Clonidine poisoning Is there any effective therapy

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鱼尼丁受体及以其为靶标的杀虫剂(C-2012)

Key words: ryanodine receptor; toxicology; chlorantraniliprole; insect behaviour 自 1998 年日本农药公司与拜耳公司联合发现氟虫双酰胺对鳞翅目害虫具有良好杀虫活性以来 [1-2]，以鱼尼丁受体 (ryanodine receptor, RYR) 为靶标的杀虫剂就成为农药研究创制单位关注的热点，2005、2006 和 2007 年，与以鱼尼丁受体为靶标的杀虫剂相关的公开专利分别有 12、11 和 6 件。尤其是杜邦公司 2000 年开发的氯虫苯甲酰胺成功商品化，并于 2008 年在多个国家同时登记用于防治鳞翅目害虫[3]，更加提升了人们对该类新型结构杀虫剂的热情，国际抗性行动委员会按其作用机理将作用于昆虫鱼尼丁受体的杀虫剂列为第 28 类杀虫剂[4]。以鱼尼丁受体为靶标的双酰胺类杀虫剂，具有高效、广谱、无交互抗性、对非靶标生物安全等特点，因而成为害虫综合治理策略 (IPM) 之一。目前，以昆虫鱼尼丁受体为靶标的杀虫剂主要有两类：一是邻苯二甲酰胺类，代表药剂为氟虫双酰胺；另一类是邻甲酰氨基苯甲酰胺类，代表药剂为氯虫苯甲酰胺[5]、溴氰虫酰胺[6]。关于这两类药剂的作用机制，众多学者曾进行过阐述。董卫莉等对 RyR 结构与功能、以鱼尼丁受体为靶标的杀虫剂作用机理进行了综述；唐振华等对鱼尼丁受体调节内环境及双酰胺类药剂作用于鱼尼丁受体分子机理作了进一步阐述[7]；关于鱼尼丁受体的激活物与抑制物也有很多报道[8-9]。本文主要是对鱼尼丁受体同工型、各结构域控制的离子通道以及双酰胺类药剂对害虫行为、生理及生殖的影
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文献标识码：A
doi：10.3969/j.issn.1671-5284.2012.03.001

(完整版)药学英语第五版原文翻译

Introduction to PhysiologyIntroductionPhysiology is the study of the functions of living matter. It is concerned with how an organism performs its varied activities: how it feeds, how it moves, how it adapts to changing circumstances, how it spawns new generations. The subject is vast and embraces the whole of life. The success of physiology in explaining how organisms perform their daily tasks is based on the notion that they are intricate and exquisite machines whose operation is governed by the laws of physics and chemistry.Although some processes are similar across the whole spectrum of biology—the replication of the genetic code for or example—many are specific to particular groups of organisms. For this reason it is necessary to divide the subject into various parts such as bacterial physiology, plant physiology, and animal physiology.To study how an animal works it is first necessary to know how it is built. A full appreciation of the physiology of an organism must therefore be based on a sound knowledge of its anatomy. Experiments can then be carried out to establish how particular parts perform their functions. Although there have been many important physiological investigations on human volunteers, the need for precise control over the experimental conditions has meant that much of our present physiological knowledge has been derived from studies on other animals such as frogs, rabbits, cats, and dogs. When it is clear that a specific physiological process has a common basis in a wide variety of animal species, it is reasonable to assume that the same principles will apply to humans. The knowledge gained from this approach has given us a great insight into human physiology and endowed us with a solid foundation for the effective treatment of many diseases.The building blocks of the body are the cells, which are grouped together to form tissues. The principal types of tissue are epithelial, connective, nervous, and muscular, each with its own characteristics. Many connective tissues have relatively few cells but have an extensive extracellular matrix. In contrast, smooth muscle consists of densely packed layers of muscle cells linked together via specific cell junctions. Organs such as the brain, the heart, the lungs, the intestines, and the liver are formed by the aggregation of different kinds of tissues. The organs are themselves parts of distinct physiological systems. The heart and blood vessels form the cardiovascular system; the lungs, trachea, and bronchi together with the chest wall and diaphragm form the respiratory system; the skeleton and skeletal muscles form the musculoskeletal system; the brain, spinal cord, autonomic nerves and ganglia, and peripheral somatic nerves form the nervous system, and so on.Cells differ widely in form and function but they all have certain common characteristics. Firstly, they are bounded by a limiting membrane, the plasma membrane. Secondly, they have the ability to break down large molecules to smaller ones to liberate energy for their activities.生理学简介介绍生理学是研究生物体功能的科学。

常用消毒药剂使用方法英语

常用消毒药剂使用方法英语## Common Disinfectant Agents and Their Usage.Disinfectants are essential in preventing the spread of infections and maintaining a healthy environment. They are used in various settings, including hospitals, clinics, homes, and public areas. Understanding the proper usage of disinfectants is crucial to ensure their effectiveness and prevent any potential adverse effects.Types of Disinfectants.There are different types of disinfectants available, each with its own properties and applications. Some common types include:Chlorine: Effective against a wide range of microorganisms, including bacteria, viruses, and fungi. Commonly used in water treatment and swimming pool disinfection.Alcohol: Rapidly kills bacteria and some viruses. Used in hand sanitizers, surface disinfectants, and medical wipes.Hydrogen peroxide: A powerful oxidizing agent thatkills microorganisms through oxidation. Used in medical settings and as a household disinfectant.Quaternary ammonium compounds (quats): Effective against bacteria and some viruses. Often used in floor cleaners and surface disinfectants.Phenolic compounds: Have a broad spectrum of activity and are effective against bacteria, viruses, and fungi. Used in hospitals and other medical settings.Usage Instructions.The proper usage of disinfectants varies depending on the specific product and intended application. Generally, the following steps should be followed:1. Read the Product Label Carefully.Pay attention to the intended use, dilution instructions, and safety precautions.Different disinfectants have different concentrations and may require specific dilutions for optimal effectiveness.2. Wear Appropriate Personal Protective Equipment (PPE)。

