Iron chelation effects on lipid peroxidation, inflammation and ventricular performance in a rat model of isoproterenol induced acute myocardial stress.

Acute cardiac pathologies represent one of the leading causes of death, while iron metabolism is recognized to be implicated in reactive oxygen species production, lipid peroxidation, and inflammation. The aim of the present study was to assess iron chelation effects in isoproterenol (ISO) induced acute cardiac stress. We divided male Wistar rats into preventive and secondary treatment groups, with the active arm consisting in deferiprone (DFP), a lipid permeable chelator. Mortality of ISO was 10-18.18% in both preventive and secondary groups. We analyzed serum and myocardial tissue parameters of inflammation, iron dynamics, and lipid peroxidation, accompanied by ultramicroscopy, histological, and ultrasound-derived parameters of left ventricular function. Results reveal that ISO-mediated lipid peroxidation and inflammation are alleviated by administration of DFP, with negligible effect on systemic ferroregulation dynamics and global ventricular function (as assessed by ultrasound). DFP administration after cardiovascular stress is associated with a decrease in lipid peroxidation and inflammation, without an improvement in gross left ventricular parameters.

Chronic oral trimethylamine-N-oxide administration induces experimental incipient atherosclerosis in non-genetically modified mice.

Atherosclerosis is a chronic inflammatory disease of the arterial wall involving inflammation, redox imbalance, and impaired cholesterol transport. A high level of trimethylamine-N-oxide (TMAO) produced by meat and fat metabolism are involved in atherosclerosis development, but the exact relationship with inflammation is not completely clear. The study aimed to identify a possible association between TMAO; atherosclerotic changes in the aortic root; oxidative stress; and inflammation quantified by highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), and interleukin-1beta (IL-1ß) levels. TMAO dihydrate was administered via gastric gavage to 20 male Wistar rats for 90 days; one separate group received vehicle. The TMAO-treated animals were divided into two groups: one group received a low dose of TMAO (20 mg/day) and the other group received a high dose of TMAO (40 mg/day). Malondialdehyde (MDA), proinflammatory markers - IL-1ß, TNF-α, and hsCRP, total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, and glucose were assessed 30 and 90 days after TMAO administration. Additionally, conventional histopathology and immunohistochemistry for collagen I distribution were performed. MDA, hsCRP, TNF-α, and IL-1ß levels increased after 90 days of TMAO administration in conjunction with significant changes suggestive of incipient atherosclerosis and inflammation of the aortic root. The increase was higher in the group treated with 40 mg/day TMAO compared with the group treated with 20 mg/day TMAO. Additionally, blood levels of TMAO were significantly correlated with hsCRP, TNF-α, IL-1ß levels, but also with MDA, low HDL-cholesterol levels, and high triglyceride levels. The increase in MDA and inflammatory cytokines and modification of lipid metabolism markers may explain the pro-atherogenic effect of TMAO.

The impact of Sambucus nigra L. extract on inflammation, oxidative stress and tissue remodeling in a rat model of lipopolysaccharide-induced subacute rhinosinusitis.

Rhinosinusitis is a common disorder related to inflammation of paranasal sinuses and nasal cavity mucosa. Herbal medicines could be an option in the treatment of rhinosinusitis due to their anti-inflammatory and anti-oxidative properties. The study aims to investigate the effect of intranasal Sambucus nigra L. subsp. nigra (SN) extract against inflammation, oxidative stress, and tissue remodeling in nasal and sinus mucosa, but also in serum, lungs, and brain, in Wistar rat model of subacute sinonasal inflammation induced by local administration of lipopolysaccharides (LPS), from Escherichia Coli. The cytokines (TNF-α, IL-1ß, IL-6) and oxidative stress (malondialdehyde) in nasal mucosa, blood, lungs, and brain were analyzed. In addition, a histopathological examination was performed, and NF-kB, MMP2, MMP9, TIMP1 expressions were also evaluated in nasal mucosa. Both doses of LPS increased the production of cytokines in all the investigated tissues, especially in the nasal mucosa and blood (p < 0.01 and p < 0.05), and stimulated their secretion in the lungs, and partially in the brain. Malondialdehyde increased in all the investigated tissues (p < 0.01 and p < 0.05). In parallel, upregulation of NF-kB and MMP2 expressions with downregulation of TIMP1, particularly at high dose of LPS, was observed. SN extract reduced the local inflammatory response, maintained low levels of IL-6, TNF-α, and IL-1ß. In lungs, SN reduced all cytokines levels while in the brain, the protective effect was noticed only on IL-6. Additionally, SN diminished lipid peroxidation and downregulated NF-kB in animals exposed to a low dose of LPS, with increased TIMP1 expression, while in animals treated with a high dose of LPS, SN increased NF-kB, MMP2, and MMP9 levels. In conclusion, SN extract diminished the inflammatory response, reduced generation of reactive oxygen species (ROS) and, influenced MMPs expressions, suggesting the benficial effect of SN extract on tissue remodeling in subacute rhinosinusitis and on systemic inflammatory response.

