Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort.

OBJECTIVES: The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012-2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. RESULTS: In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. CONCLUSIONS: Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

Investigation of occupational risk factors for the development of non-Hodgkin's lymphoma in adults: A hospital-based case-control study.

Non-Hodgkin's Lymphoma (NHL) is a malignancy of the lymphoid lineage of the hematopoietic system has worldwide, especially in developed countries. Better diagnostic and recording techniques, longer life expectancy, and greater exposure to risk factors are hypotheses for this growing incidence curve. Occupational exposures to chemical, biological, and physical agents have also been associated with NHL development, but the results are still controversial. We have investigated the occupational and lifestyle case-control study design with 214 adult patients and 452 population controls. Socio-demographic, clinical, and occupational exposure data were obtained through individual interviews with a standardized questionnaire. Clinical, laboratory, and histopathological data were obtained through medical records. Risk of NHL (any subtype), B-cell lymphoma, DLBCL, Follicular lymphoma and T-cell lymphoma was elevated among the those who had ever been exposed to any solvents, hydrocarbon solvents, pesticides, meat and meat products, and sunlight and tended to increase by years of exposure. A significant upward trend with years of exposure was detected for any solvents and hydrocarbon solvents (NHL (any subtype) p-value for trend<0.001), B-cell lymphoma (p-value for trend<0.001), and T-cell lymphoma (p-value for trend<0.023), pesticides (NHL (any subtype), p for trend<0.001) and T-cell lymphoma (p for trend<0.002), meat and meat products (NHL (any subtype) (p for trend<0.001) and DLBCL (p for trend<0.001), and sunlight (B-cell lymphoma (p for trend<0.001). The results of this study agree line with other international studies, can be extrapolated to other countries that have the same socio-demographic and occupational characteristics as Brazil and support strategies for surveillance and control of work-related cancer.

Parkinson's disease and occupational exposure to organic solvents in Finland: a nationwide case-control study.

OBJECTIVE: This study aimed to investigate the association between Parkinson's disease (PD) and occupational exposure to organic solvents generally and chlorinated hydrocarbons (CHC) in particular. METHODS: We assembled a Finland-wide case-control study for birth years 1930-1950 by identifying incident PD cases from the register of Reimbursement of Medical Costs and drawing two controls per case using incidence density sampling from the Population Information System, matched on sex, birth year, and residency in Finland in 1980-2014. Occupation and socioeconomic status (SES) were identified from national censuses. We assessed cumulative occupational exposures via FINJEM job-exposure matrix. Smoking was based on occupation-specific prevalence by sex from national surveys. We estimated confounder-adjusted PD incidence rate ratios (IRR) via logistic regression and evaluated their sensitivity to errors in FINJEM through probabilistic bias analysis (PBA). RESULTS: Among ever-employed, we identified 17 187 cases (16.0% potentially exposed to CHC) and 35 738 matched controls. Cases were more likely to not smoke and belong to higher SES. Cumulative exposure (CE) to CHC (per 100 ppm-years, 5-year lag) was associated with adjusted IRR 1.235 (95% confidence interval 0.986-1.547), with stronger associations among women and among persons who had more census records. Sensitivity analyses did not reveal notable associations, but stronger effects were seen in the younger birth cohort (1940-1950). PBA produced notably weaker associations, yielding a median IRR 1.097 (95% simulation interval 0.920-1.291) for CHC. CONCLUSION: Our findings imply that PD is unlikely to be related to typical occupational solvent exposure in Finland, but excess risk cannot be ruled out in some highly exposed occupations.

[Inhibition of GMA-induced ubiquitination process in 16HBE malignantly transformed cells on protein CD44 and MMP14].