Carbonmonoxidepoisoning阅读理解答案

Carbon monoxide poisoning 阅读理解答案Carbon monoxide poisoning (一氧化碳中毒) kills and injuries many people and animals around the world. This gas has been a problem since people first began burning fuels to cook food or to create heat. It is a problem in all parts of the world that experiencecold weather.Carbon monoxide is called the silent killer because people do not know it is in the air. The gas has no color. It has no taste. It has no smell. It does not cause burning eyes. And it does not cause people to cough. But it is very deadly. It robs the body’s ability to use oxygen.Carbon monoxide decreases the ability of the blood to carry oxygen to body tissues. It does this by linking with the blood. When the gas links with the blood, the blood is no longer able to carry oxygen to the tissues that need it.Damage to the body can begin very quickly from large amounts of carbon monoxide. How quickly this can happen depends on the length of time a person is breathing the gas and the amount of the gas he or she breathes in. Carbon monoxidepoisoning has warning signs. But people have to be awake to recognize them. Small amounts of the gas will cause a person’s head to hurt. He or she may begin to feel tired. The person may feel sick. The room may appear to be turning around. The person may have trouble thinking clearly. People develop severe head pain as the amount of the gas continues to enter their blood. They will begin to feel very tired and sleepy. They may have terrible stomach pains.Medical experts say carbon monoxide affects people differently. For example, a small child will experience health problems or die much quicker an adult will. The general health of the person or his or her age can also be important. An older adult with healthproblems may suffer the effects of carbon monoxide more quickly than a younger person with no health problems. People with heart disease may suffer chest pains. They may begin to have trouble breathing.( ) 56. Why is carbon monoxide called the silent killer?A. Because it tastes and smells good.B. Because it is not easily noticed.C. Because it kills and injures people.D. Because it is always harmful to people( ) 57. How does carbon monoxide harm people?A. It makes people’s blood unable to move.B. It decreases the amount of blood in the body.C. It makes body tissues full of blood.D. It makes the blood less able to carry oxygen.( ) 58. When people breathe in small amounts of the gas, they may_______ .A. feel a little dizzy (头晕)B. suffer a serious headacheC. go around in the roomD. have a terrible stomachache( ) 59. Which of the following about carbon monoxide poisoning is true?A. Adults are affected more seriously than children.B. Young people are more seriously affected than old people.C. People in poor health may have more serious consequences.D. People with heart problem only suffer from chest pains.( ) 60. The purpose of the passage is to_______ .A. warn people not to burn fuels to keep warm in thewinterB. list the damages that carbon monoxide brings to peopleC. give advice on how to avoid carbon monoxide poisoningD. introduce some knowledge about carbon monoxide poisoning56—60 BDACD。

中毒总论new

一、pathogencity(cause of disease)
（一）职业性中毒：
（二）生活性中毒： Accidental poisoning, Deliberate self-poisoning or suicide, Non-deliberate self-poisoning Homicidal poisoning.
[Treatment]
Principle： 1、紧急复苏 2 、立即终止接触毒物。 3、清除进入人体内已被吸收或尚未吸收的毒物。 4、特效解毒药。 5、对症治疗。
一紧急复苏
（一）（二）
呼吸支持循环支持
（三）昏迷和惊厥的治疗
二、立即终止接触毒物
吸入中毒----撤离现场、通风皮肤----脱去衣物、清水清洗
2、洗胃(Gastric lavage)：尽早6h内进行
（1） Method：患者取左侧卧位，头低位并转向一侧，以免洗液误入气管。胃管前端涂上石蜡油，由鼻或口腔向下插入50cm左右，吸出胃液或注入空气，证明胃管确在胃内，注入洗胃液，每次 200~300ml ，然后排出，反复进行，直至澄清为止。洗胃液总量至少 2~10L 。撤管时，先将胃管夹住，以免管内液体返流： ① 腐蚀性毒物中毒时。 ② 有上消化道出血或胃穿孔危险者。 ③ 休克未纠正 ④ 昏迷
Therapeutic indications：
（1）可透析毒物中毒，毒物水溶性强，血浆蛋白结合率低，半衰期长。（2）血中毒物浓度高，病情严重，一般治疗无效。（3）中毒后发生renal failure。 peritoneal dialysis ：苯巴比妥、水杨酸、甲醇、乙二醇、茶碱中毒；脂溶性强的毒物如短效巴比妥、异眠能和有机磷杀虫剂透析效果不好。 Hemodialysis ：氯酸盐、重铬酸盐poisoning result in acute renal failure。

