A case of dimethylformamide poisoning caused by skin contact / 中华劳动卫生职业病杂志

In this paper, the clinical data of a case of accidental poisoning of dimethylformamide in a traffic accident was analyzed. The patient was trapped in the driving room, his limbs were soaked in dimethylformamide for a long time, and dimethylformamide was inhaled at the same time. After 4 days of treatment in a local hospital, he was transferred to the Department of Poisoning & Occupational Diseases, Emergency Medicine of Qilu Hospital of Shandong University for treatment. The main clinical manifestation of the patient was liver damage and intractable abdominal pain, which was cured by active treatment.

Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

Compensation for Work-Related Hematologic, Liver, and Infectious Diseases

Occupational diseases may be defined only medically or scientifically, and even then, their definition is not simple. However, compensable occupational diseases involve the additional layer of legal systems and social welfare policies as well. Their multifaceted nature makes determining the work-relatedness of these diseases more complex. Korea has established standards for the recognition of occupational diseases in Schedule 5 of the Enforcement Decree of the Labor Standards Act, and specific criteria for the recognition of occupational diseases are listed in Schedule 3 of the Enforcement Decree of the Industrial Accident Compensation Insurance Act. The new list of compensable occupational diseases comprises 13 articles as an open-ended system. The newly added articles pertain to lymphohematopoietic (Article 5) and infectious diseases (Article 9), as well as diseases of other target organs. Furthermore, the article on liver diseases (Article 8) has been partially revised. The new act has been changed to clarify the meaning as it has been presented in recent research. It is necessary to achieve agreement among concerned parties, including experts from the legal, medical, and social domains to resolve the issues of work-relatedness, causation, notion of aggravation, and so on for preparing a list and a process that are more reasonable.

Effect of N, N-dimethylformamide on oxidation or antioxidation status among occupational exposed workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the effect of N,N-dimethylformamide (DMF) on oxidation or antioxidation status among occupational exposed workers.</p><p><b>METHODS</b>A total of 104 DMF exposed workers and 101 controls were recruited in this study in May 2012. The information of occupational history, age, gender, smoking and alcohol habits of all subjects were collected by questionnaire. DMF concentration in the air of workplace was tested. N-methyl-carbamoylated haemoglobin adduct (NMHb) in blood was chosen as an inner-dose biomarker, which was expressed as 3-methyl-5-isopropylhydantoin(MVH), the degeneration product of NMHb. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels were detected to reflect liver function. Serum superoxide dismutase (SOD) activity, glutathione-S-transferase (GST) activity, malondialdehyde (MDA) levels, 3- nitrotyrosine (3-NT) levels were detected to reflect oxidative/antioxidative status.</p><p><b>RESULTS</b>DMF concentration in workplace air was within the range of 3.3-12.4 mg/m(3), which did not exceed our national standard. The MVH level in exposed workers was (19.69 ± 12.52) mg/kg, but was not detectable in control group. The activity of SOD in exposed workers ((125.30 ± 21.23) U/ml) was significantly higher than the control group ((118.35 ± 18.48) U/ml, t = -2.47, P = 0.014). However, the activity of SOD showed different trends with the increasing of MVH level. When MVH ≤ 24 mg/kg, the SOD activity increased with the increasing of MVH level (r = 0.356, P = 0.002). However, when MVH> 24 mg/kg, SOD activity expressed decreasing trend with the increasing of MVH level (r = -0.260, P = 0.150). No significant differences were observed in GST, MDA, 3-NT, ALT, AST levels among the two groups.</p><p><b>CONCLUSION</b>DMF exposure might have stimulatory effect on antioxidation system of the body under low concentration; within the range of compensatory defense, DMF exposure did not cause obvious lipid and/or protein peroxidative damage.</p>

