Toxico-pathological changes induced by cypermethrin in broiler chicks: Their attenuation with Vitamin E and selenium

Ninety 1-day old broiler chicks of mixed gender (as hatched) procured from a local hatchery were randomly divided into five equal groups. All the treatments were given through crop tubing. Groups 1–4 received cypermethrin (CY) (600 mg kg^?1 b. wt.) daily for 30 days. In addition to CY (group 1), groups 2–4 received Vit E (150 mg kg^?1 b. wt.), Se (0.25 mg kg^?1 b. wt.), and Vit E (150 mg kg^?1 b. wt.)+Se (0.25 mg kg^?1 b. wt.), respectively. Group 5 served as control andreceived normal saline (2 ml kg^?1 b. wt.) for 30 days. Randomly selected six broiler chicks from each group were slaughtered at experimental days 10, 20 and 30 for the collection of serum/plasma and morbid tissues. Absolute organ weights were recorded. Total plasma proteins, fibrinogen and creatinine were significantly (P<0.05) increased while alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and urea decreased significantly (P<0.05) in CY-treated group when compared with the control group. Kidneys were swollen grossly in treated broiler chicks. In liver, necrosis of hepatocytes, cytoplasmic vacuolation, bile duct hyperplasia and mononuclear cellular infiltration were observed. In kidneys, necrosis of tubular epithelial cells, cytoplasmic vacuolation, cellular infiltration and atrophy of glomeruli were observed. Sub-arachnoid space was much dilated in CY-treated broiler chicks. It can be concluded that CY induces biochemical and histopathological alterations in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective in ameliorating toxic effects of cypermethrin in broilers chicks.     

Clinico-hematological and micronuclear changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium

This study was carried out on 90 one-day-old broiler chicks to know clinico-hematological alterations, DNA damage caused by cypermethrin (CY), and attenuation of toxic effects by vitamin E (Vit E) and selenium (Se). Birds were randomly divided into five equal groups. Groups 1–4 received CY (600 ml kg^?1 b.wt) daily for 30 days by crop tubing. In addition to CY, groups 2, 3 and 4 received Vit E (150 mg kg^?1 b.wt), Se (0.25 mg kg^?1 b.wt), and Vit E (150 mg kg^?1 b.wt)+Se (0.25 mg kg^?1 b.wt), respectively. Group 5 served as control. Birds were monitored twice daily for clinical signs. They were weighed and blood samples were collected at experimental days 10, 20 and 30 for hematological studies. CY-treated birds showed more prominent signs of toxicity compared to CY+Vit E, CY+Se and CY+Vit E+Se birds. Body weight in groups 1–3 was significantly (P<0.05) smaller at days 20 and 30 when compared with the control group. Significantly (P<0.001) higher numbers of micronuclei appeared in chicks treated with CY compared to CY+Vit E- and CY+Se-treated birds. Significantly decreased total erythrocyte counts (TEC), hemoglobin (Hb) concentration and packed cell volume (PCV) in all treated groups were recorded. Treated birds suffered from macrocytic hypochromic anemia. Leukocytosis in early stage and later leucopenia was seen in treated birds. It can be concluded that CY induces toxic effects in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective to ameliorate toxic effects of cypermethrin.     

Anzer honey prevents N-ethylmaleimide-induced liver damage in rats

N-ethylmaleimide (NEM) is a sulphydryl blocker which impairs the sulphydryl dependent antioxidant system (mainly glutathione) in the body by alkylating endogenous sulphydryls. This study was designed to investigate the effects of Anzer honey on NEM-induced liver injury in rats. Thirty female Wistar albino rats were divided equally into three groups. Group 1: control; Group 2: NEM; Group 3: Anzer honey+NEM. NEM (0.075 mg kg^?1) was given to both group 2 and 3 administered subcutaneously (s.c.) for 30 days. The animals in the Anzer honey+NEM group were treated with Anzer honey at a dose of 0.275 g kg^?1, (p.o.) at 1 h prior to every NEM injection. At the end of the 30 day treatment period, liver samples were taken for determination of the glutathione levels and histological examination. NEM treatment alone caused a significant reduction of the liver glutathione levels in group 2. Furthermore, NEM treatment caused congestion and mononuclear cell infiltration in the liver when compared to the control group. In group 3, Anzer honey treatment reversed all the changes in glutathione level, as well as histopathological alterations, normally induced by NEM. The findings imply that depletion of glutathione concentration plays a causal role in NEM-induced liver injury, and that the hepatoprotective effect of Anzer honey may be mediated through sulfhydryl-sensitive processes. They further imply that it may also possess antioxidant properties.     