Quercetin attenuates naso-sinusal inflammation and inflammatory response in lungs and brain on an experimental model of acute rhinosinusitis in rats.

This study aimed to investigate the effect of quercetin without intranasal inflammation and oxidative stress in nasal and sinus mucosa, but also in serum, lungs and brain in a rat model of acute nasal and sinus inflammation induced by administration of lipopolysaccharides (LPS) (from Escherichia coli). Wistar rats were divided into five groups of 10 animals each. The control group received an intranasal saline solution once/day, for seven consecutive days. Rats in groups 2 and 3, received low-dose (5 µg) and high-dose (10 µg) of LPS, once/day, for seven consecutive days. Rats in groups 4 and 5, received low-dose (5 µg) and high-dose (10 µg) of LPS and after 2 h, 80 mg/kg of quercetin, once/day for seven consecutive days was administered. After the treatment period, the histopathological examination of nasal and sinus mucosa was performed and levels of cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6)) and oxidative stress in the blood, nasal mucosa, lungs and brain were also analyzed. High dose of LPS increased TNF-α, IL-6 and IL-1ß levels in serum, nasal mucosa, and lungs homogenates while in brain, this effect was only on TNF-α levels. IL-1ß enhanced significantly in serum and mucosa, especially after administration of a high dose of LPS (P < 0.01 and P < 0.05). Histopathological and immunofluorescence analysis revealed acute inflammatory reaction in rats treated with both doses of LPS without significant changes of lipid peroxidation in the studied tissues. Quercetin administration diminished the exudate and degree of inflammation in lamina propria of nasal and sinusal areas, parallel with the decreased secretion of TNF-α (40.2% reduction after the low dose of LPS, and 35.4% reduction after the high dose of LPS) and IL-6 (21.4% reduction after the low dose of LPS and 35.8% reduction after the high dose of LPS). In lungs, quercetin reduced TNF-α (43.3%) and IL-6 levels (24.5%), and in the brain, the protective effect was noticed only on TNF-α (46.5%). The intranasal LPS administration successfully induced acute rhinosinusitis in a rat model and also generated an inflammatory response in the lungs and brain. Intranasal administration of quercetin diminished the nasal inflammation and also exerted protective effect on lungs and partially on brain inflammatory reaction.

Daily oral administration of chlorogenic acid prevents the experimental carrageenan-induced oxidative stress.

Inflammation and oxidative stress are interrelated processes, during which many pathological processes lead to the reactive oxygen species (ROS) and the cytokines release. The aim of this experimental study was to analyse the effects of chlorogenic acid, in oral daily administration, against the oxidative stress and oedema development in experimental carrageenan-induced rat paw inflammation. The oxidative stress parameters were investigated after a paw inflammation was produced in rats that previoulsy received, for 14 days, either chlorogenic acid (100 mg/day or 150 mg/day) or indomethacin (1 mg/kg/day). The paw oedema was measured through plethysmometry made at 2, 6 and 24 hours after carrageenan injection. The oxidative stress was investigated through spectrophotometry. Blood samples, paw skin and kidneys were collected to investigate malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG). The protein expression of oxidative stress-related pathways was analysed in skin and kidneys through Western blot. The present study showed that indomethacin and both doses of chlorogenic acid, after 14 days of oral administration, exerted antioedematous effects during the inflammation development after carrageenan local injection. Compared to the group that received only carrageenan injection, significant decreases of the inflamed paw volume were shown in the treated groups (P < 0.001), in all inflammation phases. The lipid peroxidation was significantly decreased by both doses of chlorogenic acid in inflamed skin (P < 0.0001) and kidney (P < 0.0001). In serum, it was significantly inhibited by indomethacin (P < 0.01) and by 100 mg/day of chlorogenic acid (P < 0.05). The antioxidant protection, evaluated through the ratio GSH/GSSG, was significantly increased by chlorogenic acid in inflamed skin (P < 0.0001) and kidney (100 mg/day, P < 0.01; 150 mg/day, P < 0.0001). In serum, only indomethacin administration produced significant increases of the antioxidant protection (P < 0.05). Western blot analysis showed significant decreases of COX-2 in inflamed skin and kidney in the groups of rats that received indomethacin or 100 mg/day of chlorogenic acid. The effects of chlorogenic acid on NF-κB and pNF-κB were dose-dependent.

