might aggravate the acute gastric mucosal injury, and changes in MDA and SOD contents in the gastric tissues indicated that the oxygen free radicals play an important role in this regard.

Pathophysiology of Oxidative Stress and Antioxidant Therapy in Acute Pancreatitis

Acute pancreatitis is an inflammatory disease of pancreas with varied clinical presentation ranging from mild self limiting disease to severe necrotising pancreatitis with high mortality. The exact pathogenesis of the disease is unclear despite extensive research. Recent studies have shown the role of oxidative stress in the pathogenesis of the disease. Many experimental studies have proven the role of oxygen free radicals in the initiation and progression of the disease. Antioxidant therapy has shown promising results in experimental animal models, whereas conflicting result has been seen in clinical studies in humans. This may suggest existence of different pathogenetic mechanism in humans. This review gives an overview of the role of oxidative stress in the pathophysiology of acute pancreatitis and outcomes of antioxidant therapy as a therapeutic agent in the treatment of acute pancreatitis.

A pulse radiolysis study of hyperoside isolated from Hypericum mysorense

The recent growth in knowledge of free radicals in biology is producing a medical revolution that promises a new age in health and disease management. In the last two decades there has been an explosive interest in the role of oxygen free radicals, more generally known as “reactive oxygen species” and of “reactive nitrogen species” in experimental and clinical medicine. The flowering top extract of Hypericum mysorense possessing potent anti-oxidant activity was subjected to bio-active guided isolation. Pulse radiolysis technique was used to determine the transient spectrum and rate constant for the one-electron oxidation of hyperoside by OH, N3, NO2, NO, CCl3OO radicals in aqueous solution. Three compounds were isolated and characterized as rutin, quercetin-3-O-galactoside (hyperoside) and quercetin from spectral analysis. The hyperoside radical showed pKa1 and pKa2 at 5.4 and 9.2. Both, Cu(II) and iron(II) ions form chelate with hyperoside. The Cu–hyperoside chelate was able to scavenge O2−, k=7.0(±0.3)×106 dm3 mol−1 s−1 at pH 9. The repair rates for tryptophan and guanosine radicals by hyperoside were also determined. The reduction potential of hyperoside radical was determined by cyclic voltammetric and pulse radiolysis methods.

Study of oxidative stress in different clinical severities of acne vulgaris

BackgroundAcne vulgaris is a multifactorial disease, but recent studies have focused on the role of oxygen free radicals and antioxidant enzymes. Malondialdehyde (MDA) is the end product of lipid peroxidation and is a good marker of free radical-mediated damage and oxidative stress. Superoxide dismutase (SOD) represents the major cellular defense against superoxide anions.ObjectiveThe objective of this study was to study the role of oxidative stress in acne vulgaris and to detect a possible link with the different clinical severities.Patients and methodsFifty patients with acne vulgaris and 20 healthy controls were included in this study. The severity of the disease was assessed using the Global Acne Grading System. The levels of SOD in erythrocytes and MDA in plasma were measured using a spectrophotometer.ResultsAlthough higher SOD levels and mean values were present in patients, there was no statistically significant difference compared with the controls. MDA levels showed a significant difference between patients and controls (P < 0.05), with MDA being higher in patients, indicating a condition of oxidative stress that had resulted from a high level of lipid peroxidation in acne patients. Comparison of SOD levels in patients showed that patients with severe acne had the lowest levels in comparison with patients with mild and moderate acne (P < 0.001). SOD levels were the highest in patients with mild acne. In terms of MDA levels, patients with severe acne showed the highest plasma MDA levels compared with those with mild and moderate (P < 0.05) acne, suggesting an increase in reactive oxygen species production overwhelming the antioxidant capacity. The lowest MDA levels were observed in mild acne.ConclusionOxidative stress may play a role in the etiopathogenesis of acne and⁄or the progression of the disease. Coadministration of antioxidant drugs with various lines of treatment of acne might be helpful, especially for those with inflammatory lesions.

Serum and salivary levels of albumin as diagnostic tools for oral pre-malignancy and oral malignancy

The role of oxygen free radicals in the initiation, promotion and progression of carcinogenesis and the protective role of antioxidants has been a subject of much speculation. There are few studies that report evaluation of serum albumin and only one study in which salivary albumin was found and only one study that reports of salivary albumin in oral Leukoplakia and Oral Squamous Cell Carcinoma (OSCC). We evaluated serum and salivary albumin levels in normal individuals, patients with oral pre-malignancy and patients with oral malignancy, and we compared serum and salivary albumin levels in patients with oral pre-malignancy and oral malignancy. Our study comprised 45 subjects separated into three groups of 15: normal healthy, oral pre-malignancy and oral malignancy patients. Venous blood was drawn and unstimulated saliva was collected early in the morning. Albumin levels were estimated using the bromocresol green method. Serum albumin levels decreased in oral pre-malignancy and oral malignancy cases compared to healthy individuals. Salivary albumin levels increased in oral pre-malignancy and oral malignancy cases compared to healthy individuals. Our results suggest that albumin may play a role in early diagnosis and prognosis of oral pre-malignant and oral malignant tissues.