鼠李糖乳杆菌对革兰氏阴性菌和阳性菌都有效

Isolation,Identiﬁcation,and Characterization of Small Bioactive Peptides From Lactobacillus GG Conditional Media That ExertBoth Anti-Gram-negative and Gram-positiveBactericidal ActivityÃRuiliang Lu,Ãy Serena Fasano,z Nandakumar Madayiputhiya,§Nicholas P.Morin,§James Nataro,and ÃAlessio FasanoÃMucosalBiology Research Center,{University of Maryland College Park,{Proteomic Core Facility,and §Center for Vaccine Development,University of Maryland School of Medicine,Baltimore,MDABSTRACTObjectives:Diarrheal diseases remain a major human plague that still claim millions of lives every year.Probiotics,including Lactobacillus GG (LGG),are known to have a beneﬁcial effect on diarrheal diseases,but their mechanism of action has not yet been completely established.Therefore,the main objective of this work was to identify and characterize moieties elaborated by LGG that exert antibacterial activity.Materials and Methods:Lactobacillus GG conditional media was subjected to liquid chromatography/mass spectrometry.The identiﬁed peptides were synthesized by Symphony peptide synthesizer and puriﬁed by HPLC using Dynamax reverse-phase C ing A600measurement and tested for their antibacterial activity.Results:We identiﬁed 7small peptides from LGG cultured media,2of which are NPSRQERR and PDENK,retained theantibacterial activity detected with LGG conditional media.The antibacterial activity was exerted against both Gram-negative (Escherichia coli EAEC 042and Salmonella typhi )and,with less potency,Gram-positive (Staphylococcus aureus )bacteria.Conclusions:Lactobacillus GG elaborates small peptides showing various degrees of antibacterial activity.NPSRQERR showed the most potent antibacterial effect that was detected both in Gram-negative and Gram-positive microorganisms.These synthetic peptides may represent novel tools for the treatment of bacterial infectious diseases.JPGN 49:25–32,2009.Key Words:Antibacterial peptides —Diarrhea —Lactobacillus GG —Probiotics.#2009by European Society for Pediatric Gastroenterology,Hepatology,and Nutrition and North American Society for Pediatric Gastroenterology,Hepatology,and NutritionDiarrheal diseases claim more then 2million lives per year,80%of them being children younger than age 2years (1).Disease and death caused by diarrhea are a global problem;however,it occurs predominantly in developing countries where sanitation remains an unresolved issue and education is limited (2).Although antibiotics are theoretically available for the treatment of these devastat-ing diseases,their use is contraindicated because of the risk of selecting bacterial strains that display antibiotic resist-ance (3).Vaccines remain unaffordable and are not alwayseffective or available (1).Therefore,there is an urgent need for a safe and affordable treatment to solve this serious public health problem.Treatment of diarrheal diseases remains a major chal-lenge due to the number of disease-causing pathogens,including pathogenic Escherichia coli (4,5).The primary cause of death from diarrheal diseases is dehy-dration,which causes extreme thirst,shock,and organ failure.Studies suggested that diarrheal diseases can also have a negative long-term impact on both physical and psychological growth due to reduction in appetite,altered feeding practices,and decreased absorption of nutrients (6).Probiotics are nonpathogenic bacteria that are claimed to have several beneficial effects related to their capa-bility to prevent the growth of several pathogenic micro-organisms,including E coli (7).According to the cur-rently adopted definition by FAO/WHO,probiotics are Received August 6,2008;accepted October 22,2008.Address correspondence and reprint requests to Ruiliang Lu,MD,University of Maryland School of Medicine,Mucosal Biology Research Center,Health Science Facility II,20Penn St,Baltimore,MD 21201,USA (e-mail:rlu@).Drs Lu and Fasano hold stock in Alba Therapeutics.The other authors report no conﬂicts of interest.Journal of Pediatric Gastroenterology and Nutrition49:25–32#2009by European Society for Pediatric Gastroenterology,Hepatology,and Nutrition and North American Society for Pediatric Gastroenterology,Hepatology,and Nutrition25‘‘live microorganisms which when administered in ade-quate amounts confer a health benefit on the host’’(8). There are many forms of probiotics currently commer-cially available as both pills and liquid medicine(9). Probiotics are known to have a beneficial effect on diarrheal diseases;however,their mechanism of action has not yet been completely established(10).It is well known that probiotics help in maintaining a healthy intestinal microbiota(11).There are several theories proposed to explain the antibacterial effects of probiotics,including their capa-bility to compete for nutrients,the establishment of a microenvironment in which pathogenic microorganisms are not able to survive,or the elaboration of toxins lethal for pathogenic bacteria(10).To explore these possibilities, we used a combination of microbiological,biochemical, and genetic approaches that led to the identification for the first time of Lactobacillus GG(LGG)-derived small pep-tides that retain the antibacterial properties of LGG against both Gram-negative and Gram-positive bacteria.MATERIALS AND METHODSMaterialsLuria Broth Base was purchased from GibcoBRL(Carlsbad, CA);MRS Broth was purchased from Becton Dickinson Com-pany(Franklin Lakes,NJ);MRS agar was obtained from Fluka (Buches,Switzerland);and LB Agar plates were purchased from TEKnova(Hollister,CA).Macro-prep DEAE Support anion exchange resin and Criterion precast gel(4%–20%)were obtained from Bio-Rad(Hercules,CA).Spectrophotometry was performed using a spectrophotometer Beckman Coulter DU530 (Fullerton,CA);cultures were prepared using a Forma Orbital Shakers from Thermo(Waltham,MA).StrainsLactobacillus GG,enteroaggregative E coli strain EAEC 042,Salmonella typhi,and Staphilococcus aureus strains were obtained from the collection of the Center for Vaccine Devel-opment,University of Maryland School of Medicine.Preparation of LGG Conditional Media Lactobacillus GG was cultured in5mL MRS broth,at378C, with shaking at225rpm overnight.The following day,0.1mL cultured MRS broth was diluted to10À10,10À11,10À12,spread on the MRS agar plates,cultured at378C for24hours,and then colonies were counted.The4.9mL of the cultured mixture was centrifuged at5000g for45minutes,and conditional media (CM)collected,filtered,and used for the studies described below.Ion Exchange ChromatographyThree milliliters of LGG CM was added to an anion ex-change column(d¼1.5cm,L¼2.0cm flow rate0.1mL/min).Before loading,washing the column using12mL of Tris-HCl (pH8.0);after loading,the column was washed with12mL Tris-HCl(pH8.0)again and then eluted by ImmunoPure Ig G elution buffer(pH2.8,Pierce,Rockford,IL).The fractions collected for activity assay and sodium dodecyl sulfate-poly-acrylamide gel electrophoresis(SDS-PAGE).Sodium Dodecyl Sulfate-Polyacrylamide GelElectrophoresisEach fraction eluted from anion exchange