Release Of Oxygen Free Radicals Research Articles

Evaluation of antioxidant prophylactic effects of parsley (Petroselinum crispum) on sepsis following cecal ligation and puncture

Objective: Sepsis causes the release of free oxygen radicals that disrupt membrane integrity, and damage to Mitochondria due to the production of free oxygen radicals and oxidation leads to exacerbation of sepsis, Cecal ligation and puncture (CLP) in rats mimics the characteristics and course of clinical sepsis (Hubbard et al., 2005). Methods: We evaluated the antioxidant effects of Petroselinum crispum (Pc) in a cecal ligation and puncture (CLP)-induced rat sepsis model, in a rat model of sepsis caused by cecal ligation and puncture (CLP). Wistar albino rats were separated into four groups of eight groups: a sham group with incised and sutured abdomens; a Pc extract (PcE) group, which was given 2 g/kg parsley extract for 14 days by gastric gavage; a CLP group, which was subjected to sepsis caused by CLP; and a PcE + CLP group, which was given parsley extract for 14 days. PcE was given for 14 days, after which sepsis was induced via the CLP procedure. The groups were compared in terms of hemogram, biochemical and histological characteristics. Results: The administration of PcE before CLP-induced sepsis increases neutrophil counts, PLTs and TASs, which decrease with sepsis, and decreases biochemical changes (BUN, AST, ALT, LDH, TOS, and OSI), which increase with sepsis, to protect against sepsis. Compared with that in the CLP group, the severity of intestinal infiltration was significantly lower in the PcE + CLP group; however, the degree of epithelial damage in the PcE + CLP group was similar to that in the CLP group. In the PcE + CLP group, the crypt and villus lengths were greater, and the decrease in Paneth cell degranulation intensity was greater than that in the CLP group. Conclusion: Additionally, the morphology of the cells in the PcE + CLP group was similar to that in the sham group. PcE has potential as a prophylactic agent for sepsis.

TO STUDY IN-HOSPITAL MORTALITY OF ALUMINIUM PHOSPHIDE POISONING IN RELATION TO TOTAL LEUCOCYTE COUNT

Background: Pesticide poisoning is a major problem worldwide. The incidence of aluminium phosphide poisoning has increased over decades. Phosphine, active form, binds cytochrome oxidase, induces oxidative stress with release of free oxygen radicals, lipid peroxidation, resulting acute inflammation leads to alteration of various haematological/biochemical parameters, including total leucocyte count (TLC). Objectives: 1.To study TLC in aluminium phosphide poisoning 2.To study severity of toxicity in relation to TLC 3.To study in-hospital mortality in relation to TLC Methods: A hospital based cross sectional study with sample size of 65. In-patients with aluminium phosphide poisoning attending Medicine Department in KR Hospital, Mysuru were studied. The parameters like complete hemogram including TLC, liver/renal function tests, electrolytes, electrocardiogram were assessed and correlated. With a confidence interval of 95%, level of significance was kept at 5% Results: Of the 65 subjects, mean age was 34.11 ±11.55 years and mean TLC was 10467.5 ±2991.2 . Subjects were categorised into non-severe(29%), severe(26%) and death(45%) groups. Mean TLC in non severe(8140.7±2445.9), severe(10980.3± 2471.1) and death(11691.4 ±2780.4). A high TLC was found in 15.8% non-severe, 41.2% severe and 69% death cases. A significant positive correlation of TLC with severity of toxicity and mortality of aluminium phosphide poisoning was obtained (p<0.005). Conclusion: Total leucocyte count can be used as one of the easily available cost effective predictive variable to assess the outcome of aluminium phosphide poisoning.

Apoptosis demonstration of the renal tubules after ischemia and reperfusion by acridine orange technique

