IL-6 promoter polymorphism (?174G/C) and systemic lupus erythematosus

We investigated the possible association between susceptibility to systemic lupus erythematosus (SLE) and single-nucleotide polymorphisms located in the promoter region of the interleukin-6 gene (?174 G/C) in a sample of the Egyptian population and the contribution of this polymorphism in the clinical or immunological manifestation of the disease. Forty-two Egyptian patients with SLE and 40 unrelated healthy control volunteers were genotyped by polymerase chain reaction followed by visualization on 4% agarose gel electrophoresis on ultraviolet transilluminator to detect the genotype distribution and allelic frequencies of the polymorphisms. The homozygous GG genotypes was significantly increased in SLE patients compared to control group (p value?=?0.04). On the other hand, the heterozygous G/C genotype was significantly elevated in the controls compared to SLE patients (p value?=?0.01). The odds ratio value for G/G was 2.6 with a 95% CI from 1.1 to 6.7. As regard the association of clinical manifestations to the genotype frequency, we found a statistical significant increase in the frequency of GG genotype with chest disease, nephritis, and arthritis. From this study, we suggest that G carrier is more susceptible to develop SLE and that SNP may have a role in the pathogenesis of the disease and may be associated with some of its clinical manifestations.     

Clinical and Bacteriological Efficacy of Rifampin-Streptomycin Combination for Two Weeks followed by Rifampin and Clarithromycin for Six Weeks for Treatment of Mycobacterium ulcerans Disease

Buruli ulcer, an ulcerating skin disease caused by Mycobacterium ulcerans infection, is common in tropical areas of western Africa. We determined the clinical and microbiological responses to administration of rifampin and streptomycin for 2 weeks followed by administration of rifampin and clarithromycin for 6 weeks in 43 patients with small laboratory-confirmed Buruli lesions and monitored for recurrence-free healing. Bacterial load in tissue samples before and after treatment for 6 and 12 weeks was monitored by semiquantitative culture. The success rate was 93%, and there was no recurrence after a 12-month follow-up. Eight percent had a positive culture 4 weeks after antibiotic treatment, but their lesions went on to heal. The findings indicate that rifampin and clarithromycin can replace rifampin and streptomycin for the continuation phase after rifampin and streptomycin administration for 2 weeks without any apparent loss of efficacy.     

New insights into the treatment of real N,N-dimethylacetamide contaminated wastewater using a membrane bioreactor and its membrane fouling implications

Treatment of N,N-dimethylacetamide (DMAC) wastewater is an important step in achieving the sustainable industrial application of DMAC as an organic solvent. This is the first time that treatment of a high concentration of DMAC in real wastewater has been assessed using membrane bioreactor technology. In this study, an anoxic–oxic membrane bioreactor (MBR) was operated over a month to mineralize concentrated DMAC wastewater. Severe membrane fouling occurred during the short-term operation of the MBR as the membrane flux decreased from 11.52 to 5.28 L (m² h)⁻¹. The membrane fouling was aggravated by the increased amount of protein fractions present in the MBR mixed liquor. Moreover, results from the excitation–emission matrix analysis identified tryptophan and other protein-like related substances as the major membrane-fouling components. Furthermore, analysis of the DMAC degradation mechanism via high performance liquid chromatography (HPLC) and ion chromatography (IC) revealed that the major degradation products were ammonium and dimethylamine (DMA). Although the MBR system achieved the steady removal of DMAC and chemical oxygen demand (COD) by up to 98% and 80%, respectively at DMAC₀ ≤ 7548 mg L⁻¹, DMA was found to have accumulated in the treated effluent. Our investigation provides insight into the prospect and challenges of using MBR systems for DMAC wastewater degradation.

Treatment of N,N-dimethylacetamide (DMAC) wastewater is an important step in achieving the sustainable industrial application of DMAC as an organic solvent.     

Clinical value of 18F-FDG-PET/CT in suspected serious disease with special emphasis on occult cancer

Annals of Nuclear Medicine - Suspected serious disease (SSD) is a disease designation often given to patients with one or more non-specific symptoms of severe disease that could be due to cancer;...     

Advances in nano-delivery systems for doxorubicin: an updated insight

Doxorubicin (DOX) is the most effective chemotherapeutic drug developed against broad range of cancers such as solid tumours, transplantable leukemias and lymphomas. Conventional DOX-induced cardiotoxicity has limited its use. FDA approved drugs i.e. non-pegylated liposomal (Myocet^®) and pegylated liposomal (Doxil^®) formulations have no doubt shown comparatively reduced cardiotoxicity, but has raised new toxicity issues. The entrapment of DOX in biocompatible, biodegradable and safe nano delivery systems can prevent its degradation in circulation minimising its toxicity with increased half-life, enhanced pharmacokinetic profile leading to improved patient compliance. In addition, nano delivery systems can actively and passively target the tumour resulting increase in therapeutic index and decreased side effects of drug. Foreseeing the need of a comprehensive review on DOX nanoformulations, in this article we for the first time have given an updated insight on DOX nano delivery systems.     

Human variation and CYP enzyme contribution in benfuracarb metabolism in human in vitro hepatic models

Human responses to the toxicological effects of chemicals are often complicated by a substantial interindividual variability in toxicokinetics, of which metabolism is often the most important factor. Therefore, we investigated human variation and the contributions of human-CYP isoforms to in vitro metabolism of benfuracarb. The primary metabolic pathways were the initial sulfur oxidation to benfuracarb-sulfoxide and the nitrogen-sulfur bond cleavage to carbofuran (activation). The K_m, V_max, and CL_int values of carbofuran production in ten individual hepatic samples varied 7.3-, 3.4-, and 5.4-fold, respectively. CYP2C9 and CYP2C19 catalyzed benfuracarb sulphur oxidation. Carbofuran formation, representing from 79% to 98% of the total metabolism, was catalyzed predominantly by CYP3A4. The calculated relative contribution of CYP3A4 to carbofuran formation was 93%, while it was 4.4% for CYP2C9. The major contribution of CYP3A4 in benfuracarb metabolism was further substantiated by showing a strong correlation with CYP3A4-selective markers midazolam-1′-hydroxylation and omeprazole-sulfoxidation (r = 0.885 and 0.772, respectively). Carbofuran formation was highly inhibited by the CYP3A inhibitor ketoconazole. Moreover, CYP3A4 marker activities were relatively inhibited by benfuracarb. These results confirm that human CYP3A4 is the major enzyme involved in the in vitro activation of benfuracarb and that CYP3A4-catalyzed metabolism is the primary source of interindividual differences.