Study of N-methylcarbamoylated hemoglobin in blood of being an exposure biomarker of N, N-dimethylformamide / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To assess the value of blood N-methylcarbamoylated haemoglobin (NMHb) as a biomarker of N, N-dimethylformamide (DMF) exposure.</p><p><b>METHODS</b>Seventy-two DMF processing workers in a synthetic leather factory were included in the DMF exposure group, and 12 workers in a food factory without exposure to DMF were included in the control group. Long-time individual sampling in workplace was performed among 45 workers in the exposure group, accompanied by a questionnaire survey. Blood and urine were collected for the determination of urinary N-methylformamide (NMF), urinary creatinine, and blood NMHb. Air DMF and urinary NMF were determined by gas chromatography. NMHb in blood was degraded to 3-methyl-5-isopropylhydantoin by Edman degradation before it could be determined by gas chromatography/mass spectrometry.</p><p><b>RESULTS</b>Air DMF in workplace and NMF in post-shift urine were both correlated with NMHb in blood, and the respective regression equations were LgNMHb (nmol/g globin) = 0.32×LgDMF (mg/m(3))+1.8 (r = 0.60, P < 0.005), and LgNMHb (nmol/g globin) = 0.47×LgNMF (mg/g Cr) + 1.4 (r = 0.56, P < 0.005).</p><p><b>CONCLUSION</b>NMHb can be used as a biomarker of long-term exposure to DMF.</p>

Toxicity of intragastrically administered N, N-dimethylformamide in female Wistar rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the toxicity of intragastrically administered N, N-dimethylformamide (DMF) in female Wistar rats, and to provide experimental data for the overall evaluation of DMF toxicity under different ways of exposure.</p><p><b>METHODS</b>Forty female Wistar rats weighing 150∼180 g were randomly divided into four groups: control group (treated with water) and three DMF exposure groups with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. After oral administration of DMF once a day for 14 consecutive days, the rats were weighed and sacrificed. The liver, kidney, brain, and uterus were weighed to calculate organ indices. The pathological changes in the liver were examined by HE staining. The protein expression of HSP70 in the liver, kidney, and brain was determined. Finally, peripheral lymphocytes were collected from the arteria cruralis to determine DNA damage by comet assay.</p><p><b>RESULTS</b>Fourteen days after DMF exposure, the body weight and organ indices of the kidney, brain, and uterus showed no significant changes. However, the liver index showed concentration-dependent increase in all DMF exposed groups (3.52±0.21, 3.55±0.13, and 3.88±0.22 in the low-, medium-, and high-dose groups, respectively), as compared with the control group (3.24±0.28) (P < 0.05 or P < 0.01). The pathological damage in the liver also showed a concentration-dependent manner. Inflammatory cell infiltration and granular degeneration in centrilobular hepatocytes were observed in the high-dose group. No significant change in protein expression of HSP70 was observed in the liver, kidney, or brain of DMF-exposed rats (P > 0.05). DNA damage was induced by DMF, and the DNA percentage of lymphocyte comet tail, average tail length, and tail moment in exposed groups were all significantly increased as compared with the control group (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Gavaged DMF can induce liver injury and DNA damage in lymphocytes in rats 14 days after administration. There is no significant change in protein expression of HSP70 in the liver, brain, or kidney after DMF exposure.</p>

Effect of N,N-dimethylformamide on calcium homeostasis and the calpain gene expression in human hepatocytes / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of N,N-dimethylformamide (DMF) on calcium homeostasis and calpain I and II gene expression in human hepatocytes (HL-7702).</p><p><b>METHODS</b>HL-7702 cells were exposed to different concentrations of DMF (10, 25, 50, 100, or 200 mmol/L); other HL-7702 cells, which were used as a control group, were exposed to the equal volume of DMEM; the intracellular Ca(2+) concentration was monitored using the calcium fluorescent probe (fluo-3/AM). After 24-h exposure to DMF (10, 25, 50, 100, 150, or 200 mmol/L), the morphology of hepatocytes was observed under an inverted phase contrast microscope, and the cell viability was measured by MTT assay. After 24-h exposure to DMF (10, 25, 50, 100, or 150 mmol/L), the mRNA expression levels of calpain I and II in hepatocytes were measured by real-time quantitative PCR.</p><p><b>RESULTS</b>There were significant differences in cell viability among different exposure groups (P < 0.01); the 50, 100, 150, and 200 mmol/L DMF exposure groups had a significantly lower cell viability than the control group (P < 0.05). Under the inverted phase contrast microscope, HL-7702 cells gradually lost the original shape, with swelling and shrinking, as the dose of DMF increased, and those treated with 150 mmol/L DMF even became round and floated. The fluorescence density of fluo-3 in hepatocytes increased as the dose of DMF rose, demonstrating a dose-response relationship, and there were significant differences among these exposure groups (P < 0.05). There were significant differences in mRNA expression levels of calpain I and II among these exposure groups (P < 0.01), and the expression increased as the dose of DMF rose; but DMF did not promote the mRNA expression of calpain I at a concentration of 150 mmol/L.</p><p><b>CONCLUSION</b>DMF can cause damage to hepatocytes, which is related to intracellular calcium increase and calpain mRNA increase.</p>