Ischemia – reperfusion injury is a complex phenomenon that results in cell damage through a biphasic process. Ischemia initiates the injury by a decrease or complete loss of energy supply needed to maintain homeostasis. Reperfusion increases cellular damage by a variety of proposed mechanisms such as inflammatory reaction and release of oxygen free radicals. I-R resulting in both pathological cell death (necrosis) and programmed cell death (apoptosis) in human and experiments. This study performed to demonstrate the apoptosis and necrosis the renal tubules under the effect of I/R in by florescent acridine orange. Twenty five male rats were divided into six groups: control group, ischemia group (40 minute clamping of renal artery) and ischemia – reperfusion group (the removal of renal clamping after 1, 3, and 6 hours).The samples were prepared for histological technique and the sections stained with acridine orange and examined by florescent microscope. The results observed mild changes in the ischemic group but the damage of the tissue and cells occurred in the reperfusion groups reaches the maximum effect after 1 and 3 hour, the necrosis and apoptosis were observed clearly.After 6 hours reperfusion, emit orange fluorescence as evidence of nuclear fragmentation (apoptosis) in cells.We concluded that the apoptosis and necrosis occurred in the reperfusion after 40 minutes ischemia; also the acridine orange stain is effective stain to investigate the apoptosis and the cellular changes.

The Protective Mechanism of Dexmedetomidine on Renal in Hemorrhagic Shock.

Objective To explore the protective effect of dexmedetomidine on renal function in patients with hemorrhagic shock and its possible mechanism. Methods Seventy patients with traumatic hemorrhagic shock requiring surgical treatment were randomly divided into the control group (group C) and the dexmedetomidine group (group D), with 35 patients in each group. Patients in both groups were actively treated with volumetric resuscitation while surgical hemostasis. Group D was given dexmedetomidine 0.5 μg/kg before skin incision after anesthesia induction, for 10 min, followed by intravenous infusion at a rate of 0.4 μg·kg−1·h−1 until 30 min before surgery, and group C was given equal volume of normal saline before skin resection (H1). Venous blood was collected 2 h (H2) and 4 h (H4) after skin resection, and plasma levels of BUN, creatinine (SCr), lipid peroxides (MDA), and inflammatory mediators IL-6 and IL-8 were measured on the 1st and 2nd day after surgery. Results Compared with H1, BUN and SCr levels had no significant difference at 2 h and 4 h after skin resection but significantly decreased at 1 and 2 postoperative days (D1) (P < 0.05). There were significant differences in MDA, IL-6, and IL-8 at 2 and 4 h after skin resection (P < 0.05), but there were no significant differences at 1 day after surgery (D1) and 2 days after surgery (D2). Compared with group C, the levels of MDA, IL-6, and IL-8 in group U were significantly decreased at 2 h and 4 h after skin resection (P < 0.05), and the levels of BUN and SCr in group U were significantly decreased at 1 and 2 days after skin resection (P < 0.05). Conclusion Dexmedetomidine can effectively inhibit the release of oxygen free radicals in the shock stage and the shock recovery stage in patients with hemorrhagic trauma shock and has a protective effect on renal function.

Targeting the KCa3.1 channel suppresses diabetes-associated atherosclerosis via the STAT3/CD36 axis

BackgroundIn diet-induced arterial atherosclerosis, increased KCa3.1 channel was associated with atherosclerotic plaque progression and instability. Macrophages are involved in the formation of atherosclerotic plaques, and the release of inflammatory cytokines and oxygen free radicals promotes plaque progression. However, whether the macrophage KCa3.1 channel facilitates diabetes-accelerated atherosclerosis is still unclear. This study investigated atherosclerotic plaque in ApoE-/- mice regulated by the KCa3.1 channel. Methods and ResultsIn vivo, blocking KCa3.1channel inhibit the development of the atherosclerotic lesion in diabetic ApoE-/- mice fed with a high-fat diet. In vitro, upregulation of KCa3.1 channel level occurred in RAW264.7 cells treated with HG plus ox-LDL in a time-dependent manner. Blocking KCa3.1 significantly reduced the uptake of ox-LDL in mice peritoneal macrophages. Further studies indicated the KCa3.1 siRNA and TRAM-34 (KCa3.1 inhibitor) attenuated the scavenger receptor CD36 expression via inhibiting STAT3 phosphorylation. ConclusionBlockade of macrophage KCa3.1 channel inhibit cellular oxidized low-density lipoprotein accumulation and decrease proinflammation factors expression via STAT3/CD36 axis. This study provided a novel therapeutic target to reduce the risk of atherosclerosis development in diabetic patients.

Benefits of α-lipoic acid in high-risk pregnancies (Review).

