Modulatory role of GSTM1 null genotype on the frequency of micronuclei in pesticide-exposed agricultural workers

In this study, we aimed to investigate the extent of genotoxic risk and the association between null GSTM1/GSTT1 and GSTP1 Ile105Val variants and cellular DNA damage, as measured by micronucleus (MN) assay in a group of agricultural workers from Denizli, Turkey. Peripheral blood samples were collected from 116 subjects, including 58 workers who were occupationally exposed to pesticides and 58 healthy unexposed controls. The MN frequencies of each individual were assessed by cytokinesis-blocked micronuclei assays on lymphocytes. Genotypes for different GST variants were determined using polymerase chain reaction-based methods. A significant 3.4-fold increase in MN frequency was observed in workers compared with the controls ( p < 0.001). Among the GST genotypes, only the GSTM1 null genotype was found to be significantly associated with an increased MN frequency in workers ( p = 0.01). Individuals with a concomitant null GSTM1/GSTT1 genotype demonstrated a significant ( p = 0.01) increase in MN frequency compared with those with functional isozymes in the exposed worker group. The association of the GSTM1 null genotype with higher MN frequency suggests that it may be a modifier of genotoxic risk in individuals exposed to pesticides and may thus be a candidate susceptibility biomarker for human biomonitoring studies.

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Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648390 ◽

1992 ◽

Vol 67 (01) ◽

pp. 111-116 ◽

Cited By ~ 64

Author(s):

Marcel Levi ◽

Jan Paul de Boer ◽

Dorina Roem ◽

Jan Wouter ten Cate ◽

C Erik Hack

Keyword(s):

Monoclonal Antibodies ◽

Plasminogen Activator ◽

Plasma Levels ◽

Fold Increase ◽

Fibrinolytic System ◽

Plasminogen Activation ◽

Plasminogen Activator Activity ◽

Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

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The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis

Current Diabetes Reviews ◽

10.2174/1573399814666171215120228 ◽

2018 ◽

Vol 15 (1) ◽

pp. 31-43 ◽

Cited By ~ 6

Author(s):

Sayantan Nath ◽

Sambuddha Das ◽

Aditi Bhowmik ◽

Sankar Kumar Ghosh ◽

Yashmin Choudhury

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Meta Analysis ◽

Subsequent Development ◽

Asian Population ◽

Gstm1 Null Genotype ◽

Increased Risk

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.

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The SOS Error-Prone DNA Polymerase V Mutasome and β-Sliding Clamp Acting in Concert on Undamaged DNA and during Translesion Synthesis

Cells ◽

10.3390/cells10051083 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1083

Author(s):

Adhirath Sikand ◽

Malgorzata Jaszczur ◽

Linda B. Bloom ◽

Roger Woodgate ◽

Michael M. Cox ◽

...

Keyword(s):

Dna Synthesis ◽

Dna Polymerase ◽

Pathogenic Bacteria ◽

Fold Increase ◽

Translesion Dna Synthesis ◽

Sliding Clamp ◽

Pol V ◽

Dna Polymerase V ◽

Acting In Concert

In the mid 1970s, Miroslav Radman and Evelyn Witkin proposed that Escherichia coli must encode a specialized error-prone DNA polymerase (pol) to account for the 100-fold increase in mutations accompanying induction of the SOS regulon. By the late 1980s, genetic studies showed that SOS mutagenesis required the presence of two “UV mutagenesis” genes, umuC and umuD, along with recA. Guided by the genetics, decades of biochemical studies have defined the predicted error-prone DNA polymerase as an activated complex of these three gene products, assembled as a mutasome, pol V Mut = UmuD’2C-RecA-ATP. Here, we explore the role of the β-sliding processivity clamp on the efficiency of pol V Mut-catalyzed DNA synthesis on undamaged DNA and during translesion DNA synthesis (TLS). Primer elongation efficiencies and TLS were strongly enhanced in the presence of β. The results suggest that β may have two stabilizing roles: its canonical role in tethering the pol at a primer-3’-terminus, and a possible second role in inhibiting pol V Mut’s ATPase to reduce the rate of mutasome-DNA dissociation. The identification of umuC, umuD, and recA homologs in numerous strains of pathogenic bacteria and plasmids will ensure the long and productive continuation of the genetic and biochemical journey initiated by Radman and Witkin.

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Health research capacity in Nepal: Analysis of the trend and the role of local researchers

Tropical Doctor ◽

10.1177/0049475520982770 ◽

2021 ◽

pp. 004947552098277

Author(s):

Madhu Kharel ◽

Alpha Pokharel ◽

Krishna P Sapkota ◽

Prasant V Shahi ◽

Pratisha Shakya ◽

...