Role of oxygen free radicals in the proliferation of myofibroblasts induced by AngII

Previous studies have demonstrated the important role of angiotension II (AngII) in promoting proliferation of myofibroblasts (myoFbs) and myocardial fibrosis. However, the underlying mechanisms and the role of oxygen free radicals in the proliferation of myofibroblasts induced by AngII are unclear. The present study was designed to shed light on this issue through exploration of AngII signaling pathways via in vitro experiments. Primary cultures of neonatal rat myoFbs were divided into five groups which were treated with AngII (10−8 to 10−6M), AngII with the antioxidant N-acetyl-L-cysteine (NAC), or normal culture medium. We observed the proliferation of myoFbs as induced by AngII at different concentrations with MTT. Reactive oxygen species (ROS) levels in myoFbs were detected by monitoring the fluorescence of 2′,7′-dichlorofluorescein. The contents and levels of oxygen free radicals (OH) in the three groups were detected by spectrophotometer, immunocytochemical staining, and confocal fluorescence. Western blot and image analysis were used to measure membrane translocation and expression of phospho-protein kinase Cα. MyoFbs incubated with AngII (10−8 to 10−6M) for 24h increased their rate of proliferation, the content of OH, and expression of ROS (P<0.01 vs. control group), whereas these parameters decreased in the presence of NAC. Immunocytochemistry, confocal fluorescence staining and image analysis showed that AngII could promote the translocation and expression of p-PKCα in membrane, and the antioxidant NAC blocked this increase (P<0.01). Western blot results also showed that NAC could inhibit the expression of p-PKCα.

Levels of MDA and SOD in acute gastric mucosal injury in rats exposed to positive acceleration

AIM: To determine the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in acute gastric mucosal injury in rats exposed to positive acceleration (+Gz), observe the impact of +Gz exposure on gastric mucosal injury, and clarify the role of oxygen free radicals in this process.METHODS: Thirty male SD rats were randomly divided into three groups: A (ethanol), B (ethanol with +5Gz exposure), and C (ethanol with +10Gz exposure). All rats were intragastrically given ethanol (0.4 mL/100 mg) after 24 h of fasting and water deprivation for 12 h. One hour after ethanol administration, group A did not undergo +Gz, while groups B and C were continuously exposed to +5Gz and +10Gz for 3 minutes, respectively. Immediately after +Gz exposure, gastric tissue samples were taken to observe gastric mucosal injury by light microscopy. The indexes of gastric mucosal injury were calculated, and the contents of MDA and SOD in the gastric mucosa were determined by ELISA. RESULTS: Gastric mucosal injury was observed in all the groups, and gastric mucosal injury was most severe in group C, followed by groups B and A. Group A had mildest gastric mucosal injury. Group B showed visible gastric mucosal congestion, edema and scattered bleeding spots, and light microscopy revealed acute inflammatory cell infiltration. The indexes of gastric mucosal injury were significantly higher in group B than in group A (naked eye: 23.654 ± 9.678 vs 11.410 ± 3.742; light microscopy: 5.000 ± 1.054 vs 3.800 ± 1.399; both P 0.05). Group C had heaviest gastric mucosal injury. Diffuse gastric mucosal congestion, edema, erosion and many bleeding spots were visible, and light microscopy revealed disorderly arranged gland structure, interstitial congestion, erosion, and acute inflammatory cell infiltration. The indexes of gastric mucosal injury were significantly higher in group C than in groups A and B (naked eye: 49.080 ± 10.254, light microscopy: 9.400 ± 2.011; all P 0.05). Compared with group A, the content of MDA in the gastric mucosa did not rise significantly in group B (0.255 ± 0.074 vs 0.235 ± 0.044, P 0.05); however, MDA content in group C (0.376 ± 0.084) was significantly higher than those in groups A and B (both P 0.05). The content of SOD in the gastric mucosa was significantly lower in group C than in groups A and B (8.852 ± 1.001 vs 10.000 ± 1.067, 10.694 ± 0.965, P 0.05),although no significant difference was observed between the latter two groups (P 0.05). CONCLUSION: +Gz exposure aggravates acute gastric mucosal injury in rats possibly by altering the contents of MDA and SOD in gastric tissue.