α-Lipoic acid (ALA) is a natural molecule that is inconsistently synthesized by the human body and must be provided from exogenous sources, such as food and dietary supplements. Once absorbed, the oxidized form of ALA is transformed into its reduced form, dihydrolipoic acid (DHLA). ALA/DHLA exert direct and indirect antioxidant, anti-inflammatory and fine immunomodulatory effects. ALA/DHLA reduce the levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17), while increasing the secretion of anti-inflammatory cytokines (IL-10). They also inhibit cyclooxygenase 2, thereby decreasing the secretion of prostaglandin E2 and nitrogen oxide, and reducing the risk of miscarriage in the first trimester of pregnancy. In patients at risk of abortion, administration of ALA from the first trimester has shown efficacy by accelerating subchorionic hematoma resorption, with a significant decrease in the accompanying abdominal pain. ALA has been proven to be efficient in maintaining the length of the cervix and keeping it closed following one episode of premature labor. Preeclampsia is a dysfunction caused by abnormal placentation and an excessive maternal inflammatory response, leading to extreme hypoxia in the placental bed and exaggerated oxidative stress, with release of oxygen free radicals. Oxidative stress plays a key role in the development of preeclampsia and intrauterine growth restriction. The hypothesis of antioxidant supplementation may play an essential part in disease prevention and fetal neuroprotection.

The Effects of Amino Acids Enriched Del Nido Cardioplegia on Myocardial Leucocyte Accumulation and Ventricular Functions in Patients Undergoing Coronary Artery Bypass Grafting Surgery.

One of the main sources of ischemia/reperfusion injury (IRI) and release of free oxygen radicals (FORs) during extracorporeal circulation (ECC) during cardiac surgery is neutrophils. In this study, we investigated the potential effects of our modification of del Nido cardioplegia (mDNC) (amino acids enriched del Nido cardioplegia) on myocardial polymorphonuclear leucocyte (PMNL) accumulation. We also compared the effects of our mDND and classical del Nido cardiplegia (cDNC) on ventricular contractile functions in coronary artery bypass grafting (CABG) surgery. Our study included 100 isolated CABG patients with similar characteristics, including age, gender, preoperative medications, diabetes, hypertension, and left ventricular ejection fraction (LVEF). The patients were divided into two groups. Amino acids supplemented del Nido cardioplegia (L-aspartate and L-glutamate at a dose of 13 milimol/L) in 50 patients (study group, G1). In the remaining 50 patients, we used a classical del Nido cardioplegic solution (cDNC) (control group, G2). Myocardial Tru-Cut biopsy from the right ventricle was taken before the institution of ECC and after weaning from ECC in all patients. Cardiac troponine-I (cTn-I), tumor necrosis factor-alpha (TNF-Alpha), Pro-Brain Natriuretic Peptide (Pro-BNP), and lactate levels were measured pre- and postoperatively. Invasive monitoring was performed to provide the left ventricular functions in both groups in the operating room and noted by a blinded anaesthesiologist. Five patients died post-surgery (5%) (two from SG and three from CG (P = .67), due to low cardiac output syndrome or multiorgan failure. At the postoperative period, cardiac output (CO) and stroke volume index (SVI) was higher in mDNC (mean ± SDS; 32.1 ± 7 versus 22.2 ± 6.9 mL/min/m² (P < .001). CI was significantly higher in mDNC after surgery (3.10 ± 0.76 versus 2.40 ± 0.30L/min/m² (P = .002). Ten patients (20%) in mDNC and 16 patients (32%) in cDNC required inotropic support (P < .001). The postoperative inotropic requirement was less in mDNC (6.1 ± 1.8 mg/kg versus 9.2 ± 1.9 mg/kg, P < .004). Blood gas analyses from the coronary sinus showed that myocardial acidosis was more severe in the control group [pH (0.10 ± 0.09 versus 0.054 ± 0.001; P = .34)]. Blood lactate levels were significantly high in the control group (1.01 ± 0.007 mmol/L versus 1.92 ± 0.35 mmol/L) (P = .22). No difference was found when compared with cardioplegia volume in the mDNC and cDNC groups (mDNC= 990.00 ± 385 mL in DNC = 960 ± 240 mL, P = .070). An aortic cross-clamp time in the mDNC and cDNC groups were 88.4 ± 8.9 min, and 93 ± 11 min, (P = .76), but cardiopulmonary bypass time was significantly low in mDNC (mDNC = 98.3 ± 22.5 min, DNC = 126 ± 19.5 min, P = .0020). TNF-Alpha and Pro-BNP levels in patients received mDNC were significantly low (P = .022). Postoperative cardiac enzyme levels (creatine kinase-MB and high sensitive troponin-I) were significantly low in the mDNC group (P = .0034). Myocardial biopsy results showed that myocardial PMNL accumulation was significantly high in the control group (P = .001). The amount of inotropic agent use was significantly high in the control group (P = .003). After weaning from ECC, the left ventricular stroke work index (LVSWI), cardiac index (CI), and heart rate (HR) were significantly high in the study group (P = .032; P = .002; P = .01). Postoperative blood and blood products requirements were significantly low in the mDNC group (P = .002). At pre-discharge echocardiography, the mDNC group demonstrated significantly higher ventricular ejection fraction (37.9 ± 4.3% and 29.7 ± 3.8%, respectively (P = .003). Our study findings show that glutamate-aspartate supplemented del Nido cardioplegia significantly decrease myocardial PMNL accumulation with reduced release of biochemical markers, including cardiac troponin-I, TNF-alpha, and Pro-Bnp. Our study results demonstrated that amino acids supplementation in del Nido cardioplegia has some advantages in CABG patients, including the decrease of perioperative myocardial infarction and increase significantly the left ventricular functions including ventricular SVI and CI.