column was mixed with protein sample buffer(1:1),heated at958C for5minutes, and then applied to Criterion precast gel(4%–20%),using Tris-Glycine-SDS buffer(Bio-Rad)as running buffer at constant 170V for1hour.The gel was stained by2.5%Coomassie blue and destained by10%methonol,7.5%acetic acid solution.LC/MS Analysis and Identiﬁcation of PeptidesLiquid chromatography/mass spectrometry(LC/MS) analysis of peptides derived from proteins present in the con-ditional media(CM)was performed on Thermofinnigan LCQ mass spectrometer(Thermofinnigan,San Jose,CA),which was connected to a nanoelectrospray ionizer.Initially the super-natant was prefiltered and concentrated using10,000MW cut of membranes(Microcon;Millipore,Billerica,MA).The Sur-veyor chromatographic system with auto sampler(Thermofin-nigan)was used for peptide separation.The LC system was connected to10.5cm fused silica reverse-phase C18column (Pico Frit Column;New Objective,Woburn,MA).The peptides were separated during90-minute linear gradient of5%to90% acetonitrile/water mixture,containing0.1%formic acid at a flow rate of300nL/min.The spectra were accumulated and the acquired MS scans were searched against the Lactobacillus database(IPI)using the SEQUEST search algorithm.Several peptides with different MW distribution were detected and synthesized to check for their antibacterial activity.Peptide synthesis,purification,and identification were car-ried by the Biopolymer Laboratory at the University of Mary-land School of Medicine.Briefly,the peptides were synthesized on a Symphony peptide synthesizer(PTI Instruments,Boston, MA),using the Fmoc coupling strategy.Peptide purification was performed on a Beckman Gold system consisting of two 110B pumps and a167detector(215nm)using a Dynamax reverse-phase C18column(8m L,25.6Â250mm)(Varian,Wal-nut Creek,CA).Peptide characterization was performed by reverse-phase HPLC and MALDI-TOF.Antibacterial Activity AssaysE coli Growth Time CourseTen microliters of culture from E coli strain EAEC042 (2.16Â1014CFU/mL)were added in1-mL LB broth and incubated in378C,shaking at225rpm,measuring A600every 30minutes.Measurement of Antibacterial Activity by CultureSpectrophotometry at A600The assay was performed as previously described(12),with minor modifications.Briefly,10m L E coli EAEC04226LU ET AL. J Pediatr Gastroenterol Nutr,Vol.49,No.1,July2009(7.7Â1014CFU/mL)was added to1.0-mL LB Broth,mixed, and100m L of each LGG-derived synthetic peptide solution dissolved in MRS(for peptide final concentration,see Fig.6B) was added to the mixture.MRS alone(100m L)and LGG CM 100m L(LGG concentration:19.7Â1012CFU/mL)were used as negative and positive controls,respectively.The mixture was cultured for3hours with shaking at225rpm,378C,measuring A600at the end.The relative inhibition activity was calculated according to the following formula:Sample A600Control A600Â100and expressed as percentage:Experiments With Peptide NPSRQERR for Staphylococcus orSalmonella(CVD908)GrowthIncreased concentrations of peptide NPSRQERR were dis-solved in100m L MRS and added to150-m L Staphylococcus culture(44Â106CFU/mL)or150-m L Salmonella culture (38Â106CFU/mL)in LB broth.The same Staphylococcus or Salmonella culture conditions without the peptide were used as control.The mixture was cultured at378C,225rpm for 3hours.At the end,100-m L culture mixture was spread onto LB agar plates,cultured overnight at378C,and colonies counted the next day.The relative inhibition activity calculation was performed according to the following formula:1ÀSample coloniesÂ100and expressed as percentage:Statistical AnalysisTwo-tailed Student t tests were used to test differences between2groups.Data were paired wherever appropriate. Values of P<0.05were regarded as significant.RESULTSEffect of LGG on E coli GrowthTo determine the effect of LGG on pathogenic bac-terial survival,increasing amounts of LGG cultures were added to McConkey petri dishes plated with10À8 dilution of an overnight culture of E coli EAEC042 ctobacillus GG caused a dose-dependent negative effect on E coli growth(Fig.1),suggesting LGG and/or factor(s)secreted by LGG present in the CM exert an antibacterial effect on E coli.To establish whether the LGG antibacterial effect was related to its direct action on E coli or to the secretion of an antibacterial factor(s),LGG CM was used to repeat the experiments described in Figure1.Figure2shows that LGG CM media is responsible for the antibacterial effect observed with LGG.Similar results were obtained when the antibacterial activity was monitored byspectropho-FIG.1.Effect of increasing amounts of LGG culture on EAEC042 ctobacillus GG cultures caused a dose-dependent inhibition of EAEC042growth.Open bars:EAEC042alone;gray bars:EAEC042þ100m L of LGG culture;solid bars:EAEC042þ1000m L of LGG culture.ÃP<0.001compared with EAECalone. FIG.2.Effect of LGG CM on EAEC042survival.Either50or 100m L of EAEC042cultures(starting concentration 2.2Â1014CFU/mL)were mixed with either100m L LGG con-ditional media(starting concentration19.7Â1012CFU/mL)(open bars)or100m L of nonpathogenic E coli conditional media(starting concentration19.7Â1012CFU/mL)(closed bars)used as a nega-tive control.Cultures were then plated on petri dishes,incubated overnight,and colony ctobacillus GG conditional media caused signiﬁcant decrease in colony counts compared with nonpathogenic E coli CM,irrespective of the initial EAEC042 inoculum.ÃP<0.006;ÃÃP<0.0008compared with nonpatho-genic E coli conditional media.CHARACTERIZATION OF LACTOBACILLUS GG SMALL BIOACTIVE PEPTIDES27J Pediatr Gastroenterol Nutr,Vol.49,No.1,July2009tometry,with an average inhibition rate of95.03% (n¼8).Heat StabilityTo establish whether the factor secreted by LGG was thermostable,CM was heated at958C and added to EAEC042bacterial cultures.When grown at a10À4 dilution,EAEC042growth was quantitated to be 800.5Æ96.9CFU/ctobacillus GG CM inhibited the growth of EAEC042either when the culture was heated(24Æ2.8CFU/mL,P<0.00005)or not heated (22.5Æ4.3CFU/mL,P<0.00005)(Fig.3).Similar results were obtained at higher EAEC042culture dilutions(Fig.3).These results proved that the antibac-terial moiety present in LGG CM is heat resistant.Ion Exchange Chromatography and SDS-PAGEAnalysis ResultsFive fractions were collected from ion exchange chromatography.On the overnight plates culture assay,only fraction3showed antibacterial activity(Fig.4). However,no protein bands could be detected by SDS-PAGE analysis.These results suggested that the concen-tration of the active peptide(s)was low,the molecular weight of the protein was too small,or the molecule(s) was not a protein.To address this issue,LGG CM was concentrated by dialysis against phosphatebuffered FIG.3.Effect of heat treatment on LGG conditional media anti-bacterial activity.Heat treatment of LGG conditional media did not affect its antibacterial effect,irrespective of the dilution of E coli 042cultures plated.