Comparison between hepatic and renal effects in rats treated with arsenic and/or antioxidants during gestation and lactation

The aim of this study was to determine whether biochemical changes occurred in the liver and kidney of arsenic (As) exposed pups during gestation and lactation, and investigate the potential beneficial role of antioxidants against arsenic exposure damage. Pregnant wistar rats received the following treatments as drinking water: (1) distilled water; (2) arsenic (50 mg/L); (3) antioxidants: zinc (20 mg/L) + vitamin C (2 g/L) + vitamin E (500 mg/L); (4) arsenic (50 mg/L) + antioxidants. As- intoxicated pups showed significant decreases in liver cholesterol and triglyceride concentration, whereas Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were increased. Treatment with antioxidants returns these values to control ones. TBARS production in both organs and liver glutathione peroxidase (GPx) activity also increased whereas catalase (CAT) activity in both organs decreased in arsenic-exposed pups; the antioxidant administration only recover TBARS concentration to control values. Our findings suggest that administration of antioxidants during gestation and lactation could prevent some of the negative effects of arsenic.     

Possible recovery from an acute envenomation in male rats with LD50 of Echis coloratus crude venom: I-A seven days hematological follow-up study

The effect of an acute LD₅₀ dose of Echis coloratus crude venom in male albino rats was tested on blood parameters: white blood cells (WBCs), red blood cells (RBCs), platelets count, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC), also serum glucose, total protein, triglycerides with alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) enzyme activities. The effect of the LD₅₀ dose was monitored over a period of seven days, with time intervals of 1, 3, 6, 12, 24, 72 h. All of the tested parameters show fluctuations with time and with tendency to regain normal control level after 12 h. At 12–24 h it seems to be crucial for the process of physiological recovery, in spite of the irreversible damage and tissue distraction. The process of physiological adaptation and recovery from the lethal destructive venom effect seems to stabilize after one week, leaving the animal alive with several biochemical altered metabolisms and disturbed physiological profile.     

Application of recombinant Bacillus subtilis γ-glutamyltranspeptidase to the production of l-theanine

l-Theanine, which has seen increasing use in the functional food industry, can be prepared via enzymatic synthesis using γ-glutamyltranspeptidase (GGT; EC 2.3.2.2). In this study, the GGT from Bacillus subtilis 168 was cloned and expressed as a secreted protein using Escherichia coli BL21(DE3). The enzymatic properties of the GGT and the optimal conditions for the enzymatic synthesis of l-theanine were investigated in detail. The activity of the enzyme was optimal at pH 10; the optimal temperature was 50 °C. Desirable pH stability was observed between pH 5 and pH 12, and adequate thermostability was seen at 50 °C. In 5 h at 37 °C, the enzyme converted 200 mM l-glutamine and 2.2 M ethylamine to l-theanine with a final yield of 78%. Yields of l-theanine decreased to 58% when using 500 mM Gln and 45% when using 1 M Gln. The yield of l-theanine obtained at high substrate concentration provides the basis for the industrial-scale production of l-theanine.     

Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.     

Efficiency of ginger (Zingbar officinale) against Schistosoma mansoni infection during host–parasite association

The possible protective effect of ethanolic extract of ginger against infection with Schistosome mansonii was evaluated in mice. The extract was given daily for 45 days beginning at either 2nd day or 45 days post infection. Oral supplementation of ginger extract to infected animals was effective in reducing worm burden and the egg load in the liver and intestine which coincided with the reduction in granuloma diameters. Ginger extract had also the effect to offset liver fibrosis in response to S. mansoni infection indicated by reduced liver hydroxyproline level and serum alpha–fetoprotein (AFP). The extract reduces some inflammatory mediators that play a crucial role in schistosomal liver fibrosis and its complications. These include liver xanthine oxidase (XO); nitric oxide (NO); tumour necrosis factor–alpha (TNF-α); immunoglobins E, G, and M (Ig-E, Ig-G and Ig-M, respectively), and interleukin 4, 10 and 12 (IL-4, IL-10 and IL-12, respectively). Administration of ginger extract ameliorated the infection-induced alterations in serum gamma-glutamyl transferase (GGT), alanine amintransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). It was concluded that oral administration of ginger extract to S. mansoni infected mice could minimize the deleterious effects of this parasite on the vital functions of infected animals.     

