Toxicology, Environmental Health, and the “One Health” Concept

The One Health concept promotes collaboration among veterinarians, physicians, scientists, and other professions to promote human, animal, and ecosystem health. One Health illustrates the interconnectedness and interdependence of human, animal, and ecosystem health. This concept has traditionally focused on zoonoses that are infectious diseases, not on chemical- or poison-related illnesses in animals and their relationship to the detection and prevention of human illness. The purpose of this article is to describe key experiences of scientists in the Health Studies Branch within the National Center for Environmental of Health of the Centers for Disease Control and Prevention in which the study of animal illness facilitated a public health investigation into an outbreak of chemicalassociated human disease. The experiences highlight how utilizing the One Health approach may improve chemical-associated outbreak investigations and facilitate appropriate intervention strategies. An appropriate One Health approach in toxicology and environmental health in outbreak settings should include consideration of the common environments and food sources shared by humans and animals and consideration of the potential for contaminated animal products as food sources in human exposures.     

Pharmacology and Toxicology of Herbs

S11StudiesontoxicityofChinesemedicines anddecreasedvirulencethroughthecompatibili tyofherbalingredients LIPeng Tao(CST)(BeijingUniversityofTraditionalChineseMedicine,Beijing100029,China)Beginningfromthereportoftherenalinjuryin ducedbyaristolochicacid,thepoisonoussideeffects ofChinesemedicineshaveattractedmoreandmoreat tentions,whichhaveproducedhugeinfluenceontheprogressoftraditionalChinesemedicines.Itbecomesa vitallyimportantissuetounderstandanduseChinese medicinescorrectly.Thetoxicity…     

Clinical Toxicology, Pharmacology and Therapeutic Study

P21EffectofBupleuriradix(BR)extractsonthetoxicityof5fluorouracilinnormalhuman lymphocytesandhepatomacelllines(HepG2/Hep3B)SJKANG,HDWOO,JYCHOI,YJLEE,HW CHUNG(SchoolofPublicHealth,SeoulNationalUniversity28Yonkon dong,Chongro ku,110460,Seoul,Korea;E mail:chunghw@snu.ac.kr)5Flourouracil(5FU)isoneofwellknownanti cancerdrugs,butitstoxicityinnormallymphocytesre mainsamajorprobleminchemotherapy.Theeastern traditionaldrug,Bupleuriradix(BR),hasbeenused forthetreatmentofliverdiseases…     

Cardiovascular effects of agmatine,a “clonidine-displacing substance”, in conscious rabbits

Agmatine has been identified as a clonidine-displacing substance in extracts from bovine brain. We studied its effect on cardiovascular regulation and the role played in this effect by ₂-adrenoceptors.In conscious rabbits, agmatine 10 g kg^–1 injected intracisternally (i.e.) caused no change, whereas agmatine 30, 100 and 300 g kg^–1 i.e. increased renal sympathetic nerve firing, the plasma concentration of noradrenaline and adrenaline and arterial blood pressure. Heart rate tended to be decreased. Yohimbine 1.5 g kg^–1 i.e. caused no change, whereas yohimbine 5, 15 and 50 g kg^–1 increased renal sympathetic nerve activity, the plasma concentration of noradrenaline and adrenaline, blood pressure and heart rate. In rabbit brain cortex slices preincubated with [³H]-noradrenaline, agmatine 1 to 100 M did not modify the electrically evoked overflow of tritium (either 4 pulses at 100 Hz or 36 pulses at 3 Hz). The evoked overflow was reduced by 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK 14304) 0.03 to 30 nM (4 pulses at 100 Hz), and this inhibition was not affected by agmatine 10 and 100 M. Agmatine did not change the basal efflux of tritium.The results show that agmatine, like yohimbine, causes central sympathoexcitation when given i.e., but agmatine differs from yohimbine in that it does not increase heart rate. Agmatine acts neither as an agonist nor as an antagonist at the ₂-autoreceptors in rabbit brain cortex. ₂-Adrenoceptors, therefore, are probably not involved in its cardiovascular effects. An action at imidazoline receptors in the medulla oblongata or some other hitherto unknown mechanism may be responsible for the sympathoexcitation.     

