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Oswald Schmiedeberg was born in one of the former Baltic provinces of Russia. He studied medicine in Dorpat (Tartu) and joined the Institute of Pharmacology of Rudolf Buchheim in Dorpat. After promotion (1866) and habilitation (1868), he succeeded Buchheim as director of the institute. During this time, he further developed the experimental methods leading to the improvement of pharmacological knowledge introduced by Buchheim. In 1872, he became director of the Institute of Pharmakologie of the newly founded Kaiser-Wilhelm University in Strasbourg. He held this position for over 42 years until the end of the World War 1 when all Germans had to leave the former Reichsland Elsass-Lothringen. He settled next to his friend and colleague Naunyn in Baden-Baden, where he died in 1921. Holmstedt and Liljestrand's (1963) History of Pharmacology and Toxicology noted, "Schmiedeberg was undoubtedly the most prominent pharmacologist of his time." He had about 120 pupils, about 40 of them occupied pharmacology chairs throughout the world. In the USA, John Jacob Abel, after his return to the USA, became the "father of American pharmacology". In 1873, Schmiedeberg, together with the pathologist Klebs (Prague) and the clinician Naunyn (Königsberg), founded the Archiv für experimentelle Pathologie und Pharmakologie. When Naunyn died in 1925, the periodical was named Naunyn–Schmiedeberg's Archiv, from volume 110 onwards. In 1969, the designation "experimental pathology" was dropped, since nearly all papers submitted for some time past dealt with pharmacology. In 1883, Schmiedeberg published the Grundriss der Arzneimittellehre, the later edits with the title Grundriss der Pharmakologie in Bezug auf Arzneimittellehre und Toxikologie. [ABSTRACT FROM AUTHOR]

Mechanistic models of hepatic clearance have been evaluated for more than 50 years, with the first author of this mini-review serving as a co-author of the first paper proposing such a model. However, published quality experimental data are only consistent with the first of these models, designated as the well-stirred model, despite the universal recognition that this model is physiologically unrepresentative of what occurs with respect to liver metabolism and transport. Within the last 3 years, our laboratory has recognized that it is possible to derive clearance equations employing the concepts of Kirchhoff's Laws from physics, independent of the differential equation approach that has been utilized to derive reaction rates in chemistry. Here we review our published studies showing that the equation previously believed to be the well-stirred model, when hepatic basolateral transporters are not clinically relevant, is in fact the general equation for hepatic clearance when only systemic drug concentrations are measured, explaining why all experimental data fit this equation. To demonstrate that the equations deriving the mechanistic models of hepatic elimination for the past 50 years are not valid, we show that when calculating Kpuu, the ratio of unbound drug concentration in the liver to the unbound concentration of drug in the systemic circulation, for the well-stirred, parallel tube and dispersion models, Kpuu surprisingly can never exceed 1 and is a function of FH, the hepatic bioavailability following oral dosing. We believe that knowledgeable drug metabolism scientist and clinical pharmacologist will agree that this outcome is nonsensical. [ABSTRACT FROM AUTHOR]

Hydrogenated pyrans are prevalent structural units existed in many biologically active compounds, capturing the attention of pharmacologists due to their potential therapeutic applications. Among various synthetic routes, the hetero‐Diels‐Alder (HDA) reaction stands out as a common and effective approach. The objective of this study was to employ HDA reaction in conjunction with the dehydrogenative oxidation strategy for saturated ketones to synthesize hydrogenated pyran compounds. Through systematic screening and optimization of reaction conditions, a convenient approach for the synthesis of multi‐substituted 2,3‐dihydro‐4H‐pyran compounds has been developed. Furthermore, a detailed mechanistic investigation has been performed to get a deep understanding of the reaction. [ABSTRACT FROM AUTHOR]

The integration of artificial intelligence (AI) into clinical pharmacology could be a potential approach for accelerating drug discovery and development, improving patient care, and streamlining medical research processes. We reviewed the current state of AI applications in clinical pharmacology, focusing on drug discovery and development, precision medicine, pharmacovigilance, and other ventures. Key AI applications in clinical pharmacology are examined, including machine learning, natural language processing, deep learning, and reinforcement learning etc. Additionally, the evolving role of clinical pharmacologists, ethical considerations, and challenges in implementing AI in clinical pharmacology are discussed. The AI could be instrumental in accelerating drug discovery, predicting drug safety and efficacy, and optimizing clinical trial designs. It can play a vital role in precision medicine by helping in personalized drug dosing, treatment selection, and predicting drug response based on genetic, clinical, and environmental factors. The role of AI in pharmacovigilance, such as signal detection and adverse event prediction, is also promising. The collaboration between clinical pharmacologists and AI experts also poses certain ethical and practical challenges. Clinical pharmacologists can be instrumental in shaping the future of AI-driven clinical pharmacology and contribute to the improvement of healthcare systems. [ABSTRACT FROM AUTHOR]

Cycloalkanols ring‐opening transformation is one of the most valuable and wide area of research. Among the numerous methods that have been developed, transition‐metal‐free approaches have attracted great interest from both chemists and pharmacologists. This is largely due to the advantages of being environmentally benign, cost‐effective and operationally simple. Here we provide a comprehensive outline on recent advances in the synthesis of distally substituted ketones and cyclic compounds via ring‐opening transformation of cycloalkanols under transition‐metal‐free conditions. [ABSTRACT FROM AUTHOR]

