Measurement of pesticides in hair samples from pemphigus foliaceus and pemphigus vulgaris patients in Southeastern Brazil

Abstract Background Pesticides, mainly organophosphates (OP), have been related to increased risk of pemphigus vulgaris (PV) and pemphigus foliaceus (PF), nevertheless, their measurement has not been determined in pemphigus patients. Objective To evaluate pesticide exposure and pesticide measurement, comparing PV, PF and control groups in Southeastern Brazil. Methods Information about urban or rural residency and exposure to pesticides at the onset of pemphigus was assessed by questionnaire interview; hair samples from the scalp of PV, PF, and controls were tested for OP and organochlorines (OC) by gas-phase chromatography coupled to mass spectrometry. Results The minority of PV (2 [7.1%] of 28) and PF (7 [18%] of 39), but none of the 48 controls, informed living in rural areas at the onset of pemphigus (p = 0.2853). PV (33.3%), PF (38.5%), and controls (20%) informed exposure to pesticides (p = 0.186). Twenty-one (14.8%) of 142 individuals tested positive for OP and/or OC: PV (2 [6.3%] of 32) and PF (11 [25.6%] of 43) had similar pesticides contamination as controls (8 [11.9%] of 67) (p = 0.4928; p = 0.0753, respectively), but PF presented higher contamination than PV (p = 0.034). PV did not present any positivity for OP. Three (7%) PF tested positive for both OP and OC. Some PF tested positive for three or four OP, mainly diazinon and dichlorvos. Study limitation Lack of data for some controls. Conclusion Although the frequency of PV and PF patients exposed to pesticides was similar, pesticides were more frequently detected in hair samples from PF compared to PV. The cause-effect relationship still needs to be determined.

Use of bone marrow for detection of toxic chemicals for the elucidation of poisoning in forensic veterinary medicine / Uso de medula óssea para detecção de produtos químicos tóxicos para a elucidação de intoxicação em patologia veterinária forense

In forensic toxicology, the detection of toxic chemicals from human bone marrow is often used in cases with an extended post mortem interval; however, in veterinary medicine, this practice is not used. Therefore, this study was performed to investigate the suitability of bone marrow for toxicological analysis in dogs and cats. Six animals with suspected poisoning were selected; the carcasses were sent for necropsy, and the organs were collected and preserved in buffered formalin and processed routinely for histological examination. In addition, bone marrow samples from the femur, humerus, and tibia were collected for toxicological analysis by liquid chromatography coupled to mass spectrometry detection (LC-MS). This analysis confirmed the presence of aldicarb, aldicarb sulfone, asulam, carbendazim, chlorpyrifos, dichlorvos, thifensulfuron methyl and trifloxysulfuron-sodium and associated with clinical symptoms and anatomo-histopathological alterations it was recognized the poisonings. It is expected that this study will promote the toxicological investigation of bone marrow and open avenues for the use of this tissue as an option for the detection of toxic chemicals in cases of forensic pathology.(AU)

Na toxicologia forense, a detecção de substâncias químicas tóxicas provenientes da medula óssea humana é frequentemente usada em casos com intervalo post mortem prolongado; no entanto, na medicina veterinária, essa prática não é utilizada. Portanto, este estudo foi realizado para investigar a utilização da medula óssea nas análises toxicológicas em cães e gatos. Seis animais com suspeita de intoxicação foram selecionados; as carcaças foram enviadas para necropsia e os órgãos foram coletados e preservados em formalina tamponada e processados rotineiramente para exame histológico. Amostras de medula óssea de fêmur, úmero e tíbia foram coletadas para análise toxicológica por cromatografia líquida acoplada à espectrometria de massa-massa (LC-MS). A análise por LC-MS confirmou a presença dos agrotóxicos aldicarbe, aldicarbe sulfona, asulam, carbendazim, clorpirifós, diclorvós, tifensulfuron metil e trifloxisulfuron-sódico, e em associação com sinais clínicos e achados anatomo-histopatológicos comprovou-se as intoxicações. Espera-se que este estudo promova a utilização da medula óssea como uma opção na investigação toxicológica para a detecção de produtos químicos tóxicos em casos de patologia forense.(AU)

Sex Hormone Disruption and Histological Changes in Testes on Chronic Dichlorvos Exposure in Animal Model

