职业相关性慢性磷毒性颌骨骨髓炎2例

慢性磷毒性颌骨骨髓炎(chronic phosphorus poisoning osteomyelitis of the jaw,CPPOJ)是一种由于长时间接触黄磷而导致颌骨发生慢性骨髓炎的疾病。我科于2020年8月31日诊治了2名来自同一黄磷工厂同一车间的患者,对其治疗情况和相关文献复习情况进行介绍。

舒血宁治疗有机磷中毒性心肌炎45例

目的:观察舒血宁治疗有机磷中毒性心肌炎的临床疗效。方法:将90例急性有机磷农药中毒患者分为对照组和观察组各45例,2组患者均接受常规西药保守治疗,观察组在此基础上给予舒血宁注射液10 mL+5%葡萄糖注射液250 mL,静脉滴注,1次/d,连续4周,之后改为口服,80 mg/次,3次/d,连续4周。结果:治愈率观察组为66.67%,对照组为51.11%,2组相比差异显著(P<0.05);总有效率观察组为93.33%,对照组为82.22%,2组相比差异显著(P<0.05)。肌酸磷酸激酶同工酶(CKMB)、心肌肌钙蛋白(CTnI)、白介素-6(IL-6)治疗后2组均明显改善(P<0.05),观察组改善较对照组明显(P<0.05)。结论:舒血宁治疗有机磷中毒性心肌炎临床疗效显效。

运用导赤散合清胃散加减治疗磷毒性口腔病30例

磷毒性口腔病是一种与磷毒接触有关的职业病,鉴于其临床表现颇与祖国医学之“口疮”相近似。笔者近年来认真地对本病进行深入地探索,运用导赤散合清胃散加减,治疗本病30例,取得了较为满意的疗效,现简介如下。

急性有机磷农药中毒患者炎性因子的变化

目的探讨急性有机磷农药中毒(AOPP)与炎症的关系。方法观察8例AOPP患者治疗前后血清炎性细胞因子的表达变化,并与8例健康人(对照组)进行比较。结果AOPP组有30个炎性细胞因子水平是对照组的2倍以上;经治疗后30个细胞因子中15个恢复至正常水平。结论AOPP病程中存在系统性炎症反应综合征(SIRS)过程,过度炎症反应可能是有机磷中毒重要的发病机制。

Damage effect and mechanisms of cyclophosphamide to human neuroblastoma SH-SY5Y cells

OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.

Microproteinuria for detecting calcineurin inhibitor-related nephrotoxicity after liver transplantation

AIM： To investigate whether microproteinuria could be used as an early and sensitive indicator to detect calcineurin inhibitor （CNI）-related nephrotoxicity after liver transplantation.METHODS： All liver transplant recipients with normal serum creatinine （SCr） and detectable microproteinuria at baseline were included in this study. The renal function was monitored by the blood clearance of 99mTc-diethylenetriaminepentaacetic acid every 6 mo. Microproteinuria, SCr and blood urea nitrogen （BUN） were measured at entry and at subsequent follow-up visits. The patients were divided into different groups according to the mean values of glomerular filtration rate （GFR） at the follow-up time points： Group 1, GFR decreased from baseline by 0%-10%; Group 2, GFR decreased from baseline by 11%-20%; Group 3, GFR decreased from baseline by 21%-40%; Group 4, GFR decreased from baseline by 〉 40% and/or SCr was increasing.RESULTS： A total of 143 patients were enrolled into this study （23 females and 120 males）. The mean follow-up was 32 mo （range 16-36 mo）. Downward trends in renal function over time were observed in the study groups. SCr and BUN increased significantly only in Group 4 patients （P 〈 0.001）. β2-microglobulin （β2m） and al-microglobulin （αlm） significantly increased with the subtle change of renal function in recipients who were exposed to CNI-based immunosuppression regimens. The reductions in GFR were closely correlated with elevated cclm （P = -0.728, P 〈 0.001） and β2m （r2 = -0.787, P 〈 0.001）.CONCLUSION： β2m and α1m could be useful as early and sensitive indicators of CNI-induced nephrotoxicity.

Prophylactic effect of vitamin E against hepatotoxicity,nephrotoxicity,haematological indices and histopathology induced by diazinon insecticide in mice

Considering that the involvement of reactive oxygen species （ROS） has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E （100 mg/kg body weight） on mice （25 -30 mg） treated with diazinon （32.5 or 16.25 mg/kg body weight） organophosphate insecticide for 14 days. Subehronic DZN exposure and the protective effects of vitamins E （vitE） were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase （ ALT）, aspartate aminotaransferase （ AST）, alkaline phosphatise （ ALP）, and some parameters of kidney function （urea and creatinine） in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon （DZNH） decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significandy. Moreover, there was a statistically significant decrease in haemoglobin （Hb）, red blood cell （RBC） and hematocrit （Hct） in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE ＋ DZNtreated groups. According to the present study, we conclude that vitE ean reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function [ Current Zoology 55 （3） ： 219 - 226, 2009].

