Discovery of natural products that possess novel chemical structures and pharmaceutical activities increases opportunities of drug development. In this post genomic era, it is cleared that fungi have a huge number of silent biosynthetic gene clusters and they are recognized as an attractive source for natural product discovery. The author developed methods to activate fungal silent biosynthetic gene clusters by using epigenetic modifiers and plant hormones and demonstrated their advantage to get a variety of new natural products.
There are still many diseases that have no therapeutic approach even today. Against this background, we have duty to think the future of the field of pharmacy. This paper describes the importance of sharing awareness of problems among different specialists such scientist and pharmacist. Furthermore, this paper also introduced the result of the symposium which consist of enzyme engineering, total synthesis and medicinal chemistry in the 141st annual meeting of the Pharmaceutical Society of Japan.
This research paper improves the TDBPP and BDBPP analysis methods of organic phosphorus flame retardants regulated by the Act on the Control of Household Products Containing Harmful Substances Japan. The authors proposed a GC-MS analysis method instead of the GC-FPD method. The new method is performed safely without using harmful reagents in the pretreatment. Furthermore, the high-sensitive analysis is realized by surrogate correction.
The author has an interest in unique chemical and physical properties of fullerene (C60) and fullerene derivatives, and has studied bio-active fullerene derivatives to develop novel lead compounds for drug discovery. He showed that anionic fullerene derivatives possess anti-oxidant activities, di-cationic fullerene derivatives exhibited antiproliferative activities against various cancer cell lines including drug-resistant cells, and proline-type fullerene derivatives showed anti-virus activities. The process of the studies is also written in this report.
The presence or absence of drug crystals in a matrix-type transdermal patch is generally confirmed by visual or optical observation of the exposed adhesive surface. This method consumes one patch per observation. The present study investigated the feasibility of crystal detection in a patch, enclosed in an unopened outer bag, by laboratory X-ray diffraction. The results showed that a laboratory-level high-resolution X-ray diffractometer can be used to detect unintentionally crystallized spots, and examine the crystalline state including polymorphism.
Due to aging society of Japan, ophthalmic research is becoming more importance in not only doctor and nurse but pharmacist. This symposium (review) shows the state of the art in “Age-related changes in eye function and preventive ways”, and update ophthalmic studies including senescence, antiaging, immune privilege and drug delivery system. Many members will be interested in the ophthalmic research field when they read this review, and the information will help to improve the “Quality of Vision” in aging society.
Three subtypes of peroxisome proliferator-activated receptors (PPARα, PPARγ, and PPARβ/δ) are attracting much attention as molecular targets of drugs to treat various metabolic diseases including dyslipidemia, type 2 diabetes, and non-alcoholic fatty liver disease; however, the structural information regarding their ligand binding pockets has been lacking, especially in PPARα. Kamata and Ishii give an overview of their recent success in obtaining 34 novel PPARα-ligand structures that supplement 21 previously PDB-deposited structures using their sophisticated crystallization techniques.
Authors analyzed the residual solvents by headspace (HS)-GC-MS in 29 products selected from among commercial supplements that are deeply colored or contain coating agents and extract. As a result, benzene (class 1) was detected in black-colored supplements. As raw materials used for the manufacture of the black-colored supplements from which benzene was detected commonly included activated carbon. In their analysis, benzene was detected at high concentrations in activated carbon made from hemp and bamboo for use as food additives.
Pharmacists are exposed to the drug when dispensing powder drug. The authors clarified the current status with scientific measurements. The pharmacists were exposed to 0.17 µg/d (median) of drug ingredients just in the dispensing room. Furthermore, dispensing drug powder increased the exposure to a maximum of 0.4–36 µg per one prescription. Although there are concerns about the health hazards of pharmacists due to exposure to drug dust, they found that wearing medical mask removed more than 90% of drug ingredient.
Organic compounds isolated from natural resources are called “natural products” and are important seed compounds for medicinal chemistry. Total synthesis of natural products is basic research for drug development by structure determination, including absolute stereochemistry and investigation of their chemical and physical properties. Many alkaloids show strong biological activities among the natural products and have been recognized as a drug or a drug candidate. Here, total syntheses of polycyclic natural products, Kopsia alkaloids, manzamine alkaloids, are discussed.