ÃP<0.00005compared withcontrol. FIG.4.Effect of LGG conditional media(CM)fractions obtained by anion exchange chromatography on E coli042growth.Ion exchange chromatography was carried out on a column with d¼1.5cm,L¼2.0cm,ﬂow rate0.1mL/min,washing buffer Tris-HCl(pH8.0),elution buffer ImmunoPure IgG(pH2.8).Five fractions were collected and tested on EAEC042overnight cultures used at increasing dilutions. EAEC042culture alone and EAEC042cultures plus LGG CM were used as negative and positive controls,respectively.Of the5fractions collected,only fraction3showed antibacterial activity(ÃP<5Â10À7),irrespective of the original EAEC042inoculum concentration. 28LU ET AL.J Pediatr Gastroenterol Nutr,Vol.49,No.1,July2009saline by using 1000Da molecular weight cutoff bags.The dialyzed LGG lost its antibacterial activities and,therefore,attention was paid to searching for molecular peptides smaller than 1000Da.LC/MS Analysis ResultsThe LC/MS spectra of the LGG CM were analyzed and the mass spectrometry sequences of the <1000Da pep-tides detected in the media were compared with the Lactobacillus database (IPI)using SEQUEST search algorithm.Many peptides with different molecular weight distributions were detected during the process of LC/MS (Fig.5).Of the several fragments of $1000Da molecular weight,the following 7peptides resulted being part of the LGG genome:NPSRQERR,PDENK,YTRGLPM,VHTAPK,LSQKSVK,MLNERVK,and GKLSNK.These peptides were synthesized to 95%to 99%purity and tested for potential antibacterial activity.Activities Assay ResultsThe antibacterial activity of these 7peptides was compared with the linear growth of EAEC 042over time as determined by spectrophotometry A600(Fig.6A)and analyzed at the 180-minute time point.Figure 6B shows the inhibitory effects of the 7peptides on the growth of E coli in liquid culture.The comparative antibacterial activity of the 7peptides was NPSRQERR >PDENK >VHTAPK >MLNERVK >YTRGLPM >GKLSNK >LSQKSVK.Only NPSRQERR showed an activity (81.4%E coli growth inhibition)comparable with LGG CM (95%growth inhibition).PDENK had a mod-erate activity (68.7%growth inhibition),whereas VHTAPK had a mild activity (30%growth inhibition).The remaining 4peptides had little or no activity.To establish whether the antibacterial activity of pep-tide NPSRQERR was specific for E coli ,we repeated our biological assay using both S typhi andStaphylococcusFIG.5.Identiﬁcation of antibacterial peptides from LGG CM by LC/MS/MS ctobacillus GG CM was ﬁltered and concentrated,and peptides present in CM were separated by Surveyor chromatographic system using 90-minute linear gradient of 5%–90%acetonitrile/water mixture,containing 0.1%formic acid at a ﬂow rate of 300nL/min.The spectra were accumulated and the acquired MS scans searched against the Lactobacillus database (IPI)using SEQUEST search algorithm.The ﬁgure shows the typical chromatogram marked with the 7identiﬁed peptides (MS1)by LC/MS and SEQUEST Lactobacillus database search.CHARACTERIZATION OF LACTOBACILLUS GG SMALL BIOACTIVE PEPTIDES29J Pediatr Gastroenterol Nutr,Vol.49,No.1,July 2009aureus as bacterial targets.Although the effect of peptide NPSRQERR on S typhi was similar to that observed in E coli EAEC 042(Fig.7),its effect on S aureus was only mild but dose dependent (Fig.7)DISCUSSIONProbiotics were defined by Fuller in 1989as ‘‘live microbial feed supplements that beneficially affect the host animal by improving its intestinal microbial bal-ance’’(13).Fuller’s definition emphasizes the require-ment of viability for probiotics and introduces the aspect of a beneficial effect on the host.Probiotics,which means ‘‘for life,’’have been used for centuries as natural com-ponents in health-promoting foods.The original obser-vation of the positive role played by certain bacteria was first introduced by Russian scientist and Nobel laureate Eli Metchnikoff,who in the beginning of the 20th century suggested that it would be possible to modify the gut flora and to replace harmful microbes by useful microbes (14).Experiments into the benefits of probiotic therapies suggest a range of potentially beneficial medicinal uses for probiotics.However,for many of the potential benefits,research is limited and only preliminary results are available.Among others,probiotics are claimed to protect against pathogens by means of competitive inhi-bition (ie,by competing for growth)or by improving immune functions (15,16).As concerns infection of the gastrointestinal tract,it has been reported that probiotics present in food or supplements are effective intheFIG.6.(A)EAEC 042growth time course.Ten microliters of E coli (2.16Â1014CFU/mL)were added in 1mL LB broth and incubated in 378C,shaking at 225rpm,measuring A600every 30minutes.EAEC 042shows a liner growth between 90and 210minutes.(B)LGG CM and its 7synthetic peptides relative inhibition activities on E coli growth.Ten microliters of EAEC 042(7.7Â1012CFU/mL)were added to 1mL LB broth mixed,and 100m L of each peptide solution dissolved in MRS was added to the mixture.MRS alone (100m L)and LGG CM (100m L)(initial concentration 19.7Â1012CFU/mL)were used as negative and positive controls,respectively .The mixture was cultured for 3hours and the A600measured at the end of incubation.Figure shows mean percentage inhibition ÆSD.N ¼3for all synthetic peptides tested.N ¼7for LCC CM.30LU ET AL.J Pediatr Gastroenterol Nutr,Vol.49,No.1,July 2009treatment and prevention of acute diarrhea;decreasing the severity and duration of rotavirus infections in chil-dren as well as travelers’diarrhea in adults (15,16).Despite major research efforts aimed at finding an effective treatment,diarrheal disease remains a human plague claiming millions of lives every year (1).EAEC 042is among the leading enteric pathogens in pediatrics,causing prolonged diarrheal diseases in children (4).The discovery and characterization of a small peptide elabo-rated by LGG opens unexplored horizons for an effective treatment of diarrheal diseases affordable for third world countries.Our stepwise approach was initially focused on the effect of LGG on E coli growth and on the realization that the antibacterial activity was related to a moiety secreted by LGG in the CM.These results confirmed previous reports of an antimicrobial substance elaborated from lactobacilli (17).However,the nature of this inhibitory substance has never before been characterized.For the first time,we report in this article the identification and characterization of this moiety as a molecule(s)that is heat resistant and small in size.Anion exchange chroma-tography showed that this factor(s)is peptide in nature with an approximate molecular weight of less than1000Da.MS/MS analysis identified 7peptides elabo-rated by genes present in the LGG genome,3of them showing variable antibacterial activity (see Fig.6B).Interestingly,probiotics also elaborate peptides that regulate intestinal cell survival and growth (18,19),suggesting that their beneficial action on infective gas-troenteritis can be the combined effect of both direct antibacterial activity and intestinal mucosal protection.The use of small peptides as antidiarrheal drugs is novel and