Keyword(s):

Health Research ◽

Fold Increase ◽

Research Capacity ◽

Rapid Review ◽

Evidence Based ◽

Middle Income ◽

Middle Income Countries ◽

Health Related ◽

Evidence Based Decision Making

Evidence-based decision-making is less common in low- and middle-income countries where the research capacity remains low. Nepal, a lower-middle-income country in Asia, is not an exception. We conducted a rapid review to identify the trend of health research in Nepal and found more than seven-fold increase in the number of published health-related articles between 2000 and 2018. The proportion of articles with Nepalese researchers as the first authors has also risen over the years, though they are still only in two-thirds of the articles in 2018.

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Arsenic Removal by Advanced Electrocoagulation Processes: The Role of Oxidants Generated and Kinetic Modeling

Catalysts ◽

10.3390/catal10080928 ◽

2020 ◽

Vol 10 (8) ◽

pp. 928

Author(s):

Micah Flor V. Montefalcon ◽

Meliton R. Chiong ◽

Augustus C. Resurreccion ◽

Sergi Garcia-Segura ◽

Joey D. Ocon

Keyword(s):

Kinetic Modeling ◽

Arsenic Removal ◽

Fold Increase ◽

Electrochemical Treatment ◽

Promising Alternative ◽

Iron Electrodes ◽

Removal Capacity ◽

Naturally Occurring ◽

Treatment Technologies

Arsenic (As) is a naturally occurring element in the environment that poses significant risks to human health. Several treatment technologies have been successfully used in the treatment of As-contaminated waters. However, limited literature has explored advanced electrocoagulation (EC) processes for As removal. The present study evaluates the As removal performance of electrocoagulation, electrochemical peroxidation (ECP), and photo-assisted electrochemical peroxidation (PECP) technologies at circumneutral pH using electroactive iron electrodes. The influence of As speciation and the role of oxidants in As removal were investigated. We have identified the ECP process to be a promising alternative for the conventional EC with around 4-fold increase in arsenic removal capacity at a competitive cost of 0.0060 $/m3. Results also indicated that the rate of As(III) oxidation at the outset of electrochemical treatment dictates the extent of As removal. Both ECP and PECP processes reached greater than 96% As(III) conversion at 1 C/L and achieved 86% and 96% As removal at 5 C/L, respectively. Finally, the mechanism of As(III) oxidation was evaluated, and results showed that Fe(IV) is the intermediate oxidant generated in advanced EC processes, and the contribution of •OH brought by UV irradiation is insignificant.

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Author Correction: Simultaneous Inhibition of Glycolysis and Oxidative Phosphorylation Triggers a Multi-Fold Increase in Secretion of Exosomes: Possible Role of 2′,3′-cAMP

Scientific Reports ◽

10.1038/s41598-020-70340-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Nils Ludwig ◽

Saigopalakrishna S. Yerneni ◽

Elizabeth V. Menshikova ◽

Delbert G. Gillespie ◽

Edwin K. Jackson ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Fold Increase ◽

Inhibition Of Glycolysis ◽

Simultaneous Inhibition

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Regulation of intracellular calcium in N1E-115 neuroblastoma cells: the role of Na+/Ca2+exchange

AJP Cell Physiology ◽

10.1152/ajpcell.00182.2001 ◽

2002 ◽

Vol 282 (5) ◽

pp. C1000-C1008 ◽

Cited By ~ 3

Author(s):

Kara L. Kopper ◽

Joseph S. Adorante

Keyword(s):

