Protocol of Investigation on Sudden Death at Autopsy, Including Molecular, Genetic and Toxicology Testing

The role of the autopsy: 1) Whether the death is ascribable to a natural or unnatural cause and when natural, if cardiac or extra-cardiac;2) The nosology of the cardiac diseases and the mechanism of cardiac death, whether arrhythmic or mechanical;3) If the cardiac disease is inherited, screening and counselling of the next of kin is required. About 30% of sudden deaths is ascribable to genetically determined morbid entities, mostly transmissible with the autosomal dominant pattern of inheritance, so that 50% of the first degree relatives are genetically affected (“carriers”) and exposed at risk;4) If toxic or illicit drug abuse was involved.

The value of toxicological analysis in acute poisoning patients with uncertain exposure histories:a retrospective and descriptive study from an institute of poisoning

BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison exposure.The aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis perspective.METHODS:This was a retrospective and descriptive study from an institute of poisoning.Patient registration information and test reports spanning the period from April 1,2020 to March 31,2022,were obtained.Patients with uncertain exposure histories and who underwent toxicological analysis were included.Clinical manifestations and categories of toxics were analyzed.RESULTS:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

Advances in Pharmacology and Toxicology of Marine

The natural alkaloids extracted from Chinese herbal medicine have shown high medicinal value in vivo and in vitro, such as bacteriostasis, anti-virus, anti-tumor and anti-inflammation. This paper focuses on matrine and reviews its action mechanism and toxicological action. It is concluded that the medicinal prospect of matrine is very broad, but more basic research and clinical trials are needed for more comprehensive evaluation.

A perspective on molecular and cellular biology-based developmental toxicology biomarkers

The process of development is intricate and couple-dependent phenomenon.Accordingly,the study of molecular and cellular biology-based developmental toxicology biomarkers increasingly is becoming an important part of risk assessment and management of chemicals for detection of health outcomes and/or biological endpoint like cytotoxicity,cell death,etc.Since,the evolution of developmental toxicology field a number of tools/markers have been developed or addressed to deal with developmental outcomes,which can ultimately be used for the development of adverse outcome pathways(AOPs)of developmental toxicants.As a result,this paper provides an overview of the current state of developmental toxicology biomarkers and describes the strategies used in the selection and evaluation of such biomarkers in the context of developmental toxicity studies.Here,we discuss about the biological markers that are directly linked to developmental toxicity with respect to future revolutionary perspectives.Additionally,this chapter will address different associated outcomes of developmental exposure by intriguing advance techniques.The discussion focuses on the challenges associated with the development of biomarkers for developmental toxicity and highlights some of the recent advances in this area.Finally,the chapter concludes with a brief discussion of the future prospects for the use of molecular and cellular biology-based developmental toxicity biomarkers.Hope the present state of the art will provide a succinct summary of recent developments of biomarkers of developmental toxicology.

The application of omics technologies to toxicology

The application of omics technologies,including genomics,transcriptomics,proteomics and metabolomics,has the potential to revolutionize toxicology by providing a more comprehensive understanding of the molecular mechanisms of toxicity,identifying potential biomarkers of exposure or effect,and enabling personalized risk assessments for individuals.Each omics approach has its own challenges,including data analysis and interpretation,but the integration of multiple omics approaches can provide a more comprehensive understanding of toxicity.The use of omics technologies for personalized risk assessments can inform targeted interventions and improve public health outcomes.While challenges remain,the potential benefits of omics technologies in toxicology make it an exciting area of research for the future.

Pharmacokinetics and toxicology of therapeutic proteins:Advances and challenges

Significant progress has been made in understanding pharmacokinetics (PK),pharmacodynamics (PD),as well as toxicity profiles of therapeutic proteins in animals and humans,which have been in commercial development for more than three decades.However,in the PK arena,many fundamental questions remain to be resolved.Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans,and from in vitro assays to in vivo readouts,which would ultimately lead to a higher success rate in drug development.In toxicology,it is known,in general,what studies are needed to safely develop therapeutic proteins,and what studies do not provide relevant information.One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity.In this review,we will highlight the emerging science and technology,as well as the challenges around the pharmacokinetic-and safety-related issues in drug development of mAbs and other therapeutic proteins.