would offer several advantages over current treatments (20).Being small peptides,it would be easy and cheap to produce them in large amounts and would be virtually devoid of the side effects experienced with current antidiarrheal remedies (drug resistance for anti-biotics,immune reaction for vaccines)(21).Due to the fact that these peptides are elaborated by probiotics found in common food (such as yogurt),is it conceivable to hypothesize that their use would be safe for the treatment of children and adults experiencing diarrhea.However,proper clinical trials are necessary to confirm the safety of these peptides from their clinical use.Of the 7peptides isolated and characterized,the peptide NPSRQERR showed the highest antibacterial properties,both on Gram negative and Gram positive.We note that each of the peptides is predicted to carry a net positive charge at neutral pH by virtue of the preponderance of basic amino acids.Such cationic peptides may act similarly to cationic antibacterial peptides produced by mammalian species,although this hypothesis remains to be tested.Notably,the small LGG-derived peptides are also thermostable,a characteristic that would be advan-tageous for the transport and usage of the drug in devel-oping countries.The synthesis of this small peptide would not require sophisticated equipment.Therefore,developing countries could produce their own LGG-derived peptide at relatively low,affordable costs.Never-theless,peptide formulation for proper protection against degradation and delivery to specific gastrointestinal regions are pitfalls that need to be addressed before possible clinical applications to decrease the burden of diarrheal diseases in developing countries.The object of this article may far reach beyond the development of novel treatment of diarrheal diseases.There are a growing number of reports suggesting that human-associated microbes influence human health and vice versa.The estimated 10to 100trillion microorgan-isms that inhabit the human intestine actually outnumber the body’s own cells by a factor of 10.The human microbiome is the genetic sum of this community of microorganisms living in symbiosis with their host.Therefore,it is conceivable to hypothesize that the metabolic activities of the bacterial population in the colon can be manipulated to promote health.Unfortu-nately,this hypothesis has not been rigorously challenged because of several shortcomings.First of all,the com-plexity of the colonic biota (flora)is vast and alsolargelyFIG.7.Peptide NPSRQERR antibacterial activities on both Sal-monella typhi and Staphylococcus aureus .Increased concen-trations of peptide NPSRQERR were dissolved in 100m L MRS and added to150m L S aureus culture (44Â106CFU/mL)or 150m L S typhi culture (38Â106CFU/mL)in LB broth.S aureus and S typhi cultures (using the same initial inocula)alone were used as controls.The mixture was cultured at 378C,225rpm for 3hours.At the end,100m L culture mixture was spread onto LB agar plate,cultured overnight at 378C,and colonies counted the next day .The relative inhibition activity was calculated using the formula shown in the material and method section.The results show that NPSRQERR shows a dose-dependent antibacterial effect that was more potent on S typhi (in which 100%inhibition was reached at the peptide concentration of 8mmol/L)than on S aureus (in which 100%was reached at a peptide concentration of 64mmol/L).CHARACTERIZATION OF LACTOBACILLUS GG SMALL BIOACTIVE PEPTIDES 31J Pediatr Gastroenterol Nutr,Vol.49,No.1,July 2009undefined.Consequently,many studies have lacked the proper scientific stringency necessary for meaningful readouts on the impact of probiotics on gut microflora. Another important issue is to establish the role of microbial biota in the pathogenesis of several gastroin-testinal(eg,inflammatory bowel diseases)and extrain-testinal(eg,autoimmune diseases)diseases.A third and related issue is defining conditions that may be amelio-rated by probiotic therapies.Therefore,it is possible to conceptualize the use of probiotics or probiotic-derived peptides for the treatment of these other conditions in which manipulation of the intestinal microbiome can represent a novel and yet unexplored alternative approach.REFERENCES1.Nataro JP.Vaccines against diarrheal diseases.Semin Pediatr InfectDis2004;15:272–9.2.O’Ryan M,Prado V,Pickering LK.A millennium update onpediatric diarrheal illness in the developing world.Semin Pediatr Infect Dis2005;16:125–36.3.Marano NN,Rossiter S,Stamey K,et al.The National Antimicro-bial Resistance Monitoring System(NARMS)for enteric bacteria, 1996–1999:surveillance for action.J Am Vet Med Assoc2000;217:1829–30.4.Harrington SM,Dudley EG,Nataro JP.Pathogenesis of enteroag-gregative Escherichia coli infection.FEMS Microbiol Lett2006;254:12–8.5.The US Centers for Disease Control and Prevention(CDC).Out-breaks of Escherichia coli serotype O157:H7infections in con-taminated spinach.September29issue of the Morbidity and Mortality Weekly Report.6.Mata L.Diarrheal disease as a cause of malnutrition.Am J TropMed Hyg1992;47:16–27.7.Guandalini S.Probiotics for children:use in diarrhea.J ClinGastroenterol2006;40:244–8.8.FAO/WHO.Health and Nutritional Properties of Probiotics in Foodincluding Powder Milk with Live Lactic Acid Bacteria.Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria;2001.9.Santosa S,Farnworth E,Jones PJ.Probiotics and their potentialhealth claims.Nutr Rev2006;64:265–74.10.Ljungh A,Wadstrom ctic acid bacteria as probiotics.CurrIssues Intest Microbiol2006;7:73–89.11.Broekaert IJ,Walker WA.Probiotics asﬂourishing benefactors forthe human body.Gastroenterol Nurs2006;29:26–34.12.Kreander A,Vuorela P,Tammela P.A rapid screening method fordetecting active compounds against erythromicin-resistant bacterial strains of Finnish origin.Folia Microbiol2005;50:487–93.13.Fuller R.Probiotics in man and animals.J Appl Bacteriol1989;66:365–78.14.Metchnikoff,E.Essais optimistes.Paris.The prolongation of life.Optimistic studies.Translated and edited by P.Chalmers Mitchell.London:Heinemann;1907.15.Reid G,Jass J,Sebulsky MT,et al.Potential uses of probiotics inclinical practice.Clin Microbiol Rev2003;16:658–72.16.Ouwehand AC,Salminen S,Isolauri E.Probiotics:an overview ofbeneﬁcial effects.Antonie Van Leeuwenhoek2002;82:279–89. 17.Silva M,Jacobus NW,Deneke C,et al.Antimicrobial substancefrom a human Lactobacillus strain.Antimicrob Agents Chemother 1987;31:1231–3.18.Yan F,Polk DB.Probiotic bacterium prevents cytokine-inducedapoptosis in intestinal epithelial cells.J Biol Chem2002;277:50959–65.19.Yan F,Cao H,Cover TL,et al.Soluble proteins produced byprobiotic bacteria regulate intestinal epithelial cell survival and growth.Gastroenterology2007;132:562–75.20.Yeaman MR,Yount NY.Mechanisms of antimicrobial peptideaction and resistance.Pharmacol Rev2003;55:27–55.21.Dennehy PH.Active immunization in the United States:develop-ments over the past decade.Clin Microbiol Rev2001;14:872–908.32LU ET AL. J Pediatr Gastroenterol Nutr,Vol.49,No.1,July2009。

