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The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in the older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in healthy older Japanese volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL). Conclusions: The reference interval of CSF-TP in the older population should be reconsidered for the precise diagnosis of neurological emergencies.

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in Japanese healthy older volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥ 65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL).

Body temperature is important for diagnosing illnesses. However, its assessment is often a difficult task, considering the large individual differences. Although 37 °C has been the gold standard of body temperature for over a century, the temperature of modern people is reportedly decreasing year by year. However, a mean axillary temperature of 36.89 ± 0.34 °C reported in 1957 is still cited in Japan. To assess the measured axillary temperature appropriately, understanding its distribution in modern people is important. This study retrospectively analyzed 2454 axillary temperature measurement data of healthy Japanese adults in 2019 (age range, 20–79 years, 2258 males). Their mean temperature was 36.47 ± 0.28 °C (36.48 ± 0.27 °C in males and 36.35 ± 0.31 °C in females). Approximately 5% of the 20–39-year-old males had body temperature ≥37 °C, whereas 8% had a temperature ≥ 37 °C in the afternoon. However, none of the subjects aged ≥50 years reported body temperature ≥37 °C. In multivariable regression analysis, age, blood pressure, pulse rate, and measurement time of the day were associated with axillary temperature. Our data showed that the body temperature of modern Japanese adults was lower than that reported previously. When assessing body temperature, the age, blood pressure, pulse rate, and measurement time of the day should be considered.

To evaluate the time-profile of intragastric fluid volume in humans after intragastric administration of drug solution.Eight healthy volunteers were intragastrically administered 150 mL of drug solution containing atenolol (non-absorbable marker) and salicylic acid, then, aliquots of gastric fluid (ca. 2 mL) were sampled for 2 h through the catheter. Rate constants for secretion and emptying of the fluid were obtained by fitting the time-course of atenolol concentration to the simple gastric fluid transit model. Absorption of salicylic acid from the stomach was estimated by comparing its gastric concentration with that of atenolol.Kinetic analysis of atenolol concentration in the stomach indicated a rapid emptying of the fluid with an average half-life of 4.2 min. Steady-state intragastric fluid volume in 8 volunteers was estimated as 4-133 mL with an average of 42 mL. Intragastric concentration (normalized by dose) of salicylic acid was always lower than that of atenolol, showing approximately 40% of salicylic acid was absorbed from the stomach before emptying to the intestine.This study provided valuable information on intragastric fluid dynamics and gastric drug absorption in humans to establish a better in vitro-in vivo correlation in oral drug absorption.

In order to clarify the mechanism by which pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH 2 (vasopressin-(4–9)), a major metabolite C-terminal fragment of [Arg 8 ]-vasopressin (vasopressin-(1–9)), improves learning and memory, we used several different drugs such as an acetylcholine receptor antagonist, a Ca 2+ /calmodulin-dependent protein kinase II inhibitor, vasopressin receptor antagonists and L-type Ca 2+ channel blocker to disrupt spatial memory in rats. Moreover, we examined the effect of vasopressin-(4–9) on acetylcholine release in the ventral hippocampus using microdialysis. Vasopressin-(4–9) (10 fg/brain, i.c.v.) improved the impairment of spatial memory in the eight-arm radial maze induced by scopolamine, pirenzepine and Ca 2+ /calmodulin -dependent protein kinase II inhibitor. Pirenzepine, a vasopressin V 1A receptor antagonist, and L-type Ca 2+ channel blocker, but not a vasopressin V 2 receptor antagonist, suppressed the effects of vasopressin-(4–9) on scopolamine-induced impairment of spatial memory. Moreover, vasopressin-(4–9) did not affect acetylcholine release in the ventral hippocampus of intact rats or of scopolamine-treated rats as assessed by microdialysis. These results suggest that vasopressin-(4–9) activates vasopressin V 1A receptors on the postsynaptic membrane of cholinergic neurons, and induces a transient influx of intracellular Ca 2+ through L-type Ca 2+ channels to interact with muscarinic M 1 receptors. The activation of these processes by vasopressin-(4–9) is critically involved in the positive effect of vasopressin-(4–9) on scopolamine-induced impairment of spatial memory.