Health Impacts and Mechanisms of Per- and Polyfluoroalkyl Substances (PFAS) from Epidemiological to Toxicological

This research provides a comprehensive analysis of the health impacts of Per- and Polyfluoroalkyl Substances (PFAS) through an integration of epidemiological and toxicological studies. The study identifies significant correlations between PFAS exposure and adverse health outcomes, including thyroid dysfunction, elevated cholesterol levels, and increased risk of specific cancers. Utilizing a mixed-methods approach, the research combines a systematic review and meta-analysis of recent literature with in vitro and in vivo toxicological experiments. The epidemiological analysis reveals increased risks of thyroid dysfunction, cholesterol elevation, and certain cancers among PFAS-exposed individuals. Toxicological findings further corroborate these results, showing dose-dependent cytotoxic effects in human cell lines and endocrine disruption in rodent models. The study emphasizes the importance of regulatory measures to mitigate PFAS exposure and the urgent need for more comprehensive research into their long-term effects. The integration of epidemiological and toxicological data underscores the significant health risks posed by PFAS, highlighting the necessity of immediate action to limit exposure and develop safer alternatives.

The peptide fraction of Bothrops jararaca snake venom induces toxicological effects on the male reproductive system after local envenomation in mice

Bothrops envenomation is complex and provokes prominent local tissue damage and systemic disturbances,but little is known about their effects on the male reproductive system.After intratesticular injection,the bioactive peptide fraction(Bj-PF)obtained from Bothrops jararaca snake venom changes the structure of different stages of the seminiferous epithelium cycle in adult mice.For the first time,we investigated whether local envenomation of Bj-PF induces toxicological effects on the male reproductive system,particularly on the seminiferous epithelium and Sertoli cells.Male adult mice were treated with 0.24 mg.kg^(-1) by intramuscular(i.m.)injection for 24 h.The testes samples were collected for morphological and morphometric evaluation.The toxicological effects of Bj-PF were also analyzed on mitochondrial metabolism and nitrite(NO2)production in 15P-1 Sertoli cell culture.Bj-PF changed the structure and function of the seminiferous epithelium,particularly the disruption of the epithelium and the presence of degenerated germ cells in the adluminal compartment,but there were no alterations in the basal compartment.Bj-PF increased the thickness of the seminiferous epithelium and decreased the lumen diameter of the tubule.Semiquantitative histological assessment of the degree of tubule degeneration revealed that Bj-PF also increased the number of hypospermatogenic tubules compared to control.Bj-PF reduced NO2 levels in 15P-1 Sertoli cells without changing the mitochondrial metabolism.Overall,the fact that Bj-PF alters the structure and function of the seminiferous epithelium suggests that bioactive peptides found in B.jararaca snake venom can have toxicological effects on the reproductive systems of affected male mice,providing new insight into the biological characteristics of snake venom and therapeutic strategies for envenomation inflammation.

Toxicological Assessment of Irvingia gabonensis Leaf Extracts in Albino Rats: A Comparative Study between Aqueous and Ethanol Extraction Methods

Background: This study aimed to assess the toxicity of Irvingia gabonensis leaf extracts in albino rats and investigate their effects on body weight, liver function parameters, and renal function parameters. The research specifically compared the outcomes of aqueous and ethanol extraction methods. Methods: Acute toxicity was evaluated by administering a single oral dose of Irvingia gabonensis leaf extracts to rats and monitoring them for 24 hours and during a 14-day observation period. Sub-acute toxicity was assessed through a 28-day administration of the leaf extract. Body weight changes, liver function parameters, and renal function parameters were measured and compared among treatment groups. Results: No signs of toxicity or mortality were observed in rats treated with Irvingia gabonensis leaf extracts obtained through either aqueous or ethanol extraction methods. The calculated lethal dose required to cause mortality in 50% of the tested animals (LD50) exceeded 5000 mg/kg body weight. Oral administration of the leaf extract at doses of 400 and 800 mg/kg body weight did not induce any observable signs of toxicity or adverse effects during the 28-day study period. Male and female albino rats treated with the leaf extract showed significant weight gains compared to the control group. Higher doses (800 mg/kg) of both aqueous and ethanol extracts led to increased levels of total protein, albumin, and globulin in male albino rats, with the ethanol extract exhibiting a more pronounced effect. The administration of the ethanol extract, particularly at the lower dose (400 mg/kg), resulted in decreased levels of liver enzymes (AST, ALT, and ALP), suggesting potential liver protective properties. Additionally, bilirubin levels, a marker of liver dysfunction, were significantly reduced in all treatment groups, with the lowest levels observed in the groups receiving higher doses of both aqueous and ethanol extracts. The administration of Irvingia gabonensis leaf extracts did not significantly affect renal function parameters in both male and female albino rats. Conclusion: Irvingia gabonensis leaf extracts obtained through aqueous and ethanol extraction methods showed no acute or sub-acute toxicity in albino rats. The extracts demonstrated potential beneficial effects on liver function parameters, particularly at higher doses. However, further research is needed to validate these findings and determine the optimal dosage for potential therapeutic applications in humans.

