The aging population has had an impact on society in recent decades. Aging-associated health issues are a particularly challenging aspect to regulate. Therefore, the extension of healthy life expectancy by the application of biologically active compounds is an attractive research topic in the fields of medicinal chemistry, chemical biology, and also organic synthesis. Herein, the first total synthesis of acaulide, acaulone A and 10-keto-acaudiol A is described. These compounds were originally isolated from a culture of Acaulium sp. H-JQSF. Acaulide exhibits anti-osteoporosis activity in a prednisolone-induced osteoporotic zebrafish model; hence, this natural product is expected to be a new lead compound for anti-osteoporosis drugs. The characteristic acaulide skeletons were synthesized via late-stage Michael addition inspired by the proposed biosynthetic pathways. The conformational analysis of the 14-membered macrodiolide revealed the specific conformation that enabled the late-stage stereoselective functionalization.

The polio eradication program, launched in 1988, has successfully decreased the number of poliomyelitis patients worldwide. However, in areas with immunization gaps where oral polio vaccine coverage has dropped, outbreaks of more virulent vaccine-derived polioviruses (VDPVs) have become a threat to public health. In Japan, inactivated polio vaccine replaced oral polio vaccine as the routine immunization in 2012. Polio environmental surveillance (ES) has been conducted nationwide since 2013 to efficiently monitor the wild type poliovirus or VDPV, which may be imported from overseas. ES may also be utilized to detect other viruses in stool samples. We propose a method of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection based on the polio ES network, and establish a procedure to detect fragments of SARS-CoV-2 genome in wastewater solids. Our findings suggest that polio ES can be used to simultaneously monitor SARS-CoV-2 RNA fragments in sewage waters.

To understand fungal contamination in the indoor environments of the disaster region, surveys were conducted to detect mycoflora in temporary shelters, prefabricated temporary housing, private housing, and rented apartments in areas affected by the Great East Japan Earthquake. The results from the surveys of temporary shelters indicated that the indoor-air fungal counts at all sampling points were less than 1000 colony forming units (cfu)/m³, which is the recommended limit for fungal contamination in indoor air. However, the Aspergillus counts were high compared to the indoor environments of typical housing. Since Aspergillus is a known allergenic genus, careful attention should be paid to residents' health. The results of the surveys of private housing and rented apartments also indicated that fungal counts were highest during the rainy season throughout the summer. In contrast, temporary housing had a maximum fungal count in the winter. The extremely high level of fungal condensation in indoor air may have been due to the high relative humidity and loss of heat insulation in the buildings' attics. It is thought that these problems happen most commonly in colder regions, such as the entire area affected by the Great East Japan Earthquake. The case of a patient with allergic bronchopulmonary mycosis caused by a large amount of Eurotium herbariorum mold in his temporary housing was reported to demonstrate the health risks posed by fungi in this disaster region.

Advances in food production technology and newer distribution systems have made it easier to obtain fresh ingredients from both within and outside of Japan. Although convenient, mass distribution of food over wide areas involves the risk of expanding the health damage caused by foods. Comprehensive management from production to consumption, using systems, such as hazard analysis and critical control point (HACCP), is required to ensure the safety of foods. Improved inspection methods are also required to detect the effects of environmental changes on food. In this paper, we demonstrate the use of “Methods of Analysis in Health Science 2020” for food hygiene and safety management.

Strict microbial control is required in manufacturing facilities to ensure the quality of pharmaceuticals and foods. Environmental microbial monitoring plays a fundamental role in reducing the risk of microbial contamination. Appropriate microbial control requires an understanding of abundance and community structures of microbes in the target environment. However, most of these microbes are not culturable using conventional methods. In this study, we determined the number of microbial particles and assessed the environmental microbiome in a pharmaceutical manufacturing facility, using high-throughput sequencing of rRNA gene fragments. Our results provide fundamental data for the evaluation and control of microbes in the pharmaceutical and food industries.