Publications in peer-reviewed journals are the most important currency in science. But what about publications in non-peer-reviewed magazines? The objective of this study was to analyze the publications of scientists, with a focus on pharmacologists, in the non-peer-reviewed German science magazine Biospektrum from 1999 to 2021. Biospektrum is edited by five scientific societies in Germany including the Society for Experimental and Clinical Society Pharmacology and Toxicology (DGPT) and provides opportunities to researchers to showcase their research to a broad audience. We analyzed 3197 authors of 1326 articles. Compared to the fields of biochemistry, microbiology, and genetics, pharmacology was largely underrepresented. Just three institutions in Germany contributed most papers to Biospektrum. Researchers with a doctoral degree were the largest author group, followed by researchers with a habilitation degree. Among all major fields, women were underrepresented as authors, particularly as senior authors. The Covid pandemic leads to a drop of publications of female first authors but not last authors. Compared to publications in the peer-reviewed journal Naunyn–Schmiedeberg's Archives of Pharmacology (Zehetbauer et al., Naunyn-Schmiedebergs Arch Pharmacol 395:39–50 (2022)), female pharmacologists were underrepresented in the Biospektrum. Thus, German pharmacologists as a group do not value investing in "social impact" gained by publications in Biospektrum, and this attitude is even more prominent among female pharmacologists. Investing less in "social impact" by female pharmacologists may result in reduced visibility on the academic job market and may contribute to reduced opportunities to achieve high academic positions. [ABSTRACT FROM AUTHOR]

Bacteriophages are bacterial viruses that are distributed throughout the environment. Lytic phages and prophages in saliva, oral mucosa, and dental plaque interact with the oral microbiota and can change biofilm formation. The interactions between phages and bacteria can be considered a portion of oral metagenomics. The metagenomic profile of the oral microbiome indicates various bacteria. Indeed, there are various phages against these bacteria in the oral cavity. However, some other phages, like phages against Absconditabacteria, Chlamydiae, or Chloroflexi, have not been identified in the oral cavity. This review gives an overview of oral bacteriophage and used for metagenomics. Metagenomics of these phages deals with multi-drug-resistant bacterial plaques (biofilms) in oral cavities and oral infection. Hence, dentists and pharmacologists should know this metagenomic profile to cope with predental and dental infectious diseases. [ABSTRACT FROM AUTHOR]

The growing spread of infections caused by multidrug-resistant pathogens makes the need of tailoring antimicrobial therapies by means of a 'patient-centered' approach fundamental. In this scenario, therapeutic drug monitoring (TDM) of emerging antimicrobial candidates may be a valuable approach, but expert interpretation of TDM results should be granted for making them more clinically useful. The MD Clinical Pharmacologist may take over this task since this specialist may couple PK/PD expertise on drugs with a medical background and may provide expert interpretation of TDM results of antimicrobials for tailoring therapy on real-time in each single patient based on specific both drug/pathogen issues and patient issues. This article aims to highlight the main key-points and organizational aspects for implementing a successful TDM-based expert clinical pharmacological advice (ECPA) program for tailoring antimicrobial therapies on real-time in different hospitalized patient special populations. TDM-based ECPA programs lead by the MD Clinical Pharmacologist may represent a way forward for maximizing clinical efficacy and for minimizing the risk of resistance developments and/or toxicity of antimicrobials. Stakeholders should be aware of the fact that this innovative approach may be cost-effective. [ABSTRACT FROM AUTHOR]

Copyright of Cappadocia Journal of History & Social Sciences is the property of CAHIJ and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided. [ABSTRACT FROM AUTHOR]

Introduction: Periodontitis is one of the most urgent problems of modern dentistry. The development of new paradigms and regimens of combination therapy of patients with periodontitis is a strategic task for pharmacologists and dentists. In view of this, pathomorphological examination is of high importance, since it allow us to conclude about the therapeutic effectiveness of the administered drugs with high objectivity. Aim of the study: to evaluate the effect of the composition of Soderm®-Forte and Cytoflavin® on the pathomorphological pattern of gum tissues of rats with experimental periodontitis (EP). Materials and Methods: EP was simulated in rats by ligature method. Study design: animals with intact periodontium; animals with untreated EP; animals with EP treated with traditional drug therapy (TDT); animals with EP treated with the combination of TDT and Soderm®-Forte gel; and animals with EP treated with the combination of TDT, Soderm®-Forte and Cytoflavin®. For pathomorphological examination, biopsy specimen was taken from the gingival margin of the lower incisors. Slides were stained with hematoxylin and eosin, as well as by Masson. Computer morphometry was performed using the ImageJ software. Results and Discusion: In EP, TDT has a moderate positive effect on pathomorphological changes in the gum. The combination of TDT and Soderm®-Forte and, to a greater degree, the combination of TDT, Soderm®-Forte and Cytoflavin® have high therapeutic efficacy, characterized by rapid regeneration of the gum tissues. Conclusion: The combination of TDT, Soderm®-Forte and Cytoflavin® in EP has a more pronounced therapeutic effect, manifested by early regression of pathological changes and acceleration of tissue regeneration in the gum. [ABSTRACT FROM AUTHOR]