A Fraxinus excelsior L. seeds/fruits extract benefits glucose homeostasis and adiposity related markers in elderly overweight/obese subjects: A longitudinal,randomized, crossover,double-blind,placebo-controlled nutritional intervention study

PurposeThe aim of this study was to investigate the potential benefits of an extract obtained from seeds/fruits of an Oleaceae (Fraxinus excelsior L.) on glucose homeostasis and associated metabolic markers in non-diabetic overweight/obese subjects.Materials and methodsThis study was performed in 22 participants (50–80 years-old; BMI 31.0 kg/m²). The design was a longitudinal, randomized, crossover, double-blind, placebo-controlled 7-week nutritional intervention. The participants received daily 3 capsules each containing either 333 mg of an extract from Fraxinus excelsior L. seeds (Glucevia^®) or placebo capsules (control) in a random order for 3 weeks with 1 week of washout between treatments. Moreover, they followed a balanced covert energy-restricted diet (−15% energy). All variables were measured at the beginning and at the end of each period.ResultsCompared to baseline, the administration of 1 g of Glucevia^® for 3 weeks resulted in significantly lower incremental glucose area under the curve (−28.2%; p < 0.01), and significantly lower 2 h blood glucose values (−14%; p < 0.01) following an oral glucose tolerance test. No significant changes were found in the control group (−7.9% AUC, −1.6% 2 h blood glucose). Furthermore, significant differences were found between responses in the control and Glucevia^® groups with respect to serum fructosamine and plasma glucagon levels (p < 0.01 and p < 0.05, respectively). Interestingly, administration of Glucevia^® significantly increased the adiponectin:leptin ratio (p < 0.05) and decreased fat mass (p < 0.01) compared to control (p < 0.05).ConclusionThe administration of an extract from Fraxinus excelsior L. seeds/fruits in combination with a moderate hypocaloric diet may be beneficial in metabolic disturbances linked to impaired glucose tolerance, obesity, insulin resistance and inflammatory status, specifically in older adults.     

Effects of supplementation with plant extract product containing carvacrol,cinnamaldehyde and capsaicin on serum metabolites and enzymes during the finishing phase of feedlot-fed bull calves

This study investigated the in vivo effects of a commercial blend of plant extracts (carvacrol, cinnamaldehyde and capsaicin) on serum metabolic parameters closely connected with energy and protein metabolism (glucose; l-lactate; non-esterified fatty acids, NEFA; urea nitrogen, SUN; creatinine; total protein, TSP) and enzymes associated with hepatic function (aspartate-aminotransferase, AST and gamma-glutamyl transferase, GGT) in finishing-stage Belgian Blue bull calves maintained in a commercial feedlot. Monitoring was performed over 86 days in 24 animals randomly allotted to two groups: (1) a control group (CTR, no supplementation; n = 10), and (2) a group receiving dietary supplementation with a commercial blend of plant extracts (PEX, 100 mg/kg DM of concentrate; n = 14). Under the conditions of our study, supplementation with the commercial blend did not give detrimental effects, but the opposite: the decrease in serum l-lactate, NEFA and creatinine levels and the increase in SUN concentrations; suggests an improvement in the energy status and protein turnover of the supplemented animals.     

Local control rates in stereotactic body radiotherapy (SBRT) of lung metastases associated with the biologically effective dose

