Human metapneumovirus-associated community-acquired pneumonia in adults during the first wave of COVID-19.

Objective: The clinical course of human metapneumovirus (hMPV) infection is similar to that of coronavirus 2019 disease (COVID-19). However, community-acquired hMPV infections in adults have not yet been sufficiently investigated. We examined the detection status of hMPV antigens and the clinical features of positive patients during the first wave of COVID-19, which coincided with the epidemic season of hMPV infection in Japan. Methods: In this cross-sectional, observational, and single-center study, we recruited consecutive individuals who visited the Japan Agricultural Cooperatives Kochi Hospital due to fever, respiratory symptoms, or close contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected persons during the period from January to May 2020. Results: The positive rate of immunochromatography for hMPV antigens from nasopharyngeal swabs was 9.5% (4/42), and four positive cases were community-acquired pneumonia (CAP) (5.3% of all CAP). The positive rate of hMPV antigens in the CAP group (30.8%, 4/13) was higher than that in the non-pneumonia group (0.0%, 0/19) (p < 0.05). The average age of the four adult patients with CAP was 69.8 years (range 35-93). Mean white blood cell counts and C-reactive protein blood levels were 6,250 cells/µL (3,500-12,180) and 4.30 mg/dL (4.05-7.04), respectively. Chest computed tomography images were diverse and two patients showed dense consolidation. No multi-organ disorder was noted during the clinical course in any of the four cases, and their prognoses were good. Conclusion: hMPV infection may be considered in the differential diagnosis of COVID-19 and CAP in Japan under the preventive measures for SARS-CoV-2 infection, at least during the epidemic season of hMPV infection.

A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase.

Diketopiperazines (DKPs) are naturally-occurring cyclic dipeptides with a small structure and are found in many organisms and in large amounts in some foods and beverages. We found that a chicken essence beverage, which is popular among Southeast Asians as a traditional remedy and a rich source of DKPs, inhibited the serotonin transporter (SERT) and suppressed serotonin uptake from rat brain synaptosomes, which prompted us to isolate and identify the active substance(s). We purified a SERT inhibitor from the chicken essence beverage and identified it as the DKP cyclo(L-Phe-L-Phe). Interestingly, it was a naturally occurring dual inhibitor that inhibited both SERT and acetylcholinesterase (AChE) in vitro. The DKP increased extracellular levels of the cerebral monoamines serotonin, norepinephrine, and dopamine in the medial prefrontal cortex and acetylcholine in the ventral hippocampus of freely moving rats when administered orally. Moreover, cyclo(L-Phe-L-Phe) significantly shortened escape latency in the water maze test in depressed mice previously subjected to a repeated open-space swimming task, which induces a depression-like state. Cyclo(L-Phe-L-Phe) also significantly improved accuracy rates in a radial maze test in rats and increased step-through latencies in a passive avoidance test in mice with scopolamine-induced amnesia. These animal test results suggest that cyclo(L-Phe-L-Phe), which is present abundantly in some foods such as chicken essence, may abrogate the onset of depression and, thus, contribute to preventing the development of Alzheimer's disease and other dementia, because senile depression is a risk factor for dementia.

Effects of beer and hop on ionotropic gamma-aminobutyric acid receptors.

Beer induced the response of the ionotropic gamma-aminobutyric acid receptors (GABA(A) receptors) expressed in Xenopus oocytes, indicating the presence of gamma-aminobutyric acid (GABA)-like activity. Furthermore, the pentane extract of the beer, hop (Humulus lupulus L.) oil, and myrcenol potentiated the GABA(A) receptor response elicited by GABA. The GABA(A) receptor responses were also potentiated by the addition of aliphatic esters, most of which are reported to be present in beer flavor. Aliphatic esters showed the tendency to decrease in the potentiation of the GABA(A) receptor response with an increase in their carbon chain length. When myrcenol was injected to mice prior to intraperitoneal administration of pentobarbital, the pentobarbital-induced sleeping time of mice increased additionally. Therefore, the beer contained not only GABA-like activity but also the modulator(s) of the GABA(A) receptor response.

Fragrances in oolong tea that enhance the response of GABAA receptors.