毒理学概论

原则二，实验动物必须暴露于高剂量，这是发现对人潜在危害的必需的和可靠的方法。此原则是根据质反应的概念，随剂量或暴露增加，群体中效应发生率增加。
原则三，成年的健康(雄性和雌性末孕)实验动物和人可能的暴露途径是基本的选择选用成年的健康(雄性和雌性未孕)实验动物是为了使实验结果具有代表性和可重复性。这样可降低实验对象的多样性，减少实验误差。外源化学物以不同途径染毒，实验动物表现的毒性可有很大差异。因此，毒理学试验中染毒途径的选择，应尽可能模拟人接触该受试物的方式。
由被动毒理学向主动毒理学发展
毒理学评价将贯穿于新产品发现和开发的全过程，包括按GLP规范和不受GLP 规范的研究
早期－及时发现和淘汰因毒性不适用于进一步研究开发的化学物或化学结构，指导化学物合成，帮助选择先导化学物。
微型化自动化样品量少不受GLP约束
发现毒理学(discovery toxicology) 预测毒理学 (predictive toxicology) 硅上毒理学 (In Silico toxicology) 定量构效分析 (QSAR)
中毒 (poisoning，toxication )
是生物体受到毒物作用而引起功能性或器质性改变后出现的疾病状态。
不同化学物半数致死量的比较
物质名称动物途径 LD50(mg/kg)
乙醇氯化钠硫酸钠硫酸吗啡苯巴比妥钠 DDT 硫酸番木鳖碱尼古丁筒箭毒素河豚毒素二恶英肉毒毒素
毒理学研究的方法
一、实验室研究
生物学，化学，物理学，医学，数学等研究方法研究毒物的作用机理和作用强度
二、临床观察
中毒人群的临床治疗观察记录和志愿者试验观察
三、流行病学调查

解决轻微中毒方法英语作文

解决轻微中毒方法英语作文英文回答：Being slightly poisoned can be a concerning situation, but there are several methods to address it. First and foremost, it is important to identify the source of the poisoning and remove oneself from that environment. For example, if someone accidentally ingests a toxic substance, they should immediately stop consuming it and rinse their mouth with water. Additionally, they should seek medical attention as soon as possible to receive proper treatment and advice.Another method to alleviate the effects of mild poisoning is to drink plenty of water. Water helps to flush out toxins from the body and can aid in the recovery process. It is recommended to drink at least 8 glasses of water per day, especially when dealing with poisoning. In addition to water, consuming foods that are rich in antioxidants, such as fruits and vegetables, can also helpto detoxify the body.Furthermore, it is crucial to rest and allow the body to recover. Taking a break and getting enough sleep can help the body to heal and regain its strength. It is important to listen to one's body and give it the time it needs to recover fully. Engaging in activities that promote relaxation, such as meditation or deep breathing exercises, can also be beneficial in reducing the symptoms of poisoning.In conclusion, when faced with mild poisoning, it is essential to remove oneself from the source of poisoning, seek medical attention, drink plenty of water, consume antioxidant-rich foods, rest, and engage in relaxation techniques. By following these methods, one can effectively address the situation and aid in the recovery process.中文回答：轻微中毒可能会让人感到担忧，但是有几种方法可以解决。

化学农药的危害英语作文

化学农药的危害英语作文In the heart of the bustling town, where the sun bakes the streets and the air buzzes with the chatter of life, there lies a secret that's as silent as a whisper but as loud as a thunderclap. It's the tale of the chemical pesticides, the modern-day knights in shining armor that promise to protect our crops from the menacing hordes of pests. But, what if I told you that these knights have a dark side?Picture this: a field of corn, tall and proud, swaying gently in the breeze, a golden sea under a cerulean sky. But, as the sun sets and the shadows grow long, the true cost of our protection becomes apparent. The chemical pesticides, once hailed as heroes, are now revealed to be the villains of our story.The first act of villainy is the silent war they wage against the ecosystem. These pesticides don't discriminate; they're the indiscriminate assassins of the insect world. While they may target the pests that feast on our crops, they also take down the pollinators, the bees and butterflies that dance through the fields, spreading life and color. They're the unsung heroes of our food chain, and yet, they fallvictim to the chemical onslaught.The second act is the slow poisoning of our land and water. Chemical pesticides, like a persistent stain, linger in the soil and seep into our waterways. They're the ghoststhat haunt our environment, refusing to leave even aftertheir job is done. They disrupt the delicate balance of nature, altering the very fabric of our ecosystem.But let's not forget the third act, the one that hits closest to home. The residue of these pesticides finds itsway onto our food, the very sustenance that is meant tonourish us. It's like inviting a Trojan horse into our kitchens, a silent invader that can cause long-term health issues, from neurological disorders to cancer.So, what's the punchline to this joke? It's that we've been laughing at the wrong thing all along. The real joke ison us, as we continue to rely on these chemical pesticides without fully understanding the consequences. But fear not,for there is a twist in this tale. The rise of organicfarming and the use of natural pest control methods offer a glimmer of hope, a chance to rewrite the ending of this story.In the end, it's not about choosing sides but aboutfinding a balance. It's about recognizing the need for protection while also respecting the harmony of nature. It's about laughing at the right things and crying over the wrong ones. And who knows? Maybe, just maybe, we can turn thevillain into a hero once more, with a little bit of humor and a whole lot of heart.。