OBJECTIVE: To observe the effect of the ubiquitination process on the expression of CD44 antigen(CD44) and matrix metalloproteinase-14(MMP14) in human bronchial epithelial(16HBE) malignantly transformed cells induced by glycidyl methacrylate(GMA). METHODS: Successfully resuscitated 16HBE cells were cultured using a final concentration of 8 µg/mL GMA as the treatment group and 1 µg/mL dimethyl sulfoxide as the solvent control group, each time stained for 72 h, and then stained again after an interval of 24 h. After repeating the staining three times, the cells were cultured in passages respectively. The 40th generation(P40) GMA-treated group and the same-generation solvent control group were subjected to soft agar colony formation assay and concanavalin A(ConA) agglutination test to confirm that the 40th generation of GMA-induced malignant transformed 16HBE cells possessed malignant transformed cell characteristics.5, 10, 20, 40, 60 µmol/L anacardic acid were used to inhibit the ubiquitination process of GMA-induced malignant transformed 16HBE cells. The protein expression of CD44 and MMP14 were detected by western blotting, while the transcript levels of CD44, MMP14, and TFAP2A were assessed by real-time fluorescence quantitative PCR(qPCR). RESULTS: (1) In the soft agar colony formation assay, the number of clones formed by the cells in the solvent control group was 22, and the number of clones created by the malignantly transformed cells in the GMA-treated group was 208. In the ConA agglutination test, the cells in the solvent control group were uniformly dispersed in ConA solution, and no obvious agglutination occurred for 30 min, whereas the cells in the GMA-treated group were agglutinated in the 5th min, and the agglutinated cells were larger and more rapidly agglutinated. The agglomerates were more significant and faster, and the sensitivity of agglutination was increased. (2) After differential inhibition of GMA-induced ubiquitination in malignantly transformed 16HBE cells, the expression levels of CD44 and MMP14 were reduced in GMA-induced malignantly transformed 16HBE cells compared with the control group(P<0.05). The transcript levels of MMP14 and CD44 decreased with increasing inhibitor concentration(P<0.05), and the transcript levels of the upstream transcription factor TFAP2A were also simultaneously reduced(P<0.05). CONCLUSION: Inhibition of the cellular ubiquitination process mediates the down-regulation of protein expression and transcriptional expression of CD44 and MMP14 in GMA-induced malignantly transformed 16HBE cells.

Dimethyl sulfoxide's impact on epileptiform activity in a mouse model of chronic temporal lobe epilepsy.

In the quest for novel treatments for patients with drug-resistant seizures, poor water solubility of potential drug candidates is a frequent obstacle. Literature indicated that the highly efficient solvent dimethyl sulfoxide (DMSO) may have a confounding influence in epilepsy research, reporting both pro- and antiepileptic effects. In this study, we aim to clarify the effects of DMSO on epileptiform activity in one of the most frequently studied models of chronic epilepsy, the intrahippocampal kainic acid (IHKA) mouse model, and in a model of acute seizures. We show that 100 % DMSO (in a volume of 1.5 µl/g corresponding to 1651 mg/kg) causes a significant short-term anti-seizure effect in epileptic IHKA mice of both sexes, but does not affect the threshold of acute seizures induced by pentylenetetrazol (PTZ). These findings highlight that the choice of solvent and appropriate vehicle control is crucial to minimize undesirable misleading effects and that drug candidates exclusively soluble in 100 % DMSO need to be modified for better solubility already at initial testing.

Maternal occupational exposure to selected organic and chlorinated solvents and delivery of small-for-gestational age or preterm infants.

BACKGROUND: Potential reproductive effects of organic solvent exposure during pregnancy remain unclear. We investigated the association between maternal occupational exposure during pregnancy to six chlorinated solvents, three aromatic solvents, and Stoddard solvent, and delivery of preterm infants or those born small-for-gestational age (SGA). METHODS: In this case-control study of SGA and preterm birth (PTB) nested within the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we analyzed data from 7504 singleton live births without major birth defects and their mothers. Self-reported information on jobs held in the periconceptional period was assessed for solvent exposure. Unconditional logistic regression was used to estimate the association between maternal occupational exposure (any, none) during early pregnancy to organic solvents and PTB and SGA. Linear regression was used to examine changes in mean birthweight potentially associated with maternal occupational solvent exposure. RESULTS: Maternal occupational exposure to any organic solvents overall was not associated with an increased odds of PTB (adjusted odds ratio [aOR] = 0.94; 95% confidence interval [CI] 0.67-1.33) or SGA (aOR = 0.93; 95% CI 0.65-1.34). Point estimates increased modestly for higher estimated exposure versus lower, but confidence intervals were wide and not statistically significant. Maternal exposure to solvents was not associated with a statistically significant change in term birthweight among infants. CONCLUSIONS: Occupational exposure to organic solvents at the frequency and intensity levels found in a population-based sample of pregnant workers was not associated with PTB or SGA; however, we cannot rule out any effects among pregnant workers with uncommonly high exposure to organic solvents.