Differential expression of androgen and estrogen receptors in PCB (Aroclor 1254)-exposed rat ventral prostate: Impact of alpha-tocopherol

Polychlorinated biphenyls (PCBs) are environmental toxicants, which affect male fertility by altering the androgen and estrogen levels. PCB-induced toxic manifestations are associated with the production of reactive oxygen species. Vitamin E (α-tocopherol) is a major lipophilic chain breaking antioxidant, which protects polyunsaturated fatty acids in tissues against peroxidation, a property that could be beneficial in the male reproductive biology. The purpose of this study was to determine the impact of α-tocopherol on PCB (Aroclor 1254)-induced changes in androgen receptor (AR) and estrogen receptors (ERs) expression in Wistar rat ventral prostate. Rats were divided into 3 groups of 6 animals each. Group I rats were administered corn oil (vehicle) intraperitoneally (i.p.); Group II rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.); Group III rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.) along with simultaneous oral supplementation of 50 mg kg^?1 day^?1 of α-tocopherol. Serum testosterone and estradiol titers were assayed. Prostatic acid phosphatase activity (PAcP), citric acid concentration, generation of hydrogen peroxide (H₂O₂) and lipid peroxides (LPO) were estimated. mRNA and protein expression of AR, ER-α and ER-β in ventral prostate were quantified. Serum testosterone, estradiol, PAcP, citric acid levels, AR and ER-α expressions were significantly decreased while H₂O₂ generation, LPO, ER-β were increased in PCB-exposed animals. Simultaneous supplementation of α-tocopherol in PCB-exposed rats resulted in significant restoration of all the parameters to the control. The results suggest that α-tocopherol has definite protective effect against PCB-induced toxicity in ventral prostatic dysfunction.     

Toxicity of methimazole on femoral bone in suckling rats: Alleviation by selenium

AimsSelenium has a pharmacological properties and it is well considered as an antioxidant. The present study investigated the potential ability of selenium, used as a nutritional supplement, to alleviate bone impairments in suckling rats whose mothers were treated with methimazole, an antithyroid drug.Main methodsFemale Wistar rats were randomly divided into four groups of six each: group I served as control which received standard diet; group II were rendered hypothyroid by administration of methimazole (250 mg L^?1 in their drinking water); group III received both methimazole (250 mg L^?1 in their drinking water) and selenium (0.5 mg kg^?1 of diet); group IV received 0.5 Na₂SeO₃ mg kg^?1 of diet. Treatments were started from the 14th day of pregnancy until day 14 after delivery.Key findingsMethimazole treatment decreased femur length and weight in 14-day-old rats, when compared to controls. Femur antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high femur malondialdehyde levels. Methimazole also caused a significant decrease in calcium and phosphorus levels in bone. Yet, in plasma and urine, they increased and decreased inversely. Besides, plasma total tartrate-resistant acid phosphatase was enhanced, while total alkaline phosphatase was reduced. Co-administration of selenium through diet improved the biochemical parameters cited above. Nevertheless, distorted histoarchitecture revealed in hypothyroid rat femur was alleviated by Se treatment.SignificanceThe present study suggests that selenium is an important protective element that may be used as a dietary supplement protecting against bone impairments.     