Background:Dichlorvos is an organophosphate used indiscriminately as a pesticide in homesand for agricultural purposes. This study evaluated the effects of its low dose sub-lethal chronic exposure on male reproductive function using an animal (Rattus norvegicus) model.Methodology:Three groups of rats were given dichlorvos at the dosages of 0.28mg/kg, 0.56mg/kg and 1.68mg/kg respectively on alternate days. The control group was given only plain drinkingwater. The experiment lasted for 50 weeks.Results: Dichlorvos induced a dosage variation effect on blood levels of follicle stimulating hormone but this was insignificant on levels of luteinizing hormone, oestrogen, progesterone and dihydrotestosterone. Prolonged treatment with dichlorvos had no overall influence on luteinizing hormone levels. The major histological findings in descending order of frequency included tubular atrophy and degeneration, germ cell depletion, germ cell exfoliation, tubular necrosis, spermatid retention and Leydig cell hyperplasia, each scored on a semi-quantitative scale. After 50 weeks of dichlorvos treatment, progesterone and oestrogen blood levels both had strong positive correlations with the frequency of germ cell exfoliation and residual bodies in the testes. In contrast, there was no statistically significant correlation between blood levels of follicle stimulating hormone, luteinizing hormone and dihydrotestosterone and the histological findings.Conclusion:This research evaluated the chronic effect of low dichlorvos exposure on reproductive function using an animal model. There was a strong positive correlation between progesterone and germ cell exfoliation and residual bodies. Oestrogen also correlated withgerm cell exfoliation, depletion and presence of residual bodies. Furthermore, the correlation between the blood hormone levels and histological changes in the testes was largely unpredictable

Ion Abundance Ratios of Qualitative Analysis by GC-MS of 4 Common Drugs （Poisons / 法医学杂志

Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs （poisons） in blood by gas chromatography-mass spectrometry （GC-MS） method. Methods Four common drugs （poisons） （dichlorvos, phorate, diazepam and estazolam） were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs （poisons） in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 μg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection （LOD）, 2LOD, limit of quantitation （LOQ） and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs （poisons） and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant （P>0.05）. More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration （concentration less than 2LOQ） or low signal to noise ratio （3-15）, the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs （poisons） in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.

Resistance of adult Culex pipiens quinquefasciatus to four common insecticides in Guiyang City / 中华地方病学杂志

Objective To investigate the insecticide resistance levels of adult Culex pipiens quinquefasciatus to four common insecticides in Guiyang City.Methods Larvae of Culex pipiens quinquefasciatus were collected from 8 areas of Guiyang City by larval scoop method from August to September 2015,and raised in the laboratory to adult Culex pipiens quinquefasciatus.Contact tube method was used to determine the insecticide resistance levels of adult Culex pipiens quinquefasciatus to four common insecticides,and knockdown rate of 1 h and mortality rate of 24 h recovery were calculated.The resistance level was judged according to the mortality rate:＜ 90％ was in the resistant group (R);90％-＜ 98％ was in the potential resistant group (M);and ≥98％ was in the sensitive group (S).Results The adult Culex pipiens quinquefasciatus were exposed to 7.70 g/L dichlorvos,3.30 g/L propoxur,0.25 g/L beta-cypermethrin and 0.20 g/L dehamethrin,knockdown rates of 1 h were 57.78％ (52/90)-91.11％ (82/90),86.67％ (78/90)-100.00％ (90/90),23.33％ (21/90)-77.78％ (70/90) and 27.78％ (25/90)-88.89％ (80/90),respectively;and mortality rates of 24 h recovery were 61.11％ (55/90)-94.44％ (85/90),90.00％ (81/90)-97.78％ (88/90),23.33％ (21/90)-73.33％ (66/90) and 21.11％ (19/90)-72.22％ (65/90),respectively.Conclusion Adult Culex pipiens quinquefasciatus in Guiyang City have developed some resistance to four common insecticides,in which the mosquito has a higher resistance to pyrethroid insecticides such as beta-cypermethrin and deltamethrin.

Retention Time of Four Common Poisons (Drugs) by GC-MS Qualitative Analysis / 法医学杂志

Objective To investigate the maximum allowable deviation of retention time (RT) or relative retention time (RRT) between the common poisons (drugs) and standard solvent by gas chromatography-mass spectrometry (GC-MS).Methods After pretreatment with liquid-liquid extraction, four common poisons (drugs) —dichlorvos, phorate, diazepam and estazolam—were detected by full scan mode GC-MS.RT and RRT were analyzed according to combined uncertainty and expanded uncertainty. Results The expanded uncertainty of RT and RRT were 6.0× lO-4-14.1×l0-3 and 2.5 ×l0-6-5.9× lO-5 (k=3), respectively.The RT of poisons (drugs) was relatively stable in blood samples with different mass concentrations.Among dichlorvos, phorate, diazepam and estazolam, the absolute deviation and relative deviation of RT were≤0.03 min and≤0.4％, respectively, and those of RRT were≤0.003 min and≤0.3％, respectively.Conclusion The maximum allowable deviations of RT and RRT for common poisons (drugs) in blood samples are recommended to be±0.05 min and±0.5％.