Occupational acute dimethylformamide poisoning: an analysis of 16 cases / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and diagnostic points of occupational acute dimethylformamide (DMF) poisoning and to explore the mechanism of occupational acute DMF poisoning.</p><p><b>METHODS</b>A comprehensive analysis was performed on the clinical data of 16 cases of occupational acute DMF poisoning, including symptoms, signs, and laboratory testing results.</p><p><b>RESULTS</b>The main clinical features of occupational acute DMF poisoning were digestive system impairments, especially abdominalgia. Hemorrhagic gastroenteritis was not found by gastroscopy. There was no significant correlation between the degree of abdominalgia and alanine aminotransferase level (r(s) = 0.109, P>0.05).</p><p><b>CONCLUSION</b>Abdominalgia is recommended to be one of the reference indices for the diagnosis and degrading of occupational acute DMF poisoning, The mechanism of DMF poisoning remains unclear but it is considered to be related to methyl isocyanate, the intermediate product of DMF metabolism.</p>

Hepatotoxicity in Rats Treated with Dimethylformamide or Toluene or Both

The effects of toluene in dimethylformamide (DMF)-induced hepatotoxicity were investigated with respect to the induction of cytochrome P-450 (CYP) and the activities of related enzymes. The rats were treated intraperitoneally with the organic solvents in olive oil (Single treatment groups: 450 [D1], 900 [D2], 1,800 [D3] mg DMF, and 346 mg toluene [T] per kg of body weight; Combined treatment groups: D1+T, D2+T, and D3+T) once a day for three days, while the control group received just the olive oil. Each group consisted of 4 rats. The activities of the xenobiotic metabolic enzymes and the hepatic morphology were assessed. The immunoblots indicated that the expression of CYP2E1 was considerably enhanced depending on the dosage of DMF and the CYP2E1 blot densities were significantly increased after treatment with both DMF and toluene, compared to treatment with DMF alone. The activities of glutathione-S-transferase and glutathione peroxidase were either decreased or remained unaltered after treatment with DMF and toluene, whereas the lipid peroxide levels were increased with increasing dosage of DMF and toluene. The liver tissue in the D3 group (1,800 mg/kg of DMF) showed signs of microvacuolation in the central vein region and a large necrotic zone around the central vein, in rats treated with both DMF (1,800 mg/kg) and toluene (D3T). These results suggest that the expression of CYP2E1 is induced by DMF and enhanced by toluene. These changes may have facilitated the accelerated formation of N-methylformamide (NMF) from toluene, and the generated NMF may directly induce liver damage.

Effect of acute exposure of N, N-Dimethylformamide, an industrial solvent on lipid peroxidation and antioxidants in liver and kidney of rats.

N, N-Dimethylformamide (DMF), an industrial solvent widely used throughout the world is a known toxic compound. Here, we studied the effects of acute exposure of DMF on liver and kidney in rats. Rats were treated intraperitoneally with a single dose of DMF (1.5 g/kg) for 24 and 48 h. Hepatic and nephrotoxicity was confirmed based on the significant increase in the serum levels of aspartate amino transferase, alanine amino transferase, alkaline phosphatase, g-glutamyl transferase, urea, creatinine and electrolytes. Oxidative stress was assessed by determining the levels of lipid peroxidation (LPO) and antioxidants in liver and kidney. The LPO levels were elevated in both the tissues upon DMF exposure, whereas the activities of enzymatic antioxidants SOD, CAT and Gpx and non-enzymatic antioxidants (glutathione and vitamin C) were declined. The hepatic- and nephrotoxicity was further confirmed by the increasing incidence of inflammation in the histopathological studies. The findings indicate that acute exposure of DMF results in oxidative stress, antioxidant deficiency, attenuating liver and kidney marker enzymes, resulting in tissue inflammation and damage.

Efecto del colesterol y la dimetilformamida sobre parámetros posdescongelación en espermatozoides de caballos criollos colombianos / Effect of cholesterol and dimethiyl-formamide on post-thawing parameters in Colombian creole stallion sperm

Objetivo. Evaluar el efecto del colesterol y la dimetilformamida (DMF) sobre la criosupervivencia del semen de caballos criollos colombianos. Materiales y métodos. Se recolectó semen de diez caballos y se congeló bajo el mismo protocolo, con variaciones del crioprotector (glicerol 5% o DMF 5%) y la adición o ausencia de colesterol como modificador de membrana (1.5 mg ciclodextrinas con colesterol por cada 120 x 106 células). La criosupervivencia se evaluó estimando movilidad mediante el software SCA. La vitalidad e integridad de membrana posdescongelación se estimó usando eosina-nigrosina y test hipo-osmótico respectivamente. Resultados. Incubar el semen con el colesterol, tuvo un aumento significativo del porcentaje de movilidad total y progresiva, en la velocidad de los espermatozoides y el porcentaje de espermatozoides rápidos y una disminución del porcentaje de espermatozoides con movilidad lenta. Adicionalmente se incrementó el porcentaje de espermatozoides vivos y con integridad de membrana (p<0.05). La DMF como agente crioprotector, mejoró todos los parametros evaluados al ser comparada el glicerol (p<0.05). Conclusiones. Ambos procedimientos mejoraron los parámetros evaluados debido a efectos aditivos del crioprotector y del modificador de membrana, pero no hubo interacción entre estos dos factores.

Clinical Outcomes of Occupational Exposure to N,N-Dimethylformamide: Perspectives from Experimental Toxicology

N,N-Dimethylformamide (DMF) is globally used as an organic solvent in the production of synthetic leather and resins because of its low volatility, making it an attractive industrial material. Despite its excellent property as a chemical solvent, utilization of DMF is somewhat controversial nowadays due to its hazardous effects on exposed workers in work places. Many toxification cases are being reported globally and the number of cases of liver damage is still increasing in developing countries. On account of this, a series of epidemiologic surveys are being conducted to understand the degrees of liver damage caused by DMF exposure. Furthermore, many investigations have been performed to clarify the mechanism of DMF-induced liver toxicity using both human and experimental animal models. This review summarizes the current occupational cases reported on liver damage from workers exposed to DMF in industrial work places and the research results that account for DMF-induced liver failure and possible carcinogenesis. The findings reviewed here show the synergistic toxicity of DMF exposure with other toxicants, which might occur through complicated but distinct mechanisms, which may extend our knowledge for establishing risk assessments of DMF exposure in industrial work places.

The interventions effect-assessment of the workers exposed to N, N-dimethylformamide by percutaneous in a synthetic leather factory / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To assess the effects of interventions on synthetic leather workers exposed to N, N-dimethylformamide (DMF) by skin.</p><p><b>METHODS</b>Twenty-six workers exposed to DMF were recruited. The level of DMF in ambient or handwash solution and N-methylformamide (NMF) in end-shift urine samples were detected before interventions and after interventions for six months.</p><p><b>RESULTS</b>After interventions the levels of DMF in ambient reduced 52.7% from (63.27 +/- 52.67) mg/m3 to (29.95 +/- 23.79) mg/m3. The levels of NMF in urine samples reduced 17.9% from (2.07 +/- 0.32) mg/g Cr to (1.70 +/- 0.29) mg/g Cr (P < 0.01). The mean level of DMF in handwash solution reduced 53.4% from 0.88 +/- 0.40 mg to 0.41 +/- 0.81 mg.</p><p><b>CONCLUSION</b>This study showed that the multi-intervention measures (engineering control, personal protection and health promotion) should be used for the synthetic leather workers occupationally exposed to DMF.</p>

Evaluation of the antimicrobial activity of various concentrations of Tulsi (Ocimum sanctum) extract against Streptococcus mutans: An in vitro study.

