Occupational exposure to magnetic fields from transformer stations and electric enclosures in Turkey

We aimed to provide a systematic evaluation of magnetic field (MF) exposure of staff working in the offices located above or close to transformer stations (TS) and electric enclosures (EE). Occupational short-term "spot" measurements with Narda EFA-300 and isotropic magnetic field probe were carried out in two National Banks and one Industrial Company having more than 500 employees. Extremely low-frequency (ELF) MFs up to several tens of μT were measured in the mentioned working environments. 25% of the measured MFs were found less than 0.3?μT, the background exposure level that staff receive at home, 75% were above 0.3?μT with the highest value of 6.8?μT. The mean and median personal exposures were calculated to be 1.19?μT and 0.56?μT, respectively. Most of the staff (83%) is under risk based on epidemiological studies that reported a statistically significant association between risk of leukemia and averaged magnetic fields of 0.2?μT or over. Results showed that risk evaluation should be considered to minimize the possibility of the workers being harmed due to exposure to work-related electromagnetic sources.     

Evaluation of <Emphasis Type="Italic">ERα</Emphasis> and <Emphasis Type="Italic">VDR</Emphasis> gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women

It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII “PP” and ERα XbaI “XX” genotypes than in those with “Pp/pp” genotypes and “xx” genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI “FF” genotype had lower BMD values of femoral neck and total hip compared to those with “Ff” genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI “FF” genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.     

Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18

The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors. Active caspase-1 processes pro-IL-1β and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses. Little information is available on caspase-1 and inflammasome activation during infection with the gastric bacterial pathogen Helicobacter pylori. In this study, we addressed a possible role for caspase-1 and its cytokine substrates in the spontaneous and vaccine-induced control of Helicobacter infection, as well as the development of gastritis and gastric cancer precursor lesions, using a variety of experimental infection, vaccine-induced protection, and gastric disease models. We show that caspase-1 is activated and IL-1β and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection. Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice. IL-1R(-/-) mice fail to develop protective immunity but are protected against Helicobacter-associated gastritis and gastric preneoplasia as a result of their inability to generate Helicobacter-specific Th1 and Th17 responses. In contrast, IL-18 is dispensable for vaccine-induced protective immunity but essential for preventing excessive T cell-driven immunopathology. IL-18(-/-) animals develop strongly accelerated pathology that is accompanied by unrestricted Th17 responses. In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1β, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.     

Restoration of diabetes-induced abnormal local Ca2+ release in cardiomyocytes by angiotensin II receptor blockade

Stimulation of local renin-angiotensin system and increased levels of oxidants characterize the diabetic heart. Downregulation of ANG II type 1 receptors (AT(1)) and enhancement in PKC activity in the heart point out the role of AT(1) blockers in diabetes. The purpose of this study was to evaluate a potential role of an AT(1) blocker, candesartan, on abnormal Ca(2+) release mechanisms and its relationship with PKC in the cardiomyocytes from streptozotocin-induced diabetic rats. Cardiomyocytes were isolated enzymatically and then incubated with either candesartan or a nonspecific PKC inhibitor bisindolylmaleimide I (BIM) for 6-8 h at 37 degrees C. Both candesartan and BIM applied on diabetic cardiomyocytes significantly restored the altered kinetic parameters of Ca(2+) transients, as well as depressed Ca(2+) loading of sarcoplasmic reticulum, basal Ca(2+) level, and spatiotemporal properties of the Ca(2+) sparks. In addition, candesartan and BIM significantly antagonized the hyperphosphorylation of cardiac ryanodine receptor (RyR2) and restored the depleted protein levels of both RyR2 and FK506 binding protein 12.6 (FKBP12.6). Furthermore, candesartan and BIM also reduced the increased PKC levels and oxidized protein thiol level in membrane fraction of diabetic rat cardiomyocytes. Taken together, these data demonstrate that AT(1) receptor blockade protects cardiomyocytes from development of cellular alterations typically associated with Ca(2+) release mechanisms in diabetes mellitus. Prevention of these alterations by candesartan may present a useful pharmacological strategy for the treatment of diabetic cardiomyopathy.     

Improvement of activity and stability of Rhizomucor miehei lipase by immobilization on nanoporous aluminium oxide and potassium sulfate microcrystals and their applications in the synthesis of aroma esters

In this study, Rhizomucor miehei lipase (RML) was immobilized on the hexagonally-ordered nanoporous aluminium oxide membranes (RML-Al₂O₃-NP) by adsorption and as protein-coated microcrystals (RML-PCMCs) by simultaneously precipitating RML on micron-sized potassium sulfate crystals (K₂SO₄) in pre-chilled acetone. The hydrolytic activities of immobilized lipase preparations were investigated in terms of p-nitrophenyl palmitate hydrolysis and their esterification activities were examined for the synthesis of some aroma esters such as butyl acetate, isoamyl acetate, hexyl acetate, heptyl acetate, and geranyl acetate. The immobilization yields were 33.8 and 25.1%, respectively for RML immobilized on Al₂O₃-NP membranes and potassium sulfate crystals. The catalytic efficiency ratios of RML-Al₂O₃-NP and RML-PCMCs were 2.3- and 3.9-fold higher than that of the free lipase, respectively in terms of hydrolytic activity. The free lipase was stabilized as 4.1- and 10.5-fold, respectively at 40 and 50?°C when immobilized on Al₂O₃-NP. The corresponding stabilization factors were 4.6- and 12.8-fold higher for RML-PCMCs. RML-Al₂O₃-NP and RML-PCMCs maintained 84 and 86% of their initial hydrolytic activities, respectively after 10 reuses. Of the synthesized aroma esters, the highest yield was obtained for the geranyl acetate. After 4?h reaction time, no geraniol was detected in the preparative-scale (196?g/L) synthesis of geranyl acetate for both the immobilized lipases when the initial geraniol amount, vinyl acetate amount, RML-PCMCs amount, and reaction temperature values were 1?mmol, 3?mmol, 100?mg (or 300?mg RML-Al₂O₃-NP), and 50?°C, respectively. These results show that the immobilization of R. miehei lipase by adsorption on nanoporous aluminium oxide and as protein-coated microcrystals leads to the obtention of highly stable, catalytically more active, and reusable lipase preparations.     

Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss

Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSight^TM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL.     

Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice

Introduction

Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown.

Objective

We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC).

Methods

βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured.

Results

Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements.

Conclusions

We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.     

Activity and storage stability of immobilized glucose oxidase onto magnesium silicate

Glucose oxidase (GOD) was covalently immobilized onto florisil (magnesium silicate) carrier via glutaraldehyde. Immobilization conditions were optimized: the amount of initial GOD per grams of carrier as 5 mg, pH as 5.5, immobilization time as 120 min and temperature as 10 °C. Under the optimized reaction conditions activities of free and immobilized GOD were measured. Free and immobilized GOD samples were characterized with their kinetic parameters, and thermal and storage stabilities. K_M and V_max values were 68.2 mM and 435 U mg GOD⁻¹ for free and 259 mM and 217 U mg GOD⁻¹ for immobilized enzymes, respectively. Operational stability of the immobilized enzyme was also determined by using a stirred batch type column reactor. Immobilized GOD was retained 40% of its initial activity after 50 reuses. Storage stabilities of the immobilized GOD samples stored in the mediums with different relative humidity in the range of 0–100% were investigated during 2 months. The highest storage stability was determined for the samples stored in the medium of 60% relative humidity. Increased relative humidity from 0% to 60% caused increased storage stability of immobilized GODs, however, further increase in relative humidity from 80% to 100% caused a significant decrease in storage stability of samples.