Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1

Hepatitis C virus (HCV) and HCV core protein are hypothesized to induce hepatic oxidative stress and exacerbate injury caused by other toxins such as ethanol that induce the cytochrome P450 enzyme, CYP2E1. In the current study, the effects of HCV core protein [sequence genotype 1b, (nt 342-915)] on parameters indicative of oxidative stress were evaluated in HepG2 cells stably over expressing CYP2E1 (E47), or vector controls (C34). Stable (>10 passages) expression of HCV core protein and CYP2E1 was confirmed in clonal cell lines at the level of mRNA and immunoreactive protein. Prooxidant production, as determined by cellular oxidation of dichlorodihydrofluorescin and dihydroethidium (HE), was increased by expression of HCV core protein in the presence or absence of CYP2E1. Depletion of glutathione (GSH) with buthionine sulfoximine (BSO) enhanced prooxidant production in both C34 and E47 cells. In addition, prooxidant production was greater in BSO-treated cells expressing HCV core protein, and this effect was further enhanced in cells expressing both HCV core and CYP2E1. The CYP2E1 inhibitor, 4-methylpyrazole, could suppress increased prooxidant production in E47 cells. Finally, cells co-expressing both CYP2E1 and HCV core protein showed significantly decreased viability following GSH depletion. These studies show simultaneous expression of HCV core protein and CYP2E1 increases parameters indicative of oxidative stress as well as sensitization to cell injury induced by GSH depletion. These results support the hypothesis that enhanced injury in hepatocytes over expressing both HCV core protein and CYP2E1 is mediated by increases in oxidative stress.     

Neonatal RBC transfusions: Do benefits outweigh risks?

Preterm neonates represent one of the most transfused categories of patients. Their target hematocrits, however, are mainly based on expert opinion. The risk of transfusions are very high in the smallest preterm baby with a weak immune response, immature antioxidant ability, fragile germinal matrix and impaired cerebral autoregulation, yet red cell transfusions remain the only life saving measure in the baby with symptomatic anemia.Minimizing phlebotomy losses, following a restrictive transfusion policy and using screened, leukocyte depleted, irradiated, single donor blood remain the best means of avoiding the possible risks while maximizing the benefits of red cell transfusions in the preterm newborn.     

Role of Nigella sativa and a number of its antioxidant constituents towards azoxymethane-induced genotoxic effects and colon cancer in rats

This study examined the chemopreventive effect of Nigella sativa and some of its antioxidant constituents on a number of colon cancer biomarkers in rats induced with azoxymethane (AOM). Sixty male Sprague-Dawley rats were randomly assigned into ten subgroups: vehicle (1-5) and experimental (6-10). The rats in each group were fed one of the following diets: basal diet, (200 mg/kg) Nigella sativa, (0.2 mg/kg) selenium, (1.2 mg/kg) all-trans-retinol plus (100 mg/kg) DL-alpha-tocopherol and (10 mg/kg) thymoquinone, respectively. Only rats in subgroups 6-10 were injected with AOM (15 mg/kg) once per week for 2 weeks. Both groups were fed their respective diets for 5 weeks. Then they were killed and examined for colonic aberrant crypt foci (ACF). Our result showed that only vitamin supplementation was effective on ACF. Nigella sativa revealed inhibitory effects only on DNA damage (day 34) in the AOM-treated rat group. Alternatively, selenium, thymoquinone and vitamins inhibited the MDA content in the liver. Although the exact mechanisms involved in the protective role of Nigella sativa against the initiation of colon carcinogenesis are not clearly understood, the results suggest that its inhibitory effects might depend on the combined competitive inhibition of various antioxidant constituents of this plant.     

Magnesium ascorbyl phosphate vesicular carriers for topical delivery; preparation,in-vitro and ex-vivo evaluation,factorial optimization and clinical assessment in melasma patients