Folic acid induces acute renal failure (ARF) by enhancing renal prooxidant state

Systemic administration of folic acid (FA) in mice was used for studying the pathogenesis associated with acute renal failure (ARF). However, the mechanism by which FA induces ARF remains poorly understood. The present study therefore, was planned to investigate the effect of folic acid administration on prooxidant state and associated ultrastructural changes in renal tissue. Balb/c male mice of 4–6 weeks old were divided into control and two folic acid treatment groups (Groups A and B). The animals in group A were administered intraperitoneal injection of folic acid (100 mg kg^?1 body weight) for a period of 7 consecutive days while the animal in group B were administered a single intraperitoneal dose of folic acid (250 mg kg^?1 body weight). The renal tissues were collected and used for the analyses of lipid peroxidative indices and activities of antioxidant enzymes in renal tissues. To corroborate biochemical findings scanning electron microscopy (SEM) in renal tissue was studied. Folic acid treated animals demonstrated marked renal hypertrophy accompanied by severe impairment of renal function. Glutathione levels (GSH) and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) levels were significantly decreased and LPO levels increased following FA treatment. SEM results further substantiated the observed biochemical changes as evident by severe inflammation in glomeruli, swelling in primary and secondary pedicels, blebbing in villi, and tremendous deprivation of erythrocytes (RBCs) in FA treated kidneys. The present study therefore suggests that acute administration of folic acid leads to the generation of oxidative stress and altered membrane architecture responsible for folic acid induced ARF.     

An explanation of the mineralization mechanism in osteoblasts induced by calcium hydroxide

Calcium hydroxide (Ca(OH)₂) has been broadly used in endodontics, including apexification to obtain apical closure by mineralization. However, the detailed mechanism of mineralization induced by Ca(OH)₂ is still unclear. This study focuses on the function of calcium and hydroxyl ions which dissociate from Ca(OH)₂ during the mineralization process. Though primary osteoblasts cultured in the medium without or with 0.025 mg ml^?1 Ca(OH)₂ did not show mineralization, they did exhibit mineralization when they were cultured with a higher concentration of Ca(OH)₂ (0.25 mg ml^?1). Mineralization induced in the presence of 0.25 mg ml^?1 Ca(OH)₂ was greater at pH 7.4 than at pH 8.5. The high mineralization activity observed under neutral conditions was caused by the prolonged activation of p38 and JNK. Hydroxyl ions did not have any effect on the mineralization. The results demonstrate that calcium ions dissociated from Ca(OH)₂ are critical for inducing the mineralization of osteoblasts.     

Hepcidin-to-ferritin ratio: A potential novel index to predict iron overload-liver fibrosis in ß-thalassemia major

ObjectivesWe aimed to determine a threshold cutoff for hepcidin, ferritin, and the hepcidin-to-ferritin ratio in the diagnosis of liver fibrosis caused by iron overload in chronic hepatitis C virus (HCV)-free ß-thalassemia major patients .MethodsThis 1:1-matched case-control study included 102 individuals (3–30 yr.); 51 ß-thalassemia major patients with iron overload , and 51 apparently healthy individuals.ResultsThe highest areas under the receiver operating characteristic curves (AUC-ROCs) for the diagnosis of patients vs. controls had overlapping 95% confidence intervals (CIs): serum hepcidin (0.758; 0.64–0.87;    P ? 0.001), serum ferritin (1.000; 1.00–1.00; P  ?0.001), and the hepcidin/ferritin ratio (1.000; 1.00–1.00; P ? 0.001). For differentiation of patients with liver fibrosis stages of F0–F1 vs. F2–F4 and F0–F1 vs. F3–F4, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with P-values ? 0.001 were the only statistically significant parameters, while the AUC-ROCs of the hepcidin/ferritin ratio (0.631, P = 0.188 and 0.684, P = 0.098) exhibited 90% and 89.5% sensitivity, respectively, in staging liver fibrosis.ConclusionOur results showed that the hepcidin/ferritin ratio is as effective as the APRI and maybe a better predictor for the diagnosis of liver fibrosis and discriminating its stages, with excellent sensitivity and specificity compared to its components.     

Sub-chronic oral toxicity study in Sprague-Dawley rats with hypoxia mimetic cobalt chloride towards the development of promising neutraceutical for oxygen deprivation

The present study evaluates the toxicity from sub-chronic administration of CoCl₂ (12.5 mg cobalt kg^?1 BW for 7 days) to male Sprague-Dawley rats in view of the beneficial effects of CoCl₂ in animals and for developing efficacious therapeutic regimen in humans. 32 rats weighing 200±25 g were used for all experiments. Blood was collected for hematological and biochemical analysis and various organs were dissected after perfusion of animals under anesthesia for other analyses. Mean feed consumption and feed conversion efficiency values were comparable across all study groups; however, hematological analysis depicted a significant increase in hemoglobin, hematocrit and RBC in the entire cobalt-supplemented groups, which are a component of its beneficial effect. There was a significant increase in monocytes, granulocytes and WBC after 1 and 24 h, which were comparable with control after 7 days. Other biochemical analyses also showed no change with respect to control. Though the metal content increased significantly in liver initially (1 and 24 h) after treatment, it was equivalent to control after 7 days. Moreover, histopathological analysis revealed no evidence of changes that could be attributed to cobalt pretreatment. It is therefore reasonable to conclude that the present study supports further use of the present dose of CoCl₂, which was found to be nontoxic.     