Protective effects of quercetin from oxidative/nitrosative stress under intermittent hypobaric hypoxia exposure in the rat's heart.

BACKGROUND: Exposure to high altitude in hypobaric hypoxia (HH) is considered to be a physiological oxidative/nitrosative stress. Quercetin (Que) is an effective antioxidant and free radical scavenger against oxidative/nitrosative stress. AIMS: The aim of this study was to investigate the cardioprotective effects of Que in animals exposed to intermittent HH (IHH) and therefore exposed to oxidative/nitrosative stress. MATERIALS AND METHODS: Wistar albino male rats were exposed to short-term (2 days) or long-term (4 weeks; 5 days/week) IHH in a hypobaric chamber (5,500 m, 8 h/day, 380 mmHg, 12% O2, and 88% N2). Half of the animals received natural antioxidant Que (body weight: 30 mg/kg) daily before each IHH exposure and the remaining rats received vehicle (carboxymethylcellulose solution). Control rats were kept under normobaric normoxia (Nx) and treated in a corresponding manner. One day after the last exposure to IHH, we measured the cardiac hypoxia-induced oxidative/nitrosative stress biomarkers: the malondialdehyde (MDA) level and protein carbonyl (PC) content, the activity of some antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], the nitrite plus nitrate (NOx) production, and the inducible nitric oxide synthase (iNOS) protein expression. RESULTS: Heart tissue MDA and PC levels, NOx level, and iNOS expression of IHH-exposed rats had increased, and SOD and CAT activities had decreased compared with those of the Nx-exposed rats (control groups). MDA, CP, NOx, and iNOS levels had decreased in Que-treated IHH-exposed rats compared with IHH-exposed rats (control groups). However, Que administration increased SOD and CAT activities of the heart tissue in the IHH-exposed rats. CONCLUSION: HH exposure increases oxidative/nitrosative stress in heart tissue and Que is an effective cardioprotective agent, which further supports the oxidative cardiac dysfunction induced by hypoxia.

Characterization and biological effects of Hypericum extracts on experimentally-induced - anxiety, oxidative stress and inflammation in rats.

Anxiety disorders can associate with oxidative stress and immune system alterations. Our study aimed to chemically analyze Hypericum maculatum (HM) and Hypericum perforatum (HP) dry extracts and to evaluate their effects along with quercetin (Q), on brain oxidative stress biomarkers: malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD), inflammatory cytokines: interleukin-1α, (IL-1α), IL-1ß, regulated on activation normal T cell expressed and secreted (RANTES), interferon (IFN), monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein (MIP) and serum corticosterone levels. Nuclear transcription factor κB (NFκB) signaling pathway in the hippocampus and frontal lobe in rats with N-methyl-9H-pyrido[5,4-b]indole-3-carboxamide (FG-7142) experimental-induced anxiety were also investigated. The chemical analyses of total hypericins were performed by spectrophotometric analysis and hypericin, hyperforin and polyphenols derivatives were quantified by chromatographic methods. The animals were divided in 6 groups: carboxymethylcellulose 2% (CMC); CMC + FG; alprazolam (APZ) + FG; Q + FG; HM + FG; HP + FG. APZ (0.08 mg/kg b.w.), Q (30 mg/kg b.w.), HM and HP (350 mg/kg b.w.) were orally administered for 21 days. FG (7.5 mg/kg b.w.) was intraperitoneally (i.p.) injected in a single dose. Q and hypericum extracts (HpE) exerted anti-inflammatory (decreased IL-1α, IL-1ß, MCP1, IFN and MIP mainly in hippocampus) and antioxidant effects (decreased MDA levels, increased CAT and SOD activity), enhanced NFκB and pNFκB expressions in the brain and reduced serum corticosterone levels. Our findings suggest that HpE may improve anxiety-like behavior, offer brain protection by modulation of oxidative stress and inflammation, and can contribute to overall biological activity of natural compounds-rich diet.