Synthesis,Stability, and Anti-Tumour Activity of a New Category of “Stapled” Antisense Oligonucleotides with Stimuli-Responsive Feature

The development of nucleic acid drugs with unique structures and mechanisms has stimulated great research interest. Herein, we report a general strategy to construct “stapled” structures of single-stranded antisense oligonucleotides (ASONs) with a stimuli-responsive feature. “Stapled” cyclic structures can be synthesized with reactive bifunctional handles that react with thiol groups of phosphorothioate (PS)-modified ASONs, and can be alternatively adjusted depending on the desired PS sites in the ASON strand. The disulphide group in the stapled handle can be cleaved in the reducing microenvironment of tumour cells. Thus, “stapled” ASONs may be transformed back to a linear conformation to facilitate binding to target mRNAs. Stapling conferred protection against degradation, and enhanced anti-tumour activity compared to linear counterparts. This study provides a new, effective, and convenient strategy for designing ASONs with “stapled” structures, and also adds a further contribution to facilitate the stability and biological efficacy of novel nucleic acid-based therapeutics.     

“Medicamentation” of society, non-diseases and non-medications: a point of view from social pharmacology

This review presents the definition and goals of social pharmacology, a new branch of clinical pharmacology, investigating relationships between drugs and society through the example of medicamentation, defined as the use of drugs for social problems previously not requiring drug utilisation (ageing, smoking cessation, vigilance troubles, sleep synchronisation, loss of libido, etc.). The involvement of the different actors from our society (patients, physicians, pharmaceutical industries, clinical pharmacologists, regulatory agencies, etc.) in this phenomenon is also discussed.     

“You Can’t Always Get What You Want” – Linearity as the Golden Ratio of Toxicology

Referring to the Golden Ratio (i.e. expressed in the Fibonacci sequence) in nature and art, we conclude that toxicology knows its own Golden Ration, namely linearity. The latter seems imposed on pharmaco-toxicological processes that in fact show far more complexity than simple linearity could hope to elucidate. Understanding physiological and pharmaco-toxicological processes as primarily linear is challenged in this contribution based on very straightforward principles and examples.     

Oral bioavailability of phenobarbital: a comparison of a solution in myvacet 9‐08, a suspension, and a tablet

Purpose: A threeway crossover study with seven healthy male volunteers was conducted to determine the relative bioavailability of phenobarbital after single dose administration of 100 mg of phenobarbital as oral solution in Myvacet 908, and as a suspension, compared with a 100 mg phenobarbital tablet. Materials and methods: At 4week intervals each subject received the solution in Myvacet 908, the suspension and the tablet in randomized order. Blood samples were collected for 48 h after each dose for analysis of phenobarbital. From the individual serum concentrationversustime curves C _maxand T _max were determined and AUC₀₄₈ was calculated. Results: All three oral dosage forms of phenobarbital are bioequivalent. No significant diffences in T _maxwere observed. Conclusion: The oral solution in Myvacet 908, and the suspension of phenobarbital proved to be bioequivalent to a tablet.     

“Locus of Control” as a Therapeutic Facet

We examined the relationship of HIV serostatus to drug use profile, high risk behavior, drug treatment status, and demographic characteristics of 505 intravenous drug users (IVDUs) in San Francisco. We found five identifiable drug-injection profiles described as Omnijector, Primarily Heroin, Primarily Heroin/Cocaine, Primarily Cocaine, and Primarily Speed which fell into “higher risk” and “lower risk” categories in relation to HIV seroprevalence of members (17.0 and 9.8%), respectively. This difference was not significant when effects of race were held constant (adjusted OR = 1.66,95% CI - 0.91,3.01). In logistic regression analysis, only Black race and age under 30 were significant predictors of HIV seropositivity (OR = 2.95,95% CI = 1.57,5.52 and OR = 2.05,95% CI = 1.01, 4.13, respectively). Neither membership in higher risk profile nor frequency of injection (including daily or greater injection of cocaine) contributed to the model. We conclude that Black IVDUs under 30 are at greatest risk of HIV infection, that multiple patterns of drug use injection and habituation require additional resources to treat, and that the heterogeneous distribution of HIV weakens the predictive power of known behavioral risk factors in this population.     

Search of anti-allodynic compounds from Plantaginis Semen,a crude drug ingredient of Kampo formula “Goshajinkigan”

Journal of Natural Medicines - Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is...