Membrane Potential ◽

Intracellular Calcium ◽

Normal Cell ◽

Buffer Capacity ◽

Neuroblastoma Cells ◽

Fold Increase ◽

Scorpion Venom ◽

Reverse Mode ◽

Intracellular Ca

In fura 2-loaded N1E-115 cells, regulation of intracellular Ca2+ concentration ([Ca2+]i) following a Ca2+ load induced by 1 μM thapsigargin and 10 μM carbonylcyanide p-trifluoromethyoxyphenylhydrazone (FCCP) was Na+ dependent and inhibited by 5 mM Ni2+. In cells with normal intracellular Na+ concentration ([Na+]i), removal of bath Na+, which should result in reversal of Na+/Ca2+exchange, did not increase [Ca2+]i unless cell Ca2+ buffer capacity was reduced. When N1E-115 cells were Na+ loaded using 100 μM veratridine and 4 μg/ml scorpion venom, the rate of the reverse mode of the Na+/Ca2+ exchanger was apparently enhanced, since an ∼4- to 6-fold increase in [Ca2+]ioccurred despite normal cell Ca2+ buffering. In SBFI-loaded cells, we were able to demonstrate forward operation of the Na+/Ca2+ exchanger (net efflux of Ca2+) by observing increases (∼ 6 mM) in [Na+]i. These Ni2+ (5 mM)-inhibited increases in [Na+]i could only be observed when a continuous ionomycin-induced influx of Ca2+ occurred. The voltage-sensitive dye bis-(1,3-diethylthiobarbituric acid) trimethine oxonol was used to measure changes in membrane potential. Ionomycin (1 μM) depolarized N1E-115 cells (∼25 mV). This depolarization was Na+dependent and blocked by 5 mM Ni2+ and 250–500 μM benzamil. These data provide evidence for the presence of an electrogenic Na+/Ca2+ exchanger that is capable of regulating [Ca2+]i after release of Ca2+ from cell stores.

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Abstract 103: Soluble (Pro)Renin Receptor Targets Renal V2 Vasopressin Receptor to Enhance Urine Concentrating Capability

Hypertension ◽

10.1161/hyp.68.suppl_1.103 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Fei Wang ◽

Nirupama Ramkumar ◽

Kexin Peng ◽

Xiaohan Lu ◽

Long Zhao ◽

...

Keyword(s):

Biological Fluid ◽

Collecting Duct ◽

Urine Volume ◽

Neutralizing Antibody ◽

Fold Increase ◽

Medium Level ◽

V2 Vasopressin Receptor ◽

Receptor Targets ◽

Renal Expression

The extracellular domain of (pro)renin receptor (PRR) is cleaved to produce a 28 kDa soluble receptor (sPRR) which is detected in biological fluid and elevated under certain pathological conditions. Our recent work suggests that sPRR derived from collecting duct intercalated cells acts in a paracrine fashion to regulate water transport in the principal cells. The present study attempted to further define the role of sPRR in vasopressin (AVP) signaling with emphasis on V2R regulation. In primary rat IMCD cells, treatment with a recombinant sPRR termed as sPRR-His at 10 nM for 12 h induced a 2.8 -fold increase in V2R protein and a 2-fold increase in V2R mRNA. Following AVP treatment, V2R protein expression was increased by 3-fold, which was blunted by a PRR antagonist (PRO20) and a PRR neutralizing antibody. Mice with CD-specific (CD PRR KO) developed a medium level of diabetes insipidus (urine volume: KO: 2.2±0.4 versus Floxed: 1.2±0.3 ml/day; P <0.05), accompanied with a 60% reduction of renal V2R protein and a 25% reduction of urinary sPRR excretion. Adminstration of sPRR-His at for 3 d almost completely rescued the polyuria phenotype of CD PRR KO mice (urine volume: KO+sPRR-His: 1.6±0.3 vs. KO: 2.4±0.5 ml/day, p <0.05) associated with restoration of renal V2R protein and AQP2 protein abundances. Interestingly, nephron-specific PRR KO (Neph PRR KO) exhibited more robust polyuria (urine volume: KO: 7.3±1.1 vs. Floxed: 1.2±0.5 ml/day, p <0.01) associated with suppressed renal expression of AQP2, NKCC2, and V2R. Administration of sPRR-His to Neph PRR KO mice partially attenuated polyuria (urine volume: KO+sPRR-His: 4.1±1.2 vs. KO: 7.3±1.1 ml/day, p <0.01) accompanied by restored renal expression of V2R and AQP2, as well as AVP sensitivity. In contrast, the downregulation of NKCC2 expression in the null mice was unaffected by sPRR-His infusion nor was the upregulation of autophagosome marker microtubule-associated protein 1A/1B-light chain 3 (LC3b). Together, our data suggests that sPRR selectively targets the CD to determine V2R expression and hence AVP sensitivity and urine concentrating capability, independently of autophagosome accumulation.