Large Study Links Industrial Solvent in Drinking Water to Parkinson Disease Risk in Camp Lejeune Veterans.

This Medical News story discusses a new study in JAMA Neurology that links exposure to contaminated drinking water at Marine Corps Base Camp Lejeune to an increased risk of Parkinson disease.

Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF's target molecules. METHODS: Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (-) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day. RESULTS: The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group. CONCLUSIONS: The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg.

Efectos neurológicos en trabajadores expuestos a tolueno. Revisión sistemática / Neurological effects in workers exposed to toluene. Systematic review

Introducción y objetivo: el tolueno es un disolvente orgánico derivado del benceno empleado en diversas indus-trias, con potenciales efectos nocivos para los trabajadores. Este estudio pretende conocer los posibles efectos neurológicos que presentan los trabajadores expuestos a tolueno.Material y métodos: revisión sistemática de estudios publicados en inglés y español entre enero/2000-diciem-bre/2021. Las bases de datos consultadas fueron MEDLINE, WOS, Scopus, Embase, LILACS, IBECS y Cochrane Li-brary. La calidad de los estudios se evaluó mediante la declaración STROBE y el nivel de evidencia mediante los criterios SIGN.Resultados: Se incluyeron 14 estudios observacionales (calidad entre 13-18, nivel de evidencia entre 2+ y 3). Ocho estudios examinaron síntomas neurológicos inespecíficos y alteraciones del comportamiento encontrando un au-mento de síntomas como cefalea, náuseas o vómitos, y una disminución del rendimiento motor y atención en tra-bajadores expuestos a tolueno (p<0,05). Cuatro estudios examinaron los efectos visuales, encontrando valores de Índice de Confusión de Color (CCI) más elevados en el grupo expuesto (p<0,05). Por último, dos estudios examina-ron los efectos del tolueno sobre la audición en co-exposición con ruido, observando en uno de ellos agravamiento de la pérdida auditiva en ambiente ruidoso (concentración media 33-164,6ppm), (p<0,001); mientras que en el otro estudio no se observaron efectos a concentraciones ≤50ppm.Conclusión: la exposición laboral a tolueno produce efectos neurológicos como síntomas inespecíficos, alteracio-nes del comportamiento, y efectos en la visión y en la audición. No obstante, es necesario realizar estudios con mejor diseño y calidad metodológica, ajustando factores de confusión y con mayor tamaño muestral (AU)

Introduction and objective: toluene is an organic solvent derived from benzene used in various industries, with potential harmful effects for workers. This study aims to determine the possible neurological effects of workers exposed to toluene.Material and methods: Systematic review of studies published in English and Spanish between January/2000-De-cember/2021. The databases consulted were MEDLINE, WOS, Scopus, Embase, LILACS, IBECS and Cochrane Library. Study quality was assessed using the STROBE statement and the level of evidence using the SIGN criteria.Results: 14 observational studies were included (quality between 13-18, level of evidence between 2+ and 3). Eight studies examined non-specific neurological symptoms and behavioral alterations, finding an increase in symptoms such as headache, nausea or vomiting, and a decrease in motor performance and attention in workers exposed to toluene (p<0.05). Four studies examined visual effects, finding higher Color Confusion Index (CCI) values in the exposed group (p<0.05). Finally, two studies examined the effects of toluene on hearing in co-exposure with noise observing in one of them aggravation of hearing loss in noisy environment (mean concentration 33-164.6ppm), (p<0.001); while in the other study no effects were observed at concentrations ≤50ppm.Conclusion: occupational exposure to toluene produces neurological effects such as nonspecific symptoms, behav-ioral alterations, and effects on vision and hearing. However, it is necessary to carry out studies with better design and methodological quality, adjusting for confounding factors and with a larger sample size (AU)

Neuroprotective effects of nerolidol against Alzheimer's disease in Wistar rats.