AimTo evaluate dose differences in lung metastases treated with stereotactic body radiotherapy (SBRT), and the correlation with local control, regarding the dose algorithm, target volume and tissue density.BackgroundSeveral studies showed excellent local control rates in SBRT for lung metastases, with different fractionation schemes depending on the tumour location or size. These results depend on the dose distributions received by the lesions in terms of the tissue heterogeneity corrections performed by the dose algorithms.Materials and methodsForty-seven lung metastases treated with SBRT, using intrafraction control and respiratory gating with internal fiducial markers as surrogates (ExacTrac, BrainLAB AG), were calculated using Pencil Beam (PB) and Monte Carlo (MC) (iPlan, BrainLAB AG).Dose differences between both algorithms were obtained for the dose received by 99% (D_99%) and 50% (D_50%) of the planning treatment volume (PTV). The biologically effective dose delivered to 99% (BED_99%) and 50% (BED_50%) of the PTV were estimated from the MC results. Local control was evaluated after 24 months of median follow-up (range: 3–52 months).ResultsThe greatest variations (40.0% in ΔD_99% and 38.4% in ΔD_50%) were found for the lower volume and density cases. The BED_99% and BED_50% were strongly correlated with observed local control rates: 100% and 61.5% for BED_99% > 85 Gy and <85 Gy (p < 0.0001), respectively, and 100% and 58.3% for BED_50% > 100 Gy and <100 Gy (p < 0.0001), respectively.ConclusionsLung metastases treated with SBRT, with delivered BED_99% > 85 Gy and BED_50% > 100 Gy, present better local control rates than those treated with lower BED values (p = 0.001).     

ZnO nanoparticles augment ALT,AST, ALP and LDH expressions in C2C12 cells

The present study aimed to investigate the effect of ZnO nanoparticles on alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) enzyme expressions in C2C12 cells. ZnO nanoparticles are widely used in the several cosmetic lotions and other biomedical products. Several studies report on ZnO nanoparticle mediated cytotoxicity. However, there are no reports on the effect of ZnO nanoparticles on ALT, AST, ALP and LDH enzyme expressions in C2C12 cells. A cytotoxicity assay was carried out to determine the effect of ZnO nanoparticles (1–5 mg/ml) on C2C12 cell viability at 48 and 72 h. ZnO nanoparticles increased ALT, AST, ALP and LDH enzyme mRNA expression and their activities in C2C12 cells. In conclusion, the present study showed that ZnO nanoparticles increased these enzyme activities and its mRNA expression in C2C12 cells in a dose-dependent manner.     

Optimization of an ultra-fast silicon detector for proton and carbon beams using GEANT4 Monte Carlo toolkit

AimThe purpose of this study was to investigate the crosstalk effects between adjacent pixels in a thin silicon detector with 50 um thickness.BackgroundThere are some limitations in the applications of detectors in hadron therapy. So it is necessary to have a detector with concurrent excellent time and resolution. In this work, the GEANT4 toolkit was applied to estimate the best value for energy cutoff in the thin silicon detector in order to optimize the detector.Materials and MethodsGEANT4 toolkit was applied to simulate the transport and interactions of particles. Calculations were performed for a thin silicon detector (2 cm × 2 cm×0.005 cm) irradiated by proton and carbon ion beams. A two-dimensional array of silicon pixels in the x-y plane with 100 um × 100 um × 50 um dimensions build the whole detector. In the end, the ROOT package is used to interpret and analyze the resultsResultsIt is seen that by the presence of energy cutoff, pixels with small deposited energy are ignored. The best values for energy cutoff are 0.01 MeV and 0.7 MeV for proton and carbon ion beams, respectively. By applying these energy cutoff values, efficiency and purity values are maximized and also minimum output errors are achieved.ConclusionsThe results are reasonable, good and useful to optimize the geometry of future silicon detectors in order to be used as beam monitoring in hadron therapy applications.     

Overcoming Clinical Inertia in the Management of Postoperative Patients with Diabetes

ObjectiveTo assess the impact of an intervention designed to increase basal-bolus insulin therapy administration in postoperative patients with diabetes mellitus.MethodsEducational sessions and direct support for surgical services were provided by a nurse practitioner (NP). Outcome data from the intervention were compared to data from a historical (control) period. Changes in basalbolus insulin use were assessed according to hyperglycemia severity as defined by the percentage of glucose measurements > 180 mg/dL.ResultsPatient characteristics were comparable for the control and intervention periods (all P ≥ .15). Overall, administration of basal-bolus insulin occurred in 9% (8/93) of control and in 32% (94/293) of intervention cases (P < .01). During the control period, administration of basal-bolus insulin did not increase with more frequent hyperglycemia (P = .22). During the intervention period, administration increased from 8% (8/96) in patients with the fewest number of hyperglycemic measurements to 60% (57/95) in those with the highest frequency of hyperglycemia (P < .01). The mean glucose level was lower during the intervention period compared to the control period (149 mg/dL vs. 163 mg/dL, P < .01). The proportion of glucose values > 180 mg/dL was lower during the intervention period than in the control period (21% vs. 31% of measurements, respectively, P < .01), whereas the hypoglycemia (glucose < 70 mg/dL) frequencies were comparable (P = .21).ConclusionAn intervention to overcome clinical inertia in the management of postoperative patients with diabetes led to greater utilization of basal-bolus insulin therapy and improved glucose control without increasing hypoglycemia. These efforts are ongoing to ensure the delivery of effective inpatient diabetes care by all surgical services. (Endocr Pract. 2014;20:320-328)     