How practical experiences, educational routes and multidisciplinary teams influence genetic counselors' clinical practice in Europe.

The main objective of our study was to explore whether, and to what extent, genetic counselors' characteristics impact on their tasks in practice. Specifically, we explored the complementariness between genetic counselors and medical geneticists and therefore looked at the most relevant tasks of genetic counselors, according to genetic counselors themselves and according to the medical geneticists they work with. A total of 104 genetic counselors and 29 medical geneticists from 15 countries completed a purposefully designed questionnaire. Results showed that most genetic counselors in Europe perform similar tasks, irrespective of their backgrounds. When looking at the factors influencing genetic counselors' roles data showed that the type of tasks performed by genetic counselors is associated with the years of experience in the field, not with their background or education. Of particular interest was the consensus between genetic counselors and medical geneticists regarding the genetic counselor's role. Not surprisingly, tasks with more psychosocial implications were seen as genetic counselors' eligibility while tasks with more medical implications were seen as medical geneticists' attribution. Our study shows that most genetic counselors work in tune with international recommendations and seem to be supportive of multidisciplinary teams. Corroborating our data with previous research, we discuss potential implications for practice and training in genetic counseling.

Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant.

The sensitivity of coupled enantioselective capillary electrophoresis-mass spectrometry (CE-MS) of amino acids (AAs) is often hampered by the chiral selectors in the background electrolyte (BGE). A new method is presented in which the use of a chiral selector is circumvented by employing (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as chiral AA derivatizing agent and ammonium perfluorooctanoate (APFO) as a volatile pseudostationary phase for separation of the formed diastereomers. Efficient AA derivatization with FLEC was completed within 10 min. Infusion experiments showed that the APFO concentration hardly affects the MS response of FLEC-AAs and presents significantly less ion suppression than equal concentrations of ammonium acetate. The effect of the pH and APFO concentration of the BGE and the capillary temperature were studied in order to achieve optimized enantioseparation. Optimization of CE-MS parameters, such as sheath-liquid composition and flow rate, ESI and MS settings was performed in order to prevent analyte fragmentation and achieve sensitive detection. Selective detection and quantification of 14 chiral proteinogenic AAs was achieved with chiral resolution between 1.2 and 8.6, and limits of detection ranging from 130 to 630 nM injected concentration. Aspartic acid and glutamic acid were detected, but not enantioseparated. The optimized method was applied to the analysis of chiral AAs in cerebrospinal fluid (CSF). Good linearity (R(2) > 0.99) and acceptable peak area and electrophoretic mobility repeatability (RSDs below 21% and 2.4%, respectively) were achieved for the chiral proteinogenic AAs, with sensitivity and chiral resolution mostly similar to obtained for standard solutions. Next to l-AAs, endogenous levels of d-serine and d-glutamine could be measured in CSF revealing enantiomeric ratios of 4.8%-8.0% and 0.34%-0.74%, respectively, and indicating the method's potential for the analysis of low concentrations of d-AAs in presence of abundant l-AAs.

Abdominal Obesity and Type 2 Diabetes Mellitus are Associated With Higher Seric Levels of IL 4 in Adults.

AIMS: Study of IL4 in relation to the anthropometric, biochemical and immunological parameters in patients with obesity and/or diabetes. METHODS: The relationship between IL4 and clinical and biological parameters was studied in 76 patients divided into 4 groups: obese diabetics (OD), n = 25; obese without diabetes (O), n = 25; non obese diabetics (NOD), n = 11; controls (M), n = 15. IL4 was determined using the ELISA method. Statistical analysis was done using the MedCalc statistical software, version 16.1. RESULTS: Serum IL4 was 0.38 ±0,40 pg / mL in the Control group, 0.366 (0,100-2,35) pg / ml in group O, 4.66±3.73 pg / ml in group OD, 0.30 (0.10-1.35) pg / ml in NOD. When IL4 levels were compared between the four groups, statistical significance was reached for the comparison between groups OD and M. Statistically significant correlations were detected between IL4 and age, waist circumference and hip circumference, blood glucose, glycated hemoglobin (HbA1c), VLDL, triglycerides and serum protein fraction ß1. In univariate regression, the IL4 level predictors were age, height, BMI, abdominal circumference, hip circumference, beta 1% glucose, HbA1c, total lipids, total cholesterol, VLDL triglycerides, CRP. In multivariate regression, waist circumference and glycemia were significant predictors of levels of IL4 (p = 0.0001).

