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M Oya

Publications and source records attributed to M Oya.

At least 37 records · Page 2Linked to original sources

Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.

Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.

Animals↗

Therapeutic effect of basic fibroblast growth factor on experimental pancreatitis in rat.

Basic fibroblast growth factor (bFGF) is one of the mitogens that facilitate endothelial proliferation and angiogenesis. This study was designed to examine the therapeutic effect of bFGF on experimental pancreatitis in rat. Edematous pancreatitis was induced by intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. BFGF (70 nmol/kg) was administered intraperitoneally after induction of pancreatitis. DNA synthesis of isolated pancreatic acinar cells of normal rats was determined as the uptake of 5-bromo-2'-deoxyuridine (BrdU) into the cells. Immunohistochemical staining of DNA synthesis in acinar cells during cerulein-induced pancreatitis was also examined with BrdU labeling in vivo technique. Cerulein administration increased serum amylase, lipase level, and wet weight of pancreatic tissue. Treatment with bFGF markedly ameliorated all these parameters. In primary culture system of isolated pancreatic acinar cells of normal rats, bFGF caused a dose-dependent increase in BrdU incorporation into DNA, showing an EC50 value of 0.8 nmol/L and a maximum response of 2.5-fold increase at a concentration of 400 nmol/L. bFGF treatment (70 nmol/kg) markedly increased BrdU labeling in the nucleus of acinar cells of the pancreatitis rats group in immunohistochemical examination when compared with control without bFGF treatment. Treatment with bFGF may represent a promising therapeutic concept for patients with acute pancreatitis.

Animals↗

Physiological role of endothelin-1 in nonworking muscles during exercise in healthy subjects.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. However, the role of ET-1 in exercise-induced physiological responses is still to be investigated. The purpose of the present study was to investigate in healthy volunteers whether the ET-1 plasma concentration in nonworking muscles is changed by exercise and to investigate the physiological role of ET-1 during exercise. Bicycle ergometer cardiopulmonary exercise tests were performed in 36 healthy men (mean age, 22.5 years). Blood samples for measuring ET-1 were drawn from the cubital vein during rest and immediately after the exercise test. The ET-1 change ratio was calculated as ET-1 immediately following exercise/ET-1 during the resting state. Cardiac output (CO) was measured during the exercise test by the impedance method. Arterial venous oxygen difference (AVO2D) when CO reached 10L/min or 15L/min was calculated as AVO2D = VO2/CO. Results were as follows: (1) the ET-1 change ratio correlated inversely with exercise time at the anaerobic threshold (r = -0.37, p = 0.03) and peak exercise time (r = -0.35, p = 0.04); (2) the ET-1 change ratio tended toward an inverse correlation with deltaVO2/deltawork rate (r = -0.29, p = 0.09); (3) the ET-1 change ratio correlated positively with AVO2D when CO reached 10L/min (r = 0.42, p = 0.02) and tended toward a positive correlation with AVO2D when CO reached 15 L/min (r = 0.32, p = 0.08). These results indicate that an increase in ET-1 in nonworking muscles may participate in the exercise-induced redistribution of blood flow and in increasing the blood flow to working muscles.

Adult↗

Magnesium dynamics and relation to left ventricular function in acute myocardial infarction.

