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Since the start of the 6-year program in pharmacy education, outcome-based education has progressed, and students' experience of onsite pharmacy practice has increased their awareness of their roles as pharmacists. This progress has been confirmed by student reports submitted at the end of onsite practice. In addition, the results of undergraduate students' graduation research as well as those of clinical research carried out in graduate schools are presented at the annual meetings of the Pharmaceutical Society of Japan (PSJ) and its local branches. Research activity is also promoted by the various divisions of the PSJ that represent a wide range of pharmacy-related fields, including the Division of Clinical Pharmaceutical Sciences. In this way, the PSJ effectively connects researchers in basic and clinical fields, promoting the development of both translational research and reverse-translational research based on needs and ideas brought from the clinic to the basic sciences. Following their presentation at academic meetings, clinical research outcomes are often published in academic journals, including in the three academic journals published by the PSJ: Yakugaku Zasshi, Biological and Pharmaceutical Bulletin, and Chemical and Pharmaceutical Bulletin. Yakugaku Zasshi accepts submissions of case studies, case reports, and survey reports related to clinical pharmacy, which can be submitted in either English or Japanese. As the foundational society for pharmacy and pharmaceutical sciences in Japan, the PSJ is committed to continuing advances in basic and clinical pharmacy research. In the last part of this review, I discuss graduate schools of pharmacy and pharmaceutical sciences.
In the 20th century, the medical and pharmaceutical fields in Korea and Japan were markedly developed. There was a deep relationship between the two countries as Japan had annexed Korea from 1910 to 1945, until the end of World War II. The present study was performed to investigate the Chosen Pharmaceutical Association and "The Journal of the Chosen Pharmaceutical Association" to research part of the history of Korean pharmacology in those days. In 1914, the Chosen Pharmaceutical Association was established; Takasato Kojima was appointed as the first chairman. The first issue of "The Journal of the Chosen Pharmaceutical Association" was published in 1921 as the only chemical bulletin in Korea. The contents of the journals mainly consisted of academic papers, investigations on hygiene and health in Korea and management reports of the association. Concerning the academic papers, most of them were on studies of environmental health and medicinal plants in Korea. The Chosen Pharmaceutical Association was disbanded by 1945.
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but use is constrained by potentially life-threatening neutropenia and mandatory hematological monitoring. Evidence from Western cohorts suggests risk is concentrated early in treatment, yet data from Japan where monitoring is stringent, remain limited. Retrospective study including all patients prescribed clozapine from July 2009-January 2020 in Japan. Mild neutropenia was defined as absolute neutrophil count (ANC) 1.0-1.5 × 109/L, and serious neutropenia as ANC <1.0 × 109/L. Cumulative incidence of first mild and serious neutropenia was estimated using competing-risks methods. Associations with serious neutropenia were examined using Fine-Gray regression, including 2-week titration rate. The cohort comprised 8263 individuals contributing 764 180 blood tests, with a median follow-up of 102 weeks. Overall, 3.0% patients experienced mild neutropenia and 2.2% had serious neutropenia. Among clozapine-naïve patients, cumulative incidence was 1.8% for mild and 1.6% for serious neutropenia at 18 weeks, rising to 3.1% and 2.5% at 104 weeks, respectively. Faster clozapine titration rate was associated with higher incidence of serious neutropenia (sub-distribution hazard ratio [sHR] 1.22, 95% CI, 1.02-1.45 per 50 mg dosage increase at 2-weeks), as was older age (sHR 1.05, 95% CI, 1.04-1.06), while prior clozapine exposure was associated with lower incidence (sHR 0.27, 95% CI, 0.09-0.86). In Japan, neutropenia among clozapine-treated patients accrued predominantly within the first 1-2 years, with faster titration in the first 2-weeks being associated with a 22% increase in serious neutropenia risk per 50 mg. These findings support risk-stratified, less intensive monitoring approaches beyond the first 2 years.
This study consisted of a bibliographical survey in the databases LILACS, MEDLINE and ILO-CIS BULLETIN - SAFETY AND HEALTH AT WORK, with a view to identifying the main agents that can favor contact with these risks and cause health alterations in nursing workers. 37 articles were found, only four of which were published in national journals. Articles reported on the detection of chemical risks in the manipulation of cytostatic drugs; in the exposure to anesthetic gases, formaldehyde/glutaraldehyde vapor and sterilizing gases, among others.
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We investigate the frequency and diagnostic yield of cerebrospinal fluid (CSF) analysis in adult patients with status epilepticus (SE) and its impact on the outcome. From 2011 to 2018, adult patients treated at the University Hospital Basel were included. Primary outcomes were defined as the frequency of lumbar puncture and results from chemical, cellular, and microbiologic CSF analyses. Secondary outcomes were differences between patients receiving and not receiving lumbar puncture in the context of SE. In 18% of 408 patients, a lumbar puncture was performed. Of those, infectious pathogens were identified in 21% with 15% detected ± 24 h around SE diagnosis. 74% of CSF analyses revealed abnormal chemical or cellular components without infectious pathogens. Screening for autoimmune diseases was only performed in 22%. In 8%, no or late (i.e., > 24 after SE diagnosis) lumbar puncture was performed despite persistent unknown SE etiology in all, transformation into refractory SE in 78%, and no recovery to premorbid neurologic function in 66%. Withholding lumbar puncture was associated with no return to premorbid neurologic function during hospital stay independent of potential confounders. Not receiving a lumbar puncture was associated with presumed known etiology and signs of systemic infectious complications. Withholding lumbar puncture in SE patients is associated with increased odds for no return to premorbid neurologic function, and CSF analyses in SE detect infectious pathogens frequently. These results and pathologic chemical and cellular CSF findings in the absence of infections call for rigorous screening to confirm or exclude infectious or autoimmune encephalitis in this context which should not be withheld.