Alzheimer's disease (AD) is the most common type of cognitive disorder in an elderly population associated with the accumulation of amyloid plaques and neurofibrillary tangles. Nerolidol is assumed to have neuroprotection effects. This study aimed to investigate the therapeutic effects of nerolidol on the Aß-induced model of AD in rats. Hippocampal injection of Aß was used to induce AD. Animals were randomly divided into control, sham (received PBS as Aß solvent), AD, DNPZ (AD + donepezil, 4 weeks); NRD-50 (AD + nerolidol, 50 mg/kg, 4 weeks), NRD-100 (AD + nerolidol, 100 mg/kg, 4 weeks; Prot (rats which received 100 mg/kg nerolidol for two weeks before Aß administration), and Solv (AD + sunflower oil as nerolidol solvent, 4 weeks) groups. All rats were subjected to a memory behavioral passive avoidance test by shuttle box. Thioflavin-S staining was performed to confirm Aß plaque formation and measured using ImageJ analyzing program. BDNF and CREB-1 expressions were analyzed by immunohistochemistry assay. Aß induced AD by Aß plaques formation and increasing step-through latency time. It reduced the expression of BDNF and CREB-1 protein. Administration of nerolidol or donepezil improved these features by decreasing Aß and increasing BDNF and CREB-1 expression and latency time. Nerolidol is likely to provide protection against AD. It may prevent dementia through the mediation of BDNF-CREB-1 expression and cholinergic nerve cells restoring. It seems that the administration of nerolidol before the onset of the disease will be more effective than after.

Analysis of antidiabetic, antiulcer and analgesic potential of traditional ethnomedicinal plant Emex spinosa (L.) Campd. from Azad Jammu and Kashmir.

In this research antidiabetic, analgesic and antiulcer potential of traditional ethnomedicinal plant: Emex spinosa (L.) Campd. (Family Polygonaceae) was evaluated by extracting its phytoconstituents using methanol (MeOH) solvent through maceration protocol. The quantitative phytochemical analysis of the extract revealed flavonoids were highest in leaf extract (15.63±0.93 mg/mL) and with (11.5±0.57 mg/mL) in stem. Alkaloids and tanins were also present in the samples in various conc. while saponins were absent. To confirm pharmaceutical potential of plant against ulcer, diabetes and analgesic infirmities, a model experimental animal wistar albino rats (Rattus norvegicus) were used. In antiulcer study, using hot plate method the maximum results were observed with 250 mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41, and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. For analysis of antiulcer potential of the plants parts doses of 250 and 500 mg/kg was applied to check the reclamation of ethanol-induced acute ulcer and of Aspirin-induced chronic ulcer of stomach. In order to confirm efficacy of the drug potential of plant following parameters like microscopic evaluation, gastric volume, total acidity, mucosa weight, ulcer index, pH and histopathology of stomach were analyzed. In antidiabetic analysis, in an acute study after a single dose of 500 mg/kg extract after 2hrs the blood glucose levels were 367±51.09958NS, 416±59.79548NS, 437.5±61.96437NS mg/dL for leaf, stem and fruit, respectively. After4hrs 351.75±88.27644NS mg/dl, 448.25±25.64948NS mg/dl, 445.25±27.07205NS mg/dl and after 6hrs 354.5±92.70428NS, 442±24.60691NS, a440±33.16625NS mg/dl, respectively. The analgesic activity was explored by applying hot plate, tail flick and formalin paw licking method. In hot plate method the maximum results were observed with 250mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41 and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. The respective plant extracts at 250mg/kg showed a gradual rise in latency time when compared to the control. It was concluded that all three components of E. spinosa perform proved to be significant as potential source of herbal medicines to cure different prevalently occurring diseases. Furthermore, it was confirmed through results analysis that plant t can be used to discover novel drug using dedicated high throughput techniques and ethnopharmacological approaches.

Application of Box-Behnken design for optimization of phenolics extraction from Leontodon hispidulus in relation to its antioxidant, anti-inflammatory and cytotoxic activities.