High intensity interval exercise decreases IL-8 and enhances the immunomodulatory cytokine interleukin-10 in lean and overweight–obese individuals

PurposeTo compare the effects of two interval exercises with different intensities on acute inflammatory response in lean and overweight–obese subjects.MethodsTen lean (BMI < 24.9 kg/m²) and 12 overweight–obese (BMI 25 to <34.9 kg/m²) males performed two conditions in randomly assigned: (1) high intensity interval exercise (HIIE) 10 × 60 s (85–90%P_Max)/75 s (50%P_Max); (2) moderate intensity interval exercise (MIIE) 10 × 60 s (70–75%P_Max)/60 s (50%P_Max), with blood collections at pre, immediately and 30 min post each exercise bouts to evaluate total and differential leukocyte counts, serum creatine kinase (CK), lactate dehydrogenase (LDH) and systemic levels of IL-1ra, IL-6, IL-8, IL-10, IL-17a and CCL2.ResultsIn lean group, HIIE induced a significant increase in total leukocytes and monocyte, while MIIE session did not change the number of leukocytes. Overweight–obese group presented similar increase in leukocytes, monocytes and lymphocytes in both HIIE and MIIE sessions. At baseline, overweight–obese group showed high levels of CK, IL-8, IL-6 and CCL2 and lower concentrations of IL-10 compared to lean group. The MIIE did not alter the cytokine concentrations in both groups, independently of the time analysis. The HIIE induced significant decrease in IL-8 levels 30 min post session in both the groups, and a progressive elevation in IL-10 levels immediately and 30 min post in lean and overweight–obese. Regarding IL-6, overweight–obese subjects presented progressive increase either immediately and 30 min after HIIE, while lean individuals presented significant increase only 30 min after exercise.ConclusionsThe acute inflammatory response to interval exercise is intensity-dependent. Although obesity influences the basal concentrations of several cytokines, only HIIE induced important alterations in IL-8 and IL-10 levels, which may have important implications in the control of chronic low-grade inflammation in obesity.     

Study of pharmacodynamic interaction of Phyllanthus emblica extract with clopidogrel and ecosprin in patients with type II diabetes mellitus

BackgroundDiabetes mellitus is associated with oxidative stress which impairs the platelet function. Phyllanthus emblica extract a rich source of vitamin C plays an important role in scavenging free radicals. The effect of vitamin C on platelet aggregation in healthy and coronary artery disease patients has been demonstrated. The present study attempts to study the pharmacodynamic interactions of P. emblica extract with clopidogrel and ecosprin.Materials and methodsThis was a randomized open label crossover study of 10 type II diabetic patients. The dosage schedules were either single dose of 500 mg P. emblica extract or 75 mg clopidogrel or 75 mg ecosprin or 500 mg P. emblica + 75 mg clopidogrel or 500 mg P. emblica + 75 mg ecosprin. After single dose study and washout period, patients received either 500 mg P. emblica extract twice daily or 75 mg clopidogrel or 75 mg ecosprin once daily or combinations for 10 days. Platelet aggregation was measured at baseline and at 4 h of treatment after single and multiple dose study along with recording of bleeding and clotting time.ResultsAfter single and multiple dose administration of the three treatments and with combinations there was statistically significant decrease of platelet aggregation compared to baseline. Further, the mean percent inhibition of platelet aggregation was significant, when compared between single and multiple doses of P. emblica. The bleeding and clotting time was prolonged with single and multiple dose administration of all treatments compared to baseline. All treatments were well tolerated.ConclusionP. emblica extract demonstrated significant antiplatelet activity with both single and multiple dose administration.     

