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      Dimethylacetamide-induced toxic hepatitis in spandex workers: clinical presentation and treatment outcomes

      1 , 2 , 3
      QJM: An International Journal of Medicine
      Oxford University Press (OUP)

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          Abstract

          Background

          Dimethylacetamide (DMAc) exposure has been associated with toxic hepatitis, and no clinical treatment has been reported.

          Aim

          To investigate the clinical manifestations of DMAc-induced symptoms and how to rescue the functional loss due to occupational exposure.

          Design

          Clinical observations of 60 spandex factory workers with the exposure to DMAc from January, 2017–19.

          Methods

          Chinese drugs (reduced glutathione, polyene phosphatidylcholine, glycyrrhizin compound, Hugan tablets and ornithine aspartate) were used to evaluate the therapeutic improvements in DMAc-exposed patients.

          Results

          Our data found that 58.3% patients had no distinct clinical symptoms, but 41.7% patients felt fatigue, and 21.7% patients suffered abdominal discomfort and appetite loss, and 8.3% patients had yellow skin and sclera. The ultrasonic and CT imaging revealed that some patients have fatty livers, intrahepatic calcifications, hepatomegaly, gallbladder wall edema and abdominal effusions. Biochemical analysis showed that the alanine aminotransferase (ALT) (P < 0.001), aspartate aminotransferase (AST) (P < 0.001), lactate dehydrogenase (LDH) (P < 0.001) and bilirubin (P < 0.01) statistically decreased after the drug treatment, but alkaline phosphatase (P >0.05) and glutamyl transpeptidase (P> 0.05) did not decrease. Twenty-nine out of the thirty-one patients’ abnormal blood ammonia recovered. The risk factor of ALT on hospitalization time was significantly related (P < 0.01).

          Conclusions

          The drugs above are sufficient to rescue functional loss in DMAc-induced toxic hepatitis, in part via the regulations of ALT, AST, LDH, bilirubin and ammonia. Workers with the exposure to DMAc should receive specific drugs to maintain the health and prevent functional loss in the long term.

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          Most cited references26

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          Is Open Access

          Current status, problems, and perspectives of non-alcoholic fatty liver disease research

          Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) based on the existence of ballooned hepatocytes, although the states have been known to transform into each other. Moreover, since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus, identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs.
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            Ammonia and Its Role in the Pathogenesis of Hepatic Encephalopathy.

            Hepatic encephalopathy (HE) is a commonly encountered sequela of chronic liver disease and cirrhosis with significant associated morbidity and mortality. Although ammonia is implicated in the pathogenesis of HE, the exact underlying mechanisms still remain poorly understood. Its role in the urea cycle, astrocyte swelling, and glutamine and gamma-amino-n-butyric acid systems suggests that the pathogenesis is multifaceted. Greater understanding in its underlying mechanism may offer more targeted therapeutic options in the future, and thus further research is necessary to fully understand the pathogenesis of HE.
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              Acute and subchronic toxicity of dimethylformamide and dimethylacetamide following various routes of administration.

              Dimethylformamide (DMF, CAS No. 68-12-2) and dimethylacetamide (DMAC, CAS No. 127-19-5) are widely used for their superior solvent properties. A series of single and multiple dose experiments in rodents were conducted to determine the target organs, and to establish doses which, under various routes of administration, produced those changes. DMF produced moderate irritation in the rabbit eye, with the corneal response clearing in 2 to 4 weeks. DMAC produced only mild, quickly reversible conjunctival irritation. Oral doses of DMF to the rat of 2,250 mg/kg or greater produced lethality which was associated with liver damage. Lethality occurred following oral doses of 4,500 mg/kg DMAC with LD50's for male and female rats of 5,809 and 4,930 mg/kg, respectively. The 1 hour LC50 by inhalation for DMAC in the rat was 2,475 ppm or greater. Sensory irritation was produced in the mouse at concentrations of 1,658 ppm or greater for DMF. Repeated oral doses of 450 mg DMF/kg to rats produced reduced body weight gain and liver injury with both changes being reversible. DMAC tested similarly produced body weight effects, liver injury, and testicular changes in the rat with all changes again being readily reversible. Dermal doses of 2,000 mg/kg of either DMF or DMAC were poorly tolerated by rabbits. DMAC was slightly more toxic with all treated rabbits dying of acute hepatic necrosis. Repeated inhalation of 2,000-2,500 ppm produced mortality in rats exposed to DMF but not DMAC. Liver injury was seen with DMF, testicular changes with DMAC. DMF and DMAC both produced slight anemia and leukocytosis in rats during 90 days of feeding. Liver weights were elevated in rats fed DMF, but not DMAC, at a level of 1,000 ppm. The "no-observed effect level" in rats fed DMF for 90 days was 200 ppm. The overall toxicologic profiles of both DMAC and DMF are similar with the target organ being the liver.
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                Author and article information

                Contributors
                Journal
                QJM: An International Journal of Medicine
                Oxford University Press (OUP)
                1460-2725
                1460-2393
                May 2020
                May 01 2020
                November 06 2019
                May 2020
                May 01 2020
                November 06 2019
                : 113
                : 5
                : 324-329
                Affiliations
                [1 ]Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing 314000
                [2 ]Department of Biopharmaceutical Sciences, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018
                [3 ]Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China
                Article
                10.1093/qjmed/hcz282
                d3440a0b-1b13-42b4-9a8b-ca63823460da
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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