EVALUATION OF EFFECT OF NATURAL ANTIOXIDANTS ON THE SHADE OF THE BLEACHED ENAMEL USING SPECTROPHOTOMETRY

Background and Aim: The bleached enamel surface requires application of antioxidant as there will be continuous release of free oxygen radicals. It would be beneficial if remineralizing agent which is recommended after bleaching also provides an antioxidant therapy. The natural antioxidants are colored. Hence, the aim of the present study was to evaluate the effect of natural antioxidants on the shade of the bleached enamel.&#x0D; Materials and Methods: Thirty single rooted maxillary anterior teeth were selected for the study. For all the samples middle third portion of the labial surface of the teeth was standardized using computerized cellophane stickers. Bleaching was carried out with 22% Carbamide peroxide gel (Philips Zoom Nite White). Based on the type of antioxidant solution application, samples were divided into three groups of ten samples each. Group I control (n=10) Group-II (n=10) 10% wheat grass solution (Sresta natural Bio products, India) Group-III (n=10) 5% grape seed extract (Zenith nutrition, Medizen Labs Pvt.Ltd, India). L, a, b values were recorded with spectrophotometry (Vita Zahnfabrik H. RauterGmbH &amp; Co. KG,Bad Sackingen, Germany) thrice for each sample at the three respective time periods i.e at baseline, after bleaching and after antioxidant application.&#x0D; Results: ΔE values were subjected to statistical analysis using one way ANOVA with p&gt;0.05 and the results were tabulated. It was observed that there was statistical insignificant difference between the groups with a p value of 0.295(p&gt;0.05). Conclusion: The antioxidants 5% grape seed extract and 10% wheat grass extract did not affect the shade of the bleached enamel.&#x0D; Keywords: tooth bleaching, antioxidant, shade, spectrophotometry

Antioxidative and anti-inflammatory impact of valsartan against renal ischemia-reperfusion injury; role of nitric oxide signaling pathway

Introduction: Renal ischemia reperfusion injury is one of the main causes of acute renal failure, which is associated with high mortality. Tissue damage caused by ischemia-reperfusion occurs due to the release of oxygen free radicals. Type I angiotensin receptor antagonists such as valsartan can be useful in the treatment of chronic kidney disease and hypertension. Objectives: We aimed to evaluate the protective effect of valsartan against renal ischemia reperfusion via antioxidant property and nitric oxide (NO) signaling pathway. Materials and Methods: Fifty male Wistar rats (220±10 g) were randomly divided into five groups as follows: Group 1; healthy rats without ischemia-reperfusion (control group). Group 2; rats with ischemia reperfusion (IR) (IR control group). Group 3; rats with IR which received 30 mg/kg valsartan orally. Group 4; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-NAME. Group 5; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-arginine. To induce ischemia-reperfusion, rats were anesthetized with thiopental and underwent surgery. Then, we induced ischemia with blocking blood vessels for 45 minutes by clamping. Biochemical parameters including urea and creatinine were measured using commercial kits. Oxidative stress and inflammatory parameters were measured by ELISA method. Renal tissues were stained with hematoxylin and eosin. Finally, the Kolmogorov-Smirnov test was used to determine the normal distribution of data. Results: The findings of this study indicated that treatment with valsartan and valsartan plus L-arginine leads to significant decrease in the serum levels of creatinine, urea, and albumin/creatinine, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in contrast to IR control group which has increased level of these parameters. On the other hand, treatment with valsartan and valsartan plus L-arginine lead to increase in the serum levels of glutathione peroxidase (GPX), in contrast to ischemia reperfusion control group. Conclusion: Our data revealed that valsartan as a type I angiotensin receptor antagonist could decrease oxidative stress and inflammation due to renal ischemia reperfusion injury. Hence, valsartan could propose as a therapeutic agent for kidney diseases such as renal ischemia-reperfusion injury regarded to these renoprotective effects.

