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Coronavirus disease 2019 (COVID-19) has become a serious public health problem worldwide. In general, healthcare workers are considered to be at higher risk of COVID-19 infection. However, the prevalence of COVID-19 among healthcare workers in Japan is not well characterized. In this study, we aimed to examine the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among 2160 healthcare workers in hospitals and clinics that are not designated to treat COVID-19 patients in Japan. The prevalence of SARS-CoV-2 immunoglobulin G was 1.2% in August and October 2020 (during and after the second wave of the pandemic in Japan), which is relatively higher than that in the general population in Japan (0.03–0.91%). Because of the higher risk of COVID-19 infection, healthcare workers should be the top priority for further social support and vaccination against SARS-CoV-2.

A 63-year-old diabetic man was admitted with general fatigue. Electrocardiogram (ECG) on admission showed complete atrioventricular (AV) blockade associated with prominent bifid T waves. The second component of the bifid T waves was distinguished from U waves by the beat-to-beat varying bifidity and the nadir between the two components located at > or = 1 mm above the isoelectric line. Range of absolute QT interval was 535 to 650 ms. Hypokalemia (3.6 mEq/L) was noted at admission. Partial restoration of the potassium level (3.9 mEq/L) prior to temporary ventricular demand pacing obscured the bifid T waves and attenuated the QT prolongation and dispersion to some extent (absolute QT interval ranging 520 to 620 ms). It was concluded that marked bradycardia caused by complete AV blockade (ie, a junctional escaped rhythm at a rate of 42 beats/min), hypokalemia, and underlying diabetes mellitus contributed in concert to the QT prolongation and dispersion leading to the prominent bifid T waves.

Gene therapy has been proposed as a strategy for the treatment of intractable human diseases since the early 1990s. For the expression of a specific transgene in desired cells or tissues with the proper timing, many vectors carrying transgenes have been developed (Matrai et al., 2010; Nayak & Herzog, 2010; Sliva & Schnierle, 2010). Retroviral, lentiviral, adenoviral, and adeno-associated viral vectors are used in various ways to achieve these goals. However, the introduced transgenes frequently become silenced in the host cells (Harbers et al., 1981; Jahner et al., 1982; Palmer et al., 1991). We searched for bioactive substances from Actinomycetes that enhance transgene expression, and found that trichostatin A (TSA), a histone deacetylase inhibitor (HDACi), enhanced several promoter activities remarkably (Y. Ma et al., 2009). HDACis have been used as anti-cancer drugs, because they have various effects on tumor cells to arrest cell growth, induce apoptosis, inhibit metastasis, and enhance anti-tumor immunity, by regulating the expression of the relevant genes (Bolden et al., 2006; Haberland et al. 2009; X. Ma et al., 2009; Mai et al., 2005). Here, we developed effective TSA-inducible killer constructs to enhance the anti-cancer effects of TSA, by identifying the TSA-responsive element of the herpes simplex virus thymidine kinase (hsvTK) promoter, and TSA-dependently activating some cell-death-inducing genes. We determined the most relevant regions responsive to TSA, and constructed chimeric promoters with higher fold-increases and greater induced strengths with TSA, by replacing the weak TSA-responsible region (TSA2) of the CMV promoter with two or three copies of the TSA-responsible sites (TSA1) of the hsvTK promoter. In addition, the synthetic intron sequence (0.2kb) from the pRL-TK vector and the long 3’-untranslated region (1.0kb) from the pSV2-neo vector, including the SV40 late polyA site, were important for the basal expression of the transgene and the TSA-induction, respectively. To create the TSA-inducible killer constructs, we placed the hsvTK gene for combination therapy with the prodrug Ganciclovir, and some strong death-inducing molecules (Bax, caspase8, and TRIF) under the control of the TSA-responsible chimeric promoters. They effectively killed the cells in which they were introduced, in a TSA-dependent manner. To evaluate the utility of the killer constructs for cancer gene therapy, the TSA-dependent death-inducing constructs were transferred to retroviral and adenoviral vectors.