Genotype-phenotype correlation in multiresistant Escherichia coli and Klebsiella pneumoniae strains isolated in Western Romania.

OBJECTIVE: Bacterial multidrug-resistance (MDR) to antimicrobials has become an important public health issue all over the world and it involves both hospital and community-acquired strains. MATERIALS AND METHODS: A number of 75 Escherichia coli and 77 Klebsiella pneumoniae (K.) strains identified in biological samples collected from community (CA) and hospital-acquired (HA) infections were found to be resistant to the third generation cephalosporins. Of these, 93 MDR strains were subjected to microarray analysis to detect the expression of 31 antimicrobial resistance genes. RESULTS: We found that all HA extended-spectrum ß-lactamase (ESBL) producing E. coli strains had at least one resistance gene to third generation cephalosporins, while in 54% of all CA strains genetic substrates justifying their antibiotic resistance were identified. Almost 81% of HA-ESBL (Extended-Spectrum ß Lactamase) K. pneumoniae strains had at least one resistance gene to third generation cephalosporins, while in only 6% of the CA strains a similar genotype was identified. In the HA group, the blaCTX-M-15 genotype proved to be most frequent in multidrug-resistant E. coli strains and second most frequent (after ampC) in K. pneumoniae, while in the CA group, this genotype was the fourth most frequent in ESBL E. coli (after ampC, sul1, tet(R)). CONCLUSIONS: Overall, in 67% of all ESBL producing Enterobacteriaceae strains a genetic substrate justifying the resistance to beta-lactam antibiotics was identified; most of the remaining 33.33% strains were CA with a predominance of K. pneumoniae, in which a different antibiotic resistance genetic substrate (outside the detection limit of the kit used in this study) might have been involved.

Adiponectin predicts cardiovascular events in diabetes dialysis patients.

OBJECTIVES: Adiponectin is an insulin-sensitizing, anti-inflammatory adipokine with anti-atherogenic actions in the general population. In dialysis patients it is unclear whether adiponectin conserves its protective value or is, on the contrary, associated to worse prognosis. We assessed the predictive value of adiponectin for atherosclerosis related cardiovascular events in type 2 diabetic dialysis patients. DESIGN AND METHODS: Prevalent diabetic dialysis patients from three dialysis units (n=77) were enrolled in a 3years' prospective observational study. Serum adiponectin, clinical and laboratory parameters were determined at baseline; new occurrence of atherosclerosis related events (coronary events, atherosclerosis obliterans, and stroke) was recorded. RESULTS: Baseline adiponectin was 17.25(9.53-31.97) µg/mL and significantly correlated to HDL cholesterol (r=0.29, p=0.01), triglycerides (r=-0.40, p=0.0004), ferritin (r=-0.29, p=0.02), transferrin (r=-0.28, p=0.02), and uric acid (r=-0.24, p=0.04). In multivariate analysis association to triglycerides (p=0.001), HDL cholesterol (p=0.01) and ferritin (p=0.04) remained significant. 36 new fatal and non-fatal new cardiovascular events occurred, 29 patient died. Cox proportional regression analysis showed that adiponectin below or above a ROC-derived cut-off of 27.33µg/mL significantly influenced event-free survival: hazard ratio (HR) 2.48, 95% confidence interval (CI) (1.09-5.66), p=0.031 along with fasting glucose HR 1.01, 95%CI(1.00-1.02), p=0.01 and history of cardiovascular events at inclusion HR 3.16, 95%CI(1.36-7.32), p=0.007. In multivariate analysis baseline adiponectin HR 5.02, 95%CI(0.98-25.06), p=0.05 and glycemia HR 1.01, 95%CI(1.00-1.02), p=0.01 influenced event-free survival. Adiponectin also predicted cardiovascular events in patients without cardiovascular disease at inclusion but was not associated to overall mortality. CONCLUSIONS: In diabetes dialysis patients low adiponectin favors occurrence of atherosclerosis related cardiovascular events.

Oxidative stress in blood and testicle of rat following intraperitoneal administration of aluminum and indium.

Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects, oxidative stress being one of the possible mechanisms involved in their cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip) administration induced histological disorganization of testicular tissue. In the present research we aimed at investigating the effect of Al and In ip administration on systemic and testicular oxidative stress status. Studies were performed on Wistar rats ip injected with Al, In or physiological solution for two weeks. Our results showed that In significantly decreased the absolute weight of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON) activities showed that In induced a significant augmentation in the first parameter but no changes were observed in the second. Both Al and In caused oxidative stress in testicles by increasing malondialdehyde (MDA) and protein carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH) level were enhanced in the testicles. In the blood, while concentrations of MDA was not changed, those of GSH was significantly decreased in the Al and In groups. Our results indicated that Al and In cause oxidative stress both in blood and testicles but In has cytotoxic effect as well as negative impact on testicle weights. These findings could explain the testicular histological alterations previously described after In ip administration.

Histological findings in the Wistar rat cornea following UVB irradiation.

The acute clinical effect of UVR on the eye is photokeratitis, which is an inflammatory state that might be regarded as the sunburn of the eye. In this study, we used a rat model to assess the histological injuries induced in the intact rat cornea following its exposure to UVB radiation. A total of 15 two-months-old female Wistar rats were purchased from the Animal Facility of "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. The rats were fed ad libitum and kept under standard conditions with a 12 hours light/dark cycle. The rats were randomly divided into five groups, including control group (no UVB exposure), group II (a single exposure to a dose of 45 mJ UVB/cm(2) for 47 seconds), group III (a single exposure to 90 mJ UVB/cm(2) for one minute and 57 seconds), group IV (a single exposure to 180 mJ UVB/cm(2) for three minutes and 57 seconds), and group V (a single exposure to 360 mJ UVB/cm(2)² for five minutes and 26 seconds). After 24 hours of recovery, the rats were sacrificed by cervical dislocation. The rat eyes were extracted, harvested and fixed in 10% buffered formalin. The eye samples were then processed through paraffin technique for further histological examination. We found that, following the UVB exposure, the cornea showed significant inflammatory responses (infiltration of polymorphonuclear leukocytes), hemorrhage and gross damages such as superficial and deep ulcerous keratitis and epithelial exfoliation. The severity of these findings was associated with the increase of UVB radiation intensity and exposure period.

Total necrotizing colitis proximal to obstructive left colon cancer: case report and literature review.

BACKGROUND: Necrotizing colitis (NC) is a rare complication of the obstructive cancer of the left colon and it is the result of intramural ischemia due to impairment of blood supply secondary to increased endoluminal pressure. CASE PRESENTATION: A 70 years old patient with significant comorbidities (ASA 4) was admitted for intestinal obstruction.The extensive necrosis of the entire proximal colon secondary to an obstructive sigmoid colon cancer has been diagnosed intraoperatively. Total colectomy and terminal ileostomy have been performed. The postoperative course was uneventful and the ileostomy closure with ileo-rectal anastomosis was performed 7 months later. A review of the literature discussing the epidemiology, pathogenesis, diagnosis and therapeutic approach of this type of colitis, was performed. CONCLUSIONS: NC implies diagnosis and therapeutic difficulties,especially from point of view of surgical strategy. We advocate of large colic resections, beyond the macroscopic limits of the necrosis in order to avoid the postoperative complications. We also consider seriate surgical procedures as a good choice for the high risk patients.

The effects of chitosan and low dose dexamethasone on extrahepatic cholestasis after bile duct ligation in Wistar rats.

UNLABELLED: Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction. AIM: To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats. MATERIALS AND METHODS: Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index. RESULTS: BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly. CONCLUSION: BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings.

Effects of exogenous antioxidants on oxidative stress in pregnancy.

OBJECTIVE: The present study evaluated the effects on gestation, in terms of oxidative stress, of two antioxidant factors-vitamin E and coenzyme Q10-during pregnancy, with the purpose of applying the results in further human clinical practice. METHODS: For each aspect we have studied, we used three types of female rats of Wistar race (un-pregnant, primiparous, multiparous), divided in 10 rats/group. From the blood we have sampled, we have determined the oxidative stress (OS) markers: malondialdehyde (MDA) and carbonylated proteins (CP), but also the markers of the antioxidant defense: the hydrogen donor capacity of the plasma (HD) and the sulfhydryl groups (SH). RESULTS: Vitamin E administration determines significant decreases of MDA and significant increases of CP and HD at primiparous, and also significant increases of SH groups at multiparous. In the case of pregnant animals that received CoQ10 in antioxidant complexes, we have observed an increase of oxidative stress (OS)-MDA in primiparous and CP in multiparous. CONCLUSIONS: In the case of Vitamin E, taking into account the benefits on redox homeostasis, the decrease of OS, the authors recommend vitamin E administration during pregnancy. However, because of the increase of the OS in the case of pregnant animals, the authors do not recommend the administration of CoQ(10) in antioxidant complexes during pregnancy.