In search of malignant transformation: A pilot study

The role of oxygen free radicals in the initiation, promotion and progression of carcinogenesis and the protective role of antioxidant defenses has been the subject of much speculation in the recent past, with conflicting reports in the literature. The aim of this study was to measure the concentration of serum total proteins and albumin and advanced oxidation protein products (AOPP) in the sera of patients diagnosed with speckled leukoplakia and well-differentiated oral squamous cell carcinoma. The study consisted of sera analysis of 30 new cases of histologically proven well-differentiated, oral squamous cell carcinoma and 10 patients with speckled leukoplakia aged between 40 and 60 years in addition to 25 healthy controls. One-way analysis of variance (ANOVA) was used to test the difference between groups. To find out which of the two groups' mean was significantly different, post hoc test of Scheffe was used. The study revealed variations in sera levels of albumin and advanced oxidation protein products to be statistically significant. The results obtained emphasize the need for more studies with larger sample sizes to be conducted before a conclusive role for sera levels of total protein, albumin and AOPP could be drawn as markers of transition of the various oral precancerous lesions and conditions to frank oral squamous cell carcinoma.

Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: Effects of probucol

We investigated the effects of high cholesterol diet in the presence and absence of probucol on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde (MDA), and aortic tissue chemiluminescence (CL) a marker for antioxidant reserve in rabbits. Five groups each of 10 rabbits were studied: group I, regular rabbit chow; group II, as I + cholesterol (0.5%); group III, as I + cholesterol (0.5%) and probucol (0.5 gm/kg/day); group IV, as I + cholesterol (1%), and group V, as I + cholesterol (1%) and probucol (0.5 gm/kg/day). Blood concentrations of triglyceride (TG), total cholesterol (TC), high density lipoproteincholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) were measured at monthly intervals for 4 months. The aorta was removed at the end of the protocol for assessment of atherosclerotic changes (gross and microscopic), MDA concentration and CL. TC, LDL-C, LDL-C/HDL-C ratio increased in all the groups except group I, while VLDL-C increased in group II only. HDL-C decreased in groups III, IV and V but remained unchanged in groups I and II. There was a decrease in HDL-C and VLDL-C components and an increase in LDL-C components of total cholesterol in all the groups II, III, IV and V, the changes being greater in group IV than in group II. Probucol did not appreciably affect the changes in lipid profile except that it decreased HDL-C significantly. Aortic tissue MDA increased in groups II, IV and V to a similar extent. Aortic CL which was measured only in groups I, IV and V increased to similar extent in the latter two groups. Atherosclerotic changes were greater in group II than in group III but similar to that in groups IV and V. Histological changes were practically similar in groups II, III, IV and V. The increased levels of aortic MDA and CL, which were associated with development of atherosclerosis, suggest a role for oxygen free radicals in the pathogenesis of hypercholesterolemia-induced atherosclerosis. Protection afforded by probucol was associated with a decrease in aortic MDA in spite of hypercholesterolemia. Ineffectiveness of probucol in 1% cholesterolfed rabbits was associated with its inability to reduce MDA and increase antioxidant reserve. These findings further support for the hypothesis that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis.

Effects of tobacco smoke on IL-16 in CD8+cells from human airways and blood: a key role for oxygen free radicals?

Chronic exposure to tobacco smoke leads to an increase in the frequency of infections and in the number of CD8(+) and CD4(+) cells as well as the CD4(+) chemoattractant cytokine IL-16 in the airways. Here, we investigated whether tobacco smoke depletes intracellular IL-16 protein and inhibits de novo production of IL-16 in CD8(+) cells from human airways and blood while increasing extracellular IL-16 and whether oxygen free radicals (OFR) are involved. Intracellular IL-16 protein in CD8(+) cells and mRNA in all cells was decreased in bronchoalveolar lavage (BAL) samples from chronic smokers. This was also the case in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro, in which oxidized proteins were markedly increased. Extracellular IL-16 protein was increased in cell-free BAL fluid from chronic smokers and in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro. This was not observed in occasional smokers after short-term exposure to tobacco smoke. A marker of activation (CD69) was slightly increased, whereas other markers of key cellular functions (membrane integrity, apoptosis, and proliferation) in human blood CD8(+) cells in vitro were negatively affected by water-soluble tobacco smoke components. An OFR scavenger prevented these effects, whereas a protein synthesis inhibitor, a β-adrenoceptor, a glucocorticoid receptor agonist, a phosphodiesterase, a calcineurin phosphatase, and a caspase-3 inhibitor did not. In conclusion, tobacco smoke depletes preformed intracellular IL-16 protein, inhibits its de novo synthesis, and distorts key cellular functions in human CD8(+) cells. OFR may play a key role in this context.

