Painters are constantly exposed to organic solvents containing volatile organic compounds (VOCs), a primary source of indoor air pollution. Prolonged exposure to solvents generates significant health ...repercussions on pulmonary and neurological functioning. Few studies have assessed the neurological function of unorganized sector painters objectively, especially in developing nations. The current research evaluates the effects of organic solvents on neurological functions in painters working in unorganized sectors like construction sites in Chennai.
A validated questionnaire was used to assess solvent-exposed neurological symptoms in full-time painters (n = 75) aged 25–55, stratified by years of exposure (≤10 years, >10 years). A subset of 35 painters underwent bilateral median nerve motor and sensory nerve conduction studies. Personal exposure monitors measured VOC concentration during the painting processes.
Toluene and benzene concentrations were greater in paint scraping. 47% of painters reported neurological symptoms, and those with >10 years of experience had a higher AOR (95%CI): 3.4 (1.3, 9.6). 13% had diplopia, 18% had ocular discomfort. Painters with more than 10 years of experience had longer motor and sensory onset latency of the left median nerve, as well as decreased bilateral sensory conduction velocities (Right median nerve: 53.8 ± 13.9 vs 64.2 ± 5.2; Left median nerve: 55.75 ± 6.5 vs 64.3 ± 6.2).
Paint emits toluene, a major solvent. The impact of occupational exposure to organic solvents on neurological functions has been observed to exhibit a progressive deterioration over time. Health awareness and strict protective measure legislation are needed to reduce morbidity and mortality in these unorganized sectors.
Changes in the enzymatic activity of protein arginine methyltransferase (PRMT) 5 have been associated with cancer; however, the protein's role in acute myeloid leukemia (AML) has not been fully ...evaluated. Here, we show that increased PRMT5 activity enhanced AML growth in vitro and in vivo while PRMT5 downregulation reduced it. In AML cells, PRMT5 interacted with Sp1 in a transcription repressor complex and silenced miR-29b preferentially via dimethylation of histone 4 arginine residue H4R3. As Sp1 is also a bona fide target of miR-29b, the miR silencing resulted in increased Sp1. This event in turn led to transcription activation of FLT3, a gene that encodes a receptor tyrosine kinase. Inhibition of PRMT5 via sh/siRNA or a first-in-class small-molecule inhibitor (HLCL-61) resulted in significantly increased expression of miR-29b and consequent suppression of Sp1 and FLT3 in AML cells. As a result, significant antileukemic activity was achieved. Collectively, our data support a novel leukemogenic mechanism in AML where PRMT5 mediates both silencing and transcription of genes that participate in a 'yin-yang' functional network supporting leukemia growth. As FLT3 is often mutated in AML and pharmacologic inhibition of PRMT5 appears feasible, the PRMT5-miR-29b-FLT3 network should be further explored as a novel therapeutic target for AML.
Background Paint industry workers are constantly exposed to paints and organic solvents that contain a substantial quantity of volatile organic compounds (VOCs). Exposure to VOC emissions could ...result in pulmonary, neurobehavioral, and hematological consequences. Limited studies have been undertaken in India to assess the health consequences of VOCs among paint industry workers in unorganized sectors. Aim To assess the effects of VOCs on pulmonary function in paint industry workers of unorganized sectors. Methodology A hundred and twenty full-time male construction painters and small-scale paint manufacturing workers aged 25-60 were assessed for respiratory symptoms using a questionnaire, and pulmonary functions using Wright's Peak Expiratory Flow Meter (PEFR). Participants were randomly selected for VOC assessment and the cumulative solvent exposure index was calculated. A pulmonary function test (PFT) was performed on a subset of construction painters (n=30) using a Koko spirometer. Results The concentration of VOCs such as benzene, ethylbenzene, toluene, and xylene (BETX) and dichloromethane levels exceeded American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (TLVs) among the paint manufacturing workers. About 52% of paint workers reported respiratory symptoms. Around 22% of the participants showed reduced pulmonary function (PEFR<400 L/min). There was a significant weak negative correlation between PEFR and work experience (r = -0.2, p=0.03). PFT parameters among a subset of construction painters revealed a significant moderate negative correlation with work experience forced expiratory volume at the onset of the first second (FEV1) (r = -0.6, p=0.001) and forced vital capacity (FVC) (r = -0.53, p=0.005) and cumulative VOC exposure index FEV1 (r = -0.53, p = 0.004) and FVC (r = -0.5, p = 0.008). Conclusion The concentration of VOCs was higher among paint industry workers of unorganized sectors and they reported respiratory symptoms and diminished pulmonary function. To reduce morbidity, it is critical to enhance awareness about occupational safety and services in these unorganized sectors.
Background: Paints are a major source of volatile organic compounds (VOCs) among painters. Limited information is available on neurobehavioral effect of long-term exposure to VOCs among painters ...working in unorganised industrial sectors such as construction site. Hence, this study was conducted to evaluate the neurobehavioral impact of long-term exposure to VOCs among construction painters.