The present study investigated the serial changes in serum magnesium (Mg) and erythrocyte concentration of Mg in patients with acute myocardial infarction (AMI) and the relationship between these changes and left ventricular ejection fraction (LVEF) at 1 month after the onset of infarction. The study group comprised 26 patients with AMI (mean age, 57.9+/-8.9 years). Serum Mg and erythrocyte Mg were measured on hospital days 1, 2, 4, 7 and 21. The change in erythrocyte Mg during the acute phase was calculated as a ratio: [(erythrocyte Mg at day 2)-(erythrocyte Mg at day 1)]/(erythrocyte Mg at day 1). The change in serum Mg was calculated similarly. The following results were obtained. (1) Serum Mg tended to increase from the onset of myocardial infarction (day 1: 1.86+/-0.19, day 2: 1.93+/-0.22, day 4: 2.17+/-0.23; day 7: 2.25+/-0.20; day 21: 2.12+/-0.15 mg/dl). (2) Erythrocyte Mg on day 2 and day 4 showed a significant decrease compared with day 1 (day 1: 2.45+/-0.40, day 2: 2.09+/-0.41, day 4: 2.07+/-0.37, day 7: 2.22+/-0.33, day 7: 2.34+/-0.28 mg/dl per 400x10(4)/mm3 cells). (3) A significant positive correlation was observed between the change in serum Mg and LVEF (r=0.55, p<0.05), and a significant negative correlation was observed between the change in erythrocyte Mg and LVEF (r=-0.57, p<0.05). Thus, it was concluded that an extracellular shift in intracellular Mg occurred during the first 2 days after the onset of myocardial infarction. This responsive increase in the extracellular Mg level may be an important factor for maintaining left ventricular function in patients 1 month after the onset of AMI.

Aged↗

Serum interleukin 6 as a prognostic factor in patients with prostate cancer.

The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.

Aged↗

'Serrated' adenoma of the colorectum, with reference to its gastric differentiation and its malignant potential.

Serrated adenoma of the colorectum was a newly proposed entity in 1990, characterized by epithelial neoplasia combining the architectural features of a hyperplastic (metaplastic) polyp with the cytological features of an adenoma. Its histogenesis and natural history still remain unclear. Forty-six serrated adenomas were obtained from 46 patients. The clinicopathological features were summarized. Paraffin-embedded blocks from 34 serrated adenomas were available for immunohistochemical studies using pS2, human gastric mucin, and p53 protein. Eighteen hyperplastic (metaplastic) polyps, 16 tubular adenomas, and 12 early-stage adenocarcinomas were randomly selected as control groups for immunohistochemical analysis. The patients' ages ranged from 32 to 86 (average 61.4) years. Males were more frequently affected than females. Serrated adenomas were predominantly present in the left-side of the colon and in the rectum (72 per cent). Their sizes ranged from 3 to 26 mm (average 9. 2mm). Six lesions (13 per cent) contained foci of high-grade dysplasia. These adenomas were significantly larger (12.7 mm) than those containing no high-grade dysplasia (8.6mm). pS2 and human gastric mucin were expressed significantly more frequently in both hyperplastic (metaplastic) polyps and serrated adenomas than in tubular adenomas or adenocarcinomas. p53-positive cells were present in 18 of the 29 pure serrated adenomas (62 per cent) and in one of the five areas of low-grade dysplasia in serrated adenomas with high-grade dysplasia (20 per cent), most of which revealed a sporadic distribution. Only five of the 29 serated adenomas with no high-grade dysplasia (17 per cent) were regarded as demonstrating p53 overexpression. On the other hand, three of the five areas of high-grade dysplasia in serrated adenomas (60 per cent) revealed diffuse positivity (3+) for p53 protein. The serrated adenoma, which possibly shows gastric differentiation, is considered to be an independent histological entity among the various phenotypes of colorectal adenomas. Serrated adenoma would seem to be a precursor of carcinoma, its potential for malignant transformation being similar to that of the traditional tubular adenoma. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.

Adenoma↗

Preoperative anal sphincter high pressure zone, maximum tolerable volume, and anal mucosal electrosensitivity predict early postoperative defecatory function after low anterior resection for rectal cancer.