It is known that glucagon is a peptide hormone consisting of 29 amino acids and regulates glycometabolism by acting in coordination with insulin. However, there are not many reports regarding its pharmacokinetics. The glucagon described in these reports are of animal pancreatic origin, but a glucagon by utilization of genetical engineering technique by the use of yeast fungus has been developed recently.We have made an assessment this time regarding the safety and pharmacokinetics in man of the glucagon (GL-G) by genetical engineering by administering it subcutaneously and intravenously in a single dose (1mg) each to ten Japanese healthy volunteers as subjects (age 20-25, average 22).The results were as follows:1) No subjective symptom, abnormal clinical laboratory value or abnormal physiological test result ascribable to GL-G administration or found problematic in the clinical aspect was observed.2) The findings obtained regarding the blood glucagon concentration (IRG) by subcutaneous administration were: Tmax-8.0±1.1min(mean±SE); Cmax-6, 629±476pg/ml; AUC-4, 710±301pg·hr/ml; and T1/2-19.9±1.5min. The findings by intravenous administration turned out to be T1/2-3.1±0.2min and AUC-6, 394±937pg·hr/ml, the latter being about 1.4 times as large as that by subcutaneous administration.3) The in vivo pharmacokinetics of BS, IRI, CPR and GH agreed well with the glucagon of animal pancreatic origin, from which it was assumed that the glucagon has the same physiological activity.From the above, it has been concluded that GL-G poses no problem regarding its safety within the range of the dosage used in present test and is a preparation with the possibility of clinical application in future.

Prolonged dietary restriction has been reported to suppress age-induced phenomena. In order to investigate how prolonged caloric restriction reduces age-related deterioration of hippocampal synaptic transmission, we compared the levels of major hippocampal polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid between 4- and 26-month-old rats. The Ca(2+) responses upon perfusion of NMDA or 30 mM K(+) between 4- and 26-month-old rats with prolonged dietary restriction were also compared using the fluorescent probe Fura-2. A decrease in membrane arachidonic acid is thought to be a major causal factor in the age-related impairment of long-term potentiation. Long-term caloric restriction seems to increase arachidonic acid levels regardless of age. However, there is no significant difference of hippocampal arachidonic acid levels between in freely feeding 4- and 26-month-old rats. Similar results were obtained from the measurement of hippocampal docosahexaenoic acid levels. Under caloric restriction, the 500 microM N-methyl-D-aspartate-induced Ca(2+) response was greatly reduced by aging, while the 30 mM K(+)-induced Ca(2+) response was not affected. In our preliminary data, the amplitude of the population spike after tetanic stimulation did not differ between 4- and 26-month-old rats under caloric restriction, while 50 microM of 2-amino-5-phosphonovaleric acid, a N-methyl-D-aspartate antagonist, markedly inhibited a potentiation of the population spike in 4-month-old rats, but with negligible inhibition in 26-month-old rats. From these results, an age-related impairment of hippocampal excitatory synaptic transmission may not be solely due to the reduction of membrane arachidonic acid. Caloric restriction might prevent age-related reduction in hippocampal synaptic transmission by enhancing non-N-methyl-D-aspartate mechanisms.

The effects of high-protein food on the bioavailability of both the racemate and individual enantiomers of verapamil were investigated in 12 healthy volunteers using a randomized crossover design. Food had no effect on any parameter of bioavailability for both the racemate and the individual enantiomers of verapamil except time to maximum concentration (tmax), which was significantly prolonged after food intake. The pharmacokinetics of the enantiomers of norverapamil were not significantly changed by food intake. These results suggest that high-protein food does not alter the pharmacokinetics and bioavailability of either the racemate or the individual enantiomers of verapamil. Therefore, the clinical efficacy of verapamil is not related to food intake, except for a slight prolongation in the time to onset of the pharmacologic effects. The present data can be applied to the high-protein content meal intake.