Gene expression profile of mouse fibroblasts exposed to a biodegradable iron alloy for stents

Iron-based materials could constitute an interesting option for cardiovascular biodegradable stent applications due to their superior ductility compared to their counterparts – magnesium alloys. Since the predicted degradation rate of pure iron is considered slow, manganese (35% w/w), an alloying element for iron, was explored to counteract this problem through the powder metallurgy process (Fe–35 Mn). However, manganese presents a high cytotoxic potential; thus its effect on cells must first be established. Here, we established the gene expression profile of mouse 3T3 fibroblasts exposed to Fe–35 Mn degradation products in order to better understand cell response to potentially cytotoxic degradable metallic material (DMM). Mouse 3T3 cells were exposed to degradation products eluting through tissue culture insert filter (3 μm pore size) containing cytostatic amounts of 3.25 mg ml^?1 of Fe–35 Mn powder, 0.25 mg ml^?1 of pure Mn powder or 5 mg ml^?1 of pure iron powder for 24 h. We then conducted a gene expression profiling study from these cells. Exposure of 3T3 cells to Fe–35 Mn was associated with the up-regulation of 75 genes and down-regulation of 59 genes, while 126 were up-regulated and 76 down-regulated genes in the presence of manganese. No genes were found regulated for the iron powder. When comparing the GEP of 3T3 fibroblasts in the presence of Fe–35 Mn and Mn, 68 up-regulated and 54 down-regulated genes were common. These results were confirmed by quantitative RT-PCR for a subset of these genes. This GEP study could provide clues about the mechanism behind degradation products effects on cells of the Fe–35 Mn alloy and may help in the appraisal of its potential for DMM applications.     

Al2O3(w)–Al2O3(n)–ZrO2 (TZ-3Y)n multi-scale nanocomposite: An alternative for different dental applications?

The influence of the addition of Al₂O₃ whiskers (2.5 wt.% up to 30 wt.%) on Vickers hardness and fracture toughness in an Al₂O_3(n)+ZrO₂ (TZ-3Y)_n (90, 80 and 70 wt.%) composite was investigated. Green compacts were obtained by uniaxial pressing at 50 MPa and pressureless sintering at 1500 °C in air for 2 h. After sintering, relative densities ranging from 75% to 97% were reached. The whiskers resisted particle rearrangement owing to the extensive sliding distances along the whisker boundaries during sintering and the high length/diameter ratios. Sintering becomes more difficult with increasing whisker content, because whiskers come into contact with each other, forming a rigid network which hinders densification. The 2.5 wt.% Al₂O₃ whiskers + 27.5 wt.% Al₂O₃ nanoparticles + 70 wt.% TZ-3Y composite showed a hardness > 13 GPa and a maximum fracture toughness of 6.9 MPa m^?1/2, with an average grain size of 0.4 ± 0.17 μm. The observed crack deflection was an important mechanism in the improved fracture toughness of the composite. In addition, the grain size and residual porosity also seem to be factors in obtaining a wide range of hardness as well as fracture toughness by varying the Al₂O₃ whiskers and ZrO₂ (TZ-3Y) content. The use of alumina-whisker-reinforced composites in dental applications could be promising for increasing hardness and fracture toughness compared with other materials. The reported values for these composites can compete with those of commercially available materials in different dental applications.     