Aim: To determine if Tulsi (Ocimum sanctum) extract has an antimicrobial activity against Streptococcus mutans and to determine which concentration of Tulsi (Ocimum sanctum) extract among the 15 concentrations investigated has the maximum antimicrobial activity. Setting and Design: Experimental design, in vitro study, Lab setting. Materials and Methods: Ethanolic extract of Tulsi was prepared by the cold extraction method. The extract was then diluted with an inert solvent, dimethyl formamide, to obtain 15 different concentrations (0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7% 8%, 9%, 10%) of the extract. 0.2% chlorhexidine was used as a positive control and dimethyl formamide was used as a negative control. The extract, along with the controls, was then subjected to microbiological investigation to determine which concentration among the 15 different concentrations of the extract gave a wider inhibition zone against Streptococcus mutans. The zones of inhibition were measured in millimeters using a vernier caliper. Results: At the 4% concentration of Tulsi extract, a zone of inhibition of 22 mm was obtained. This was the widest zone of inhibition observed among all the 15 different concentrations of Tulsi that were investigated. Conclusion: Tulsi extract demonstrated an antimicrobial property against Streptococcus mutans.

Investigation on dermal contamination among workers occupationally exposed to dimethylformamide / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish a method for the determination of dimethylformamide (DMF) and investigate dermal contamination and absorption among workers occupationally exposed to DMF.</p><p><b>METHOD</b>37 workers exposed to DMF were divided randomly into two groups. DMF was washed down by isopropyl alcohol in A group (16 workers) and water in B group(21 workers).Gas chromatography was used for the quantification of dermal contamination and N-methylformamide(NMF) in urine, correlative study was done between them.</p><p><b>RESULTS</b>DMF could be detected in all samples in A group, but could not be detected in B group. The miscellaneous peaks could be completely separated from the DMF peak in the sample spectrum, without manual inference. The highest degree of total dermal contamination was observed in wet spinning workshop [(2.84 +/- 1.31) mg], postprocessing workshop [(2.50 +/- 0.95) mg] and dry spinning workshop [(1.95 +/- 0.61) mg] were lower. The respiratory cumulative exposure dosages were 351.3, 201.3 and 135.2 mg respectively. The average DMP concentration in air of the third printing processing workshop, the dry spinning workshop and the wet spinning workshop was 60.2, 89.6, 156.4 mg/m3 respectively, and the respiratory tract contamination in the workers of the three workshops were 135.2, 201.3 and 351.3 mg respectively. There was statistical independence between the quantification of total dermal contamination and NMF in urine (r = 0.176, P > 0.05).</p><p><b>CONCLUSION</b>Isopropyl alcohol is the effective washing solvent.When the concentration of DMF in workplace air is above the occupational exposure limit, respiratory tract absorption is the principal pathway of DMF absorption,but dermal contamination of DMF should not be ignored.</p>

Abnormal liver function associated with polymorphism of GSTT1, GSTM1 and CYP2E1 in workers exposed to N, N-dimethylformamide / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate abnormal liver function associated with polymorphism of GSTT1, GSTM1 and CYP2E1 in workers exposed to N, N-dimethylformamide.</p><p><b>METHODS</b>Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case. One hundred and twenty five control subjects with similar work tasks were selected from the same factory. Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR, and for CYP2E1 PstI by PCR-RFLP assay.</p><p><b>RESULTS</b>The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control, with an odds ratio (OR) of 2.34,95% CI: 1.29-4.29 (P=0.005). For GSTT1 and CYP2E1 PstI, the frequencies of genotypes showed no significant difference between case and control.</p><p><b>CONCLUSION</b>GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N, N-dimethylformamide.</p>