Effects of Arginine Vasopressin on Migration and Respiratory Burst Activity in Human Leukocytes.

Arginine vasopressin can bind to high-affinity vasopressin V1a receptors in human leukocytes. This study aims to investigate the effects of arginine vasopressin on migration and chemotaxis of neutrophils and oxygen free radical release by human leukocytes. Neutrophils and monocytes were obtained from peripheral blood samples of ten healthy volunteers. Leukocyte migration was microscopically assessed in a modified 48-blind well microchemotaxis chamber, and respiratory burst activity was estimated using 2’,7’-dichlorofluorescin diacetate in descending concentrations of arginine vasopressin. Arginine vasopressin stimulates migration of monocytes and neutrophils depending on concentration and on interaction with other chemoattractants. The strongest chemotactic responses of monocytes to arginine vasopressin were observed in the micro and nanomolar range and in the nanomolar range for neutrophils (p<0.001). Pre-incubation of leukocytes with arginine vasopressin decreased migration of leukocytes in a dose-dependent manner. Arginine vasopressin did not stimulate release of oxygen free radicals by neutrophils. Arginine vasopressin stimulates in a dose-dependent manner the migration of monocytes and neutrophils. However, pre-incubation of leukocytes with arginine vasopressin decreased the migratory response of monocytes and neutrophils to other chemoattractants. These findings may be of importance in the treatment regimen of patients with septic shock.

May inflammatory markers be used for monitoring the continuous positive airway pressure effect in patients with obstructive sleep apnea and arrhythmias?

IntroductionObstructive sleep apnea syndrome (OSAS) is defined by recurrent episodes of significant reduction or absence of the oro-nasal airflow during sleep, in the presence of thorax and abdominal movements and snoring. The pathophysiological consequences of intermittent hypoxia determined by OSAS are represented by systemic inflammation, the release of free oxygen radicals and activation of the sympathetic nervous system. Cardiac arrhythmias are a frequent comorbidity in patients with OSAS. HypothesisWe hypothesized that the continuous positive airway pressure (CPAP) therapy has an effect on inflammatory markers (erythrocyte sedimentation rate, fibrinogen, and red cell distribution width) in patients with OSAS and cardiac arrhythmias. Evaluation of the hypothesisWe tested this hypothesis on 52 patients diagnosed with OSAS and cardiac arrhythmias, divided into two groups: group A (patients who received CPAP therapy and pharmacological therapy) and group B (only pharmacological therapy). The patients were evaluated at enrollment (T0), at 3 and 6 months. We did not find a statistically significant difference of erythrocyte sedimentation rate (ESR) and fibrinogen levels between the two groups. Regarding the red cell distribution width (RDW), the CPAP treatment seems to have improved the RDW values in patients who received this treatment. Also, in patients from group A, a significant decrease in the average heart rate was noticed after 3 months. ConsequencesFibrinogen and ESR cannot be used for monitoring the CPAP therapy in patients with OSAS and arrhythmias. Instead, the beneficial effect of CPAP in patients with OSAS and cardiac arrhythmias can be monitored with the help of the RDW, which could also be used for evaluating the cardiovascular risk in patients with OSAS and arrhythmias.

The Possible Pathophysiological Outcomes and Mechanisms of Tourniquet-Induced Ischemia-Reperfusion Injury during Total Knee Arthroplasty.