Cellular and nephrotoxicity of selenium species

ProjectBeside its useful functions at very low concentrations, selenium including supplementary Se sources pose a potential toxicological risk. The toxicity of selenium species was tested in HaCaT cell culture and related nephrotoxicity in mice.ProcedureThe apoptotic shrinkage and necrotic expansion of cells were measured by time-lapse image microscopy. Acute nephrotoxicity was estimated upon administration of various selenium species to mice for two weeks. To confirm or to refute the accumulation of Se in the kidney and its potential chronic effect, Se concentration in kidney tissue and histopathlology were tested.ResultsThe comparison of selenium species showed that organic lactomicroSe did not affect cell growth at 5 ppm, but inorganic nanoSe severely hampered it at lower concentration (1 ppm). The in vivo Se treatment (0.5, 5, 50 ppm, corresponding to 4, 40 and 400 μg/kg) was misleading as it did neither affect the outward appearance nor the weight of the kidney. Se accumulation was observed after selenate, selenite, SelPlex, selenite and nanoSe administration, while lactomicroSe caused no traceable accumulation. In vivo, ex vivo and in vitro experiments reflected this order of selenium toxicity: selenate > selenite > SelPlex = nanoSe > lactomicroSe.ConclusionWithin the tested species lactomicroSe was the only non-nephrotoxic selenium source recommended for nutritional Se supplementation.     

Comparison and relationship of thyroid hormones,IL-6, IL-10 and albumin as mortality predictors in case-mix critically ill patients

ObjectiveTo compare the ability of thyroid hormones, IL-6, IL-10, and albumin to predict mortality, and to assess their relationship in case-mix acute critically ill patients.MethodsAPACHE II scores and serum thyroid hormones (FT3, FT4, and TSH), IL-6, IL-10, and albumin were obtained at EICU admission for 79 cases of mix acute critically ill patients without previous history of thyroid disease. Patients were followed for 28 days with patient’s death as the primary outcome. All mean values were compared, correlations assessed with Pearson’ test, and mortality prediction assessed by multivariate logistic regression and ROC.ResultsNon survivors were older, with higher APACHE II score (p = 0.000), IL-6 (p < 0.05), IL-10 (p = 0.000) levels, and lower albumin (p = 0.000) levels compared to survivors at 28 days. IL-6 and IL-10 had significant negative correlation with albumin (p = 0.001) and FT3 (p ⩽ 0.05) respectively, while low albumin had a direct correlation with FT3 (p < 0.05). In the mortality prediction assessment, IL-10, albumin and APACHE II were independent morality predictors and showed to have a good (0.70–0.79) AUC-ROC (p < 0.05). Despite that the entire cohort showed low FT3 serum levels (p = 0.000), there was not statistical difference between survivors and non-survivors; neither showed any significance as mortality predictor.ConclusionsIL-6 and IL-10 are correlated with Low FT3 and hypoalbuminemia. Thyroid hormones assessed at EICU admission did not have any predictive value in our study. And finally, high levels of IL-6 and IL-10 in conjunction with albumin could improve our ability to evaluate disease’s severity and predict mortality in the critically ill patients. When use in combination with APACHE II scores, our model showed improved mortality prediction.     

Extended rhodamine photosensitizers for photodynamic therapy of cancer cells

Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700 nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0 J cm⁻² laser light delivered at λ_max ± 2 nm with values of EC₅₀ of (2.8 ± 0.4) × 10⁻⁷ M for sulfur-containing analogue 6-S and (6.4 ± 0.4) × 10⁻⁸ M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10 J cm⁻² of broad-band light (EC₅₀’s ⩽ 2.4 × 10⁻⁷ M).     

A combination of ascorbic acid and α-tocopherol or a combination of Mg and Zn are both able to reduce the adverse effects of lindane-poisoning on rat brain and liver

The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of supplementation with ascorbic acid (Vit C) and α-tocopherol (Vit E) or with Mg and Zn upon lindane-induced damages in liver and brain. Under our experimental conditions, lindane poisoning (5 mg/kg body weight per day for 3 days) resulted in (1) an increased level of plasma glucose, cholesterol and triglycerides, (2) an increased activity of LDH, ALP, AST, ALT, (3) an oxidative stress in liver and brain as revealed by an increased level of lipids peroxidation (TBARS) and a decrease of glutathione-peroxidase, superoxide dismutase and catalase activities in liver and brain. In conclusion, both Vit C + E or Mg + Zn treatments display beneficial effects upon oxidative stress induced by lindane treatment in liver and brain.     