Use of Purified Rabbit Serum Paraoxonase 1 Compared with the Traditional Method of Curative Effect on Dichlorvos-induced Liver Injury in Rats / 中国医科大学学报

Objective To explore whether the use of purified rabbit serum paraoxonase 1 (PON1) for the treatment of dichlorvos-induced liver injury in rats is superior to traditional method.Methods Thirty male SD rats were randomly divided into the followint 5 groups,with 6 rats in each group:control group (A group),dichlorvos group (B group),traditional treatment group (C group),PON 1 treatment group (D group),combined treatment group (E group).Rats in groups B,C,D and E were adminstered dichlorvos by intraperitoneal injection 9 mg/kg.In group C,atropine 10 mg/kg and iodine solution 45 mg/kg were injected intraperitoneally within 2 min after dichlorvos administration.In group D,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning.In group E,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning,followed by in travenous injection of atropine 10 mg/kg and iodine solution 45 rng/kg within 2 min after poisoning.Rats in A group received normal saline.Blood was collected at different time points to examine the acetyl cholinesterase (AChE)-levels by ELISA method.Liver tissue were collected at 12 hours after model establishment to observe the pathological changes.The expression of 4 hydroxy 2-nonenal (4-HNE) in the liver tissue was detected by immunohistochemistry and Western blotting.Results In group B,AChE levels decreased significantly,liver cells showed severn fatty degeneration,karyopyknosis and other pathological changes,and 4-HNE expression increased.The pathological changes of group D and group E were less obvious than those of group C,and the 4-HNE expression in the group D and group E were significantly different from that in the group C (P＜ 0.05).Conclusion PON1 plays a protective role in dichlorvos-induced liver injury in rats,and this protection is better than that offered by traditional treatment.

The protective effect of rabbit serum paraoxonase-1 on the renal injury induced by dichlorvos in rats / 中华急诊医学杂志

Objective To assess the protective effect of rabbit serum paraoxonase-1 (PON-1) on renal injury induced by dichlorvos in rats.Methods Totally 30 healthy S-D rats were randomly divided into 5 groups:control group (group A,n =6),exposure group (group B,n =6),PON-1 pretreatment group (group C,n =6),traditional atropine,pralidoxime treatment group (group D,n =6) and combination therapy group (group E,n =6).The rats of group A were given normal saline in equal volume of dichlorvos injected into abdominal cavity to make a false model of dichlorvos poisoning.In rats of groups B,C,D and E,9 mg/kg dichlorvos was administered.In rats of groups C and E,PON-1 4 500 units/kg was injected into vein of the tails half an hour before dichlorvos administration.After dichlorvos exposure,rats in group D and E were treated with 45 mg/kg iodoprofen and 10 mg/kg atropine by intraperitoneal injection.The activity of blood urea nitrogen (BUN) was assayed with urease.Serum creatinine (Cr) were measured by picric acid colorimetry.Serum Cys-C,KIM-1 and NAG in urine were determined by ELISA.Ultrastructural changes in renal tissues of rats were examined by light microscopy.The differences in laboratory findings between groups were compared.Results The creatinine level in group B was significantly higher than that in other groups (P ＜0.05).The levels of Cys-C,KIM-1 and NAG in group B and group D were significantly higher than those in group A (P ＜ 0.01).But there were no significant differences in above biomarkers among group C,group E and group A.There were no significant differences in above biomarkers between group B and group D.In group B,inflammatory cells infiltrated extensively in renal tissues and,the renal cells were congested and edematous,the lumen was obliterated and the border of the brush disappeared.The tubular structures were not clearly distinct found in group B,but edema and inflammatory cell infiltration with lesser degree were found in group D than those in dichlorvos exposure groups.The clearly distinct structure of the tube without completely occluded lumen in group D,and the most serious lesions were found in distal convoluted tubules.In group C,and group E,there were only mild congestion and edema without significant cell degeneration and necrosis.In group A,the structure of renal tubular epithelium was clearly distinct with brush-shaped margin,and without tubular or necrotic cell debris in the lumen.Conclusion The rabbit serum PON-1 can protect the renal tissue of rats after dichlorvos exposure.