Ischemia and reperfusion (I/R) injury induced by tourniquet (TQ) application leads to the release of both oxygen free radicals and inflammatory cytokines. The skeletal muscle I/R may contribute to local skeletal muscle and remote organ damage affecting outcomes after total knee arthroplasty (TKA). The aim of the study is to summarize the current findings associated with I/R injury following TKA using a thigh TQ, which include cellular alterations and protective therapeutic interventions. The PubMed database was searched using the keywords “ischemia reperfusion injury,” “oxidative stress,” “tourniquet,” and “knee arthroplasty.” The search was limited to research articles published in the English language. Twenty-eight clinical studies were included in this qualitative review. Skeletal muscle I/R reduces protein synthesis, increases protein degradation, and upregulates genes in cell stress pathways. The I/R of the lower extremity elevates local and systemic oxidative stress as well as inflammatory reactions and impairs renal function. Propofol reduces oxidative injury in this I/R model. Ischemic preconditioning (IPC) and vitamin C may prevent oxygen free radical production. However, a high dose of N-acetylcysteine possibly induces kidney injury. In summary, TQ-related I/R during TKA leads to muscle protein metabolism alteration, endothelial dysfunction, oxidative stress, inflammatory response, and renal function disturbance. Propofol, IPC, and vitamin C show protective effects on oxidative and inflammatory markers. However, a relationship between biochemical parameters and postoperative clinical outcomes has not been validated.

Daño por isquemia-reperfusión miocárdico en cirugía cardiaca con circulación extracorpórea. Aspectos bioquímicos

IntroductionSince the beginning of the cardiac surgery with cardiopulmonary bypass, myocardial-reperfusion injury has been recognized as one of the leading causes of morbidity and mortality related with this type of surgery. MethodologyA bibliographic review in Pubmed and other data base including Teseo has been carried out. ResultsFundaments of the cellular changes during the ischemic time, cellular changes in the reperfusion time, release of oxygen free radicals, complement activation, proinflammatory cytokines activation and neutrophil-endothelium interaction are exposed. A table with a selected list of drugs and compounds used against the myocardial ischemic -reperfusion injury syndrome is included. ConclusionsAt present, the myocardial reperfusion injury syndrome is an active line of research. There are many trials and studies on investigating new agents .The cardiac surgeon should be well informed in new strategies in myocardial protection in cardiac surgery.155 words

Trimetazidine in the prevention of contrast-induced nephropathy in chronic kidney disease.

Contrast induced nephropathy (CIN) may be defined as Acute Renal Failure (ARF) that occurs within 24-72h of exposure to intra-venous or intra-arterial iodinated contrast media that cannot be attributed to other causes. CIN occurs in up to 5% of hospitalized patients with normal renal function prior to injection of contrast media. It occurs more frequently in patients with renal impairment particularly if associated with diabetic nephropathy. Among all procedures utilizing contrast agents for either diagnostic or therapeutic purposes, coronary angiography and percutaneous coronary interventions are associated with the highest rates of CIN. Trimetazidine has been described as a cellular anti-ischemic agent. Previous studies demonstrated that Trimetazidine prevents the deleterious effects of ischemia-reperfusion at both the cellular and mitochondrial levels and exerts an anti-oxidant effect. It inhibits excess release of oxygen free radicals, limits cellular acidosis, protects Adenosine Triphosphate (ATP) stores, reduces membrane lipid peroxidation and inhibits neutrophil infiltration. To evaluate the role of Trimetazidine (TMZ) in prevention of contrast induced nephropathy (CIN) in patients with renal impairment undergoing coronary angiography. This study was conducted on one hundred patients having a basal creatinine clearance below 90ml/min and presenting for coronary angiography procedures. The patients were divided into two equal groups each including fifty patients where both groups received parenteral hydration in the form of isotonic saline at a rate of 1mg/kg body weight per hour starting 12h before angiography and up to 12h thereafter. In Group 1, patients received additional medication in the form of trimetazidine 35mg twice daily for 72h and starting 48h before the procedure which was not received in group 2 (control). There was a significant difference regarding the rate of CIN among TMZ versus control groups (10% vs. 26%). The amount of contrast was significantly higher in the CIN group (165.00±108.41 vs 89.85±38.60, P=0.000). Administration of trimetazidine in a dose of 35mg twice daily orally in conjunction with standard early saline hydration is an effective method to prevent or reduce the incidence of contrast-induced renal dysfunction following the administration of contrast media during coronary angiography procedures in patients with mild-moderate basal renal insufficiency.