Non-invasive oxidative stress markers for liver fibrosis development in the evolution of toxic hepatitis.

Oxidative stress is related to the liver fibrosis, anticipating the hepatic stellate cells' (HSC) activation. Our aim was to correlate oxidative stress markers with the histological liver alterations in order to identify predictive, noninvasive parameters of fibrosis progression in the evolution of toxic hepatitis.CCl4 in sunflower oil was administered to rats intragastrically, twice a week. After 2, 3, 4 and 8 weeks of treatment, plasma levels of malondialdehyde (MDA), protein carbonyls (PC), hydrogen donor capacity (HD), sulfhydryl groups (SH), and glutathione (GSH) were measured and histological examination of the liver slides was performed. Dynamics of histological disorders was assessed by The Knodell score. Significant elevation of inflammation grade was obtained after the second week of the experiment only (p=0.001), while fibrosis started to become significant (p=0.001) after 1 month of CCl4 administration. Between plasma MDA and liver fibrosis development a good correlation was obtained (r=0.877, p=0.05). Correlation between PC dynamics and liver alterations was marginally significant for inflammation grade (r=0.756, p=0.138). HD evolution revealed a marginally inverse correlation with inflammation grade (r=-0.794, p=0.108). No correlations could be established for other parameters with either inflammation grade or fibrosis stage.Our study shows that MDA elevation offers the best prediction potential for fibrosis, while marginal prediction fiability could be attributed to high levels of plasma PC and low levels of HD.

Blood oxidative stress generation after intraperitoneal administration of functionalized single-walled carbon nanotubes in rats.

Single-walled carbon nanotubes (SWCNTs) have been proposed for various medical applications. However, their safety for human administration has not been yet fully demonstrated. In vitro studies have pointed oxidative stress as a mechanism involved in their cytotoxic effects. In the present study we have evaluated the capacity of DNA functionalized SWCNTs to induce oxidative stress in blood after intraperitoneal (ip) administration in rats. The presence of SWCNTs in blood was confirmed by Raman spectroscopy 30 minutes after their ip administration. Oxidative stress parameters (malondialdehyde - MDA, protein carbonyls - PC, antioxidant capacity measured as hydrogen donating capacity - HD, sulfhydryl groups - SH, glutathione - GSH and nitrites - NO) were assessed in blood at 3, 6, 24, respectively, and 48 hours after ip injection. MDA, PC and NO exhibited a significant increase at 3-6 hours interval from exposure, followed by a recovery trend. The levels of HD reached a bottom level at 6 hours after administration, while SH strongly decreased at 3 hours interval and increased slightly up to 48 hours without attending the initial values. GSH level recorded an increasing tendency at the 3rd hour, an incomplete recovery process at 24 hours followed by a secondary significant increase following a 48-hour interval. Significant inverse correlations were obtained between the PC and SH levels and between the NO and HD values. In conclusion, the ip administration of DNA functionalized SWCNT in rats results in oxidative stress generation in plasma, with a transient pattern of evolution.

On kinetics of phage adsorption.

Adsorption of lambda-phage on sensitive bacteria Escherichia coli is a classical problem but not all issues have been resolved. One of the outstanding problems is the rate of adsorption, which in some cases appears to exceed the theoretical limit imposed by the law of random diffusion. We revisit this problem by conducting experiments along with new theoretical analyses. Our measurements show that upon incubating lambda-phage with bacteria Ymel, the population of unbound phage in a salt buffer decreases with time and in general obeys a double-exponential function characterized by a fast (tau(1)) and a slow (tau(2)) decay time. We found that both the fast and the slow processes are specific to interactions between lambda-phage and its receptor LamB. Such specificity motivates a kinetic model that describes the interaction between the phage and the receptor as an on-and-off process followed by an irreversible binding. The latter may be a signature of the initiation of DNA translocation. The kinetic model successfully predicts the double exponential behavior seen in the experiment and allows the corresponding rate constants to be extracted from single measurements. The weak temperature dependence of the reversible and the irreversible binding rate suggests that phage retention by the receptor is entropic in nature and that a molecular key-lock interaction may be an appropriate description of the interaction between the phage tail and the receptor.