The protective effect of rabbit serum paraoxonase-1 on the renal injury induced by dichlorvos in rats / 中华急诊医学杂志

Objective To assess the protective effect of rabbit serum paraoxonase-1 (PON-1) on renal injury induced by dichlorvos in rats.Methods Totally 30 healthy S-D rats were randomly divided into 5 groups:control group (group A,n =6),exposure group (group B,n =6),PON-1 pretreatment group (group C,n =6),traditional atropine,pralidoxime treatment group (group D,n =6) and combination therapy group (group E,n =6).The rats of group A were given normal saline in equal volume of dichlorvos injected into abdominal cavity to make a false model of dichlorvos poisoning.In rats of groups B,C,D and E,9 mg/kg dichlorvos was administered.In rats of groups C and E,PON-1 4 500 units/kg was injected into vein of the tails half an hour before dichlorvos administration.After dichlorvos exposure,rats in group D and E were treated with 45 mg/kg iodoprofen and 10 mg/kg atropine by intraperitoneal injection.The activity of blood urea nitrogen (BUN) was assayed with urease.Serum creatinine (Cr) were measured by picric acid colorimetry.Serum Cys-C,KIM-1 and NAG in urine were determined by ELISA.Ultrastructural changes in renal tissues of rats were examined by light microscopy.The differences in laboratory findings between groups were compared.Results The creatinine level in group B was significantly higher than that in other groups (P ＜0.05).The levels of Cys-C,KIM-1 and NAG in group B and group D were significantly higher than those in group A (P ＜ 0.01).But there were no significant differences in above biomarkers among group C,group E and group A.There were no significant differences in above biomarkers between group B and group D.In group B,inflammatory cells infiltrated extensively in renal tissues and,the renal cells were congested and edematous,the lumen was obliterated and the border of the brush disappeared.The tubular structures were not clearly distinct found in group B,but edema and inflammatory cell infiltration with lesser degree were found in group D than those in dichlorvos exposure groups.The clearly distinct structure of the tube without completely occluded lumen in group D,and the most serious lesions were found in distal convoluted tubules.In group C,and group E,there were only mild congestion and edema without significant cell degeneration and necrosis.In group A,the structure of renal tubular epithelium was clearly distinct with brush-shaped margin,and without tubular or necrotic cell debris in the lumen.Conclusion The rabbit serum PON-1 can protect the renal tissue of rats after dichlorvos exposure.

Direct Detection of Dichlorvos in Honey by Neutral Desorption-Extractive Electrospray Ionization Mass Spectrometry / 分析化学

In this study, a neutral desorption-extractive electrospray ionization mass spectrometry ( ND-EESI-MS) method was developed for the direct and rapid detection of dichlorvos ( DDVP) in honey samples without any sample pretreatment procedure. Under the positive ionization mode, the main characteristic parent ion of DDVP was m/z 223 (MW:222) and daughter ions were m/z 109 and m/z127. Under the optimized working conditions, with the signal intensity of m/z 127 as quantitative index, the quantitative information of DDVP residues in honey was acquired effectively. The results showed that the linear range of DDVP for spiked honey was 5-1000 ng/mL (R2=0. 998) with the limit of detection (LOD) of 1. 0 ng/mL (n=3) and the recoveries for the DDVP spiked honey samples at the concentration levels of 10 , 30 and 400 ng/mL were 93 . 0%-103. 0%, with the relative standard deviations (RSDs, n=6) of less than 4. 4%. Meanwhile, for detection of spiked honey with gas chromatography-flame photometric detector ( GC-FPD ) , the linear range was 5-1000 ng/mL (R2=0. 999) with the LOD of 1. 6 ng/mL(n=3), and the recoveries of DDVP at the spiked honey concentration levels of 10 , 30 and 400 ng/mL were 94 . 9%-110 . 3%, with the RSDs of less than 7. 6%.

The protective effect of regulation of paraoxonase 1 gene on liver oxidative stress injury induced by dichlorvos poisoning in mice / 中华危重病急救医学