We electrophysiologically investigated the effect of some fragrant compounds in oolong tea on the response of ionotropic gamma-aminobutyric acid (GABA) receptors (GABAA receptors) which were expressed in Xenopus oocytes. Of the tested fragrances in oolong tea, cis-jasmone, jasmine lactone, linalool oxide and methyl jasmonate significantly potentiated the response. Among these, cis-jasmone and methyl jasmonate potently potentiated the response, having a respective dissociation constant of the compound (Kp) and maximum potentiation (Vm) of 0.49 mM and 322% for cis-jasmone, and 0.84 mM and 450% for methyl jasmonate. Inhalation of 0.1% cis-jasmone or methyl jasmonate significantly increased the sleeping time of mice induced by pentobarbital, suggesting that these fragrant compounds were absorbed by the brain and thereby potentiated the GABAA receptor response. Both of these compounds may therefore have a tranquillizing effect on the brain.

Aging of whiskey increases 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity.

1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of Japanese whiskey after various aging periods in oak barrels was measured to evaluate the antioxidative effects of whiskey. The activity of the whiskey increased with the aging period with high correlation. The activity of various types of whiskey was measured and shown to be correlated to the potentiation of the GABAA receptor response measured in a previous paper. However, the fragrant compounds in the whiskey which potentiated the GABAA receptor response had low DPPH radical scavenging activity, while phenol derivatives had high radical scavenging activity. The whiskey was extracted by pentane. The aqueous part showed the scavenging activity, whereas the pentane part did not. Thus, both the DPPH radical scavenging activity and the potentiation of the GABAA receptor response increased during whiskey aging in oak barrels, but were due to different components. The whiskey protected the H2O2-induced death of E. coli more than ethanol at the same concentration as that of the whiskey. The changes that occurred in the whiskey during aging may be the reason aged whiskies are so highly valued.

Effects of coffee components on the response of GABA(A) receptors expressed in Xenopus oocytes.

The effects of both coffee components and coffee extract on the electrical responses of GABA(A) receptors expressed in Xenopus oocytes were studied by injecting cRNAs of the alpha(1) and beta(1) subunits of the bovine receptors. The aqueous extract of coffee dose-dependently inhibited the GABA-elicited responses, whereas the lipophilic extract of coffee by diethyl ether slightly potentiated it at low doses (0.1-0.4 microL/mL) but showed inhibition at high doses (0.5-0.8 microL/mL). Theophylline inhibited the response in a noncompetitive mechanism (K(i) = 0.55 mM), whereas theobromine and trigonelline hydrochloride inhibited it in a competitive manner, K(i) = 3.8 and 13 mM, respectively. Benzothiazole, catechol, 2,4-dimethylstyrene, guaiacol, 1-octen-3-ol, sotolone, and 2,3,5-trimethylphenol potentiated the responses significantly. Potentiation elicited by guaiacol and sotolone was independent of GABA concentrations, whereas that by 1-octen-3-ol was dependent. When 1-octen-3-ol (100 mg/kg) was orally administered to mice prior to intraperitoneal administration of pentobarbital, the sleeping time of mice induced by pentobarbital increased significantly.

Aging of whiskey increases the potentiation of GABA(A) receptor response.

It is known that the target of most mood-defining compounds such as ethanol is an ionotropic gamma-aminobutyric acid receptor (GABA(A) receptor). The potentiation of the response of these inhibitory neurotransmitter receptors induces anxiolytic, sedative, and anesthetic activities in the human brain. Because both extracts of whiskey by pentane and fragrant components in whiskey potentiate the GABA(A) receptor-mediated response, GABA(A) receptors were expressed in Xenopus oocyte by injecting cRNAs prepared from the cloned cDNA for the alpha(1) and beta(1) subunits of the bovine receptors in order to study the effects of whiskey itself on the GABA(A) receptor-mediated response. Whiskey itself also potentiated the electrical responses of GABA(A) receptors generally more than ethanol at the same concentration as that of the whiskey. The potentiation of the GABA(A) receptor-mediated response increased with the aging period of the whiskey. Inhalation of whiskey to mice increased the sleeping time induced by pentobarbital more than that of the same concentration of ethanol as the whiskey. These results suggest that not only ethanol but also minor components in whiskey play an important role in the potentiation of GABA(A) receptor-mediated response and possibly the sedative effect of whiskey. Although the minor components are present in extremely small quantities compared with ethanol in alcoholic beverages, they may modulate the mood or consciousness of humans through the potentiation of the GABA(A) receptor response after absorption into the brain, because these hydrophobic compounds are easily absorbed into the brain across the blood-brain barrier and are several thousands times as potent as ethanol in the potentiation of the GABA(A) receptor-mediated response.

Effects of oolong tea on metabolism of plasma fat in mice under restraint stress.