Research advances in phytochemistry,pharmacology and toxicology of oleanolic acid

Oleanolic acid(OA)is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1.OA is widespread in traditional Chinese herbal medicine(Ligustri Lucidi Fructus,Achyranthis Bidentate Radix,Red Sage)and berries(blueberries,grapes).In recent years,because of the extensive pharmacological effects of OA,its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers.OA has effective therapeutic effects on a series of chronic diseases such as inflammation,cancer,diabetes,and cardiovascular diseases through multiple signaling pathways and various targets.Especially in cancers,such as colorectal cancer,liver cancer,gastric cancer,lung cancer,breast cancer and other malignancies,OA presents substantial efficacy.However,its poor aqueous solubility,needy bioavailability,and unsatisfactory pharmacological activity excessively restrict its clinical application.More importantly,the improper utilization of OA can cause adverse reactions,toxic effects and even damage to organs in some specific situations.With the discovery of various pharmacological effects,the complex action mechanisms of OA,the continuous progress in structural modification of OA,as well as the synthesis of OA derivatives,its application is expanding gradually.Among numerous studies,there is a clear indication that OA and its derivatives,if fully developed,may provide an alternative and cheaper treatment for a variety of chronic diseases.However,the specific molecular mechanisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer,diabetes,cardiovascular disease and other chronic diseases remain to be clarified.Therefore,it is necessary to further study the pharmacokinetics,pharmacological activity,specific targets and related mechanisms of OA to lay a solid foundation for drug development and the application of OA in clinical settings.

Source,migration,distribution,toxicological effects and remediation technologies of arsenic in groundwater in China

Groundwater with high arsenic(As) content seriously threatens human life and health. Drinking high-As groundwater for a long time will lead to various pathological changes such as skin cancer, liver cancer,and kidney cancer. High-As groundwater has become one of the most serious environmental geological problems in China and even internationally. This paper aims to systematically summarize the sources,migration, distribution, toxicological effects, and treatment techniques of As in natural groundwater in China based on a large number of literature surveys. High-As groundwater in China is mainly distributed in the inland basins in arid and semi-arid environments and the alluvial and lacustrine aquifers in river deltas in humid environments, which are in neutral to weakly alkaline and strongly reducing environments.The content of As in groundwater varies widely, and As(Ⅲ) is the main form. The main mechanism of the formation of high-As groundwater in China is the reduced dissolution of Fe and Mn oxides under the action of organic matter and primary microorganisms, alkaline environment, intense evaporation and concentration, long-term water-rock interaction, and slow groundwater velocity, which promote the continuous migration and enrichment of As in groundwater. There are obvious differences in the toxicity of different forms of As. The toxic of As(Ⅲ) is far more than As(V), which is considered to be more toxic than methyl arsenate(MMA) and dimethyl arsenate(DMA). Inorganic As entering the body is metabolized through a combination of methylation(detoxification) and reduction(activation) and catalyzed by a series of methyltransferases and reductases. At present, remediation methods for high-As groundwater mainly include ion exchange technology, membrane filtration technology, biological treatment technology, nanocomposite adsorption technology, electrochemical technology, and so on. All the above remediation methods still have certain limitations, and it is urgent to develop treatment materials and technical means with stronger As removal performance and sustainability. With the joint efforts of scientists and governments of various countries in the future, this worldwide problem of drinking-water As poisoning will be solved as soon as possible. This paper systematically summarizes and discusses the hot research results of natural high-As groundwater, which could provide a reference for the related research of high-As groundwater in China and even the world.