PURPOSE: The aims of this study were to correlate postoperative defecatory function after low anterior resection with clinical factors and physiologic parameters and to explore the possibility of predicting early postoperative defecatory function after low anterior resection. METHODS: Thirty-two patients who underwent low anterior resection for rectal cancer were studied. Anorectal physiologic studies were performed preoperatively and six months postoperatively; maximum resting pressure, maximum squeeze pressure, length of the high pressure zone, neorectal sensory threshold, neorectal maximum tolerable volume, and anal mucosal electrosensitivity were recorded. Preoperative and postoperative defecatory function was scored between 0 (worst) and 6 (best) on the basis of bowel frequency, fecal incontinence, and urgency. RESULTS: In univariate regression analyses, a longer preoperative high pressure zone and a more sensitive anal mucosa were associated with better postoperative defecatory function. Using multiple regression analysis, in which age, gender, the level of anastomosis, and preoperative physiologic parameters were examined as independent variables, a longer preoperative high pressure zone, a larger preoperative maximum tolerable volume, and lower sensory threshold of the anal canal were associated with better postoperative defecatory function. Postoperative function score was found to be predictable using the following formula: 1.47 + 0.496 x high pressure zone (cm) + 0.007 x maximum tolerable volume (ml) - 0.247 x sensory threshold (mA) of the anal canal. CONCLUSION: Early postoperative defecatory function after low anterior resection is predictable from preoperative high pressure zone, maximum tolerable volume, and anal mucosal electrosensitivity.

Aged↗

Adrenomedullin promotes epithelial restitution of rat and human gastric mucosa in vitro.

We have investigated the effect of adrenomedullin (AM) on restitution of mucosal integrity following damage in rat and human gastric mucosa, measuring the potential difference (PD) on a mucosal strip mounted on an Ussing chamber. Mucosal damage was induced by 0.5, 1.0, and 2.0 M NaCl solution, and it caused an immediate and significant decrease in PD. In the rat AM group, PD recovered significantly more than in control group at 120 min after exposure to 0.5 M (p < 0.01) and 1.0 M (p < 0.05) NaCl solution. In the human AM group, PD completely recovered at 120 min after exposure to 0.5 M (p < 0.05) NaCl solution. In rat mucosa damaged by 0.5 M NaCl solution, the effect was inhibited by human (h)-CGRP(8-37) and there was no significant difference between the h-CGRP(8-37) group and control group. On immunohistochemical examination of rat gastric mucosa, AM was detected within the chief cell. AM probably promotes epithelial restitution primarily through the CGRP receptor, but it does not ameliorate more severe damage of gastric mucosa in vitro.

Adrenomedullin↗

Aminoguanidine has both an anti-inflammatory effect on experimental colitis and a proliferative effect on colonic mucosal cells.

BACKGROUND: The aim of this study was to assess the effect of aminoguanidine (AG) on developed colitis and cell proliferation. METHODS: Colitis was induced by means of trinitrobenzene sulphonic acid (TNB) in male Wistar rats weighing about 250 g. Seven days after induction of TNB colitis the rats were divided into two groups at random, and one group was orally treated with 1.5 micromol/kg AG each day. We assessed the effect of AG by measuring the mucosal damage, the ulcer area, myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOs) activity, and nitrogen oxide in serum 7 days after the beginning of treatment. RESULTS: AG significantly ameliorated the macroscopic damage score (AG versus control, 5.25 +/- 0.80 versus 7.50 +/- 0.50), the microscopic damage score (5.88 +/- 1.13 versus 9.25 +/- 0.31), ulcer area (0.57 +/- 0.14 versus 1.24 +/- 0.17 cm2), decreased MPO activity (51.5 +/- 9.4 versus 192.2 +/- 60 units/g tissue), and nitrogen oxide in serum (27.2 +/- 1.4 versus 32.3 +/- 1.8 microM) but did not decrease iNOs activity (8732 +/- 435 versus 8672 +/- 357 cpm/g tissue). Moreover, AG accelerated T84 cell proliferation in a dose-dependent manner. CONCLUSIONS: These results suggest that AG ameliorates TNB colitis not only by its anti-inflammatory effect but also by accelerating the proliferation of colonic mucosal cells. AG, accordingly, might well be a useful new medicine to ameliorate inflammatory bowel disease.

Analysis of Variance↗

Magnetic resonance imaging of pseudotumors of the craniovertebral junction in long-term hemodialysis patients.