Lakes Sagami and Tsukui are reservoirs constructed by connecting to the Sagami River. Because of eutrophication of the lakes, cyanobacteria have appeared every year. This review deals with phenomena related to occurrence of cyanobacteria that have been observed for 40 years since 1974 at the lakes. These 40 years of observations raised three interesting issues including the retention of cyanobacteria on their surfaces. These phenomena have been attributed to the usual factors, such as illuminance, nutrition and water temperature, but our research results suggested that they cannot be resolved without the introduction of another factor. We have attempted to elucidate various phenomena involving cyanobacteria in lake ecosystems by chemical ecological methods using volatile organic compounds (VOCs) produced by the cyanobacteria as indicators. One of the VOCs, β-cyclocitral, was significantly involved in the above phenomena, which was considered to be produced by the carotenoid cleavage dioxygenase (CCD) of the cyanobacteria. β-Cyclocitral was not produced in the two known CCDs, but two additional CCDs to Microcystis aeruginosa participated to produce the β-cyclocitral. These CCDs did not directly produce β-cyclocitral, but it was accumulated in cells as their precursors. The released β-cyclocitral underwent a Baeyer-Villiger-like oxidation. It was speculated that Microcystis activated the CCD genes through density stress and produced β-cyclocitral, which acted as an allelopathic substance. As a result, the number of cells of cyanobacteria decreased, and the resulting nitrogen and phosphorus were fed to the living cyanobacteria. It is postulated that this “quorum sensing” was functioning in the above-mentioned issues.

The crystallization of active pharmaceutical ingredients (APIs) in matrix-type transdermal patches has implications for the rate of drug absorption through the skin and patch adhesion strength. Therefore, the presence or absence and the degree of API crystallinity must be controlled to guarantee the quality of patches. In this study, the utility of laboratory-level X-ray diffractometers for the detection and analysis of crystalline APIs in transdermal patches was investigated using medical patches of tulobuterol and isosorbide dinitrate. Several matrix-type patches employ a controlled drug delivery system containing intentionally crystallized API. Both benchtop and high-resolution laboratory X-ray diffractometers can detect several characteristic peaks of the APIs in these patches even if the patches are wrapped in an outer bag, although a benchtop model provides peak heights one-seventh to one-fifth that of a high-resolution instrument. An isosorbide dinitrate patch containing an unintentionally crystallized spot was wrapped in an outer bag, followed by measurements using both X-ray diffractometers. For both instruments, several isosorbide dinitrate-derived peaks were detected only at the crystallized spot, although the signal-to-noise ratio was poorer for the benchtop model. These results show that a high-resolution X-ray diffractometer is advantageous for high-detection sensitivity and offers a high degree of freedom of the measurement position on the sample. It was concluded that a laboratory-level high-resolution X-ray diffractometer can be used to examine the crystalline state of APIs in patches inside an unopened outer bag.

The spread of COVID-19 has re-affirmed the crucial importance of the pharmaceuticals industry in improving the level of citizens' health and medical care, as well as the industry's importance in terms of contribution to economic growth and tax revenues. Although some time has passed since the importance of industry-academia collaboration was first raised in relation to the creation of innovative new drugs and the continuation of global competitiveness, conflicts between academia and companies have also been highlighted as barriers that hinder efforts to promote the practical realization of academia-initiated seeds. The authors have hypothesized that conflicts between academia and companies can be attributed to the vulnerability of innovation creation environments, including drug discovery, on the academia side, insufficient awareness concerning human resources that will undertake industry-academia operations, and inadequate development of structures. Consequently, we implemented fact-finding investigations in relation to universities and public research institutions in Japan, with the objective of ascertaining the actual status of innovation creation environments, including drug discovery, on the academia side. From the results of these investigations, we will clarify the issues that may present barriers to innovation creation, and consider policies, etc. for the enhancement of innovation creation environments.

Recombinant tissue plasminogen activator (rt-PA), which is used to treat acute cerebral infarction, may cause angioedema immediately after administration particularly in patients who are taking angiotensin-converting enzyme (ACE) inhibitors. On the other hand, unlike ACE inhibitors, angiotensin II receptor blockers (ARBs) do not act directly on bradykinin, and are therefore considered an alternative to ACE inhibitors in patients with bradykinin-related side effects. We report a case of orolingual angioedema in an 82-year-old male patient who is taking ARB, which occurred after rt-PA administration for acute cerebral infarction. The patient, who has been on medications for hypertension including ARB (olmesartan 40 mg/day) and for hyperuricemia, was transported to our hospital with the chief complaint of right conjugate deviation of the eyes and left hemiplegia. Head magnetic resonance imaging revealed cerebral infarction in the right mesencephalic artery area including the insular cortex. He was diagnosed with cardiogenic cerebral embolism, and rt-PA administration was started 4 h after onset. The patient developed eyelid edema 2.5 h after the start of administration, and orolingual angioedema and breathing difficulty 15.5 h after. The patient was treated with methylprednisolone, d-chlorpheniramine maleate, and famotidine, and the symptoms improved gradually in 1.5 h. We should pay attention to the occurrence of orolingual angioedema not only at the beginning of rt-PA administration but also for a long time thereafter when it is used in patients taking ARBs.