Analysis of Toxicological Test Results of 580 Detergents

To evaluate the safety of detergents,the toxicological test results of 580 collected detergents were analyzed.The results showed that,in the acute oral toxicity test,94.4%and 5.6%of the samples were classified as non-toxic and toxic respectively.In skin irritation test,95.1%of the samples were mild irritation or below,and 4.9%were moderate irritation or above.In the vaginal mucosa irritation test,79.0%of the samples were very mild irritation or below,while 21.0%were mild irritation or above.In the acute inhalation toxicity test,the proportion of the samples classified as actually non-toxic and toxic were 87.9%and 12.1%respectively.In the eye irritation test,95.7%of the samples belonged to mild irritation or below,and 4.3%of the samples belonged to moderate irritation or above.The products at risk in category A,B and C products account for 6.3%,7.7%and 14.2%respectively.Of the 580 tested samples,90.9%were relatively safe,while 9.1%were at risk.These data showed that most of the tested samples meet the safety requirements for use.

Taxonomical outlines of bio-diversity of Karnataka in a 14th century Kannada toxicology text Khagendra Mani Darpana

Origin of ancient Indian toxicology can be dated back to vedic literature.Toxins of both animate and inanimate world were very well understood during the era.Rig and Atharva vedic texts describe such details.After classifying such toxins,Charaka Samhitha,thebasic literature of Indian Medicine used gold and ghee as panaceas to counter act them.Ayurveda considers toxicology as one among the eight specialized branches of medical wisdom.Unfortunately,the available literature on this is very limited.Moreover,they have been discussed briefly in Charaka and Sushrutha Samhitha.Mangarasa I,a Jain scholar who lived on the foothills of the Western Ghats,in Southern India in 1350 A.D.,felt this vacuum and composed an independent,elaborate Kannada text on toxicology.His less known text Khagendra Mani Darpana(KMD)is the first ever documented complete text on toxicology in the world.Medieval Indian wisdom on plant and animal diversities are very well reflected in this unique toxicological text.Centuries past to Linnean era,KMD gives vivid descriptions on zoological and botanical diversities of the time.This astonishing fact is an evidence of our ancestor's curiosities about the nature around them.A critical overview of the bio-diversity described in KMD text is discussed in this paper.

Review on pharmacological and toxicologyical effects of oleum azadirachti oil

Oleum azadirachti consists of the oil obtained from dried seeds of Azadirachta indica A.Juss.(family:Meliaceae).Local names of Azadirachta indica A.Juss.are Abodua,aforo-oyinbo,anwe egyane,arista,azad dirakht,azadarakht,azedarach and bead tree.Indigenous to India,and widely distributed in South and South-East Asia and cultivated in Africa,the South Pacific Islands,South and Central America and Australia,and in southern Florida and California,United States of America,it is a straight-boled deciduous tree,which is 6-25 m high.Bark is dark-brown,externally fissured with a buff inner surface and fibrous fracture,Leaves alternately arranged,pinnately compound and up to 40 cm long,and composed of 8-18 short-petiolate narrow-ovate,pointed and curved toothed leaflets,3-10 cm long and 1-4 cm wide arranged in alternate pairs.The major constituents are oxidized tetranortriterpenes including azadirachtin(azadirachtin A),azadiriadione,epoxyazadiradione,azadirone,nimbidin,nimbin,deacelylnimbin,salannin,gedunin,mahmoodin,17-hydroxydiradione and related derivatives.It is of various medicinal uses,such as a contraceptive for intravaginal use,a mosquito repellent,and treatment of vaginal infections,treatment of gastric ulcers,cardiovascular disease,malaria,rheumatism and skin disorders,external applications for treatment of septic wounds,ulcers and boils,treatment of allergic skin reactions,asthma,bruises,colic,conjunctivitis,dysmenorrhoea,fever,gout,headache,itching due to varicella,kidney stones,leukorrhoea,psoriasis,scabies,sprains and muscular pain,and wounds.It is also used as an emmenagogue.tonic,stomatic and vermicide.In conclusion,the plant oil had antifertility,antihyperglycaemic,anti-inflammatory,antimicrobial,antiviral,antiulcer,estrogenic,immune,contraceptive,autibacterial,insect repellent,and skin treatment effects.