We investigated the effects of oolong tea on the basic metabolism of plasma lipids in mice under restraint stress. When a lipid emulsion (Intralipid 20%; a lipid emulsion containing 20% soybean oil) was injected intravenously into mice, the restraint stress prolonged the half-life (T 1/2) of elimination for plasma triglyceride (TG) from 28.7 to 55.5 min. The elimination rate per minute was 48.2% in stressed mice with the rate in starved control mice as 100%. Therefore, TG metabolism was disrupted by the stress, and the use of TG as an energy source decreased. We found that the metabolism of lipids significantly response to the restrained stress in the present study. Plasma TG was 515.9 +/- 29.9mg/dl 35min after Intralipid administration in control stressed mice, 478.7 +/- 26.7 mg/dl in the stressed group given caffeine 100 mg/kg of body weight, and 418.3 +/- 18.4 mg/dl in the stressed group given 1,000 mg/kg oolong tea, an improvement by 7.2% and 18.9%, respectively, with the value for the untreated control group. The intake of oolong tea alleviated the stress-induced decrease in the rate of blood lipid metabolism; this effect may have arisen from some non-specific stress-relieving property of the tea or from acceleration of lipid metabolism by properties of polyphenols, etc. in tea. Oolong tea had anti-stress effects on plasma TG metabolism, and the effects did not depend on caffeine.

Potentiation of the ionotropic GABA receptor response by whiskey fragrance.

It is well-known that the target of most mood-defining compounds is an ionotropic gamma-aminobutyric acid receptor (GABA(A) receptor). The potentiation of the response of these inhibitory neurotransmitter receptors induces anxiolytic, sedative, and anesthetic activity in the human brain. To study the effects of whiskey fragrance on the GABA(A) receptor-mediated response, GABA(A) receptors were expressed in Xenopus oocyte by injecting rat whole brain mRNA or cRNA prepared from the cloned cDNA for the alpha(1) and beta(1) subunits of the bovine receptors. Most whiskey components such as phenol, ethoxy, and lactone derivatives potentiated the electrical responses of GABA(A) receptors, especially ethyl phenylpropanoate (EPP), which strongly potentiated the response. When this compound was applied to mice through respiration, the convulsions induced by pentetrazole were delayed, suggesting that EPP was absorbed by the brain, where it could potentiate the GABA(A) receptor responses. The extract of other alcoholic drinks such as wine, sake, brandy, and shochu also potentiated the responses to varying degrees. Although these fragrant components are present in alcoholic drinks at low concentrations (extremely small quantities compared with ethanol), they may also modulate the mood or consciousness of the human through the potentiation of the GABA(A) receptor response after absorption into the brain, because these hydrophobic fragrant compounds are easily absorbed into the brain through the blood-brain barrier and are several thousands times as potent as ethanol in the potentiation of the GABA(A) receptor-mediated response.

Contribution of the antioxidative property of astaxanthin to its protective effect on the promotion of cancer metastasis in mice treated with restraint stress.

We investigated the effects of astaxanthin on the antitumor effector activity of natural killer (NK) cells suppressed by stress in mice in order to define the immunological significance of astaxanthin (ASX) when combined with restraint stress treatment. When the mice were treated with restraint stress alone, the total number of spleen cells, and the level NK cell activity per spleen were reduced to a nadir on day 3. The stress also caused a significant increase in the lipid peroxidation of liver tissue. ASX (100 mg/kg/day, p.o., 4 days) improved the immunological dysfunction induced by restraint stress. On the other hand, metastatic nodules were observed in the livers of syngenic DBA/2 mice on day 12 after inoculation of P815 mastocytoma cells. Hepatic metastasis was promoted further by restraint stress when applied on day 3 before the inoculation of P815. Daily oral administration of ASX (1 mg/kg/day, p.o., 14 days) markedly attenuated the promotion of hepatic metastasis induced by restraint stress. These results suggested that astaxanthin improves antitumor immune responses by inhibiting of lipid peroxidation induced by stress.

Absorption and metabolism of antioxidative polyphenolic compounds in red wine.

We have shown that drinking red wine reduces oxidation of LDL. This reduction in oxidation has been attributed to the polyphenolic compounds in red wine, but the mechanisms of absorption and metabolism of these compounds has been unclear. We therefore investigated the absorption and metabolism of polyphenols using rats to identify their active forms in biological fluids. We also investigated the effect of tartaric acid (TA), a major organic acid in wine, on the absorption of polyphenols. Our results suggested that low molecular weight polyphenols are absorbed in the intestine and metabolized to their glucuronide conjugates, which exhibit antioxidative activity in plasma, and that TA can enhance the bioavailability of wine polyphenols.