Ascorbic acid (vitamin C) is an antioxidant that is widely used in cosmetics in skincare products. Due to the excessive low stability of ascorbic acid in cosmetic formulations, the stabilized ascorbic acid derivative, magnesium ascorbyl phosphate (MAP) was formulated as vesicular carriers; ethosomes and niosomes. The aim was to deliver MAP at the intended site of action, the skin, for sufficient time with enhanced permeation to get an effective response. Ethosomes were formulated using a full 3² factorial design to study ethanol and phospholipid concentration effect on ethosomes properties. Niosomes were formulated using 2³ factorial designs to study the effect of surfactant type, surfactant concentration and cholesterol concentration on niosomes properties. The prepared formulations were evaluated for their Entrapment efficiency, particle size, polydispersity index, zeta potential and % drug permeated. The optimized ethosomal and niosomal formulations were incorporated into carbopol gel and evaluated for their permeation, skin retention and stability. A comparative split-face clinical study was done between the ethosomal and niosomal formulations for melasma treatment using Antera 3 D^® camera. The optimized ethosomal and niosomal gels showed comparable controlled permeation and higher skin retention over their ethosomes and niosomes formulations respectively. Magnesium ascorbyl phosphate ethosomal gel showed clinically and statistically significant melanin level decrease after one month while MAP niosomal gel showed clinically and statistically significant melanin level decrease after six months. A combination of MAP ethosomes and niosomes could be promising skincare formulations for melasma and hyperpigmentation short and long-term treatment.     

Multiple Familial Trichoepithelioma with Malignant Transformation

Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colored papules predominantly on the face. When more than one family member is affected, the disease is known as multiple familial trichoepithelioma (MFT). It is a rare autosomal dominant (AD) skin disease. Malignant transformation is very rare. We present a case of MFT in a female patient and her father with malignant transformation to basal cell carcinoma (BCC) in the father. We summarized the main histological differential parameters between TE and BCC and applied immunophenotyping for both by administration of Bcl2, CD34, CD10 and androgen receptor (AR) antibodies.     

Unintentional carbon monoxide poisoning in Northwest Iran: A 5-year study

This paper describes the epidemiology of unintentional carbon monoxide (CO) poisoning in Northwest Iran between 2003 and 2008. Data were obtained from the records of the main provider of emergency medical transportation and from death certificate reports of the Legal Medicine Organization. During the study period, a total of 3078 hospital admissions were recorded against which 346 deaths were due to unintentional CO related poisoning caused by gas appliances in the homes. The ratio of unintentional CO related poisoning cases in relation to all poisonings was 11.6%. With regard to gender differences, non-fatal CO poisoning was higher in females than males, whereas actual fatalities were higher in males than females. Non-fatal CO poisoning was most prevalent in adults aged between 20 and 49 years, whereas the age specific death rate was highest for those over 60 years. The highest frequency of both non-fatal poisonings and actual fatalities occurred in the month January. The results suggest that CO poisoning has a high prevalence in this geographic region, with elderly adults being at the greatest risk, especially during the winter season. This represents a serious, but often neglected area of public health, and Health Authorities should be encouraged to promote public awareness against the dangers of CO exposure. This paper reviews the data and evidence surrounding the issue of CO poisoning and makes recommendations that a range of agencies and authorities should be involved in setting stricter standards and environmental legislations in this respect.     

Separability analysis of multifrequency SAR polarimetric features for land cover classification

Polarimetric Synthetic Aperture Radar (PolSAR) imagery can provide valuable observables at different frequencies for classification tasks. In this paper, we assessed separability rate of various polarimetric features in three frequencies of X-, C-, and L- bands. To this end, Jeffries–Matusita distance was firstly used to measure separability of each polarimetric feature in each frequency band. Random Forest classifier was then applied to map various land cover classes in study area. The classification outputs indicated that C-band results were better and more reliable than L-band results and L-band results were subsequently better than X-band results. These results were perfectly compatible with the results obtained by the separability analysis of multifrequency PolSAR features.     

Short Communication: Collagenated Cortico‐Cancellous Porcine Bone Grafts. A Study in Rabbit Maxillary Defects

Background: Bone substitutes of collagenated porcine bone (CPB) have previously been shown to have osteoconductive properties and to be resorbed with time. The influence of different ratios between bone particles and collagen on bone response is not yet known. Purpose: The objective of the study was to evaluate the effect of different collagen ratios on the bone tissue responses to CPB grafts. Materials and Methods: Eight rabbits were used in the study. Bilateral bone defects, 5 × 8 × 3 mm, were created in the maxilla and were filled with 60% CPB/40% collagen gel or with 80% CPB/20% collagen gel. Animals were killed after 8 weeks for histological and morphometrical evaluations. Results: There were no differences between the two biomaterials tested. Both materials showed a high degree of bone formation, 42% and 46%, respectively. Both materials were showing signs of resorption at time of sacrifice. Conclusions: Different collagen/CPB ratios do not influence the bone tissue responses to CPB. Both materials exhibited osteoconductive properties and were starting to be resorbed at 8 weeks.