A perspective on toxicology of Conus venom peptides

The evolutionarily unique and ecologically diverse family Conidae presents fundamental opportunities for marine pharmacology research and drug discovery.The focus of this investigation is to summarize the worldwide distribution of Conus and their species diversity with special reference to the Indian coast.In addition,this study will contribute to understanding the structural properties of conotoxin and therapeutic application of Conus venom peptides.Cone snails can inject a mix of various conotoxins and these venoms are their major weapon for prey capture,and may also have other biological purposes,and some of these conotoxins fatal to humans.Conns venoms contain a remarkable diversity of pharmacologically active small peptides;their targets are an iron channel and receptors in the neuromuscular system.Interspecific divergence is pronounced in venom peptide genes,which is generally attributed to their species specific biotic interactions.There is a notable interspecific divergence observed in venom peptide genes,which can be justified as of biotic interactions that stipulate species peculiar habitat and ecology of cone snails.There are several conopeptides used in clinical trials and one peptide(Ziconotide) has received FDA approval for treatment of pain.This perspective provides a comprehensive overview of the distribution of cone shells and focus on the molecular approach in documenting their taxonomy and diversity with special reference to geographic distribution of Indian cone snails,structure and properties of conopeptide and their pharmacological targets and future directions.

Assessment of toxicology knowledge in the fourth-year medical students:Three years of data

BACKGROUND:Pharmacology and toxicology are core content knowledge for physicians.Medical students should demonstrate understanding of general pharmacology and basic treatment of poisoning.The objective of this study was to measure the knowledge of the 4th-year medical students(MS4)on these topics over 3 years.METHODS:A multiple-choice exam(15 questions)was administered to MS4 students in spring of 2010,2011,and 2012.Questions were developed by medical toxicologists to evaluate basic knowledge in three areas:pharmacologic effects(PE),treatment of poisoning(TOP),and pharmacokinetics(PK).The students were grouped by intended specialtiesinto pharmacologic intense(anesthesia,emergency medicine,internal medicine,pediatrics,and psychiatry),less pharmacologic intense specialties(dermatology,OB/GYN,ophthalmology,pathology,physical medicine and rehabilitation,radiology,and surgery)and by completion of a pharmacology or toxicology elective.Mean group scores were compared using ANOVA.RESULTS:Totally 332 of 401(83%)students completed the survey.Mean scores were stable over the three years,higher for students completing a toxicology rotation and for students entering a pharmacologically intense specialty.CONCLUSION:The external validity is limited to a single medical school with incomplete participation and content was limited by the survey length.Consistent results over the three-year period and correlation of performance with completing a toxicology rotation and intent to enter a pharmacology intensive specialty suggest this survey may correlate with toxicology knowledge.Implementation of required core courses focused on toxicology may improve core content knowledge in fourth year medical students.

Genetic Toxicology of Lanthanum Trichloride in Mice

In the present paper, the damage ratio of mice medulla cells, which were fed on LaCl_3 treated food, was surveyed by imitating a biological chain of ecosystem. And it was attempted to provide the toxicological basis for the rational application of the rare earth elements.

STUDY OF PROPERTIES AND TOXICOLOGY OF MEDICAL ORGANIC SILICON GEL CRYSTALS

The authors perpared artifical crystals from silicon elastomer, which ensured medical purity, studied how to improve the light transmittance and the characteristics of moulding (sulfurization). This material has been applied to many clinical cases.

Chinese Journal of Pharmacology and Toxicology

Chinese Journal of Pharmacology and Toxicology(CJPT)started its publication in 1986.It is amonthly and distributed to readers both at home and abroad.This journal is collaboratiyely sponsored by the Chinese Pharmacological Society,the Chinfese Society of Toxicology and BeijingInstitute of Pharmacology and Toxicology.This journal focuses on the presentation of the latestfindings in the fields of pharmacology and toxicology in order to promote academic exchangesworldwide and steer this sphere of research forward.