Urinary and air biomonitoring of occupational exposure to benzene in oil pit workers

Abstract

The purpose of this study is to evaluate the personal exposure to benzene and its relationship with biomonitoring and quantitative risk assessment among the personnel working and living near oil pits. This study was conducted in one of oil subsidiary companies in Kharg in 2017. Airborne benzene exposure was evaluated over 8-h periods during work-shift by using personal active samplers. Urinary O-Cresol levels were determined using GC-FID for separation and detection. The highest mean concentration of airborne benzene was at monitoring location, A (0.53?ppm), monitoring location H (0.59?ppm) in the spring, monitoring location M (0.72?ppm) and monitoring location P (0.8?ppm) in the summer, which was more than suggested by the American Conference of Governmental Industrial Hygienists. No direct linear relationship was found between the concentration of airborne benzene, age, work experience, urinary creatinine, and O-Cresol in this study (p?>?.05). No significant difference was observed between urinary O-Cresol and benzene in occupational groups and different seasons (p?>?.05). The highest mean quantitative risk of cancers was observed in summer (1.21?±?0.47). According to the results of this study, urinary biomarker O-Cresol is not a suitable measure for evaluating exposure to environmental benzene.     

The role of protein kinase C in the increased generation in isolated rat hepatocytes of the hydroxyl radical by puromycin aminonucleoside

Puromycin aminonucleoside (PAN) has been known to induce proteinuria. The increased generation of reactive oxygen species (ROS) has been implicated in this toxicity of PAN. We have reported that PAN increases the synthesis of methylguanidine (MG) and creatol which are the products of the reaction of creatinine and the hydroxyl radical in isolated rat hepatocytes. However, the mechanism for the increased ROS induced by PAN is still unclear. In this paper, we investigate the role of protein kinase C (PKC) on the PAN induced reactive oxygen generation in isolated rat hepatocytes. Isolated hepatocytes were incubated in Krebs-Henseleit bicarbonate buffer containing 3% BSA, 16.6 mM creatinine and tested reagents. MG and creatol were determined by high-performance liquid chromatography using 9,10-phenanthrenequinone for the post-labeling. PAN increased MG and creatol synthesis in isolated rat hepatocytes by 60%. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a PKC inhibitor, at 10 and 100 μM significantly inhibited MG and creatol synthesis with or without PAN. The inhibition rate is dose dependent from 10 to 100 μM. H1004, a reagent used as control for H-7, did not affect (at 10 μM) or increased little (at 100 μM) the synthesis of MG and creatol. Ro31-8425, a potent PKC inhibitor, significantly inhibited (at 10 μM) MG synthesis in the presence of PAN. PKC in the membrane fraction, a marker of PKC activation, increased over the initial concentration by a factor of 1.65-fold at 60 min incubation and 2.16-fold at 120 min with PAN, while it changed little without PAN. These results indicate that PAN activates PKC resulting in increased hydroxyl radical generation in isolated rat hepatocytes.     

A trs20 Mutation That Mimics an SEDT‐Causing Mutation Blocks Selective and Non‐Selective Autophagy: A Model for TRAPP III Organization

TRAPP is a multisubunit complex that functions in membrane traffic. Mutations in the mammalian TRAPP protein C2 are linked to the skeletal disorder spondyloepiphyseal dysplasia tarda (SEDT) that is thought to arise from an inability to secrete procollagen from the endoplasmic reticulum. Here, we show that C2 binds to the SNARE protein Syntaxin 5 and this interaction is weakened by an SEDT‐causing missense mutation (D47Y). Interestingly, the equivalent mutation (D46Y) in the yeast C2 homolog Trs20p does not block anterograde traffic but did affect endocytosis. The trs20D46Y mutation interfered with the interaction between Trs20p and Trs85p (TRAPP III‐specific subunit), Trs120p and Trs130p (TRAPP II‐specific subunits). Size exclusion chromatography suggested that this yeast mutation destabilized the TRAPP III complex that is involved in autophagy. We further show that this mutation blocks both the selective cytosol‐to‐vacuole (cvt) pathway as well as non‐selective autophagy. We demonstrate that the apparent molecular size of the TRAPP III complex is dependent upon membranes, and that the presence of TRAPP III is dependent upon Atg9p. Finally, we demonstrate that lipidated Bet3p is enriched in TRAPP III and that lipidation increases the efficiency of autophagy. Our study suggests that Trs20p acts as an adaptor for Trs85p and Trs120p and reveals complexities in TRAPP III assembly and function. The implications of C2D47Y in SEDT are discussed .     