Importance of IL-10 and IL-6 during chronic hepatitis c genotype-1 treatment and their relation with IL28B

This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6 (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of each with clinical and virological characteristics, how they affect the response to combined therapy and their relation with the IL28B polymorphisms rs12979860. Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin (pegIFN-α/RBV) for 48 weeks, in the following samples: baseline, week-12 (during treatment) and week-72 (post-treatment). 77 patients (56%) presented Sustained Virological Response (SVR) and 61 (44%) were non-SVR. Multivariate logistic regression showed that age ? 40 years (aOR = 3.7, 95%CI = 1.5–8.9, P = 0.004), low activity of gamma glutamyl transferase (GGT) (aOR = 0.9, 95%CI = 0.98–0.99, P = 0.028), CC genotype of IL28B polymorphim (aOR = 2.7, 95%CI = 1.0–7.2, P = 0.044) and low IL-6 (aOR = 0.5, 95%CI = 0.3–1.0, P = 0.038) were predictor factors of virological response. In all patients, following treatment, IL-6 decreased at week-12 (P = 0.004) from baseline and had returned to basal values at week-72. Serum IL-10 concentration was significantly decreased at week-72 only in SVR patients (P ? 0.001). When patients were stratified by IL28B polymorphisms rs12979860 CC vs non-CC patients, a statistically significant decrease in IL-10 at week-72 in both groups was observed (P = 0.003 and P ? 0.001, respectively). None of the polymorphisms of IL-10 or IL-6 studied were associated with SVR.ConclusionsCC genotype of IL28B and low IL-6 serum concentration are factors associated independently with SVR. Moreover, decreased IL-10 at week-72 is associated with SVR in both CC and non-CC patients, and both factors are important to determine the effectiveness of treatment.     

Elements of margin of safety,toxicity and action of sodium selenite in a lipopolysaccharide rat model

ProjectBoth septic shock and sodium selenite (Na₂SeO₃) lead to multiple organ failure through oxidation. Na₂SeO₃ has direct oxidant effects above the nutritional level and indirect anti-oxidant properties.In a lipopolysaccharide (LPS) rat model we assessed margin of safety, toxicity and beneficial effect of pentahydrate Na₂SeO₃ (5H₂O·Na₂SeO₃) at oxidant doses.ProcedureIn a three-step study on 204 rats we: (i) observed toxic effects of Na₂SeO₃ injected intraperitoneously (IP) and determined its Minimum Dose Without Toxic effect (MDWT) 0.25–0.35 mg/kg selenium (Se) content; (ii) injected IP LPS at 70% lethal dose (LD) followed, or not, one hour later by IP Na₂SeO₃ at MDWT and (iii) by doses > MDWT. At 48 h, in survivors, we measured plasma creatinine, lactate, aspartate and alanine aminotransferase (AST, ALT), nitric oxide (NO) and Se concentrations.Results(i) Na₂SeO₃ alone did not increase NO and lactate. Encephalopathy appeared at 1 mg Se/kg. Creatinine increased at 1–1.75 mg Se/kg, AST, ALT at 3–4.5 mg Se/kg, and the minimum LD was 3 mg Se/kg. (ii) Mortality after LPS was 37/50 (74%, [62–86%]) vs. 20/30 (67%, [50–84%]) when followed by Na₂SeO₃ at MDWT (p = 0.483) with a decreased in NO (−31%, p = 0.038) a trend for lactate decrease (−19%, p = 0.068) and an increased Se in plasma of survivals. (iii) All rats died at doses ≥0.6 mg/kg (p < 0.001).ConclusionMechanisms of LPS and Na₂SeO₃ toxicity differ (i.e. NO, lactate). In septic shock 5H₂O·Na₂SeO₃ toxicity increased, margin of safety decrease, but IP administration of dose considered as oxidant of 5H₂O·Na₂SeO₃ showed beneficial effects.