Exposure Level, Toxicity Effects and Health Risk Assessment of Organophosphorus Flame Retardants in Water Environment

Organophosphorus flame retardants(OPFRs) are gradually replacing brominated flame retardants(BFRs), which are widely used in the world. The increasing output of OPFRs and the increasing detection of OPFRs in environmental media have attracted wide attention of scholars at home and abroad. OPFRs are generally semi-volatile, easy to enter the environment and accumulate in organisms,causing potential hazards to the environment and human health. In this paper, the pollution status and toxic effects of OPFRs in aquatic environment were introduced,and the research progress of human health risk caused by them was summarized.The existing problems were pointed out, and the future research was prospected. In the future, the analytical methods of various environmental and biological media should be improved, and comprehensive and in-depth environmental investigation and ecological and health risk assessment should be carried out. Attention should be paid to the effects of combined pollution on organisms and the study of biological acceptability.

Effects of low dose pre-irradiation on the toxicity of cyclophosphamide

Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.

Cytocompatibility of Highly Dispersed Nano Hydroxyapatite Sol

Nano hydroxyapatite (HA) crystals were prepared and dispersed in water to form HA sol by simple methods. The cytotoxicity of the sols were tested by MTT assay and lymphocytotoxicity test. Results show that the average secondary particle size of the sol containing uncalcined HA crystals is around 750 nm, within micrograde; while the sol of calcined HA contains over 88% nanoparticles with the size between 65～86 nm, in which nano HA crystals are highly dispersed. Both the HA sols have no toxicity on the proliferation of 3T3 cells and lymphocytes. It demonstrates that the nano sol is safe for the application of drug delivery.

Survey of cyanomyovirus abundance in Shantou coastal waters by g20

To understand the genetic diversity and population changes in cyanophages in the coastal waters of Shantou, northeast South China Sea, we used the capsid assembly protein gene g20 as a marker of the abundance and phylogeny of natural cyanomyovirus communities. The abundance of total viruses, heterotrophic bacteria, and picophytoplankton in the coastal waters was monitored with flow cytometry. Hydrological parameters （NO3^-, NO2^-, NH3, soluble reactive phosphorus, total dissolved nitrogen, total dissolved phosphorus, dissolved oxygen, chemical oxygen demand, temperature, salinity, and chlorophyll a concentration） and microbial abundance （total viruses, total bacteria, Prochlorococcus, Synechococcus, and eukaryotes） were measured in the upper and lower layers at four sampling sites in the research area. In the direct viral counts, cyanomyoviruses accounted for 1.92% to 〉10% of the total viral community. A phylogenetic analysis showed that the g20 sequences in the Shantou coastal waters were very diverse, distributed in eight distinct operational taxonomic units, including the newly formed Cluster W. The g20 gene copies inferred from real time PCR assay indicated that cyanomyovimses were correlated significantly with the heterotrophic bacteria numbers and the nitrate and chlorophyll a concentrations. These results suggest that cyanomyoviruses are ubiquitous and are an abundant component of the virioplankton in Shantou coastal waters.

Pros and Cons in Therapeutic Evaluation of Paraoxonase 1 in Nerve Agent Toxicity

PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.

Statistics of Acute Aluminium Phosphide Poisoning in Fez, Morocco

Aluminium phosphide is a rodenticide widely used in agriculture to protect grains and foods. Poisoning with this product represents a real problem in developing countries, as an interested young people and it causes high mortality. Aims of this study are to analysis epidemiological aspects, clinics, therapeutic, outcome of this acute poisoning and determine the factors of mortality. It is a retrospective study, concerned 47 patients intoxicated by the Aluminium phosphide between January 2009 and December 2012. It represents 23.4% of all poisonings. The mean age was 24.5 years with a female predominance （63.8%）. The poisoning was in a suicidal goal in 95.7% of cases. The mean ingested quantity was 3 grams. The initial clinical picture was dominated by vomiting, abdominal pain, shock and disorders of consciousness in 57.4%, 48.9%, 31.9% and 21.3%, respectively. Electrocardiogram abnormalities were observed in 38.3% of cases. Increase of Troponin was observed in 27.7% of cases. 36.2% of patients were intubated and ventilated and 40.4% have been placed under vasoactive drugs. The mortality rate was 38.3%. The prognostic factors were： delay of management, potassium disorders, elevated of Troponin, hypotension, tachycardia, need for mechanical ventilation, vasoactive drugs and shock. To improve the prognosis, the management should be rapid and the governement should focus more on prevention, so the aluminium phosphide will not be avaible to general population.