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The role of coinfection with influenza viruses in the pathogenesis of severe infection in patients with COVID-19

Medical academic journal ◽

10.17816/maj78155 ◽

2021 ◽

Vol 21 (3) ◽

pp. 159-164

Author(s):

Tamara N. Shvedova ◽

Olga S. Kopteva ◽

Polina A. Kudar ◽

Anna A. Lerner ◽

Yuliya A. Desheva

Keyword(s):

Influenza A ◽

Fold Increase ◽

Igg Antibodies ◽

C Reactive Protein ◽

S Protein ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Reactive Protein ◽

Coronavirus Infection

BACKGROUND: Despite the continuing global spread of the coronavirus infection COVID-19 caused by the SARS-CoV-2 coronavirus, the mechanisms of the pathogenesis of severe infections remain poorly understood. The role of comorbidity with other seasonal viral infections, including influenza, in the pathogenesis of the severe course of COVID-19 remains unclear. MATERIALS AND METHODS: The present study used sera left over from ongoing laboratory studies of patients with varying degrees of severity of COVID-19. The study was approved by the Local Ethics Committee of the Federal State Budgetary Scientific Institution IEM (protocol 3/20 from 06/05/2020). We studied 28 paired samples obtained upon admission of patients to the hospital and after 57 days of hospital stay. Paired sera of patients with COVID-19 were tested for antibodies to influenza A and B viruses. The presence of IgG antibodies specific to the SARS-CoV-2 spike (S) protein was studied using an enzyme-linked immunosorbent assay (ELISA). The serum concentration of C-reactive protein and the neutrophil-lymphocyte ratio on the day of hospitalization were also assessed. RESULTS: At least a 4-fold increase in serum IgG antibodies to SARS-CoV-2 S protein was found both in patients with PCR-confirmed SARS-CoV-2 infection and without PCR confirmation. It was shown that out of 18 patients with moderate and severe forms of COVID-19 infection, six of them showed at least a 4-fold increase in antibodies to influenza A/H1N1, in one to influenza A/H3N2 and in two cases to the influenza B. Laboratory data in these two groups were characterized by significant increases in serum C-reactive protein and neutrophil-lymphocyte ratio concentrations compared with the moderate COVID-19 group. CONCLUSIONS: Serological diagnostics can additionally detect cases of coronavirus infection when the virus was not detected by PCR. In moderate and severe cases of COVID-19, coinfections with influenza A and B viruses have been identified. The results obtained confirm the need for anti-influenza immunization during the SARS-CoV-2 pandemic. Influenza virus screening can significantly improve patient management because recommended antiviral drugs (neuraminidase inhibitors) are available.

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Abstract 5858: Role of Oxygen Tension and Oxidative Stress in Human Saphenous Vein Remodeling

Circulation ◽

10.1161/circ.118.suppl_18.s_1017-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Binata Joddar ◽

Rashmeet K Reen ◽

Michael Firstenberg ◽

Keith J Gooch

Keyword(s):

Oxidative Stress ◽

Oxygen Tension ◽

Ex Vivo ◽

Neointimal Hyperplasia ◽

Fold Increase ◽

List Type ◽

Saphenous Veins ◽

Arterial Po2 ◽

And Oxidative Stress

Vessels cultured ex vivo maintain viability and vasoactivity for weeks and can remodel in response to mechanical cues. When cultured in the presence of 5% CO2/balance air veins develop neointimal hyperplasia (IH) while arteries do not suggesting that exposure to significant increases in pO2 levels might stimulate IH. Neointimal hyperplasia (IH) is a known mechanism by which saphenous veins have a decreased patency compared to arterial conduits when used for coronary artery bypass. We sought to explore the role of oxygen tension and oxidative stress in IH. Test the hypothesis that exposure of human saphenous veins (HSV) to arterial pO2 stimulates IH via ROS-mediated pathways. Almost 40 HSV remnants acquired following CABG were cultured ex vivo with arterial (~95mmHg) pO2 or venous (~40mmHg) pO2 for 14 days. All differences reported have a p<0.05 via Student’s t-test. Results: HSV cultured at arterial pO2 exhibited significant IH as evidenced by disruption of the IEL, invasion of cells from the media, and a 2.8-fold greater intimal area than fresh HSV, a 5.8-fold increase in cell proliferation compared to fresh HSV, increased ROS levels and oxidative stress as evidenced by 4-fold increase in 4-HNE level (a marker of oxidative stress), increased DHE staining (indicative of superoxide generation), and a progressive increase in total ROS levels with time as assessed by DCF fluorescence, and a 3-fold increase in phosphorylated p38-MAPK, which is implicated in SMC proliferation. In stark contrast vessels culture at arterial pO2, HSV cultured with venous pO2 did not develop increased IH and were indistinguishable from fresh vessels with respect to proliferation, markers of oxidative stress, and MAPK expression levels. Supplementing culture medium with antioxidants including Tiron or NAC blocked the pO2-induced changes. These data indicate that exposure to arterial pO2 increases cellular proliferation and stimulates IH, potentially via oxidative stress or ROS signaling and also suggest that exposure to elevated arterial pO2 might stimulate pathological remodeling of veins grafted into the arterial circulation. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

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