Control of cellular adhesiveness in an alginate-based hydrogel by varying peroxidase and H2O2 concentrations during gelation

An aqueous solution of alginate possessing phenolic hydroxyl (Alg-Ph) groups is gellable via a horseradish peroxidase (HRP)-catalyzed oxidative crosslinking reaction between Ph groups, consuming H₂O₂ as an electron acceptor. This study evaluates the effect of H₂O₂ and HRP concentrations on cellular adhesiveness and proliferation on the resultant enzymatically crosslinked Alg-Ph gels. After 4 h of seeding, 81.1% of L929 fibroblast cells adhere to an Alg-Ph hydrogel prepared with 1 U ml^?1 HRP and 1 mM H₂O₂. Increasing the concentration of H₂O₂ to 15 mM decreases the percentage of adhering cells to 28.4%. The cellular adhesion at this H₂O₂ concentration is increased to 82.6% by increasing the HRP concentration to 10 U ml^?1. The cells adhering to the Alg-Ph hydrogels with higher cellular adhesiveness establish a confluent monolayer during 168 h of culture. A cell sheet can then be harvested within 5 min of immersion in a medium containing alginate lyase at 1.0 mg ml^?1. The harvested cell sheet re-adhere, and the cells contained in the sheet proliferate after being transferred to another cell culture dish.     

In vitro cytotoxicity of porous silicon microparticles: Effect of the particle concentration,surface chemistry and size

We report here the in vitro cytotoxicity of mesoporous silicon (PSi) microparticles on the Caco-2 cells as a function of particle size fractions (1.2–75 μm), particle concentration (0.2–4 mg ml^?1) and incubation times (3, 11 and 24 h). The particle size (smaller PSi particles showed higher cytotoxicity) and the surface chemistry treatment of the PSi microparticles were considered to be the key factors regarding the toxicity aspects. These effects were significant after the 11 and 24 h exposure times, and were explained by cell–particle interactions involving mitochondrial disruption resulting from ATP depletion and reactive oxygen species production induced by the PSi surface. These events further induced an increase in cell apoptosis and consequent cell damage and cell death in a dose-dependent manner and as a function of the PSi particle size. These effects were, however, less pronounced with thermally oxidized PSi particles. Under the experimental conditions tested and at particle sizes >25 μm, the non-toxic threshold concentration for thermally hydrocarbonized and carbonized PSi particles was <2 mg ml^?1, and for thermally oxidized PSi microparticles was <4 mg ml^?1.     

The age- and gender-dependent effects of desflurane and sevoflurane on rat liver

ObjectiveThis study aimed to investigate the age- and gender-dependent effects of desflurane and sevoflurane on the liver.Material and methodUpon the approval of ethics committee, 84 rats were divided into four groups as 21 young male, 21 young female, 21 old male, and 21 old female rats. Then, each group was further divided into three groups as desflurane, sevoflurane, and control groups. Maintaining the minimum alveolar concentration of 1, desflurane at 6 vol% and sevoflurane at 2 vol% in 6 L min^?1 100% O₂ were administered for 2 h in a transparent plastic container of 40 cm×40 cm×70 cm. Each liver preparation was evaluated for hydropic degeneration, nuclear polymorphism, portal neutrophile infiltration, portal lymphocyte infiltration, and focal necrosis, and each preparation was assigned injury points of 0–3; thus, the number of histopathologically injured cases, total injury scores of each preparation, and the mean injury scores of each group were determined.ResultsDesflurane and sevoflurane did not significantly increase hepatic injury in the young male rats, while both agents caused significantly more hepatic injury in the young female rats. In the old rats, both desflurane and sevoflurane inflicted more hepatic injury on both genders. In addition, desflurane caused more hepatic injury in the old female rats than in the young female or the old male rats.ConclusionHepatic injury associated with desflurane and sevoflurane was mild to moderate, suggesting that both agents can be safely used in routine anaesthesia procedures.     

Effects of alcohol consumption on biomarkers of oxidative damage to DNA and lipids in ethanol-fed pigs

Chronic alcohol consumption is known to result in tissue injury, particularly in the liver, and is considered a major risk factor for cancers of the upper respiratory tract. Here we assessed the oxidative effects of subchronic ethanol consumption on DNA and lipids by measuring biomarkers 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and malondialdehyde (MDA), respectively. Physiological responses of pigs (n = 4) administered ethanol in drinking water for 39 days were compared with those of water-fed pigs (n = 4). Alcoholisation resulted in serum ethanol concentration of 1.90 g L^?1 and in a moderate but significant increase in alanine aminotransferase activity, an index of liver injury. However, between the alcoholised and control groups there were no significant differences in the levels of 8-oxodG (8-oxodG per 10⁶ 2′deoxyguanosine) from leucocytes (2.52 ± 0.42 Vs 2.39 ± 0.34) or from target organs, liver, cardia and oesophagus. Serum MDA levels were also similar in ethanol-fed pigs (0.33 ± 0.04 μM) and controls (0.28 ± 0.03 μM). Interestingly, levels of 8-oxodG in cardia were positively correlated with those in oesophagus (Spearman correlation coefficient R = 1, P < 0.0001). Our results suggest that alcohol consumption may not cause oxidative damage to DNA and lipids as measured by 8-oxodG and MDA, respectively. The duration of alcoholisation and the potential alcohol-induced nutritional deficiency may be critical determinants of ethanol toxicity. Relevant biomarkers, such as factors involved in sensitization to ethanol-induced oxidative stress are required to better elucidate the relationship between alcohol consumption, oxidative stress and carcinogenesis.     