ObjectiveTo investigate the protective effect of paraoxonase 1 (PON1) gene against liver oxidative stress injury in mice due to dichlorvos poisoning.Methods Experiment 1: 12 male Balb/c mice were randomly divided into three groups, with 4 mice in each group: control group, green fluorescent protein lentivirus control group (Lv-GFP group), and recombinant PON1 lentivirus group (Lv-PON1 group). 2×107 TU of Lv-GFP or Lv-PON1 was transfected via tail vein, while normal saline was given to those in control group. Blood was collected on 0, 1, 3, 5, 7, 9 days via fundus venous plexus for the assay of serum PON1 activity. PON1 mRNA and protein expression levels were respectively determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot on the 3rd post-lentivirus transfection day. Experiment 2: according to the random number table method, another 96 male Balb/c mice were divided into four groups of 24 mice in each control group, dichlorvos group, Lv-GFP intervention group, and Lv-PON1 intervention group. Lv-GFP or Lv-PON1 was transfected via tail vein followed by intraperitoneal injection of dichlorvos 9 mg/kg, while those in control group were given normal saline. Six mice in each group were sacrificed respectively at 6, 12, 24, 48 hours, and liver tissue was collected. PON1 mRNA and nuclear factor E2-related factor 2 (Nrf2) mRNA expression levels were determined by RT-PCR, and PON1 protein level was determined by Western Blot. The content of malondialdehyde (MDA) and glutathione (GSH) in the liver tissue were determined by chemical colorimetry. The activity of superoxide dismutase (SOD) and catalase (CAT) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA).Results Experiment 1: after Lv-PON1 was transfected to normal mice, PON1 activity in serum gradually increased and maintained a high level on 3rd day, while that of the control group and Lv-GFP group showed a normal low level. On the 3rd post-lentivirus transfection day, PON1 mRNA and PON1 protein expressions in liver were significantly higher than those of control group and Lv-GFP group. Experiment 2: compared with control group, the mice in dichlorvos group showed significant decreases in PON1 mRNA, PON1 protein, Nrf2 mRNA as well as GSH, SOD, CAT levels at 6 hours [PON1 mRNA (gray value):0.237±0.075 vs. 0.674±0.011, PON1 protein (gray value): 0.602±0.086 vs. 0.998±0.124, Nrf2 mRNA (gray value): 0.089±0.012 vs. 0.126±0.010, GSH (mg/g): 3.84±0.33 vs. 5.52±0.40, SOD (μg/g): 0.383±0.040 vs. 0.564±0.052, CAT (ng/g): 7.32±1.28 vs. 12.46±1.54, allP 0.05), and it was higher than that of the control group at 48 hours (0.206±0.028 vs. 0.124±0.010,P< 0.05). Compared with that of the dichlorvos group, Lv-PON1 intervention group showed a significant increase in PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels [PON1 mRNA (gray value): 0.726±0.021 vs. 0.237±0.075, PON1 protein (gray value): 0.739±0.050 vs. 0.602±0.086, Nrf2 mRNA (gray value): 0.158±0.007 vs. 0.089±0.012, GSH (mg/g): 4.30±0.22 vs. 3.84±0.33, SOD (μg/g): 0.454±0.062 vs. 0.383±0.040, CAT (ng/g): 8.98±1.02 vs. 7.32±1.28, allP< 0.05], and a decrease in MDA content (nmol/g: 6.56±0.44 vs. 7.78±0.41,P< 0.05).Conclusion Regulation of PON1 gene can reduce MDA content, enhance SOD and CAT activities, increase GSH content, and it may also up-regulate Nrf2 mRNA expression to play a protective effect against oxidative stress of liver injury induced by dichlorvos poisoning.

Effect of a spray formulation on the reproductive parameters of a susceptible population of Rhipicephalus (Boophilus) microplus / Efeitos de uma formulação pulverização sobre os parâmetros reproductivos de uma população susceptível de Rhipicephalus (Boophilus) microplus

The number of studies emphasizing the possible damage that acaricidal spray formulations can cause on engorged female ticks' reproductive parameters is small. The present study evaluated the deleterious effects of a spray formulation (dichlorvos 60% + chlorpyrifos 20%) on the reproductive parameters of a susceptible population of Rhipicephalus (B.) microplus females, using the Stall Test. The ticks were allocated randomly to treatments according to the mean numbers of females detached from each cow on days -3, -2 and -1 and the cattle pen location. The numbers of engorged female ticks that naturally detached from the cattle were counted daily from day 1 to day 30. For each group, 20 detached engorged female ticks or the available number collected daily were evaluated regarding reproductive parameters. Associations of organophosphates demonstrated elevated acaricidal efficacy, as well as deleterious effects on the reproductive parameters of R. (B.) microplus females. The engorged female weight (days 1 to 7), weight of egg masses (days 5 to 10) and larval hatching percentage (days 5 to 19) were decreased (P ≤ 0.05). It is possible that a formulation can lead to deleterious effects on R. (B.) microplus females when the tick population analyzed shows elevated sensitivity towards a particular formulation. However, further studies need to be conducted.