The Effects of Selenium Supplementation on Clinical Symptoms and Gene Expression Related to Inflammation and Vascular Endothelial Growth Factor in Infertile Women Candidate for In Vitro Fertilization

Biological Trace Element Research - This study was performed to determine the effects of selenium supplementation on clinical symptoms and gene expression related to inflammatory markers in...     

MicroRNA and exosome: Key players in rheumatoid arthritis

Rheumatoid arthritis (RA) is known as one of important autoimmune disorders which can lead to joint pain and damage throughout body. Given that internal (ie, genetic and epigenetic alterations) and external factors (ie, lifestyle changes, age, hormones, smoking, stress, and obesity) involved in RA pathogenesis. Increasing evidence indicated that cellular and molecular alterations play critical roles in the initiation and progression of RA. Among various targets and molecular signaling pathways, microRNAs (miRNAs) and their regulatory networks have key roles in the RA pathogenesis. It has been showed that deregulation of many miRNAs involved in different stages of RA. Hence, identification of miRNAs and their signaling pathways in RA, could contribute to new knowledge which help to better treatment of patients with RA. Besides miRNAs, exosomes have been emerged as key messengers in RA pathogenesis. Exsosomes are nanocarriers which could be released from various cells and lead to changing of behaviors recipient cells via targeting their cargos (eg, proteins, messenger RNAs, miRNAs, long noncoding RNAs, DNAs). Here, we summarized several miRNAs involved in RA pathogenesis. Moreover, we highlighted the roles of exosomes in RA pathogenesis.     

Increased release of serotonin from rat ileum due to dexfenfluramine

Plasma levels of serotonin are elevated in primary pulmonary hypertension even after bilateral lung transplantation, suggesting a possible etiologic role. Serotonin is released primarily from the small intestine. Anorectic agents, such as dexfenfluramine, which can cause pulmonary hypertension, are known to inhibit potassium channels in vascular smooth muscle cells. We examined the hypothesis that dexfenfluramine may stimulate release of serotonin from the ileum by inhibition of K+ channels. In an isolated loop of rat ileum perfused with a physiological salt solution, the administration of dexfenfluramine, its major metabolite D-norfenfluramine, the potassium channel blocker 4-aminopyridine (5 mM), and caffeine (30 mM) increased serotonin levels in the venous effluent. Potassium chloride (60 mM) tended to increase serotonin levels. In genetically susceptible individuals, dexfenfluramine may induce pulmonary hypertension by increasing cytosolic calcium in enterochromaffin cells of the small intestine, thus releasing serotonin and causing vasoconstriction. This work indicates that dexfenfluramine and its major metabolite d-norfenfluramine can increase serotonin release from the small intestine.     

A novel approach in the assessment of polymeric film formation and film adhesion on different pharmaceutical solid substrates

The purpose of this study was to evaluate the nature of film formation on tablets with different compositions, using confocal laser scanning microscopy (CLSM), and to measure film adhesion via the application of a novel “magnet probe test”. Three excipients, microcrystalline cellulose (MCC), spray-dried lactose monohydrate, and dibasic calcium phosphate dihydrate, were individually blended with 0.5% magnesium stearate, as a lubricant, and 2.5% tetracycline HCl, as a fluorescent marker, and were compressed using a Carver press. Tablets were coated with a solution consisting of 7% hydroxypropyl methylcellulose (HPMC) phthalate (HP-55), and 0.5% cetyl alcohl in acetone and isopropanol (11:9). The nature of polymer interaction with the tablets and coating was evaluated using CLSM and a designed magnet probe test. CLSM images clearly showed coating efficiency, thickness, and uniformity of film formation, and the extent of drug migration into the film at the coating interfaces of tablets. Among the excipients, MCC demonstrated the best interface for both film formation and uniformity in thickness relative to lactose monohydrate and dibasic calcium phosphate dihydrate. The detachment force of the coating layers from the tablet surfaces, as measured with the developed magnet probe test, was in the order of MCC>lactose monohydrate>dibasic calcium phosphate dihydrate. It was also shown that the designed magnet probe test provides reliable and reproducible results when used for measurement of film adhesion and bonding strength.     

Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate

Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several ribosylhomocysteine analogues have been tested as LuxS inhibitors.