Volumetric analysis of osteoclastic bioresorption of calcium phosphate ceramics with different solubilities

Commonly, to determine osteoclastic resorption of biomaterials only the resorbed area is measured. The depth of the resorption pit, however, may also be important for the performance of a material. To generate such data we used two calcium phosphate ceramics (Ca₁₀ and Ca₂). The solubility of the materials was determined according to DIN EN ISO 10993-14. They were scanned three-dimensionally using infinite focus microscopy and subsequently cultivated for 4 weeks in simulated body fluid without (control) or with human osteoclasts. After this cultivation period osteoclasts number was determined and surface changes were evaluated two- and three-dimensionally. Ca₁₀ and Ca₂ showed solubilities of 11.0 ± 0.5 and 23.0 ± 2.2 mg g^?1, respectively. Both materials induced a significant increase in osteoclast number. While Ca₁₀ did not show osteoclastic resorption, Ca₂ showed an increased pit area and pit volume due to osteoclastic action. This was caused by an increased average pit depth and an increased number of pits, while the average area of single pits did not change significantly. The deduced volumetric osteoclastic resorption rate (vORR) of Ca₂ (0.01–0.02 μm³ μm^?2 day^?1) was lower than the remodelling speed observed in vivo (0.08 μm³ μm^?2 day^?1), which is in line with the observation that implanted resorbable materials remain in the body longer than originally expected. Determination of volumetric indices of osteoclastic resorption might be valuable in obtaining additional information about cellular resorption of bone substitute materials. This may help facilitate the development of novel materials for bone substitution.     

Hemocompatibility evaluation of different silver nanoparticle concentrations employing a modified Chandler-loop in vitro assay on human blood

Due to their antibacterial effects, the use of silver nanoparticles (AgNPs) in a great variety of medical applications like coatings of medical devices has increased markedly in the last few years. However, blood in contact with AgNPs may induce adverse effects, thereby altering hemostatic functions. The objective of this study was to investigate the hemocompatibility of AgNPs in whole blood. Human whole blood (n = 6) was treated with different AgNPs concentrations (1, 3 and 30 mg l^?1) or with saline/blank solutions as controls before being circulated in an in vitro Chandler-loop model for 60 min at 37 °C. Before and after circulation, various hematologic markers were investigated. Based on the hematologic parameters measured, no profound changes were observed in the groups treated with AgNP concentrations of 1 or 3 mg l^?1. AgNP concentrations of 30 mg l^?1 induced hemolysis of erythrocytes and α-granule secretion in platelets, increased CD11b expression on granulocytes, increased coagulation markers thrombin–antithrombin-III complex, kallikrein-like and FXIIa-like activities as well as complementing cascade activation. Overall, we provide for the first time a comprehensive evaluation including all hematologic parameters required to reliably assess the hemocompatibility of AgNPs. We strongly recommend integrating these hemocompatibility tests to preclinical test procedures prior to in vivo application of new AgNP-based therapies.     

Serum fetuin A concentration is elevated in children with non-alcoholic fatty liver disease