To the best of our knowledge, there have been no phytochemical studies concerning the wild plant Leontodon hispidulus Boiss. (Asteraceae). Optimization of the green extraction process of the plant aerial parts, identification of main phenolic compounds, evaluation of antioxidant, anti-inflammatory and anticancer activities of the optimized extract have been carried out. HPLC-analysis was performed using 95% ethanolic extract. 3-Level Box-Behnken Design was applied for optimization of extraction yield and total phenolic content using 3-factors (ethanol/water ratio, material/solvent ratio and extraction time). Antioxidant, anticancer and anti-inflammatory activities were evaluated by ABTS-assay, prostate and cervical carcinoma human cell lines and carrageenan-induced rat paw edema model, respectively. HPLC-analysis showed the presence of quercetin, rutin, kaempferol, chlorogenic and ρ-coumaric acids. Increasing both ethanol/water ratio and material/solvent ratio decreased the yield, while, it increased by prolongation of the extraction time. High material/solvent ratio increased the phenolic content. The optimized extract showed high total phenolic content (104.18 µg/mg) using 201 ml of 74.5% ethanol/water at 72 h and good biological activities. Antioxidant activity was found to be 41.89 mg Trolox-equivalent/gm, with 80% free radicals inhibition. For anti-inflammatory activity, 100 mg/kg of the extract inhibited the edema in rats by 83.5% after 4 h of carrageenan injection as compared to 81.7% inhibition by indomethacin. Prostate carcinoma cell line was more sensitive to the anticancer activity of the extract than cervical carcinoma cell line (IC50 = 16.5 and 23 µg/ml, respectively). The developed extraction procedure proved to be efficient in enriching the extract with phenolic compounds with promising anticancer, anti-inflammatory and antioxidant activities.

Occupational exposures to pesticides and other chemicals: a New Zealand motor neuron disease case-control study.

OBJECTIVES: To assess associations between occupational exposures to pesticides and other chemicals and motor neuron disease (MND). METHODS: A population-based case-control study that included 319 MND cases (64% male/36% female) recruited through the New Zealand MND Association complemented with hospital discharge data, and 604 controls identified from the Electoral Roll. For each job held, a questionnaire collected information on 11 exposure categories (dust, fibres, tobacco smoke, fumes, gas, fumigants, oils/solvents, acids/alkalis, pesticides, other chemicals and animals/animal products). ORs were estimated using logistic regression adjusting for age, sex, ethnicity, socioeconomic status, education, smoking, alcohol consumption, physical activities, head/spine injury and other occupational exposures. RESULTS: Two exposure categories were associated with increased MND risks: pesticides (OR 1.70, 95% CI 1.17 to 2.48) and fumigants (OR 3.98, 95% CI 1.81 to 8.76), with risks increasing with longer exposure duration (p<0.01). Associations were also observed for: methyl bromide (OR 5.28, 95% CI 1.63 to 17.15), organochlorine insecticides (OR 3.28, 95% CI 1.18 to 9.07), organophosphate insecticides (OR 3.11, 95% CI 1.40 to 6.94), pyrethroid insecticides (OR 6.38, 95% CI 1.13 to 35.96), inorganic (copper) fungicides (OR 4.66, 95% CI 1.53 to 14.19), petrol/diesel fuel (OR 2.24, 95% CI 1.27 to 3.93) and unspecified solvents (OR 1.91, 95% CI 1.22 to 2.99). In women, exposure to textile fibres (OR 2.49, 95% CI 1.13 to 5.50), disinfectants (OR 9.66, 95% CI 1.29 to 72.44) and cleaning products (OR 3.53, 95% CI 1.64 to 7.59) were also associated with MND; this was not observed in men (OR 0.80, 95% CI 0.44 to 1.48; OR 0.72, 95% CI 0.29 to 1.84; OR 0.57, 95% CI 0.21 to 1.56, respectively). CONCLUSIONS: This study adds to the evidence that pesticides, especially insecticides, fungicides, and fumigants, are risk factors for MND.

N,N-Dimethylformamide Delays LPS-Induced Preterm Birth in a Murine Model by Suppressing the Inflammatory Response.