Methods: This cross-sectional study was conducted among male painters in Chennai. VOC exposure index was calculated using questionnaire as well as personal exposure monitors. Neurobehavioral tests including hand dexterity, auditory (ART) and visual reaction time (VRT) were used to assess motor coordination, fine motor activity, focused attention, and psychomotor speed.
Results: Prevalence of prolonged ART and VRT in painters was 69% and 73%, respectively and 65% exhibited reduced hand dexterity. Hand dexterity had mild negative correlation (r = -0.3, p = 0.01) with VOC exposure index and work experience (r = -0.3, p = 0.02), whereas VRT had mild positive correlation (r = 0.3, p = 0.01) with VOC exposure index. Independent t-test showed a significant decrease in motor coordination with higher VOC exposure index (≤ 18.5*103 ppm-hrs = 60.1 ±10.1, >18.5*103 ppm-hrs = 53.3 ±12.3, p=0.03) and increase in work experience (≤ 10 years = 58.8 ±11.6, >10years = 52.5 ±11.5, p=0.05).
Conclusion: Neurobehavioral functions gradually decline with VOC exposure in painters working in unorganized sectors indicating a need to create awareness among the public and workers in unorganized sectors about the organic solvent-induced neurobehavioral changes.
In this study, we tested the hypothesis that reduced bioavailability of tetrahydrobiopterin (BH4) is a major mechanism responsible for pathogenesis of endothelial dysfunction in cerebral microvessels ...of transgenic mice expressing the Swedish double mutation of human amyloid precursor protein (APP) (Tg2576 mice). Endothelial nitric oxide synthase (eNOS) protein expression was significantly increased in cerebral vasculature of Tg2576 mice. In contrast, bioavailability of BH4 was significantly reduced (p < 0.05). Moreover, superoxide anion production was increased in cerebral microvessels of Tg2576 mice (p < 0.05). Incubation with NOS inhibitor, Nω‐nitro‐L‐arginine methyl ester, decreased superoxide anion indicating that uncoupled eNOS is most likely the source of superoxide anion. Increasing BH4 bioavailability either exogenously by BH4 supplementation or endogenously by treatment with the selective peroxisome proliferator‐activated receptor – delta activator GW501516 (2 mg/kg/day, 14 days) attenuated eNOS uncoupling and decreased superoxide anion production in cerebral microvessels of Tg2576 mice (p < 0.05). Treatment with GW501516 restored the biological activity of endothelial nitric oxide in cerebral microvessels of Tg2576 mice, as indicated by the increased nitrite/nitrate content and 3,5‐cyclic guanosine monophosphate levels (p < 0.05). Our studies indicate that sub‐optimal BH4 bioavailability in cerebral vasculature is an important contributor to oxidant stress and endothelial dysfunction in Tg2576 mouse model of Alzheimer's disease.
Existing evidence suggests that Aβ peptides‐induced up‐regulation of expression and activity of NADPH oxidase causes increased production of superoxide anion (.O2−). .O2− can also be converted to hydrogen peroxide (H2O2) by enzymatic activity of superoxide dismutase (SOD) or spontaneous dismutation. Elevation of .O2− and H2O2 might cause oxidation of tetrahydrobiopterin (BH4) to dihydrobiopterin (BH2) and subsequent uncoupling of endothelial nitric oxide synthase (eNOS) (a) thus reducing levels of nitric oxide (NO) and 3′,5′‐cyclic guanosine monophosphate (cGMP). Supplementation of BH4 or activation of PPARδ prevents detrimental effects of eNOS uncoupling by restoring bioavailability of BH4 and scavenging of .O2−, respectively (b). Activation of PPARδ also increases expression of catalase thereby inactivating H2O2. Generation of H2O2 by uncoupled eNOS in cerebral microvessels of Tg2576 mice is hypothetical.
Existing evidence suggests that Aβ peptides‐induced up‐regulation of expression and activity of NADPH oxidase causes increased production of superoxide anion (.O2−). .O2− can also be converted to hydrogen peroxide (H2O2) by enzymatic activity of superoxide dismutase (SOD) or spontaneous dismutation. Elevation of .O2− and H2O2 might cause oxidation of tetrahydrobiopterin (BH4) to dihydrobiopterin (BH2) and subsequent uncoupling of endothelial nitric oxide synthase (eNOS) (a) thus reducing levels of nitric oxide (NO) and 3′,5′‐cyclic guanosine monophosphate (cGMP). Supplementation of BH4 or activation of PPARδ prevents detrimental effects of eNOS uncoupling by restoring bioavailability of BH4 and scavenging of .O2−, respectively (b). Activation of PPARδ also increases expression of catalase thereby inactivating H2O2. Generation of H2O2 by uncoupled eNOS in cerebral microvessels of Tg2576 mice is hypothetical.
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