É relativamente pequeno o número de estudos que enfatiza os danos que uma formulação acaricida spray pode desencadear sobre os parâmetros reprodutivos das teleóginas. O presente estudo teve como objetivo avaliar os efeitos deletérios de uma formulação spray comercial (dichlorvos 60% + Clorpirifós 20%), sobre os parâmetros reprodutivos de uma população susceptível de R. (B.) microplus, desprendidas de bovinos experimentalmente infestados, utilizandose o teste de estábulo. Os animais foram alocados aos grupos de tratamentos de acordo com a contagem média de fêmeas desprendidas dos bovinos nos dias -3, -2 e -1. O número de teleóginas desprendidas foi quantificado do dia 1 ao 30. Para cada grupo, diariamente 20 fêmeas, ou a quantidade disponível, foram selecionadas e submetidas à avaliação dos parâmetros reprodutivos. A associação de organofosforados demonstrou elevada eficácia acaricida e também apresentou efeitos deletérios sob os parâmetros reprodutivos de Rhipicephalus (B.) microplus, diminuindo (P≤0,05) o peso das teleóginas (dos dias 1 ao 7), o peso da massa de ovos (dos dias 5 ao 10) e a eclodibilidade das larvas (dos dias 5 ao 19). Talvez uma formulação pode apresentar efeitos deletérios sobre os parâmetros reprodutivos de fêmeas de R. (B.) microplus, quando existe um elevado grau de sensibilidade dessa cepa de carrapato a um determinado composto. De qualquer maneira, futuros estudos devem ser realizados.

Left Facial Swelling Caused by Organophosphate (Dichlorvos) Poisoning: A Case Report and Review of the Literature

In organophosphate intoxication, the neurotransmitter acetylcholine accumulates in synapses, causing excessive stimulation of nicotinic and muscarinic receptors, producing various signs and symptoms. Organophosphates are highly toxic compounds that are readily absorbed through the skin, mucous membranes, and gastrointestinal and respiratory tracts. Organophosphate intoxication leads to many well defined complications, including cholinergic crisis, intermediate syndrome, and acute pancreatitis. However, parotitis caused by organophosphate intoxication is very rare. We experienced such a case of a 55 year old woman who visited the emergency center because of organophosphate intoxication. The next day, she complained of left facial redness, swelling, and pain. We checked serum lipase, amylase, and amylase-isoenzymes, and found elevation of salivary type amylase only. The mechanism of parotitis due to organophosphate intoxication is assumed to be similar to that of pancreatitis caused by organophosphate. In patients with elevated amylase caused by organophosphate intoxication, the possibility of parotitis must be considered.

Protective role of vitamins C and E in diclorvos-induced oxidative stress in human erythrocytes in vitro

Organophosphate (OP) pesticides such as dichlorvos (DDVP) intoxication has been shown to produce oxidative stress due to the generation of free radicals, which alter the antioxidant defense system in erythrocytes. In this study, the effects of DDVP (1, 10, 100 µM) or DDVP + vitamin C (VC; 10 µM) or vitamin E (VE; 30 µM), on the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in human erythrocytes were examined in vitro. There were no statistical differences between all groups for 1 µM concentration of DDVP. Treatment with DDVP alone produced an increase in the level of MDA and decreased activities of antioxidant enzymes (P < 0.05). Groups treated with vitamins and DDVP showed protective effects of vitamins against DDVP-induced changes in antioxidant enzyme activity and lipid peroxidation (LPO) (10 µM). At 100 µM concentration of DDVP vitamins had no effect on DDVP-induced toxicity. The results show that administration of DDVP resulted in the induction of erythrocyte LPO and alterations in antioxidant enzyme activities, suggesting that reactive oxygen species (ROS) may be involved in the toxic effects of DDVP. Also the data show that the plasma level of VC and VE may ameliorate OP-induced oxidative stress by decreasing LPO in erythrocytes at certain doses of OP pesicides.

The roles of catecholamine in cardiac injury after severe acute dichlorvos poisoning / 中华急诊医学杂志

ObjectiveTo study the role of catecholamine in genesis of myocardium injury after organophosphorus poisoning (OP) in order to elucidate the underlying mechanisms of OP-induced cardiotoxicity.Methods Of 92 patients with severe acute dichlorvos poisoning,41 were consecutively enrolled for study and followed up for three months. The levels of serum creatine kinase isoenzyme myocardium (CK-MB),cardiac troponin Ⅰ (cTnI),acetylcholinesterase (AChE),acetylcholine (Ach),epinephrine and norepinephrine were assayed on the 1st,3rd and 5th days after admission and on the day of discharge.Electrocardiography was recorded every day after admission.ResultsOf them,37 (90.2％ )patients survived and four ( 9.8％ ) patients died during treatment.Sinus tachycardia was found in 37 (90.2％ ) patients and ST-T changes in 33 (80.4％ ) patients.CK-MB and cTnI levels peaked 3 days after admission,and then decreased to normal levels.Serum Ach,epinephrine and norepinephrine peaked on the 1st day after admission and then decreased.ConclusionsSevere acute dichlorvos poisoning is associated with myocardial dysfunction likely caused by increase in catecholamine levels.