Preterm birth accounts for the majority of perinatal mortality worldwide, and there remains no FDA-approved drug to prevent it. Recently, we discovered that the common drug excipient, N,N-dimethylacetamide (DMA), delays inflammation-induced preterm birth in mice by inhibiting NF-κB. Since we reported this finding, it has come to light that a group of widely used, structurally related aprotic solvents, including DMA, N-methyl-2-pyrrolidone (NMP) and dimethylformamide (DMF), have anti-inflammatory efficacy. We show here that DMF suppresses LPS-induced TNFα secretion from RAW 264.7 cells and IL-6 and IL-8 secretion from HTR-8 cells at concentrations that do not significantly affect cell viability. Like DMA, DMF protects IκBα from degradation and prevents the p65 subunit of NF-κB from translocating to the nucleus. In vivo, DMF decreases LPS-induced inflammatory cell infiltration and expression of TNFα and IL-6 in the placental labyrinth, all to near baseline levels. Finally, DMF decreases the rate of preterm birth in LPS-induced pregnant mice (P<.0001) and the rate at which pups are spontaneously aborted (P<.0001). In summary, DMF, a widely used solvent structurally related to DMA and NMP, delays LPS-induced preterm birth in a murine model without overt toxic effects. Re-purposing the DMA/DMF/NMP family of small molecules as anti-inflammatory drugs is a promising new approach to delaying or reducing the incidence of inflammation-induced preterm birth and potentially attenuating other inflammatory disorders as well.

[Analysis of Flame Retardants Bis(2,3-dibromopropyl) phosphate and Tris(2,3-dibromopropyl) phosphate in Textile Products by GC-MS].

The use of flame retardants, namely bis(2,3-dibromopropyl) phosphate (BDBPP) and tris(2,3-dibromopropyl) phosphate (TDBPP), in textile products such as curtains, carpets and sleeping clothes is banned in Japan under the 'Act on the Control of Household Products Containing Harmful Substances'. Herein, we developed a GC-MS based method to quantify these compounds with greater accuracy and safety than the current official method. For accurate and sensitive quantification, deuterated compounds, BDBPP-d10 and TDBPP-d15, were used as surrogate standards. In consideration of the safety of the analyst, certain solvents and reagents used for the pretreatment that are carcinogenic or have a risk of explosion were replaced. For the extraction step, benzene was replaced by ethyl acetate, and for the methyl derivatization step, the reagent was changed from a self-prepared solution of diazomethane in ether to a solution of trimethylsilyl diazomethane in hexane, a safe and easy-to-use commercially available reagent. The calibration curves were liner in the range of 0.5-8.0 µg/mL for both methylated BDBPP (BDBPP-Me) and TDBPP. The detection limit was 0.05 µg/g for BDBPP-Me and 0.3 µg/g for TDBPP, which is sufficiently low compared to the current detection limits of 10 µg/g for BDBPP-Me and 8 µg/g for TDBPP. The recoveries in various curtain material were 66-108% and relative standard deviations were 1.2-10.2% when 5 µg BDBPP and TDBPP were added to 0.5 g of samples. Thus, the developed method is applicable to textile products of various materials.

Reported transfusion-related acute lung injury associated with solvent/detergent plasma - A case series.

BACKGROUND: Antibody-mediated transfusion-related acute lung injury (TRALI) is caused by donor HLA or HNA antibodies in plasma-containing products. In the Netherlands 55,000 units of solvent/detergent plasma (SDP), a pooled plasma product, are transfused yearly. It's produced by combining plasma from hundreds of donors, diluting harmful antibodies. Due to a lack of reported cases following implementation, some have labeled SDP as "TRALI safe". STUDY DESIGN AND METHODS: Pulmonary transfusion reactions involving SDP reported to the Dutch national hemovigilance network in 2016-2019 were reviewed. Reporting hospitals were contacted for additional information, cases with TRALI and imputability definite, probable, or possible were included and informed consent was sought. RESULTS: A total of three TRALI and nine TACO cases were reported involving SDP. The imputability of one TRALI case was revised from possible to unlikely and excluded; in one case no informed consent was obtained. We present a case description of TRALI following SDP transfusion in a 69-year-old male, 3 days following endovascular aortic aneurysm repair. The patient received one unit of SDP to correct a heparin-induced coagulopathy, prior to removal of a spinal catheter post-operatively. Within five hours he developed hypoxemic respiratory failure requiring intubation, hypotension, bilateral chest infiltrates, and leucopenia. The patient made a full recovery. CONCLUSION: This case of TRALI, following transfusion of a single unit of SDP to a patient without ARDS risk factors, demonstrates that TRALI can occur with this product. Clinicians should remain vigilant and continue to report suspected cases, to help further understanding of SDP-associated TRALI.

Paint-thinner-induced Acute Kidney Injury: A Case Series and Review.