Intermittent Hypoxia Contributes to the Lung Damage by Increased Oxidative Stress, Inflammation, and Disbalance in Protease/Antiprotease System.

Intermittent hypoxia as a surrogate of obstructive sleep apnea is associated with different cardiovascular complications. However, the effects of intermittent hypoxia on the lung tissue are less known. Therefore, the aim of our present study was to investigate if intermittent hypoxia may influence oxidative stress, inflammation, and protease/antiprotease system in the lung. Additionally, potential protective properties of anti-inflammatory and anti-oxidative drugs have been evaluated. 32 mice were divided into four groups: (1) intermittent hypoxia, (2) intermittent hypoxia with infliximab, (3) intermittent hypoxia with L-glutathione, and (4) normoxia. After 4weeks, lungs and blood were collected. Levels of reactive oxygen species in the lung were calculated by L-O12-enhanced chemiluminescence. CD68-positive lung macrophages were detected by immunofluorescence. Concentrations of elastase and desmosine in lung and of alpha-1-antitrypsin in blood were calculated by means of enzyme-linked immunosorbent assay. Compared to a control, intermittent hypoxia augmented the release of free oxygen radicals, expression of CD68+ macrophages, and concentration of elastase in the lung tissue. Despite increased blood levels of protective alpha-1-antitrypsin, concentrations of desmosine-degradation product of elastin were higher versus control. The application of anti-inflammatory infliximab und anti-oxidative L-glutathione prevented at least partly the above-observed hypoxia-associated changes. Intermittent hypoxia contributes to the lung damage by increased oxidative stress, inflammation, and disbalance in protease/antiprotease system. Infliximab and L-glutathione may prevent adverse hypoxia-induced lung alternations.

Lipotransfer for radiation-induced skin fibrosis.

Radiation-induced fibrosis (RIF) is a late complication of radiotherapy that results in progressive functional and cosmetic impairment. Autologous fat has emerged as an option for soft tissue reconstruction. There are also sporadic reports suggesting regression of fibrosis following regional lipotransfer. This systematic review aimed to identify cellular mechanisms driving RIF, and the potential role of lipotransfer in attenuating these processes. PubMed, OVID and Google Scholar databases were searched to identify all original articles regarding lipotransfer for RIF. All articles describing irradiated fibroblast or myofibroblast behaviour were included. Data elucidating the mechanisms of RIF, role of lipotransfer in RIF and methods to quantify fibrosis were extracted. Ninety-eight studies met the inclusion criteria. A single, definitive model of RIF is yet to be established, but four cellular mechanisms were identified through in vitro studies. Twenty-one studies identified connective tissue growth factor and transforming growth factor β1 cytokines as drivers of fibrotic cascades. Hypoxia was demonstrated to propagate fibrogenesis in three studies. Oxidative stress from the release of reactive oxygen species and free radicals was also linked to RIF in 11 studies. Purified autologous fat grafts contain cellular and non-cellular properties that potentially interact with these processes. Six methods for quantifying fibrotic changes were evaluated including durometry, ultrasound shear wave elastography, thermography, dark field imaging, and laser Doppler and laser speckle flowmetry. Understanding how lipotransfer causes regression of RIF remains unclear; there are a number of new hypotheses for future research.

Reactive oxygen radicals – the therapeutic effectiveness of antioxidants

Abstract Oxidative stress occurring in cells is a consequence of an excessive activity of reactive oxygen forms, resulting from an imbalance between the release of free oxygen radicals and their removal from the cell by antioxidant systems. 90% of reactive oxygen radicals emerge in mitochondrial respiratory chain during an incomplete four-electron oxygen reduction. The remaining 10% originate from different reactions occurring in the cell. The established compounds are characterised by a short half-life and are highly reactive. Sparse quantities of free oxygen radicals have a positive effect on cell functions. Oxidative stress leads to damage in cellular membranes, enzymatic and non-enzymatic proteins, as well as DNA. Therapy with antioxidants as exogenous dietary supplements aims at preventing or reducing the risk of development of diseases involving the presence of the oxygen radicals. Whether the antioxidant therapy will bring positive or negative effects depends on numerous factors that need to be considered before their inclusion in the applied treatment.