BACKGROUND/AIMS: Pseudotumors of the craniovertebral junction (PTCVJ) are observed in long-term hemodialysis (HD) patients. There are neither criteria for diagnosis nor guidelines for screening. We attempted to determine magnetic resonance imaging (MRI) findings that could be used to detect PTCVJ, to determine the prevalence of PTCVJ, and to evaluate whether destructive spondyloarthropathy (DSA) might be a yardstick for selection of patients for MRI examination for PTCVJ. METHODS: MRI were examined in 19 DSA patients (8 males, 11 females, age 61.4 +/- 7.3 years, HD duration 17.0 +/- 4.4 years) and in 20 sex-, age-, and HD-duration-matched non-DSA patients (9 males, 11 females, age 57.5 +/- 6.6 years, HD duration 17.7 +/- 4.9 years). We evaluated MRI characteristics of PTCVJ according those which occur due to rheumatoid arthritis. RESULTS: PTCVJ were characterized as follows: disappearance of fat pads in the upper region (supradental PTCVJ), intensity change of the 'predental triangle' in the anterior region (predental PTCVJ), and thickening of cruciform ligaments (retrodental PTCVJ). The prevalence of PTCVJ among patients undergoing HD more than 10 years was high (26 out of 39; 66.7%). The prevalence of PTCVJ was not different between DSA and non-DSA groups. CONCLUSION: We verified that the above MRI findings might be helpful in the detection of PTCVJ. These findings were observed frequently and independently also in patients with DSA.

Amyloidosis↗

Exercise-induced changes in plasma atrial natriuretic peptide and brain natriuretic peptide concentrations in healthy subjects with chronic sleep deprivation.

Recent observations have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) correlate with cardiac function or prognosis in heart failure patients. However, relatively little is known about changes in their plasma concentration during commonly occurring physiological states such as fatigue. Therefore, this study was designed to examine the physiological changes of plasma ANP and BNP concentrations using a chronic sleep-deprivation model. Bicycle ergometer cardiopulmonary exercise tests were performed in 10 healthy volunteers (mean age: 22.7 years). Blood samples for measuring ANP and BNP were drawn during the resting state and immediately after each exercise test. Cardiac output (CO) was measured during the exercise test by the impedance method. The study conditions were designed as follows: (A) a day following a period of normal sleep (control state) and (B) a day preceded by 1 month during which sleep lasted <60% of normal (chronic sleep-deprived state). Results were as follows. (1) Peak oxygen uptake and peak CO decreased during the sleep-deprived state compared with the control state. (2) There was no difference between peak heart rates measured during exercise under the 2 conditions. (3) Plasma ANP concentration during exercise increased significantly during the control state, whereas only a tendency toward increase was observed during the sleep-deprived state. (4) Plasma BNP concentration during exercise tended to increase in the control state compared with the resting state, whereas there was no difference in plasma BNP between after exercise and resting state in the sleep-deprived state. These results indicate that changes of ANP or BNP induced by exercise tended to be decreased by chronic sleep deprivation.

Adult↗

Effects of exercise training on the recovery of the autonomic nervous system and exercise capacity after acute myocardial infarction.

This study investigated the effects of aerobic exercise training on the early phase of the recovery process following acute myocardial infarction (AMI) in terms of the autonomic nervous system, cardiac function and exercise capacity. Twenty-eight patients in the first week after the onset of AMI were assigned randomly to either a training group or a control group. The training group performed aerobic exercise for 2 weeks. Cardiopulmonary exercise testing was performed 3 times during the 3 months after the onset. Heart rate variability, plasma norepinephrine (NE) levels, and cardiac index (CI) during exercise were measured. In the training group, plasma NE level and deltaCI (peak CI-rest CI) were significantly improved from 1 to 3 weeks after the onset, and the high frequency of heart rate variability and peak oxygen uptake were significantly increased up to 3 months after the onset. In the control group, the plasma NE level and the deltaCI during the 1-3 weeks post-AMI, the high frequency of heart rate variability and the peak oxygen uptake showed a tendency to improve up to 3 months after the onset. These results indicate that sympathetic nervous activity improves soon after the onset of AMI, in conjunction with improvement in cardiac function, and that this improvement is not affected by exercise training. In contrast, the recovery of parasympathetic nervous activity requires a longer period, along with the recovery of exercise capacity, which is facilitated by even short-term aerobic exercise training.