Analysis of therapeutic effect of lipid emulsion on acute organophosphorus poisoning and acute lung injury in rats / 中华急诊医学杂志

Objective To explore the therapeutic effect of lipid emulsion on acute organophosphorus poisoning and its consequence of acute lung injury. Methods A total of 48 sealant - grade Sprague-Dawley (SD) rats were randomly divided into four groups A,B,C,D,namely saline control group,lipid emulsion control group,the conventional therapy group and lipid emulsion administration group. After dichlorvos (DDVP) 11 mg/kg was given by intra-peritoneal injection,if there was no loss of DDVP during the injection process,the model of poisoning was considered to be made successfully.Then the rat models in four groups were respectively treated:with normal saline (5 ml/kg) intravenous injection in group A,lipid emulsion (5ml/kg) intravenous injection in group B,atropine (5 mg/kg) and pralidoxime chloride (40 mg/kg) intramuscular injection in group C,and combined use of lipid emulsion (5 ml/kg) with atropine and pralidoxime chloride in group D after administration of DDVP by intra-peritoneal injection.The activity of cholinesterase (CHE) in blood was detected before and 0.5 h,2 h and 4 h after DDVP poisoning. The clinical manifestations,the survival of rats,the wet weight of rat' s lung and the pathological changes of the lung tissue were observed within following 24 h. The rates of survival and symptoms of rats were compared between paired groups by using the x2 test,and the mean values of biomarkers were compared paired groups by using t test. Results In groups A and B,the intensity of muscular fasciculation and salivation were more severe and appeared sooner after DDVP exposure in comparison with groups C and D leading to lower survival rates in group A and B. Compared with group C,the rate of 24 h survival was higher and the intensity of muscular fasciculation was weaker in group D ( P ＜ 0.05 ).In group A and group B,the 24-hour survival rates were 1/12 and 2/12,respectively ( P ＜ 0.05 ).The levels of CHE in blood significantly decreased after DDVP poisoning ( P ＜ 0.05 ).There was no significant difference in activity of CHE between group B and group A,and in groups C and D,the levels of CHE in blood were not significantly higher than that in the group B 0.5 h after DDVP poisoning ( P ＜ O.05 ).In groups C and D,the activity of CHE in blood was significantly higher compared with group A and B,and that in group D was higher compared with C,and that in group B was higher compared with A 2 and 4 hours after DDVP poisoning ( P ＜ 0.05 ).In groups C and D,the wet weight of rat lung was significantly lighter compared with groups A and B,and that in group D was lighter compared with C,and that in group B was lighter compared with A 24 h after DDVP poisoning P ＜ 0.05 ).The electron microscopic findings showed the combined use of lipid emulsion with atropine and pralidoxime chloride obviously lessened the lung histopathologic changes after DDVP poisoning.Conclusions The lipid emulsion combined with atropine and pralidoxime chloride can be beneficial to controlling the toxic symptoms,reduce the death rate,accelerate the resume of the activity of CHE in blood,and relieve the lung injury induced by acute organophosphorus poisoning.

Transpulmonary thermodilution for evaluating respiratory function in swine after severe acute dichlorvos poisoning / 中华急诊医学杂志

