In vitro cytotoxicity and phototoxicity of N-piperazinyl quinolone derivatives with a 2-thienyl group.

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA) irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6 having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4 position of piperazine ring of enoxacin showed the highest cytotoxicity potential on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml, respectively). While some of the other tested compounds exhibited clear phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential of phototoxicity. These findings suggest the high potential of 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic compound with low potency of phototoxic reactions. The mentioned chemical was identified to be of special interest for further characterization.     

Efficacy of allogeneic cord blood platelet gel on wounds of dystrophic epidermolysis bullosa patients after pseudosyndactyly surgery

Epidermolysis bullosa (EB) is a rare genetic disorder characterized by the formation of blisters and wounds in skin and mucous membranes; it is classified into four types and has various methods of treatment. Management of previous wounds and prevention of formation of new lesions are the most important strategies in the course of therapy to improve patient's quality of life; lack of wound management can lead to further complications such as infection. The current study investigated the therapeutic effects of allogeneic platelet gel (prepared from umbilical cord blood) in a group of children diagnosed with dystrophic epidermolysis bullosa (DEB) eligible for surgical correction of pseudosyndactyly in the hand. The post‐surgical clinical outcome in this group was compared with the clinical outcomes of DEB patients receiving the standard treatment (paraffin gauze wound dressing and topical antibiotics) after corrective surgery. The current study results showed an increase in the rate of recovery and promotion of tissue granulation, complete wound healing, and a decrease in pain level and treatment period. The application of cord blood platelet gel topical dressing was not a conventional method of treatment in patients with DEB wounds and blisters. However, the current study results demonstrated that this gel dressing could effectively accelerate epithelialization and healing of the wounds and decrease patients' pain and post‐surgical recovery period, which altogether leads to improvements in patients' overall quality of life.     

Central auditory processing and word discrimination in patients with multiple sclerosis

Many multiple sclerosis (MS) patients with normal pure tone threshold suffer from difficulties in their hearing especially speech perception in background noise, which is possibly because of incompetence of central auditory processing in this group. Three audiologic tests including gap in noise test (GIN), duration pattern sequence test (DPST) and word discrimination score (WDS) were used for comparing a number of aspects of central auditory processing between patients with MS and normal subjects. Approximate threshold and percent of correct answers in GIN test, percent of correct answers in DPST test and monosyllabic discrimination in WDS test were obtained through cross-sectional non-invasive study conducted on 26 subjects with relapsing-remitting multiple sclerosis who had mean age of 28.9 (SD 4.1) years, and 26 18–40-year-old ones with normal hearing and mean age of 27.7 (SD 5.2). Results of this study demonstrate increased approximate threshold and reduction of percent of correct answers obtained from GIN test in patients with multiple sclerosis (Pv = 0.0001). Furthermore in patients with MS, the average of correct answers in DPST was lower than normal subjects and finally performance of MS subjects in WDS test in quiet environment was correlated with GIN threshold (r = ?/624, Pr = /003). Results of the present study showed that patients with MS had defect in aspects of central auditory processing consisting of temporal resolution, auditory pattern and the memory for auditory task and difficulty in discrimination of speech in noisy environment that are related to the involvement of central nervous system.     

Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice

Methimazole is the most widely prescribed antithyroid medication in humans. However, hepatotoxicity is a deleterious adverse effect associated with methimazole administration. No specific protective agent has been developed against this complication yet. This study was designed to investigate the role of taurine as a hepatoprotective agent against methimazole-induced liver injury in mice. Different reactive metabolites were proposed to be responsible for methimazole hepatotoxicity. Hence, methimazole-induced liver injury was investigated in intact and/or enzyme-induced animals in the current investigation. Animals were treated with methimazole (200 mg/kg, by gavage), and hepatic injury induced by this drug was investigated in intact and/or enzyme-induced groups. Markers such as lipid peroxidation, hepatic glutathione content, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in plasma, and histopathological changes in the liver of animals were monitored after drug administration. Methimazole caused liver injury as revealed by increased plasma ALT. Furthermore, a significant amount of lipid peroxidation was detected in the drug-treated animals, and hepatic glutathione reservoirs were depleted. Methimazole-induced hepatotoxicity was more severe in enzyme-induced mice. The above-mentioned alterations in hepatotoxicity markers were endorsed by significant histopathological changes in the liver. Taurine administration (1 g/kg, i.p.) effectively alleviated methimazole-induced liver injury in both intact and/or enzyme-induced animals.     

Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention

Introduction: The current review aimed to outline the functions of the renin angiotensin system (RAS) in the context of the oxidative stress-associated liver disease.