DMF-induced adult hepatocyte apoptosis and its effects on expression of Bcl-2, Bax and Caspase-3 / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the apoptosis-inducing effect of DMF on the human liver cells (HL-7702) in vitro.</p><p><b>METHODS</b>Liver cells were exposed to different concentrations of DMF (0, 50, 100, 150, 200 mmol/L) for 12 hours. Apoptotic rate, the expression of Bax, Bcl-2 and Caspase-3 in liver cells were measured by FCM and western blotting respectively.</p><p><b>RESULTS</b>The increase in apoptotic rate of hepatocytes in concentration-manner was shown after DMF treatment for 12 h. After treatment the expression of Bcl-2 was decreased steadily and lower than the control group (P < 0.01), the expression of Bax showed no significant difference among the groups of different dosage by one-factor analysis of variance (P > 0.05), as the increase of the dosage of DMF. The ratio of Bcl-2/Bax dropped with the dosage of DMF increasing, and the ratio in 200 mmol/L of DMF was significantly lower than that of the control (P < 0.01). The new lands of procaspase-3 in 150, 200 mmol/L were observed, which demonstrated that there was active caspase-3.</p><p><b>CONCLUSION</b>DMF can induce apoptosis of cultured adult normal hepatocytes in vitro, and the mechanism might be related to the decrease of Bcl-2/Bax and the cleavage of Caspase-3.</p>

Radiosynthesis of 11C6-OH-BTA-1 in Different Media and Confirmation of Reaction By-products / 핵의학분자영상

PURPOSE: [11C]6-OH-BTA-1 ([N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, 1), a -amyloid imaging agent for the diagnosis of Alzheimer's disease in PET, can be labeled with higher yield by a simple loop method. During the synthesis of [11C]1, we found the formation of by-products in various solvents, e.g., methylethylketone (MEK), cyclohexanone (CHO), diethylketone (DEK), and dimethylformamide (DMF). MATERIALS AND METHODS: In Automated radiosynthesis module, 1 mg of 4-aminophenyl-6-hydroxybenzothiazole (4) in 100 l of each solvent was reacted with [11C]methyl triflate in HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 14.4, 16.3 and 17.6 min were collected and analyzed by analytical HPLC and LC/MS spectrometer. RESULTS: The labeling efficiencies of [11C]1 were 86.0+/-5.5%, 59.7+/-2.4%, 29.9+/-1.8%, and 7.6+/-0.5% in MEK, CHO, DEK and DMF, respectively. The LC/MS spectra of three products eluted at 14.4, 16.3 and 17.6 mins showed m/z peaks at 257.3 (M+1), 257.3 (M+1) and 271.3 (M+1), respectively, indicating their structures as 1, 2-(4'-aminophenyl)-6-methoxybenzothiazole (2) and by-product (3), respectively. Ratios of labeling efficiencies for the three products ([11C]1:[11C]2:[11C]3) were 86.0+/-5.5%:5.0+/-3.4%:1.5+/-1.3% in MEK, 59.7+/-2.4%:4.7+/-3.2%:1.3+/-0.5% in CHO, 9.9+/-1.8%:2.0+/-0.7%:0.3+/-0.1% in DEK and 7.6+/-0.5%:0.0%:0.0% in DMF, respectively. CONCLUSION: The labeling efficiency of [11C]1 was the highest when MEK was used as a reaction solvent. As results of mass spectrometry, 1 and 2 were conformed. 3 was presumed.

Abnormal liver function associated with occupational exposure to N, N-dimethylformamide in synthetic leathers works / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the hepatotoxic effects of N, N-dimethylformamide (DMF) in the workers of a synthetic leathers factory, and the effects on liver function of covariates such as alcohol consumption and other factors.</p><p><b>METHODS</b>The workers were classified into three groups (low, high and the control) by the concentration of DMF in workplace which was determined in the past two years. A questionnaire was drawn up for relevant demographic characteristics and other factors influencing liver function. The bloods were collected for laboratory test which included parameters especially relevant to the liver (ALT AST and gamma GT).</p><p><b>RESULTS</b>Low and high-exposure groups were significantly associated with elevated ALT and gamma GT, and high-exposure group was significantly associated with elevated Liver index. Modeling by stepwise regression analysis demonstrated that high concentration of DMF and BMI were associated with and elevated ALT, gamma GT and Liver index, besides DMF and BMI, the elevation of ALT was also associated with high TRIG. AST was only associated with alcohol consumption. The AST/ALT ration < 1 was present in 86.7% of the exposure workers of liver function abnormal.</p><p><b>CONCLUSION</b>DMF can cause liver function alternations even if air concentration of DMF was below PC-TWA. Besides the levels of DMF exposure, obesity (BMI) and alcohol consumption are covariates alternating liver function. Liver index can be a parameter for assessment liver function, and the AST/ALT ration < 1 may serve as markers of risk in health screening programs.</p>