Objective In order to extrapolate the respiratory dysfunction of patients in early stage of acute organophosphorus pesticide poisoning (AOPP),transpulmonary thermodilution technique was used in swine models of severe acute dichlorvos poisoning (SADP) to evaluate respiratory function.Methods Twenty healthy female swine were randomly divided into dichlorvos ( n =7 ),atropine ( n =7 ) and control (n =6) groups.In the dichlorvos group,the swine were administered with 80％ emulsified dichlorvos (100mg/kg) via the gastric tube toinduce SADP.In the atropine group,swinewere administered with dichlorvos,and 0.5h later,atropine was injected to obtain and maintain atropinization.The swine of control group were administered with saline solution instead.Arterial and venous blood samples were collected 0,0.5,1,2,4 and 6 hours after modeling for blood gas analysis and detecting acetylcholinesterase levels.Both extravascular lung water index (EVLWI) and pulmonary vascular permeability index ( PVPI ) were measured by using PiCCO (pulse indicator continuous cardiac output ). At the termination of the experiment,the animals were sacrificed and the lung wet/dry weight ratio was determined and histopathological changes of lung tissue were also observed under microscope.Results In the dichlorvos group,EVLWI and PVPI were substantially increased from 0.5 h to 6 h after modeling but PaO2/FiO2 decreased from 0-6 h after modeling.In the atropine group,EVLWI and PVPI increased initially,but then they decreased 1 h afterwards and PaO2/FiO2 was also gradually decreased from 0-1 h.In both dichlorvos group and atropine group,the EVLWI was negatively correlated with PO2/FiO2 and positively correlated with PVPI.Compared with the control group,the lung wet/dry weight ratio increased markedly in the dichlorvos group and mildly increased in the atropine group.Meanwhile,the histopathological changes of lung tissue were obvious in the dichlorvos group and mild in the atropine group.Conclusions SADP swine experienced substantial changes in respiratory function. EVLWI was a reliable and valuable indicator for evaluating respiratory function in the early stage of AOPP.

A Biosensor Using Poly(4-Aminophenol)/acetylcholinesterase modified graphite electrode for the detection of dichlorvos

The properties of poly(4-aminophenol) modified graphite electrode as material for the immobilization of acetylcholinesterase were investigated by the Cyclic Voltammetry, Electrochemical Impedance Spectroscopy and Atomic Force Microscopy. The polymer was deposited on graphite electrode surface by the oxidation of 4-aminophenol and then acetylcholinesterase was immobilized on the surface of the electrode. The biosensor coupled in the continuous flow system was employed for the detection of dichlorvos. The detection and quantification limits were 0.8 and 2.4 μmol L-1 dichlorvos, respectively. Graphite electrodes modified with the poly(4-aminophenol) showed to be an efficient and promising material for immobilization of acetylcholinesterase enzyme. The proposed method requires simple parts which are easy to build, involves only one biosensor and the potentiometric detection is simple.

The myocardial injury in the early stage of acute dichlorvos poisoning in rats / 中华急诊医学杂志

Objective To investigate the myocardial injury in the early stage of acute dichlorvos poisoning in rats. Method A total of 24 Sprague Dawley rats were randomly (random number) divided into control group(n = 12) and poisoning group(n = 12). Hemodynamic variables were monitored by using an arterial cannula inserted into right arteria carotis communis. Serum levels of cardiac troponin T(CTnT) and brain natriuretic peptide (BNP) were measured. Myocardial tissue was observed with HE stain under microscope. Results The rats of poisoning group showed that the heart rate (HR) and maximum ascending rates of left ventricular pressure(+ dp/dtmax)were significant decreased in an hour after poisoning (P ＜0.01). The maximum descending rates of left ventricular pressure(-dp/dtmax)and left ventricular end diastolic pressure (LVEDP)were markedly increased (P＜0. 01) and reached peak in 7 minutes in the poisoning group. Compared with the control group, cardiac troponin T obviously changed in rats poisoned with dichlorvos in the first hour. BNP was not affected after poisoning(P ＞ 0. 05). Myocardial damage was found in the poisoning rats.Conclusions Myocardial injury and heart failure occurred in the early stage of acute organophosphorus pesticides poisoning(AOPP) in rats. CTnT could play a major role in AOPP while BNP might not be involved in.

Cellular and molecular mechanisms of dichlorvos neurotoxicity: Cholinergic, nonchlolinergic, cell signaling, gene expression and therapeutic aspects.

Inappropriate use of toxic chemicals is common in developing countries, where it leads to excessive exposure and high risks of unintentional poisoning. Risks are particularly high with the pesticides used in agriculture, poor rural populations live and work in close proximity to these compounds and often store these compounds in and around their homes. It is estimated that most of the death from pesticide poisoning occur in developing countries. Organophosphate insecticides have been extensively used in agriculture in developing countries. Dichlorvos is a synthetic insecticide and belongs to a family of chemically related organophosphate pesticides (OP). Toxicity of dichlorvos has been documented in accidental human poisoning, epidemiological studies, and animal models. In this review, molecular mechanisms of dichlorvos neurotoxicity have been described. Usage, biotransformation, environmental levels, general population and occupational exposure, effects on cell signaling receptors, mitochondrial metabolism, oxidative stress and gene expression of dichlorvos have been reviewed. Assessment of acute and chronic exposures as well as neurotoxicity risk for lifetime exposures to dichlorvos have also been considered. In addition special emphasis has been given to describe, the role of dichlorvos in the chronic neurotoxicity and its molecular targets that ultimately lead to neurodegeneration.