In the present study, the effects of coadministration of fexofenadine hydrochloride and erythromycin on the pharmacokinetics and electrocardiographic findings, focussed on QTc, were investigated. A double-blind, randomized, placebo-controlled, repeated-dose, orthogonal Latin square crossover study was conducted in 18 male healthy volunteers. Trial medication was given for three periods of 7 days separated by washout periods of 14 days. Fexofenadine hydrochloride (120 mg) was given twice a day for 7 days. Erythromycin (300 mg) was concomitantly given four times a day for 7 days.During the administration of fexofenadine hydrochloride alone as well as during that of concomitant administration of fexofenadine hydrochloride and erythromycin, no problematic abnormality was observed in subjective/objective symptoms, blood pressure, pulse rate, body temperature or clinical laboratory findings.The effect of concomitant administration on maximum plasma concentration at steady state (Cmax, ss), the steady-state area under the plasma concentration-time curve from 0 h to 12 h [AUCss (0-12)] and the apparent oral clearance from 0 h to 12 h at steady state [CLpo, ss (0-12)] was assessed comparing 90% confidence intervals with the range of 0.80-1.25 in accordance with EU and US FDA operating guidelines. When fexofenadine hydrochloride was coadministered with erythromycin, both mean Cmax, ss and mean AUCss (0-12) of fexofenadine were significantly higher than those for the administration of fexofenadine alone (p

We investigated the relationship between the induction of spatial cognition impairment in the 8-arm radial maze task and regional changes (ventral hippocampus (VH), dorsal hippocampus, frontal cortex, and basolateral amygdala nucleus) in brain acetylcholine (ACh) release using microdialysis in rats treated with muscarinic (M) receptor antagonists. In a behavioral study, two M1 antagonists, scopolamine (0.5 mg/kg, i.p. and 20 microg, i.c.v.) and pirenzepine (80 microg, i.c.v.), but not an M2 antagonist, AF-DX116 (40-80 microg, i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain microdialysis with Ringer's solution containing 0.1 mM eserine sulfate, scopolamine and AF-DX116, but not pirenzepine, increased ACh release in the VH. Moreover, in the bilateral injection of scopolamine (2 microg/side), the VH and dorsomedial thalamus nucleus were important regions for scopolamine-induced impairment of spatial cognition. A simultaneous determination of the behavioral changes revealed that scopolamine (0.5 mg/kg, i.p.) markedly decreased the ACh contents and also increased the ACh release in all regions tested. Especially, the changes in the ACh release of the VH closely paralleled the induction of the scopolamine-induced impairment of spatial cognition. These results suggest that the blocking balance between M1 and M2 muscarinic receptor in the VH therefore plays a major role in the spatial cognition impairment induced by scopolamine in the 8-arm radial maze task.

Major local adverse reactions in the nicotine patches are skin reactions. To assess the skin reaction of PHK-301p, a newly developed nicotine patch, we conducted a phase I study that consisted of 2 parts: a skin irritation test (48-h closed patch test) and a photosensitivity test (24-h closed patch test + Ultraviolet A irradiation). Twenty healthy men were treated with PHK-301p and placebo. Both preparations were punched out to a circle of 6-mm diameter and were applied simultaneously to each participant. Skin irritation and photosensitivity were assessed by a physician who was kept unaware of the treatment. In the skin irritation test, moderate and mild erythemas were observed in each participant 72 h after application (24 h after removal) for PHK-301p. Mild erythema was observed in one participant 49 h after application (1 h after removal) for placebo. The skin irritation index, which was calculated based on the skin reactions of participants, was 7.5 for PHK-301p and 2.5 for placebo. In the photosensitivity test, one participant had mild erythema (±) approximately 25 and 72 h after application of PHK-301p. No solar urticaria was observed. From these results, we concluded that PHK-301p is an acceptable product as a nicotine patch. Keywords:: nicotine replacement therapy, patch test, smoking cessation, nicotine patch, skin reaction