The purpose of this article is the historical survey of the foundation and development of pharmacology in Tartu (Dorpat), Estonia. Pharmacology was founded in Tartu by Naunyn, Buchheim, and Schmiedeberg. Genealogy and biographies including selected references of pharmacologists and pupils, who acted from the very beginning to today as directors of the Department of Pharmacology, as well as its successor, the Institute of Pharmacology and Toxicology, are presented and commented. This history also illustrates the conditions that are important for the development of new scientific areas. It is not a central geographical location or a formal "center of excellence" with lots of financial resources but rather brilliant researchers with the right spirit and vision and academic freedom. The implications of the early history of pharmacology for the future of science are discussed. [ABSTRACT FROM AUTHOR]

Improved global access to novel age‐appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age‐appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children‐centric formulation design for new chemical entities, or to repurpose/reformulate off‐patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age‐appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however, the proposed paediatric Quality Target Product Profile could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product. [ABSTRACT FROM AUTHOR]

Covering: up to December 2021 Picrotoxane sesquiterpenoids are a special category of natural products known to have a picrotoxane skeleton and are characterised by a highly oxidised cis-hydrindene core, lactone rings, and epoxide functionalities. Ever since the first picrotoxane was isolated from Menispermum cocculus in the early 19th century, these compounds have long attracted the attention of natural product chemists, synthetic chemists, and pharmacologists for their particular structures and powerful biological activities. This review extensively summarizes a total of 132 naturally occurring picrotoxane sesquiterpenoids, taking into account their distributions, structural classifications, chemical and bio-synthetic researches, and bioactivities. It provides a comprehensive and in-depth perspective for further investigation on picrotoxane sesquiterpenoids. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Psicoterapia y Psicosomática is the property of Instituto de Estudios Psicosomaticos & Psicoterapia Medica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neuroscience did not suddenly become a global endeavor. This article examines the way neuroscience took shape in South Korea focusing on Chan-Woong Park, who launched the Korean Society for Neuroscience in 1992. Park was a pharmacologist who studied ginseng and the brain from the 1970s. By revealing the way Park noted both opportunity and difficulty in the interdisciplinarity of neuroscience, this article reveals the context in which interdisciplinarity shaped studies of the brain in South Korea. To date, historians have followed the flow of knowledge, embedded in materials or instruments, to understand the transnational development of science and technology. This article focuses on the flow of value—interdisciplinarity, per se—which mediated uncertainties in studying the brain and galvanized ignorance in the name of neuroscience. By revealing the materiality and locality of interdisciplinarity and its role in facilitating ignorance, the article sheds new light on the transnational development of neuroscience. [ABSTRACT FROM AUTHOR]

In the proposed review, the pharmacological profile of unique, rare, and unusual fatty acids derived from natural amides is considered. These amides are produced by various microorganisms, lichens, and fungi. The biological activity of some natural fatty acid amides has been determined by their isolation from natural sources, but the biological activity of fatty acids has not been practically studied. According to QSAR data, the biological activity of fatty acids is shown, which demonstrated strong antifungal, antibacterial, antiviral, antineoplastic, anti-inflammatory activities. Moreover, some fatty acids have shown rare activities such as antidiabetic, anti-infective, anti-eczematic, antimutagenic, and anti-psoriatic activities. For some fatty acids that have pronounced biological properties, 3D graphs are shown that show a graphical representation of unique activities. These data are undoubtedly of both theoretical and practical interest for chemists, pharmacologists, as well as for the pharmaceutical industry, which is engaged in the synthesis of biologically active drugs. [ABSTRACT FROM AUTHOR]

Commonly employed methods for reducing unwanted variation in pharmacology studies, such as data normalisation to baseline or control values, are suboptimal and potentially detrimental. This article highlights the value of using a technique called analysis of covariance (ANCOVA) to incorporate supplementary measurements in the analysis to improve the precision of the treatment comparisons and reduce the required sample size. This technique is not new, but unfortunately, it has been under‐utilised in the statistical analysis of pharmacological data. ANCOVA is an extension of the methods of analysis of variance (ANOVA) and simply requires that we take additional measurements that are statistically related to the response measurements but which are themselves unaffected by the treatments being studied. Most often, in pharmacological studies, these additional measurements would be the baseline or pre‐dose reading corresponding to the response measurement. As many pharmacologists routinely make use of baseline readings in their analysis through normalisation, this article describes a more appropriate method to account for the variation in the baseline readings. [ABSTRACT FROM AUTHOR]

At the individual patient level, the clinical pharmacologist could be involved in the resolution of several drug-related issues, which can vary from some advice regarding drug administration, to the choice of a drug in specific population subgroups, such as pregnant women. Recent years, particularly the COVID-19 pandemic, can be considered a turning point for pharmacovigilance and pharmacoepidemiology in terms of their role in drug safety and drug utilisation monitoring in clinical practice [[1]]. 32350861 24 Crescioli G., Lanzi C., Mannaioni G., Vannacci A., Lombardi N. Adverse Drug Reactions in SARS-CoV-2 Hospitalised Patients: A Case-Series with a Focus on Drug-Drug Interactions-Reply. In proactive and preventive approaches, the clinical pharmacologist could take part in the resolution/prevention of adverse reactions, cooperating with other healthcare professionals to improve the appropriateness of use of drugs and CAM products and to increase personalised medicine [[25]]. [Extracted from the article]