Exogenous Superoxide Dismutase Prevents Peroxynitrite-Induced Apoptosis in Non-Heart-Beating Donor Livers

Objective: To investigate the role of oxygen free radicals in the induction of apoptosis in non-heart-beating donor (NHBD) livers, and if superoxide dismutase (SOD) ameliorates these alterations. Methods: Rat livers were perfused via the portal vein with histidine/tryptophan/α-ketoglutarate solution from heart-beating donors (HBD) or 60-min warm ischemia from NHBD, with or without the addition of SOD. After 24 h, cold storage livers were evaluated by isolated reperfusion. Results: NHBD showed significantly higher enzyme leakage and elevated portal venous pressure (PVP) versus HBD. Bile and total adenine nucleotides (TAN) were significantly decreased. Apoptosis was prominent in sinusoidal lining cells, coupled with strong nitrotyrosine staining (NTR). The concentrations of nitric oxide and lipoperoxides were largely increased. SOD medication reduced hepatic enzyme release by 30% and lipoperoxides by nearly 50%. Apoptosis and NTR were significantly decreased, and PVP was strikingly reduced to normal values. A 3-fold enhancement in bile production and 1.5-fold increase in TAN of the liver tissue were also observed. Conclusion: NHBD livers are prone to severe reoxygenation injury promoted by oxygen free radicals, massive nitrite oxide production and peroxynitrite-induced apoptosis within the sinusoids. Antioxidant medication with SOD should be considered as a useful means of preserving NHBD livers.

Characterization of Mutant MUTYH Proteins Associated With Familial Colorectal Cancer

The human mutyh gene encodes a base excision repair protein that prevents G:C to T:A transversions in DNA. Biallelic mutations in this gene are associated with recessively inherited familial colorectal cancer. The aim of this study was to characterize the functional activity of mutant-MUTYH and single-nucleotide polymorphism (SNP)-MUTYH proteins involving familial colorectal cancer. MUTYH variants were cloned and assayed for their glycosylase and DNA binding activities using synthetic double-stranded oligonucleotide substrates by analyzing cleavage products by polyacrylamide gel electrophoresis. In this study, we have characterized 9 missense/frameshift mutants and 2 SNPs for their DNA binding and repair activity in vitro. Two missense mutants (R260Q and G382D) were found to be partially active in both glycosylase and DNA binding, whereas 3 other missense mutants (Y165C, R231H, and P281L) were severely defective in both activities. All of the frameshift mutants (Y90X, Q377X, E466X, and 1103delC) were completely devoid of both glycosylase and DNA binding activities. One SNP (V22M) showed the same activity as wild-type MUTYH protein, but the other SNP (Q324H) was partially impaired in adenine removal. This study of MUTYH mutants suggests that certain SNPs may be as partially dysfunctional in base excision repair as missense-MUTYH mutants and lead to colorectal carcinogenesis.

Oxygen in neonatal and infant anesthesia – current practice in the UK

There is an increasing awareness of the role of oxygen free radicals in the pathogenesis of many conditions associated with prematurity, which has led to caution in the use of oxygen in neonatal resuscitation. We surveyed the practice of UK pediatric anesthetists with regard to oxygen use in neonatal and infant anesthesia. A postal questionnaire survey of 460 UK-based members of the Association of Pediatric Anesthetists of Great Britain and Ireland. Responses were received from 247 pediatric anesthetists (54%). Seventy-five percent of anesthetists aim to avoid the use of 100% oxygen during routine infant anesthesia and 52% aim for an FiO(2) of < 0.4 in neonates. The factors most influencing choice of carrier gas are optimal oxygenation and the avoidance of pulmonary atelectasis. Sixteen percent stated that unavailability of medical air is a factor. Opinion was divided on concern about the effects of anesthetic agents on the developing brain. Moderate levels of concern were expressed about the potential toxic effects of oxygen on the eyes and lungs of premature newborns but this concern does not extend to term newborns. Only 20% of anesthetists had any recent knowledge of these issues. This survey indicates that there is no consistency in attitudes and practices and demonstrates considerable variation in the use of oxygen during anesthesia in premature and newborn babies and infants. This may reflect the paucity of evidence in the anesthetic literature on the potential harmful effects of high concentrations of oxygen in vulnerable groups of infants.