Glutamate Excitotoxicity and Oxidative Stress in Epilepsy: Modulatory Role of Melatonin.

Epilepsy is thought to be associated with oxidative stress, glutamate excitotoxicity, and mitochondrial dysfunction. The enhanced synthesis and release of oxygen free radicals is linked to the low and oxidative potential of the central nervous system. Glutamate excitotoxicity also contributes significantly to the production of reactive nitrogen species that cause nitrosative stress. A decrease in adenosine triphosphate synthesis, which leads to free radical formation, is associated with mitochondrial dysfunction. The brain is very much susceptible to degeneration and oxidative stress because of its low antioxidant enzyme activity. Melatonin, a hormone secreted by the pineal gland, has remarkable antioxidant properties. Melatonin and its analogs that bind to melatonin receptors have a significant role in suppressing seizures. Melatonin scavenges oxygen free radicals such as hydroxyl radical, peroxy radical, peroxynitrite anion, and superoxide radical and stimulates synthesis of superoxide dismutase and glutathione peroxidase, which are potent antioxidant enzymes. Melatonin administration has been shown to be effective in both experimental models and patients suffering from epilepsy. In this review, we compile the literature supporting consequences of seizures and the protective role of melatonin during seizures.

Histamine H2 Receptor in Blood Cells: A Suitable Target for the Treatment of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) consists in a cancer of early hematopoietic cells arising in the bone marrow, most often of those cells that would turn into white blood cells (except lymphocytes). Chemotherapy is the treatment of choice for AML but one of the major complications is that current drugs are highly toxic and poorly tolerated. In general, treatment for AML consists of induction chemotherapy and post-remission therapy. If no further post-remission is given, almost all patients will eventually relapse. Histamine, acting at histamine type-2 (H2) receptors on phagocytes and AML blast cells, helps prevent the production and release of oxygen-free radicals, thereby protecting NK and cytotoxic T cells. This protection allows immune-stimulating agents, such as interleukin-2 (IL-2), to activate cytotoxic cells more effectively, enhancing the killing of tumor cells. Based on this mechanism, post-remission therapy with histamine and IL-2 was found to significantly prevent relapse of AML. Alternatively, another potentially less toxic approach to treat AML employs drugs to induce differentiation of malignant cells. It is based on the assumption that many neoplastic cell types exhibit reversible defects in differentiation, which upon appropriate treatment results in tumor reprogramming and the induction of terminal differentiation. There are promissory results showing that an elevated and sustained signaling through H2 receptors is able to differentiate leukemia-derived cell lines, opening the door for the use of H2 agonists for specific differentiation therapies. In both situations, histamine acting through H2 receptors constitutes an eligible treatment to induce leukemic cell differentiation, improving combined therapies.

Upregulation of ICAM-1 and IL-1β protein expression promotes lung injury in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a devastating lung disorder characterized by sustained airway flow restriction that is not fully reversible. The precise pathogenic mechanisms are unknown, but it is clear that cigarette smoking and chronic inflammatory stimulation are the major causes of COPD. Lung inflammation associated with COPD involves multiple cytokines, aggregation, and activation of neutrophils in the airway and lung tissue, and release of proteases and oxygen free radicals. In this study, a rat model of COPD was established by daily cigarette smoke exposure plus endotoxin treatment (the experimental group). Respiratory curves were recorded by the BL-420 biological signal collecting and processing system. Furthermore, the contents of inflammatory mediators, intercellular adhesion molecular (ICAM)-1 and interleukin (IL)-1β, in bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay for experimental, smoke-exposed only (control), and untreated (blank) rat groups. Protein expression levels of ICAM-1 and IL-1β in the lung tissue were also compared among groups by the immunohistochemical streptavidin-peroxidase method. The COPD model rats exhibited severe dyspnea and lung inflammation as evidenced by significantly prolonged expiratory duration, higher respiratory rate, elevated ICAM-1 and IL-1β in BALF, and higher ICAM-1 and IL-1β protein expression in lung tissue compared to control and blank group rats. Chronic cigarette smoke exposure plus endotoxin is a feasible and reliable model of COPD that recapitulates many clinical signs and pathogenic responses. ICAM-1 and IL-1β upregulation are possible early contributors to COPD-associated inflammatory lung injury.