Areas covered: Angiotensin II (Ang II) as the major effector peptide of the RAS is a pro-oxidant and fibrogenic cytokine. Mechanistically, NADPH oxidase (NOX) is a multicomponent enzyme complex that is able to generate reactive oxygen species (ROS) as a downstream signaling pathway of Ang II which is expressed in liver. Ang II has a detrimental role in the pathogenesis of chronic liver disease through possessing pro-oxidant, fibrogenic, and pro-inflammatory impact in the liver. The alternative axis (ACE2/Ang(1-7)/mas) of the RAS serves as an anti-inflammatory, antioxidant and anti-fibrotic component of the RAS.

Expert commentary: In summary, the use of alternative axis inhibitors accompanying with ACE2/ Ang(1-7)/mas axis activation is a promising new strategy serving as a novel therapeutic option to prevent and treat chronic liver diseases.     

Fumaric acids as a novel antagonist of TLR-4 pathway mitigates arsenic-exposed inflammation in human monocyte-derived dendritic cells

Abstract

Exposure to environmentally relevant doses of arsenic has several harmful effects on the human immune system. In traditional Eastern medicines, nettle has been used as an anti-inflammatory agent to treat rheumatism and osteoarthritis. Fumaric acid (FA) as a major effective compound in nettle was chosen based on very accurate virtual screening to find antagonist for TLR4/MD structure. In this study, the in vitro therapeutic effects of FA on arsenic-exposed monocytes-derived dendritic cells (MDDCs) were evaluated. All the canonical functions of dendritic cells in bridging innate and adaptive immune system including phagocytosis and antigen-presenting capacity, and also cytokines secretion, were evaluated after exposure to arsenic/FA. FA profoundly over-expressed antigen-presenting capacity of MDDCs after exposure to arsenic through the upregulation of MHCιι. However, phagocytosis capacity of arsenic-exposed MDDCs is not compensated for, by treatment with FA. Arsenic up-regulates pro-inflammatory cytokines independents of TLR4 pathway. FA surprisingly mitigates the up-regulation of IL-1β and TNF-α but not TLR4 and NF-kB. Moreover, FA increases the viability of MDDCs even at a high dose of arsenic. Totally, FA reduced inflammatory factors induced by arsenic. This finding confirmed that nettle and other medicinal plants containing similar structures with FA could be further analyzed as valuable candidates for the reduction of drastic effects of arsenic in human immune systems.     

Morphological modeling of cardiac signals based on signal decomposition

In this paper a general framework is presented for morphological modeling of cardiac signals from a signal decomposition perspective. General properties of a desired morphological model are presented and special cases of the model are studied in detail. The presented approach is studied for modeling the morphology of electrocardiogram (ECG) signals. Specifically, three types of ECG modeling techniques, including polynomial spline models, sinusoidal model and a model previously presented by McSharry et al., are studied within this framework. The proposed method is applied to datasets from the PhysioNet ECG database for compression and modeling of normal and abnormal ECG signals. Quantitative and qualitative results of these applications are also presented and discussed.     

Radiological landmarks for the safe extra-capsular placement of supra-acetabular half pins for external fixation

Purpose

Low anterior external fixators are constructed by placing half pins in the dense bone tunnel of the supra-acetabular region in an anterior to posterior direction. Although the placement of these pins is extra-articular, they may still breach the hip capsule on the anterior inferior iliac spine and thus be intra-capsular. We aim to provide radiological markers for the most superior fibres of the capsule to allow safe extra-capsular pin placement within the supra-acetabular bone tunnel.

Methods

Thirteen cadaveric pelves were used for this study. The supra-acetabular bone tunnel was visualised with an image intensifier. The proximal most fibres of the hip joint capsule were marked with a K-wire so that their relation to the bone tunnel could be clearly seen on the images. Once all images were acquired they were calibrated and analysed to estimate the dimensions of the supra-acetabular bone tunnel and the reflection of the hip capsule.

Results

The median height of the bone tunnel was 23.6 mm (18.9–33.2) and maximum width was 11.4 mm (7.6–16.3). The inferior margin of the bone tunnel was 6.7 mm (1.1–14.5) superior to the acetabular dome, and the most proximal fibres of the capsule were 9.3 mm (4.7–6.1) superior to the acetabular dome. The inferior portion of the tunnel was 3.7 mm (0.3–8.9) within the joint.

Conclusion

Half pins for the construction of a pelvic external fixator should be placed in the upper half of the supra-acetabular bone corridor to minimise the risk of intra-capsular placement.