Selective proliferation of human γδ T cells in vitro

The effect of monoethylphosphate (MEP, commercial available or synthesized) together with IL-2 on the selective proliferation of human γ~δ T cells in Vitro from peripheral blood mononuclear cells (PBMC) of healthy donors and of cancer patients was investigated. The γ~δ T cells were stimulated by MEP to proliferate in a dose-dependent manner. The effect of synthesized MEP was 10 times greater than that of commercial MEP. When the PBMCs of healthy donors were cultured for 25 d in the medium containing different concentrations of MEP, the total cell number increased about 1000-3000 fold; and the ratio of γ~δ T cells reached to 70-80%. The selective expansion of γ~δ T cells depended on the synergic action of MEP and IL-2. The bulk cultured γ~δ T cells exhibited obvious cytotoxic activities against allogenic tumor cell lines (SQ-5,K562 alld Daudi) and autologous tumor cells. The culture system described here not only offers a simple method for obtaining a large number of γ~δ T cells which may become a new effector in the adoptive immunotherapy, but also provides a useful model for the further studies of the structure and function of γ~δ T cells in vitro.

Analysis Method for Pesticide Residues in Biological Matrices： Gas Chromatography-mass Spectrometry

Pesticides have done a great service to human, but their use is not safe for public health. Apart from pesticides acute toxicity, their chronic toxicity can cause various problems for human health. The objective of this work was to validate a liquid-liquid extraction method, which allows a fairly reliable analysis of pesticides using gas chromatography-spectrometry mass （GC/MS） in toxicology laboratory at National Institute of hygiene, Rabat Morocco. The equipment required to perform these analyzes are the biological matrices （blood, gastric fluid）, in which the authors have doped the Organophosphorus pesticides such as Chlorpyrifos, Dichlorvos and Organochlorine pesticide： dichlorodiphenyltrichloroethane （DDT） and Heptachlor. After extracting the mixture with toluene, the supernatant was collected after centrifugation and concentrated in a small volume of 1.5 mL and then analyzed in GC/MS. After analyzing, the authors found that the yields of each pesticide in samples are significant; respectively they represented 73.4% of Chlorpyrifos, 70.8% of Dichlorvos, 47.8% of DDT and 71.6% of Heptachlor. The blood has a strong link with the most pesticides, where it＇s important to use the GC/MS to identify these products. The extraction with toluene was effective, especially to OP, but it＇s also sensitive to OC.

Toxicity of organophosphorus pesticide sumithion on larval stages of stinging catfish Heteropneustes fossilis

Sumithion is widely used to control brittle in paddy fields and tiger bug in fish larval rearing ponds. The objective of this study was to elucidate the toxic effects of sumithion on larval stages of stinging catfish Heteropneustes fossilis. Larvae were exposed to two concentrations(150 and 250 μg/L) of sumithion with one control in three replicates of each. Larvae samples were collected at 20- and 24-h intervals followed by observation under a digital microscope. Exposures of stinging catfish larvae to sumithion produced deformities including irregular head shape, lordosis, yolk sac edema, body arcuation, tissue ulceration, etc. The mortality rates of larvae were significantly increased in response to increase in sumithion concentrations. Furthermore, around 30% of the total adult stinging catfish reared in sumithiontreated aquaculture ponds were found to be deformed permanently. These findings highlight that exposure of stinging catfish to sumithion at the critical and sensitive stages in their life cycle may significantly reduce the number of returning adults. Therefore, the use of sumithion for crop protection needs to be considered carefully and alternatives to sumithion should to be developed for controlling aquatic insects in aqua-ponds during larval rearing.

Upregulation of Nrf2-regulated gene expression by tBHQ alleviates cyclophosphamide-induced hematotoxicity in mice

Hematological toxicity （bone marrow suppression） is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 （Nrf2） is a pivotal coordinator of cellular defensive responses against chemical insults in many tissues including bone marrow. In the present study, the effects of tert-butylhydroquinone （tBHQ） on the expression of Nrf2-regulated genes in peripheral blood cells and cyclophosphamide （CTX）-induced hematotoxicity in mice were investigated. CTX induced apoptosis of peripheral blood nucleated cells and leukopenia in mice, accompanied by mobilization of bone marrow hematopoietic cells, tBHQ treatment induced the expression of Nrf2-regulated genes such as heine oxygenase 1 （HO1） and glutamate-cysteine ligase catalytic subtmit （GCLC） in RAW264.7 mouse macrophage cells and peripheral blood cells both in vitro and in vivo. Interestingly, pretreatment with tBHQ alleviated CTX-induced mouse peripheral blood cell apoptosis and leukopenia in vivo, indicating possible involvement of Nrf2 in the protection against CTX-induced hematotoxicity. This study provides new information on the chemotherapy-induced hematotoxicity, and suggests Nrf2 could serve as a target for the development of chemoprotectants against hematotoxicity.