Microplastic pollution of our environment has seen major data reporting in the last decade. Microplastics produce harmful effects on marine organisms and in humans. Despite the fact that microplastics (MPs) have inert or sublethal toxicity in many circumstances, their long-term presence can have negative ecological consequences. However, there is a paucity of comprehensive literature on the present study and future development trend of MPs in aquatic ecosystems, to our knowledge. In this scientometric study, the literature was evaluated between years 2011 and 2019. The data show increasing importance of microplastics in terms of increase in publication in concurrence of granting funds in this area by major funding agencies. Most research articles were published by authors (~ 49%) affiliated with Chinese Academy of Sciences. Journals 'Marine Pollution Bulletin' and 'Environmental Pollution' were identified as important journals with 273 and 185 research publications, respectively. We have also identified the upcoming research trend and shift from microplastic presence in water to microplastic presence in air. However, in the year 2017, researchers from the UK started publishing more articles in this field with 11 publications with top authors affiliated to University of Plymouth. The journal Environmental Pollution has been found to be the leading journal (~ 20%) addressing the issue of microplastics in the environment. Our co-authorship analysis demonstrated that China (its institutions and authors) is the most collaborative country followed by the USA, together forming top cluster with a link strength of 42. Finally, our analysis provides information about prospective research and emerging trends that can be explored in the coming years.
This study aimed to assess the level of therapeutic innovation of new drugs approved in Brazil over 13 years and whether they met public health needs. Comparative descriptive analysis of therapeutic value assessments performed by the Brazilian Chamber of Drug Market Regulation (CMED) and the French drug bulletin Prescrire for new drugs licensed in Brazil, from January 1st 2004 to December 31st 2016. The extent to which new drugs met public health needs was examined by: checking inclusions into government-funded drug lists and/or clinical guidelines; comparing Anatomical Therapeutic Chemical Classification (ATC) codes and drug indications with the list of conditions contributing the most to the national disease burden; and assessing new medicines aimed to treat neglected diseases. 253 new drugs were approved. Antineoplastics, immunossupressants, antidiabetics and antivirals were the most frequent. Thirty-three (14%) out of 236 drugs assessed by the Brazilian chamber and sixteen (8.2%) out of 195 assessed by the French bulletin Prescrire were considered innovative. Thirty-six drugs (14.2%) were selected for coverage by the Brazilian Unified National Health System (SUS), seven of which were therapeutically innovative, and none were aimed to treat neglected disease. About 1/3 of the drugs approved aimed to treat conditions among the top contributors to Brazil's disease burden. Few therapeutically innovative drugs entered the Brazilian market, from which only a small proportion was approved to be covered by the SUS. Our findings suggest a divergence between public health needs, research & development (R&D) and drug licensing procedures.
Phenotype-based screening has emerged as an alternative route for discovering new chemical entities toward first-in-class therapeutics. However, clarifying their mode of action has been a significant bottleneck for drug discovery. For target protein identification, conventionally bioactive small molecules are conjugated onto solid supports and then applied to isolate target proteins from whole proteome. This approach requires a high binding affinity between bioactive small molecules and their target proteins. Besides, the binding affinity can be significantly hampered after structural modifications of bioactive molecules with linkers. To overcome these limitations, two major strategies have recently been pursued: (1) the covalent conjugation between small molecules and target proteins using photoactivatable moieties or electrophiles, and (2) label-free target identification through monitoring target engagement by tracking the thermal, proteolytic, or chemical stability of target proteins. This review focuses on recent advancements in target identification from covalent capturing to label-free strategies.
Oseltamivir, an anti-influenza virus drug, has strong antipyretic effects in mice (Biological and Pharmaceutical Bulletin, 31, 2008, 638) and patients with influenza. In addition, hypothermia has been reported as an adverse event. The prodrug oseltamivir is converted to oseltamivir carboxylate (OC), an active metabolite of influenza virus neuraminidase. In this study, core body temperature was measured in mice, and oseltamivir and OC were administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p). Low i.c.v. doses of oseltamivir and OC dose-dependently produced hypothermia. Zanamivir (i.c.v.), another neuraminidase inhibitor, did not produce hypothermia. These results suggested that the hypothermic effects of oseltamivir (i.p. and i.c.v.) and OC (i.c.v.) are not due to neuraminidase inhibition. OC (i.p.) did not lower body temperature. Although mecamylamine (i.c.v.) blocked the hypothermic effect of nicotine-administered i.c.v., the hypothermic effects of oseltamivir and OC (i.c.v.) were not blocked by mecamylamine (i.c.v.). The effect of oseltamivir (i.p.) was markedly increased by s.c.-pre-administered mecamylamine and also hexamethonium, a peripherally acting ganglionic blocker, suggesting their potentiating interaction at peripheral sites. The hypothermic effect of nicotine (i.c.v.) was decreased by lower doses of oseltamivir (i.c.v.), suggesting the anti-nicotinic action of oseltamivir. These results suggest that oseltamivir (i.p.) causes hypothermia through depression of sympathetic temperature regulatory mechanisms via inhibition of nicotinic receptor function and through unknown central mechanisms.