PurposeTo assess the serum fetuin A concentration as a potential marker of subclinical atherosclerosis in obese children with NAFLD.Material/methodsA prospective analysis of 45 obese children initially diagnosed with liver pathology (elevated serum ALT activity and/or ultrasonographic liver brightness and/or hepatomegaly) was conducted. The diagnosis of NAFLD was established in the children with elevated serum ALT activity and liver steatosis on ultrasound examination. Viral hepatitis, autoimmune, metabolic liver diseases (Wilson disease, alpha-1-antitrypsin deficiency, cystic fibrosis) and drug and toxin-induced liver injury were excluded in all children. The degree of liver steatosis was graded according to Saverymuttu scale and the total liver lipids concentration was assessed using proton magnetic resonance spectroscopy (¹H MRS).ResultsSerum fetuin A concentration was significantly higher in examined children compared to the control group (n = 30) (p = 0.00002). Higher serum fetuin A concentration was also observed in children with NAFLD (n = 19) in comparison to the controls (p = 0.000026). Additionally, higher BMI values, waist circumferences, ALT and GGT activity, intensity of liver steatosis on ultrasound and total concentration of lipids in the liver in ¹H MRS were found in children with NAFLD compared to the rest of the examined obese patients (n = 26). There was not found any correlation of the investigated glycoprotein with any other assessed parameters both in children with NAFLD and obese children without NAFLD.ConclusionHigher serum fetuin A concentration found in children with NAFLD compared to the control group support the hypothesis that atherosclerotic processes may develop faster in hepatopatic obese patients.     

Co-administration of quercetin with pantoprazole sodium prevents NSAID-induced severe gastroenteropathic damage efficiently: Evidence from a preclinical study in rats

Management of Nonsteroidal anti-inflammatory drug (NSAID)-induced gastroenteropathy has emerged as a major medical and socioeconomic problem mainly because the highly efficacious gastroprotective drugs i.e. proton pump inhibitors (PPIs) like pantoprazole sodium (PTZ), worsen the NSAID-induced enteropathic damage and lack of approved therapeutic strategies/interventions to prevent this damage. Hence, the primary objective of the current study was to assess whether we can protect the GI mucosa against gastroenteropathic damage caused by diclofenac sodium (DIC) in rats by co-administration of PTZ and quercetin (QCT). Rats were treated twice daily with QCT (35, 50 and 100 mg kg^?1 peroral) and/or PTZ (4 mg kg^?1) or vehicle for a total of 10 days. In some experiments, DIC (9 mg kg^?1) was administered orally twice daily for the final 5 days of PTZ/QCT + PTZ/vehicle administration. Rats in all the groups were fasted after the last dose on 9th day, but, water was provided ad libitum. 12 h after the last dose on 10th day, rats were euthanized and their GI tracts were assessed for haemorrhagic damage, lipid peroxidation, intestinal permeability and GI luminal pH alterations along with haematological and biochemical estimations. The experimental evidences suggested that co-administration of QCT with PTZ significantly attenuated the exacerbation of NSAID-induced enteropathic damage in a dose dependent manner. The combination of PTZ 4 mg kg^?1 and QCT at the doses of 50 or 100 mg kg^?1 was found to effective in preventing the DIC-induced gastroenteropathy. The present report focuses on the gastroenteroprotective ability of QCT and the mechanisms may be related to its ability to prevent GI blood loss, the lipid peroxidation, intestinal permeability alteration and alteration in GI luminal pH.     

Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging

Iron oxide nanoparticles are effective contrast agents for enhancement of magnetic resonance imaging at tissue, cellular or even molecular levels. In this study, manganese doped superparamagnetic iron oxide (Mn-SPIO) nanoparticles were used to form ultrasensitive MRI contrast agents for liver imaging. Hydrophobic Mn-SPIO nanoparticles are synthesized in organic phase and then transferred into water with the help of block copolymer mPEG-b-PCL. These Mn-SPIO nanoparticles are self-assembled into small clusters (mean diameter ≈ 80 nm) inside micelles as revealed by transmission electron microscopy. Mn-SPIO nanoparticles inside micelles decrease PCL crystallization temperatures, as verified from differential scanning calorimetry and Fourier transform infrared spectroscopy. The Mn-SPIO based nanocomposites are superparamagnetic at room temperature. At the magnetic field of 1.5 T, Mn-SPIO nanoparticle clustering micelles have a T₂ relaxivity of 270 (Mn + Fe) mM^?1 s^?1, which is much higher than single Mn-SPIO nanoparticle containing lipid–PEG micelles. This clustered nanocomposite has brought significant liver contrast with signal intensity changes of ?80% at 5 min after intravenous administration. The time window for enhanced-MRI can last about 36 h with obvious contrast on liver images. This sensitive MRI contrast agent may find applications in identification of small liver lesions, evaluation of the degree of liver cirrhosis, and differential diagnosis of other liver diseases.