For instance, rather than elaborating on the technical details, the QSP scientist should communicate something such as "compared with the current practice, incorporation of the modeling and analysis could help reduce the needed time by 21%~25%" for nonmodeling decision makers. The rapidly evolving field of Quantitative Systems Pharmacology (QSP) calls for updated education curriculums and programs. In addition, a QSP scientist should also have a solid grasp in the principles of clinical pharmacology and pharmacokinetics (PK), including being able to understand and predict drug pharmacology using traditional, PK/pharmacodynamics-type modeling. [Extracted from the article]

A course on vaccine development asked students to write a blog addressing general anti‐vaccination strategies and their significance today, in the context of the resistance seen against novel SARS‐CoV‐2 mRNA vaccines. This perspective explores how and why these efforts are successful at reducing vaccine uptake and why, for the most part, efforts to combat the movement have been unsuccessful. This summary of the collective view of the class provides recommendations for combatting current and future campaigns of misinformation. It is hoped that this perspective will serve as a call to action for clinical pharmacologists and translational scientists to do their part to educate the lay community and promote the science in an open and transparent manner to ensure that current and future vaccines fulfill their potential. [ABSTRACT FROM AUTHOR]

Gertrude Belle Elion was a woman who had to overcome many difficulties to achieve her dream of studying to be able to cure illnesses, especially those of the heart. These difficulties were imposed both by the limited economic resources of herself and her family, which did not allow her to pay the academic fees of the university in which she wanted to enroll, as well as gender, since she also had to fight against inequalities of that type prevalent in the society of her time. However, and despite these obstacles, she managed to graduate in Chemistry, based on interest, effort and tenacity, and later began a research career full of successes, which led her to discover relevant active substances which allow her to be awarded the Nobel Prize in Physiology or Medicine in 1988. This article presents the most relevant features of her personal and professional life and completes previous biographies about her life. Its main objective is to reintroduce her to society and put her as a reference to other people. The methodology followed has been the search for those data about her life and work that would allow completing the previous existing biographies about her. [ABSTRACT FROM AUTHOR]

The plants of the genus Schisandra of the Schisandraceae family include the genus Schisandra and the genus Kadsura. In recent years, many kinds of triterpenoids have been isolated from the plants of genus Schisandra. Triterpenoids have attracted the attention of phytochemists and pharmacologists because they have novel skeletons and good anti-HIV, immunosuppressive and anti-tumor activities. This study provides an overview of the triterpenoids from the genus Schisandra and their biological activities. [ABSTRACT FROM AUTHOR]

Backgrounds: Most of the cancer patients with solid tumor are subjected to chemotherapy with cisplatin (CP) in clinic. However, the most side effect of CP is nephrotoxicity, which limits the treatment. The aim of study was to develop a general consensus statement for CP therapy in clinic to limit the drug-induced nephrotoxicity. Methods: A total of 30 oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologist clinical pharmacologist, and renal physiologist participated in a workshop, and in order to reduce the incidence of CP-induced nephrotoxicity, a general consensus was developed. Results: The developed general consensus was focused on some items such as age, sex, female hormone, nonsteroidal anti-inflammatory drugs (NSAID), renin-angiotensin system inhibitor drugs, glomerular filtration rate, hydration methods, contrasts, antioxidants, dextrose, and magnesium. Conclusion: The agreement between participants for CP therapy in clinic was achieved, and this general consensus was announced to be implemented in the hospitals. [ABSTRACT FROM AUTHOR]

In the middle of the last century, pharmacologists at the University of Melbourne led by Professor Frank Shaw inadvertently discovered that an amino-acridine they were using in other experiments reversed the respiratory depressive effects of morphine. They widened their search for such activity, experimenting with a range of heterocyclic substances and achieving success with a thiazole derivative, provided to them by the Professor of Organic Chemistry at the university, that countered the effects of morphine. Working with chemists and pharmacologists at a company with which Shaw had close links, Nicholas Pty Ltd, they discovered a glutarimide that offered the same benefit in cases of barbiturate intoxication. While this collaboration between pharmacologists and chemists, in industry and university, promised much, neither of these drugs survived into modern medical practice. The reasons for this include the development of better drugs or more appropriate patient care, Shaw's withdrawal from the work because of illness, and decisions in the company that might have been influenced by increasingly stringent requirements for the registration of new drugs. Nonetheless this was important research that drew on the depth of expertise in pharmacology and chemistry among university researchers and a major Australian company with whom they collaborated and exchanged personnel. In the 1950s, pharmacologists and chemists at the University of Melbourne and the pharmaceutical company Nicholas Pty Ltd discovered substances that could alleviate the respiratory depression caused by morphine and by barbiturates. Although this was a significant development in Australian science, the substances never became commercial drugs because of uncertainty about their efficacy, the development of better drugs, the reluctance of Nicholas to commit to further research in the face of increasing regulatory requirements for the registration of new drugs, and the early death of the research leader, Professor Frank Shaw. [ABSTRACT FROM AUTHOR]

Catalpol and its derivatives were found in a variety of Chinese medicinal plants and possess various biological activities, such as anti‐inflammatory, anti‐oxidant, neuroprotective, cardiovascular protective, anti‐tumor and hypoglycemic and so on. The extensive pharmacological activities of catalpol have been attracted much attention to researchers, but the clinical applications are limited by poor lipid solubility, low bioavailability and short half‐life, so pharmacologists have made various structural modifications to catalpol, such as increasing lipid solubility to enhance its biological activities in the hope that it can be widely used in clinical applications. In this paper, using "Catalpol" and "Catalpol derivatives" as the keywords, more than 200 articles from 1965 to 2021 were obtained from databases, such as CNKI, PubMed, Scifinder and so on. Finally, 93 articles were selected to systematically analyze the structure and efficacy of catalpol and its derivatives according to pharmacological activity, which will provide ideas for the development of new catalpol drugs in the future. [ABSTRACT FROM AUTHOR]

The application of traditional medicine to veterinary medicine has been termed ethno-veterinary medicine. Interview survey was conducted using a structured questionnaire to generate data on ethno-veterinary medicinal (EVM) practices used for treating pests and diseases of small ruminants in Akinyele Local Government Area, Oyo State, Nigeria. Information from one hundred and nine respondents was obtained through a multi-stage sampling technique. The data were analysed using simple descriptive statistics to generate frequencies and percentages. Demographic characteristics of the respondents showed that 62.39% were males and majority of them fell within 41 – 50 year, married (48.62%), Christians (68.81%), practiced extensive system of rearing (83.49%) with all of them into goat farming (100%) and 30.28% also having sheep in addition to goats. Secondary level education (38.53%) was the most attended by respondents. Majority sourced their EVM from family and relatives (76.15%), whereas greatest causes of loss, constraint and ill-health were diseases (46.79%), feed resources (35.78%) and PPR (35.78%) respectively. Most of them agreed that EVM has medicinal value (91.74%), cheaper than orthodox drugs (93.58%), has side effects (52.29%) and also easier to administer (77.06%). Eighteen (18) plant products that include fruit, leaf, root and bark were used to treat various diseases such as mange, cough, mastitis, diarrhoea, PPR, anthrax and snake bite. It is therefore recommended that these findings be used as baseline information by identifying the effective herbal remedies for livestock health which can be utilized by veterinarians and pharmacologists for the development of new therapies as well as isolation of bioactive compounds. [ABSTRACT FROM AUTHOR]

Within a few years after the first successful clinical use of penicillin, investigations were conducted in animal infection models to explore a range of factors that were considered likely to influence the antibacterial response to the drug. Those studies identified that the response was influenced by not only the total daily dose but also the interval between individual doses across the day, and whether penicillin was administered in an intermittent or continuous manner. Later, as more antibiotics were discovered and developed, antimicrobial pharmacologists began to measure antibiotic concentrations in biological fluids. This enabled the linking of antibacterial response at a single time point in an animal or in vitro infection model with one of three summary pharmacokinetic (PK) measures of in vivo exposure to the antibiotic. The summary PK exposure measures were normalised to the minimum inhibitory concentration (MIC), an in vitro measure of the pharmacodynamic (PD) potency of the drug. The three PK-PD indices (ratio of maximum concentration to MIC, ratio of area under the concentration-time curve to MIC, time concentration is above MIC) have been used extensively since the 1980s. While these MIC-based summary PK-PD metrics have undoubtedly facilitated the development of new antibiotics and the clinical application of both new and old antibiotics, it is increasingly recognised that they have a number of substantial limitations. In this article we use a historical perspective to review the origins of the three traditional PK-PD indices before exploring in detail their limitations and the implications arising from those limitations. Finally, in the interests of improving antibiotic development and dosing in patients, we consider a model-based approach of linking the full time-course of antibiotic concentrations with that of the antibacterial response. Such an approach enables incorporation of other factors that can influence treatment outcome in patients and has the potential to drive model-informed precision dosing of antibiotics into the future. [ABSTRACT FROM AUTHOR]

There has been high interest in the use of traditional medicines for COVID‐19 from early in the course of the pandemic. Significant advances in the science of ethnopharmacology have helped to introduce chemical entities identified from natural sources into modern medicine. However, the wider integration of natural products into the modern drug discovery process will require enhanced collaboration amongst the pharmaceutical industry, academic research units, regulatory bodies, ethics review committees and local, regional, continental and international organizations. Revisiting this topic holds promise of benefit for both the current and future pandemics. [ABSTRACT FROM AUTHOR]

Molecular simulations and molecular docking are widely used tools to investigate ligand/target interactions and in drug design. High‐performance computing (HPC) is boosting both the accuracy and predictive power of these approaches. With the advent of exascale computing, HPC may become standardly applied in many drug design campaigns and pharmacological applications. This review discusses how innovative HPC algorithms and hardware are being exploited in current simulations and docking codes, pointing also at some of the limitations of these approaches. The focus is on technical aspects which might not be all that familiar to the computational pharmacologist. This article is categorized under:Software > Molecular ModelingSoftware > Simulation MethodsStructure and Mechanism > Computational Biochemistry and Biophysics [ABSTRACT FROM AUTHOR]

Toxicity related failures in drug discovery and clinical development have motivated scientists and regulators to develop a wide range of in-vitro, in-silico tools coupled with data science methods. Older drug discovery rules are being constantly modified to churn out any hidden predictive value. Nonetheless, the dose–response concepts remain central to all these methods. Over the last 2 decades medicinal chemists, and pharmacologists have observed that different physicochemical, and pharmacological properties capture trends in toxic responses. We propose that these observations should be viewed in a comprehensive property-response framework where dose is only a factor that modifies the inherent toxicity potential. We then introduce the recently proposed "Drug Toxicity Index (DTI)" and briefly summarize its applications. A webserver is available to calculate DTI values (https://all-tool-kit.github.io/Web-Tool.html). [ABSTRACT FROM AUTHOR]

Introduction: Adverse drug reaction is defined by WHO as any response to a drug which is noxious and unintended, and which occurs at doses used in man for the prophylaxis, diagnosis or therapy of disease or for the modification of physiological function. Material and Methods: It was comparative, prospective and cohort study. The study was conducted at SMBT Medical Institute and Research Centre Dhamangaon Nashik and private Diabetic clinic. Group A: SMBT Medical Institute and Research Centre Dhamangaon Nashik. Group B: Private Diabetic clinic. All suspected ADRs were initially assessed by the Consultant Incharge - Diabetes Clinic and subsequently the information was collected and analyzed by the pharmacologists for causality assessment. Result: All the reported ADRs i.e. 22 (100%) were of type A reactions which are predictable. On the other hand, in Private clinic, a total of 18 patients of various age groups, belonging to either gender suffered from the adverse drug reactions. Among them, 17 (94.4%) cases were of type A reactions which are predictable. Only 1 (5.55%) suffered from Type B reaction. During the study period, 22 cases of adverse drug reactions were reported in Tertiary care hospital, out of which all (100 %) were of predictable type. The most commonly occurring ADR were hypoglycaemia was the most common ADR observed accountable 8 (36.3%). The most commonly occurring ADRs were hypoglycaemia was the most common ADR observed accountable 7 (38.8%) followed by Abdominal pain, Dizziness, Pedal edema. The percentages of other adverse drug reactions were comparatively less in Group B. Conclusion: ADRs are drug related problems which is considered as important drawback for drug safety. The spontaneous reporting used in study allowed the detection and characterization of ADRs. [ABSTRACT FROM AUTHOR]

Medical postgraduation in India is available across various disciplines, one among them being pharmacology. As with the other MD courses, MD Pharmacology is a 3-year-long course that involves strenuous theoretical, practical, and clinical training. However, the curriculum does not clearly enlighten MD residents on the career vistas available for them once they pass out. The awareness level of majority of MD pharmacology postgraduates or freshers on these career options is meagre due to lack of professional guidance or literature, and hence, majority of them tend to travel along the path that is most commonly traversed by their seniors and peers. This comprehensive review details a few of the different vistas that an MD pharmacologist can pursue, highlighting the scope, roles, responsibilities, and monetary compensation of each, in an honest attempt to educate and enlighten the MD pharmacology fraternity. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the pharmacy professionals' understanding and viewpoints on drug information center (DIC) services and differences, if any, with pharmacologist's survey conducted earlier. Materials and Methods: An electronic cross-sectional knowledge, practice, and attitude survey was carried out. A questionnaire in the form of the hyperlink was sent to pharmacy professionals through e-mail, Facebook messenger, and WhatsApp. Factors linked to pharmacy professionals' vision in expanding countrywide DIC services were studied with logistic regression in R. Results: A total of 125 pharmacy professionals responded. The participant believing in the published literature as a standard reference for establishing and running the DIC services; participants identifying more challenges in the day-to-day DIC functioning; and participants believing in the ability of DIC in reducing morbidity, mortality, and cost of care had 4.76 (95% confidence interval [CI] = 0.97-6.44), 4.24 (95% CI = 0.97-6.44), and 2.43 (95% CI = 0.97-6.44) times association with good knowledge score. Good attitude scores were discovered of participants working in fully and partially functional DIC (odds ratio [OR] = 9.66, CI = 0.97-6.44 and OR = 9.49, CI = 0.97-6.44) to participants not involved in DIC duties. The participant who understood DIC services' real purpose had 2.83 (95% CI = 0.97-6.44) times association with good practice scores. Overall, pharmacy professionals carried better attitude scores, but lesser knowledge, and practice scores than pharmacology professionals. Conclusion: Lower knowledge and practice score of pharmacy professionals asks for training in critical appraisal of published literature and due modifications in graduate and postgraduate curricula. A collaborative approach between pharmacists and pharmacologists is needed to improve the quality of drug information services and evidence-based medicine practice in low-resource countries like India. [ABSTRACT FROM AUTHOR]

Notably, both clinical pharmacologists and clinical pharmacists should have a valuable expertise in critical care and in antimicrobial therapy to optimize treatment in patients with NSTIs. 10.1007/s00134-017-4813-1 5 Gatti M, Gasparini LE, Laratta M, Sigurtà A, Rossi A, Brioschi P. Intensive multidisciplinary management in critical care patients affected by severe necrotizing soft tissue infections: a cooperative method to improve the efficacy of treatment. Necrotizing soft-tissue infections (NSTIs) are uncommon severe bacterial infections characterized by a high morbidity and mortality rate, frequently requiring intensive care unit (ICU) admission because of the occurrence of septic shock and multiorgan failure [[1]]. [Extracted from the article]

Since the early stages of its academic professionalization, pharmacology has been an interdisciplinary field strongly influenced by the natural sciences. Using the Nobel Prize as a lens to study the history of pharmacology, this article analyzes nominations of pharmacologists for two Nobel Prize categories, namely "chemistry" and "physiology or medicine" from 1901 to 1950. Who were they? Why were they proposed, and what do the Nobel dossiers say about excellence in pharmacology and research trends? This paper highlights the evaluation of "shortlisted" candidates, i.e., those candidates who were of particular interest for the members of the Nobel Committee in physiology or medicine. We focus on the US scholar John Jacob Abel (1857–1938), repeatedly referred to as the "Founder of American Pharmacology." Nominated 17 times in both categories, Abel was praised by his nominators for both basic research as well as for his influential positions as editor and his work as chair at Johns Hopkins University. The Abel nominations were evaluated for the Nobel Committee in chemistry by the Swedish professor of chemistry and pharmaceutics Einar Hammarsten (1889–1968), particularly interested in Abel's work on hormones in the adrenal glands and in the pituitary gland. Eventually, Hammarsten did not view Abel's work prizeworthy, partly because other scholars had done—according to Hammarsten—more important discoveries in the same fields. In conclusion, analyses of Nobel Prize nominations help us to better understand various meanings of excellence in pharmacology during the twentieth century and beyond. [ABSTRACT FROM AUTHOR]

Smoking cessation is underestimated in terms of drug interactions. Abrupt smoking cessation is common in cases of emergency hospitalization and restrictions of movement. Tobacco is a known cytochrome P450 1A2 (CYP1A2) inducer, its consumption and withdrawal can lead to major pharmacokinetic drug interactions. Nevertheless, references do exist, but may have different results between them. The objective of our work was to establish the broadest and most consensual list as possible of CYP1A2 substrates treatments and propose a pharmacological approach. We searched the widest possible list of CYP1A2 substrates based on various international references. We compared the references and defined probability and reliability scores of our results to sort the substances based on the scores. For the 245 substances identified as CYP1A2 substrates, we focused on the 63 CYP1A2 substrates with both probability and reliability scores >50%. Our work establishes adaptive pharmacological approaches for the management of patients initiating smoking cessation which must be integrated into the management of smoking cessation. Pharmacologists can now adopt adaptive pharmacological approaches to complement patient-specific clinical information about smoking cessation by considering pharmacokinetic risk. This work establishes an unprecedented list. It should guide in the care of patients initiating smoking cessation to prevent pharmacokinetic drug interactions. [ABSTRACT FROM AUTHOR]

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Clinical Pharmacology Leadership Group (CPLG) held its first meeting of Japan‐based representatives at Astellas Pharma headquarters in Tokyo on October 1, 2019. The meeting was also attended by Japan Pharmaceutical Manufactures Association (JPMA) Clinical Pharmacology Task Force (CPTF) members. Overall, nearly 30 clinical pharmacologists representing 14 companies attended the event. The meeting met its goal of enhancing mutual understanding of each organization's activities. In a number of break‐out sessions, participants identified scientific topics for potential future collaboration between JPMA CPTF and IQ CPLG. [ABSTRACT FROM AUTHOR]

Expedited development programs for biological products to be used in the treatment of serious conditions bring about challenges because of the compressed clinical development timeframes. As expedited development does not lessen the quality expectations, one challenge is providing adequate chemistry, manufacturing, and control (CMC) information required to support approval of a biological product. In particular, the analytical comparability and, in some cases, pharmacokinetic comparability studies needed to bridge the clinical material to the commercial material could delay submission of applications for life-saving medicines. While there is the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Topic Q5E guidance on assessing comparability of biological products before and after manufacturing changes, specific guidance on the emerging issue of conducting comparability exercises in the face of expedited drug development is lacking. In July 2019, clinical pharmacologists and product quality chemists from the US FDA and industry representatives convened an FDA workshop for a scientific exchange about considerations and challenges around conducting comparability exercises for expedited programs for biological products. This article highlights discussions from the workshop. [ABSTRACT FROM AUTHOR]

In this review, we identify opportunities for drug discovery in the treatment of COVID‐19 and, in so doing, provide a rational roadmap whereby pharmacology and pharmacologists can mitigate against the global pandemic. We assess the scope for targeting key host and viral targets in the mid‐term, by first screening these targets against drugs already licensed, an agenda for drug repurposing, which should allow rapid translation to clinical trials. A simultaneous, multi‐pronged approach using conventional drug discovery methods aimed at discovering novel chemical and biological means of targeting a short list of host and viral entities which should extend the arsenal of anti‐SARS‐CoV‐2 agents. This longer term strategy would provide a deeper pool of drug choices for future‐proofing against acquired drug resistance. Second, there will be further viral threats, which will inevitably evade existing vaccines. This will require a coherent therapeutic strategy which pharmacology and pharmacologists are best placed to provide. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc [ABSTRACT FROM AUTHOR]

Isoquinolines constitute an important class of natural alkaloids, that demonstrate a wide range of biological activities. Therefore, development of new methods for efficient synthesis of isoquinoline and its derivatives has attracted considerable attention of chemists and pharmacologists over recent years. In this review the progress of isoquinoline synthesis that provides creative inspiration and expands novel ideas for researchers in this field is summarized. [ABSTRACT FROM AUTHOR]

Three major classes of natural products (NPs) for medicinal purposes or improving wellbeing are generally available in the US: conventional drugs of herbal origin, botanical drugs, and dietary supplements (DSs). Consumer consumption of DSs is growing annually. The U.S. FDA regulates conventional and botanical drugs for safety and efficacy; however, DSs are minimally regulated. This article will: i) highlight the importance of NP as a significant source of prescription drugs; ii) discuss differences in the regulation of conventional drugs of NP product, botanical drugs, and DSs; iii) discuss the safety and efficacy of DSs and iv) make recommendations for improvement of safety for minimally regulated NPs. Toxicities associated with the use of NPs, including vitamins and DSs, are mainly due to excessive use and interactions with conventional drug(s) and may represent challenges for clinicians. Conventional and botanical-based prescription drugs are rarely associated with unknown toxicities. However, DSs are minimally regulated and can produce severe adverse effects. We believe that clinical pharmacologists can have a role in developing criteria for DS safety analysis. There is also the potential for a standardized NP stewardship program(s) and the development of NP policies and practices nationally and globally. [ABSTRACT FROM AUTHOR]

The idea of a conventional solution is generally acknowledged in different pieces of the world. All things considered, it has neglected to pick up notoriety in India because of elements, for example, non-accessibility and doubt on product quality. Nonetheless, the Indian government started selective nonexclusive medication stores named as Jan Aushadhi in 2012. Materials and Methods: This survey was based on a study where the team talked with all-out 100 patients devouring conventional and ethical branded medications, separately. The anticipated efficacy, cost of treatment, nature of medications was inquired. Results: In our investigation, 71 % of respondents found out about conventional medications and 64% knew the contrast among nonexclusive and ethical branded medicines. 66% concurred that nonexclusive meds are less expensive than ethical branded medications yet just 35% of them liked to purchase nonexclusive meds. The majority (64%) of the patients neither requested their physician or pharmacologist (60%) to convey nonexclusive medications. A larger part of them (66%) accepted that nonexclusive meds have lower quality than marked prescriptions. As indicated by patients, 45% reacted that specialists favored marked medications over conventional prescriptions. Right now, patients were endorsed by conventional medications. A large portion of them (65%) didn't turn into mindful of the administration controls about endorsing nonexclusive medications. Just 25% reacted that the legislature ought to advance nonexclusive drugs. Inference: The results indicate that respondents had freakish athleticism and perspective regarding nonexclusive medications. Many of them had inaccurate knowledge and that is not a positive symbol of Jan Aushadhi’s scheme being enforced and maintained in government hospitals. [ABSTRACT FROM AUTHOR]

Experimental pharmacologists rely on the application of models to describe biological observations in order to learn about a drug's effective concentration, the strength with which it binds its target and drives a response (at either molecular or system level), and the nature of more complex drug actions (allosterism/functional selectivity). Models in current use build upon decades of basic principles, going back to the beginning of the last century. Yet often, researchers are only partially familiar with these underlying principles, creating the potential for confusion due to failure to recognise the underpinning assumptions of the models that are used. Here, we describe the history of receptor theory as it underpins receptor stimulus-response models in use today, emphasising particularly attributes and models relevant to GPCRs-and point to some current aims of model development. [ABSTRACT FROM AUTHOR]

As the field of artificial intelligence and machine learning (AI/ML) for drug discovery is rapidly advancing, we address the question "What is the impact of recent AI/ML trends in the area of Clinical Pharmacology?" We address difficulties and AI/ML developments for target identification, their use in generative chemistry for small molecule drug discovery, and the potential role of AI/ML in clinical trial outcome evaluation. We briefly discuss current trends in the use of AI/ML in health care and the impact of AI/ML context of the daily practice of clinical pharmacologists. [ABSTRACT FROM AUTHOR]

Application of contemporary molecular biology techniques to clinical samples in oncology resulted in the accumulation of unprecedented experimental data. These "omics" data are mined for discovery of therapeutic target combinations and diagnostic biomarkers. It is less appreciated that omics resources could also revolutionize development of the mechanistic models informing clinical pharmacology quantitative decisions about dose amount, timing, and sequence. We discuss the integration of omics data to inform mechanistic models supporting drug development in immuno‐oncology. To illustrate our arguments, we present a minimal clinical model of the Cancer Immunity Cycle (CIC), calibrated for non‐small cell lung carcinoma using tumor microenvironment composition inferred from transcriptomics of clinical samples. We review omics data resources, which can be integrated to parameterize mechanistic models of the CIC. We propose that virtual trial simulations with clinical Quantitative Systems Pharmacology platforms informed by omics data will be making increasing impact in the development of cancer immunotherapies. [ABSTRACT FROM AUTHOR]

"Skin is Like an Ocean's Surface Which Tells Deep Stories if you Watch Carefully" Four years ago, one of us received a call from a senior internist in our tertiary medical care, teaching, and research center. Drug skin metabolites and allergic drug reactions. Carbamazepine-mediated adverse drug reactions: CBZ-10,11-epoxide but not carbamazepine induces the alteration of peptides presented by HLA-B*15:02. [Extracted from the article]