Occupational health hazards contribute significantly to the morbidity and mortality of workers in factories. Toluene has become a widely abused inhaled volatile drug. The spectrum of toluene-induced renal injury includes rhabdomyolysis, myoglobinemia, distal renal tubular acidosis (RTA), acute tubular necrosis, glomerulonephritis, and interstitial nephritis. We describe two patients with paint-thinner-induced kidney injury who were affected through different routes of exposure and recovered well, with one requiring dialysis support; the second patient, who had developed Type 1 distal RTA and mild kidney injury, was managed with conservative measures. Toluene can cause acute neurological symptoms, accompanied by severe metabolic alterations, as well as organ injury and dysfunction. A common association of the development of hypokalemic paralysis and metabolic acidosis with toluene intoxication was observed. Liver injury and rhabdomyolysis are also common. Vomiting, dehydration, tubular injury, and rhabdomyolysis are all possible additional causes of acute renal failure in toluene intoxication. Type 1 distal RTA, which is characterized by an inability to lower urine pH despite acidemia, results in hyperchloremic metabolic acidosis with hypokalemia. The management of acute toluene toxicity is largely conservative, consisting of correcting the electrolytes and the acid-base balance, fluid alterations, and renal replacement therapy in severe acute kidney injury. A clinical suspicion of organ failure and prompt supportive care leads to encouraging results. Adequate protective steps for workplaces involved in the use of such substances in confined spaces include prior risk assessment, using low-toxicity chemical products, ensuring adequate ventilation, safety training, and using appropriate personal protective equipment.

Pure Tone Audiometry Evaluation Method Effectiveness in Detecting Hearing Changes Due to Workplace Ototoxicant, Continuous Noise, and Impulse Noise Exposures.

OBJECTIVES: The purpose of this retrospective cohort study was to compare the relative risks (RR) of hearing impairment due to co-exposure of continuous noise, impulse noise, metal ototoxicants, and organic solvent ototoxicants using several pure tone audiometry (PTA) evaluation methods. DESIGN: Noise and ototoxicant exposure and PTA records were extracted from a DoD longitudinal repository and were analyzed for U.S. Air Force personnel (n = 2372) at a depot-level aircraft maintenance activity at Tinker Air Force Base, Oklahoma using an historical cohort study design. Eight similar exposure groups based on combinations of ototoxicant and noise exposure were created: (1) Continuous noise (reference group); (2) Continuous noise + Impulse noise; (3) Metal exposure + Continuous noise; (4) Metal exposure + Continuous noise + Impulse noise; (5) Solvent exposure + Continuous noise; (6) Solvent exposure + Continuous noise + Impulse noise; (7) Metal exposure + Solvent exposure + Continuous noise; and (8) Metal exposure + Solvent exposure + Continuous noise + Impulse noise. RR of hearing impairment compared to the Continuous noise-exposed reference group was assessed with five PTA evaluation methods including (1) U.S. Department of Defense (DoD) Significant Threshold Shift (STS), (2) Occupational Safety and Health Administration (OSHA) age-adjusted STS, (3) National Institute for Occupational Safety and Health (NIOSH) STS, (4) NIOSH Material Hearing Impairment, and (5) All Frequency Threshold Average. RESULTS: Hearing impairment was significantly worse for SEG (2) combined exposure to continuous noise and impulse noise only for the PTA evaluation method (2) OSHA Age Adjusted with an RR of 3.11, [95% confidence interval (CI), 1.16-8.31] and was nearly significantly different using PTA evaluation method (4) NIOSH Material Hearing Impairment with an RR of 3.16 (95% CI, 0.99-10.15). Despite no significant differences for SEGs with an ototoxicant exposure, PTA evaluation method (3) NIOSH STS was most sensitive in detecting hearing changes for SEG (8) Metal exposure + Solvent exposure + Continuous noise + Impulse noise as demonstrated by a RR of 1.12 (95% CI, 0.99-1.27). CONCLUSIONS: Results suggest that a single PTA evaluation technique may not be adequate in fully revealing hearing impairment risk due to all stressors and tailoring the PTA evaluation technique to the hazards present in the workplace could better detect hearing impairment. Additionally, results suggest that PTA may not be effective as the sole technique for evaluating hearing impairment due to ototoxicant exposure with continuous noise co-exposure.

Formulation of stomach-specific floating microparticles of nizatidine and their radiographic evaluation

Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 µ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer