Adult ; Chronic Disease ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Occupational Diseases ; Radiation Injuries

OBJECTIVETo study the effect of dimethoate on the expression of heat shock protein 70 (HSP70) in peripheral blood lymphocytes of human beings and to explore the feasibility of HSP70 in biomonitoring among workers exposed to organophosphorous pesticides.

METHODSPeripheral blood lymphocytes were isolated from subjects, comprising 11 people of the control group and 35 workers of the exposure group exposed to dimethoate. Flow cytometry was used for detecting both the basic level and the level of the dimethoate-induced expression of HSP70. The activity of whole blood acetylcholinesterase (AChE) was examined at the same time. Then the potential influential factors to HSP70 expression and AChE activity were analyzed.

RESULTSThe basic level of HSP70 expression in the exposure group and the control group was 41.24% +/- 10.45% and 23.97% +/- 4.29% respectively. The activity of AChE in these two groups were (125.23 +/- 7.97) and (145.36 +/- 8.78) U/ml respectively. Both differences were statistically significant (P < 0.01). Among the exposure group, the basic level of HSP70 expression of the two categories comprising operators and packers, were 47.34% +/- 11.87% and 38.05% +/- 8.20% respectively (P < 0.05), while there was no significant difference (P > 0.05) in AChE activity between these two categories. The factors that had significant influence on the HSP70 basic level of the exposure group were the health condition, the environmental concentration of dimethoate and the exposure time in order, according to their significance of influence. At least 88% variance of HSP70 could be explained by these factors. The only factor that could influence AChE activity significantly was the exposure time, and it could only explain about 12% variance of AChE activity. After the treatment of dimethoate in vitro, the level of the induced expression of HSP70 in the control group was significantly higher than that of the exposure group (P < 0.01). The increasing order was the control group, the group of packers and the group of operators according to the increasing extent and there were significant difference among them (P < 0.01). The factors that could significantly influence the change ratio of HSP70 expression were the environmental concentration and the exposure time.

CONCLUSIONHSP70 is a potential index that can reflect the individual and environmental conditions of workers exposed to dimethoate comprehensively.

Acetylcholinesterase ; blood ; Adult ; Cells, Cultured ; Dimethoate ; toxicity ; Female ; HSP70 Heat-Shock Proteins ; biosynthesis ; Humans ; Insecticides ; toxicity ; Lymphocytes ; drug effects ; metabolism ; Male ; Middle Aged ; Occupational Exposure

OBJECTIVETo investigate the influence of pyrrolidine dithiocarbamate (PDTC) on the expression of transforming growth factor beta(1) (TGF-beta(1)), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-1 of metalloproteinase (TIMP-1) in rats with pulmonary damage induced by paraquat (PQ).

METHODSFifty-four healthy male SD rats were randomly assigned into the control group (normal saline), the PQ-treatment groups (4 groups) and the PDTC treatment groups (4 groups). Except the rats in the control group, the rats in the PQ group were gavaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC (i.p). On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-beta(1) protein in the plasma, the mRNA expression of TGF-beta(1), MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR, while pathological changes of lung were examined under optical microscope and electrical microscope.

RESULTSThe TGF-beta(1) protein, TGF-beta(1) and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration (P < 0.05 or P < 0.01), while the mRNA level of TIMP-1 was augmented continuously (P < 0.01) throughout the study compared to the control group. In comparison with the PQ group, in the PDTC treatment group, the TGF-beta(1) mRNA expression on the 3rd and the 14th day, 0.54 +/- 0.08 and 0.72 +/- 0.04 respectively, the MMP-2 mRNA expression on the 7th and 14th day, 1.62 +/- 0.50 and 1.97 +/- 0.34 respective-ly, and the TIMP-1 mRNA on the 7th and 21st day, 1.79 +/- 0.21 and 2.00 +/- 0.34 respectively, were significantly decreased (P < 0.05 or P < 0.01).

CONCLUSIONPDTC could attenuate paraquat-induced up-regulation of TGF-beta(1) and its mRNA expression, MMP-2 and TIMP-1 mRNA levels, which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation damage and adjust-ing the balance between MMPs and TIMPs. However, further studies are still warranted to investigate and clarify the underlying mechanisms involved in this complicated process.

Acute Lung Injury ; chemically induced ; metabolism ; pathology ; Animals ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Paraquat ; poisoning ; Pyrrolidines ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo study the activity of esterases, including butyrylcholinesterase (BchE), carboxylesterase (CarbE), paraoxonase (PonE) and acetylcholinesterase (AChE), and to explore the effect of genetic polymorphism on the activity of esterase for workers exposed to organophosphorus pesticides (OPs).

METHODSTwo hundred and forty-one long term OPs directly exposed workers and 151 indirectly exposed workers in the same factory were taken as study group. One hundred and sixty unexposed persons were taken as control group. The activity of serum enzymes was measured and the polymorphic distribution was detected using 7900 genotype detecting system and CMOS Chip technique. The effect of long-term exposure to organophosphorus pesticides was analyzed.

RESULTSThe activities of BchE, CarbE and PonE were independent on the gender or age in control group. Average values of Carb and BchE activities of directly and indirectly exposed workers were lower than those in control group respectively. PonE activity in directly exposed group was lower than that in control group. AChE activity in directly exposed group was lower than that in indirectly exposed group. All the differences were significant (P < 0.01). In the direct exposure group, the frequency of three variants of butyrylcholinesterase gene K (BCHE-K) polymorphism was 74.3%, 24.1% and 1.6% for UU, UK and KK respectively. Frequency of allele U and K was 0.863 and 0.137 respectively in the same group. Frequency of three variants of PON192 polymorphism was 15.0%, 45.5% and 39.5% for AA, AB and BB respectively in direct exposure group. Gene frequency of low activity (PON*A) and high activity (PON*B) was 0.378 and 0.622 respectively. Frequency of three variants of PON55 polymorphism was 96.2%, 3.8% and 0% for MM, LM and LL respectively in direct exposure group. Frequency of allele M and L was 0.981 and 0.019 respectively in the same group. The activity of PON was different in various genotypes of PON192 and PON55.

CONCLUSIONThe long-term exposure to OPs could inhibit the activities of CarbE, BchE, PonE and ACh E in different level. The genetic polymorphisms of PON192 and PON55 affect the activity of PonE, which is related to the detoxification of OPs and health impact.

Acetylcholinesterase ; metabolism ; Adult ; Alleles ; Aryldialkylphosphatase ; genetics ; metabolism ; Butyrylcholinesterase ; genetics ; metabolism ; Carboxylesterase ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Organophosphorus Compounds ; adverse effects ; Pesticides ; adverse effects ; Polymorphism, Single Nucleotide

Coronary Artery Bypass ; adverse effects ; Female ; Humans ; Male ; Mammary Arteries ; injuries

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

OBJECTIVETo investigate the protective effects of vigabatrin and atropine against the acute toxicity of dimethoate in male Kun-min mice.

METHODSThe therapeutic schedules of vigabatrin (50 or 100 mg/kg) and (or) atropine (2.5 or 5.0 mg/kg) were performed according to the L(9) (3(4)) orthogonal test table. The survival time, the righting reflex and the onset of muscle fasciculations were observed after the administration of dimethoate.

RESULTSFirst, the main effects of vigabatrin, atropine and the interaction between them were statistically significant in the Univariate analysis of the survival time at the alpha level of 0.05 (F(V)= 4.73, P(V)= 0.015, F(A)= 50.88, P(A)= 0.000, F(VxA)= 4.17, P(VxA)= 0.007). The range of atropine was more than double of that of vigabatrin or their interaction (R(A)> 2RV or 2R(VxA)). So not only atropine and vigabatrin but also their combination interaction protected mice against dimethoate lethality. The atropine played the major role in diminishing the lethality induced by dimethoate. Second, only vigabatrin, while not atropine, delayed the mice from dimethoate-induced muscle fasciculation according its statistical results (F(V)= 6.87, P(V)= 0.003, F(A)= 0.03, P(A)= 0.968, F(VxA)= 1.134, P(VxA)= 0.356). It should be noted that vigabatrin could not completely prevent dimethoate induced-muscle fasciculation in the test. At last, both atropine and vigabatrin could maintain the righting reflex in the intoxication, however there was no interaction between them (F(V)= 5.81, P(V)= 0.006, F(A)= 9.05, P(A)= 0.001, F(VxA)= 1.34, P(VxA)= 0.257).

CONCLUSIONCombined treatment with atropine and vigabatrin in the organophosphates intoxication seems reasonable and acceptable.

Acute Disease ; Animals ; Atropine ; therapeutic use ; Dimethoate ; poisoning ; Disease Models, Animal ; Insecticides ; poisoning ; Male ; Mice ; Vigabatrin ; therapeutic use

OBJECTIVETo examine a) the effect of organophosphorus pesticide exposure on activity of carboxylic esterases, namely butyrylcholinesterase (BChE), carboxylesterase (CarbE) and paraoxonase (PonE); and b) the association of polymorphisms of BChE and PonE with individual genetic susceptibility to organophosphorus pesticide exposure.

METHODSA cross-sectional study was conducted in 75 workers exposed to organophosphorus pesticides and 100 non-exposed controls. The serum activity of these enzymes was measured. Variant forms of BCHE-K, PON-192, and PON-55 were detected. A symptom score was developed as a proxy measure of clinical outcomes.

RESULTSActivities of both BChE and CarbE were lower in exposed workers (27.3+/-21.65 nmolxh(-1)xmL(-1) and 235.6+/-104.03 nmolxmin(-1)xmL(-1)) than in non-exposed workers (78.313+/-30.354 nmolxh(-1)xmL(-1) and 362.681+/-194.997 nmolxmin(-1)xmL(-1)). The activity of PonE was not associated with exposure status. The AChE activity in the exposed workers with BCHE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) was 105.05, 84.42 and 79.00 mmolxh(-1)xmL(-1), respectively and the accumulative symptom scores were 3.74, 9.17, and 12.50 accordingly. The AChE activity in the exposed workers with PON-192 genotypeBB (37), genotype AB (27) and genotype AA (11) was 116.8, 91.2, and 72.3 mmolxh(-1)xmL(-1), respectively and the symptom scores were 2.00, 6.74, and 9.73 accordingly. The AChE activity in those with PON-55 genotype LL (70) and genotype LM (5) was 102.4 and 82.8 mmolxh(-1)xmL(-1) and the symptom scores were 4.53 and 9.20. The symptom score was the highest in individuals with abnormal homozygote for each of the three gene loci.

CONCLUSIONSLong-term exposure to organophosphorus pesticides can inhibit BChE and CarbE activity, but exerts no inhibitory effect on PonE activity. Different genotypes of BCHE-K, PON-192, and PON-55 may be related to the severity of adverse health effects of organophosphorus pesticide exposure. Implications of potentially higher susceptibility of workers with mutant homozygotes should be evaluated to reduce health risks.

Adult ; Base Sequence ; Butyrylcholinesterase ; drug effects ; Carboxylesterase ; antagonists & inhibitors ; DNA Primers ; Environmental Exposure ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Organophosphorus Compounds ; toxicity ; Pesticides ; toxicity ; Polymerase Chain Reaction

OBJECTIVETo investigate strategy of treatment of hemofiltration on severe acute pancreatitis (SAP) and fulminant acute pancreatitis (FAP).

METHODSOne hundred and thirty patients with SAP and eighty-one patients with FAP treated with hemofiltration (HF) were prospectively observed from March 1997 to December 2008. Indications for HF, variables (time interval for hemofiltration), mode, therapeutic dosage, blood rate, heparin dosage and components of hemofiltration, therapeutic efficacy (time of disapearance of abdominal pain, intra-abdominal pressure and survival rate) and complications (incidence of bleeding and blood infection).

RESULTSAll patients underwent high volume hemofiltration (HVHF) or hemodialysis-filtration (HDF) within 72 hours after onset of the disease. Dose of SAP and FAP was (53 +/- 6) mlxkg(-1)xh(-1) and (59 +/- 10) mlxkg(-1)xh(-1) (P < 0.05), respectively. Rate of short veno-venous hemofiltration in SAP (76.9%) was higher than that of FAP (38.3%) (P < 0.05); however, rate of continuous veno-venous hemofiltration (23.1%) was lower than that of FAP (37.0%) (P < 0.05). Rate of HDF was much higher in FAP than that of SAP. Low molecular weight heparin and heparin were both available to anticoagualte;but dosage required in patients with FAP was much higher than that of SAP (P < 0.05). Time intervals for amelioration of abdominal pain in SAP and FAP were (9 +/- 6) h and (15 +/- 10) h, respectively. Itra-abdominal pressure was decreased significantly at the end of hemofiltration compared to prior to hemofiltration in SAP and FAP (P < 0.05). Level of serum triglyceride decreased abruptly after adsorption (P < 0.05). Rate of operation within 28 days in SAP (73.8%) was lower than FAP (87.7%). The in-hospital survival rates in SAP and FAP were 88.5% and 67.9%, respectively. Amount of platelet decreased in patients with blood flow rate less than 240 ml/min was higher than that of more than 240 ml/min (P < 0.05). And incidence of blood stream infection and bleeding increased significantly (P < 0.05).

CONCLUSIONSHVHF and HDF used in SAP and FAP patients underwent conservative treatment within 72 hours, respectively, can increase survival rate significantly.

Acute Disease ; Hemofiltration ; Humans ; Pancreatitis ; therapy ; Survival Rate

OBJECTIVETo study the effect of dimethoate on the monoamine Neurotransmitters, including norepinephrine (NE), epinephrine (E), serotonin (5-HT), dopamine (DA) and its metabolite (3, 4-hydroxyphenylacetic acid, DOPAC) in the serum of rats and furthermore to explore the non-cholinergic mechanism of organophosphate induced toxicity.

METHODSGroups of rats were treated with saline and 38.9, 83.7 and 180 mg/kg dimethoate respectively and were decapitated at the different time course from 0.5 to 24 hours after the administration. The monoamines neurotransmitters were determined by the reverse-phase high-performance liquid chromatography with the electrochemical detection.

RESULTSThe serum concentrations of DA (8.42% - 248.42% of the control), DOPAC (17.22% - 68.21% of the control) increased, according with the DM dosage and the exposure time, while the levels of NE (9.65% - 38.26% of the control) and E (11.00% - 32.62% of the control) contents decreased at the same time.

CONCLUSIONThese findings indicate that dimethoate induced toxic effects can alter the monoamine levels at the different dosage and the time exposure in the serum of rats. It suggests that some non-cholinergic mechanisms may be involved in the dimethoate intoxication.

3,4-Dihydroxyphenylacetic Acid ; blood ; Animals ; Biogenic Monoamines ; blood ; Dimethoate ; toxicity ; Dopamine ; blood ; Dose-Response Relationship, Drug ; Epinephrine ; blood ; Male ; Norepinephrine ; blood ; Rats ; Rats, Sprague-Dawley ; Serotonin ; blood