解决轻微中毒方法英语作文

解决轻微中毒方法英语作文英文回答：Mild poisoning.Mild poisoning is a condition that occurs when a person has ingested a small amount of a toxic substance. The symptoms of mild poisoning can vary depending on the typeof substance that was ingested, but they may include nausea, vomiting, diarrhea, abdominal pain, and headache. In some cases, mild poisoning can also cause more serious symptoms, such as difficulty breathing, seizures, and coma.If you think that you or someone you know has been poisoned, it is important to seek medical attention immediately. The sooner treatment is started, the betterthe chances of a full recovery.There are a few things that you can do to help treat mild poisoning at home while waiting for medical help toarrive. These include:Activated charcoal: Activated charcoal is a substance that can help to absorb toxins from the stomach. It is available over-the-counter in most pharmacies.Ipecac syrup: Ipecac syrup is a medication that can be used to induce vomiting. This can help to remove toxins from the stomach.Laxatives: Laxatives can help to move toxins through the intestines and out of the body.Plenty of fluids: It is important to drink plenty of fluids to help flush toxins out of the body.It is important to note that these treatments are only for mild poisoning. If you or someone you know is experiencing more serious symptoms, such as difficulty breathing, seizures, or coma, it is important to seek medical attention immediately.中文回答：轻微中毒。

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c
Clonidine: Pharmacodvnamics Pathophvsiology and
Clonidine is an imidazoline with central and peripheral effects. Related to oxymetazoline, tetrahydrozoline, naphazoline, and xylometazoline, clonidine was marketed initially as a topical nasal decongestant in 1962 because of its vasoconstrictive properties. Later, it was found to have a potent antihypertensive effect that was mediated by the central nervous system.4 Subsequently, adrenergic receptor studies elucidated clonidine’s role as an Qadrenergic agonist. Alpha,-adrenergic receptors are found in a variety of tissues within the central and peripheral nervous system. In the brainCLONIDINE POISONING / JAMES F. WILEY II
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CLONIDINE POISONING I JAMES F. WILEY II
stem, clonidine produces inhibition of norepinephrine release.13J4 The result is a reduction in sympathetic tone that is centrally mediated and produces decreased heart rate, blood pressure, lethargy, coma, and miosis. Clonidine stimulation of a,-adrenergic receptors in the hypothalmus increases growth hormone secretion.ij In the spinal cord, clonidine binding leads to analgesia and decreased sympathetic outflow.5 The peripheral effects of clonidine are complex and center on vascular smooth muscle.16 Clonidine binding at presynaptic a,-adrenergic receptors reduces vasomotor tone that complements the central sympatholytic effect, especially at therapeutic doses. Binding at postsynaptic receptors in other blood vessels produces vasoconstriction, although in therapeutic doses, clonidine’s central action overshadows this effect. However, after large overdose, hypertension and pallor may occur, especially in patients with renal insufficiency who have decreased ability to excrete clonidine.l7Js Clonidine toxicity produces clinical findings that are remarkably similar to opiate overdose. The following support a shared mechanism of action between these drug classes: the use of clonidine as a successful agent in ultrashort opiate detoxification,a the improvement after naloxone administration in some patients poisoned by clonidine,l%* and the decrease in density of central a,-adrenergic receptors found in heroin addicts postmortem.i9 One attractive theory suggests that clonidine promotes the action of endorphins and enkephalins. Proposed mechanisms include increased endogenous opiate secretion mediated through aa-adrenergic binding in the brainstem, increased secretion as part of a stress response to clonidine’s toxic effects, or inhibition of endogenous opiate breakdown.*0,21 The recent discovery of imidazoline receptors in a variety of tissues and animal species adds further knowledge about the pharmacodynamic actions of clonidine. These receptors, like a,-adrenergic receptors, also are located in the ventrolateral medulla in humans. Clonidine binding at these receptors reduces blood pressure independent of ozadrenergic effects. Furthermore, the existence of an endogenous substance with imidazoline receptor affinity has been confirmed.** This information suggests that actions beyond the adrenergic system mediate clonidine’s pharmacological effects. This point is pertinent to the inconsistent response patients have had to various therapies for clonidine toxicity that are aimed at the central a!,-adrenergic receptor.
Clonidine IsThere Poisoniniley II, MD,FAAP, F. FACMT
HARTFORD, CONNECTICUT
LONIDINE INTOXICATION remains a significant problem in pediatric emergency care, accounting for approximately 0.1% of reported poisonings. Clonidine exposure frequently results in hospital and intensive care unit admission.1-3 Clonidine still has many therapeutic uses, such as control of hypertension, augmentation of spinal anesthesia, moderation of menopausal flushing, smoking cessation, ultrashort opiate detoxification, and treatment of behavior disordersb-lo Recently, the use of clonidine in children to manage aggressive behavior, Tourette’s syndrome, and attention deficit-hyperactivity disorder has been associated with an increased incidence of pediatric clonidine poisoningi Children are most susceptible to the toxic effects of clonidine. Ingestion of only 0.1 mg, or 1 clonidine tablet, has been associated with life-threatening symptoms.l* This report provides a review of the current knowledge of clonidine toxicity, with focus on clinical manifestations and effectiveness of potential therapies for clonidine intoxication.