The authors retrospectively investigated the potential DDIs among three or more drugs that involve the same CYP molecular species in metabolic process in outpatients’ setting. This study found out that the more than half of the patients who took six or more drugs had potential DDIs among three or more drugs, and CYP3A4-related drugs are especially important. These findings would be useful for avoidance or early detection of adverse drug reactions caused by DDIs among three or more drugs.
MTF-1 is a transcription factor activated in response to an increase in concentration of intracellular free zinc. In this article, MTF-1 is reviewed from its discovery to unique characteristics as an intracellular zinc sensor, mainly based on the author’s research results. It is indicated that clarification of the zinc signaling system mediated by MTF-1, together with the analysis of the genes under its control, is useful for unraveling novel biological roles of essential zinc.
This study investigated the effects of fenofibrate and bezafibrate on risk of diabetic retinopathy (DR) in Japanese working age patients with type 2 diabetes and dyslipidemia using electronic medical records. Although these fibrates did not affect development of DR, poor control of hemoglobin A1c (HbA1c) and low-density lipoprotein cholesterol (LDL-C) within the follow-up period increased the risk of DR. Thus, controlling HbA1c and LDL-C levels under coexistence type 2 diabetes and dyslipidemia is more important than the selection of fibrate.
The author introduced three methods to characterize the blood-brain barrier (BBB) transport function. It was shown that the BBB plays an important role in protecting the brain by transporting small molecules such as neurotransmitters, uremic toxins and xenobiotics together with proteins. Significant species differences were shown in the expression amounts of various BBB transporter proteins. Moreover, in vivo BBB efflux transport activity was predicted from in vitro study and transporter protein concentration.
The authors report on pharmacists’ work that is unique to surgical departments. Pharmacists prepare drug solutions utilizing anesthesia recording systems, which they were involved in developing. Anesthesiologists request pharmacists to prepare drug solutions after estimating the degree of postoperative pain in the surgical field during surgery. Pharmacists then prepare specific solutions after consultation and discussion with anesthesiologists. In this study, the authors investigated the evaluation of pharmacists’ practices by anesthesiologists and found that pharmacists received favorable evaluations.
Distigmine is a cholinesterase inhibitor, which is used in Japan for the treatment for underactive bladder. Although the effectiveness of distigmine for underactive bladder treatment has been confirmed by many clinical reports, the pharmacological effects of distigmine on urinary bladder (UB) motility have not been well studied. In this review, the authors discuss the long-lasting potentiating effect of distigmine on guinea pig UB motility and the mechanism of these effects in guinea pig UB smooth muscle and recombinant human acetylcholinesterase.
In this review, the authors first discuss the mechanisms of phototoxicity and how they can be evaluated. They then discuss the state of the art and challenges now faced in photosafety evaluation of pharmaceuticals and cosmetics. Additionally, they describe the latest developments in OECD test guidelines for assessing photosafety, including revisions to the 3T3 NRU phototoxicity test (TG 432) and the newly adopted ROS assay (TG 495).
The authors formulated a “Rubric assessment for pharmacotherapy” to continuously assess students’ ability to perform pharmacotherapy and provide patients with proper pharmacotherapy during student clinical rotations, and evaluated its usefulness. The rubric consists of three domains with 31 subdomains. Students were able to continuously self-assess their performance using the rubric, while continuously improving their achievement level. The rubric assessments may be useful for students to assess and improve their ability to practice pharmacotherapy.
The authors investigated the connection between differences in argatroban administration and worsening of symptoms after day 3 in ischemic stroke patients. Worsening of symptoms was not related to either intravenous or continuous infusion group. Bleeding was also not associated with either group. They suggest that the differences in the mode of argatroban administration were not related to the worsening of symptoms in ischemic stroke patients. They also found that safety was equivalent regardless of the administration route.
The authors investigated the drug–drug interactions between warfarin and tolvaptan by measuring drug blood concentrations in clinical patients and conducting in vitro albumin-binding experiments. They indicated that tolvaptan causes the free warfarin concentration to increase within 2 weeks of starting the combined treatment and the mechanism was albumin-binding substitution. This study shows that investigating and demonstrating various phenomena from the bedside enable pharmacists to provide better pharmaceutical care for patients.