Aged↗

Troglitazone inhibits bicarbonate secretion in rat and human duodenum.

Troglitazone is a new, orally effective antidiabetic agent that decreases plasma glucose in obese patients with non-insulin-dependent diabetes mellitus. Unfortunately, troglitazone also has a propensity to cause edema. This study was designed to determine how troglitazone affects intestinal ion transport and water absorption. Short circuit current (I(sc)) was measured in rat and human duodenal mucosa in Ussing chambers. Five minutes later, the serosal addition of troglitazone caused I(sc) to decrease gradually, and after 50 min, I(sc) reached the peak of decrease. EC(50) values and maximum response to I(sc) in rat and human mucosa were 8.4 and 8.7 microM and 8.56 +/- 1.0 and 8.00 +/- 2.0 microA/cm(2), respectively. In an HCO(3)(-)/CO(2)-free system, the decrease in I(sc) caused by troglitazone was 1.31 +/- 0.83 microA/cm(2). When 10 mM acetazolamide was preadministered, the small decrease in I(sc) evoked by troglitazone (20 microM) was 4.56 +/- 0.22 microA/cm(2), whereas the preadministration of 100 microM amiloride and 100 nM tetrodotoxin did not influence the decrease in I(sc) evoked by troglitazone. The serosal preadministration of 100 nM vasoactive intestinal peptide potently enhanced the decrease in I(sc) evoked by 20 microM troglitazone (21.1 +/- 1.63 microA/cm(2)). The cyclic AMP contents of rat duodenal mucosa incubated with and without troglitazone (20 microM) for 50 min were 3.2 +/- 0.25 and 5. 8 +/- 0.46 pmol/mg protein, respectively (P <.01). These results indicate that the ionic basis for the decrease in I(sc) that is induced by troglitazone may be inhibition of electrogenic bicarbonate secretion. The alteration of intestinal ion transport by troglitazone could cause edema.

Animals↗

GPT genotyping by polymerase chain reaction and restriction fragment length polymorphism analysis.

Polymorphism of GPT was investigated in blood samples from 241 unrelated Japanese individuals by PCR-RFLP analysis. Three common types were identified which agreed with those obtained by starch gel electrophoresis. The allele frequencies were GPT*1 = 0.604 and GPT*2 = 0.396. The population data fitted the Hardy-Weinberg law. The PCR-RFLP patterns of GPT were also demonstrated in semen, and the types coincided with those in the corresponding blood. The present method permitted GPT genotyping in bloodstains and semen stains stored for 20 years. The GPT system determined by PCR-RFLP can still be a useful supplement in medicolegal individualization of biological stains.

DNA↗

Plasma D-dimer level in patients with colorectal cancer: its role as a tumor marker.

The purpose of this study was to explore the relationship between the preoperative plasma D-dimer (DD) levels and the tumor pathology of colorectal cancer. The plasma DD levels were measured preoperatively in 108 patients with colorectal cancer, and then were correlated with the tumor pathology and stage. The diagnostic value of the DD levels for the tumor stage was then compared with that of the preoperative carcinoembryonic antigen (CEA) levels. The preoperative DD levels were higher in patients with either a large-sized tumor or a tumor showing deep wall penetration. Lymph-node metastasis, lymphatic invasion, hepatic metastasis, and peritoneal dissemination were all associated with higher DD levels. A stepwise increase in the median DD level was found with the tumor stage. The preoperative DD levels also significantly correlated with CEA levels. When a cutoff value of 0.6 microg/ml was used in the DD assay, the sensitivity and specificity for Dukes C or D cancer were 67.2% and 64.0%, and those for Dukes D cancer were 91.3% and 57.6%, respectively. Although the DD assay was less specific, its diagnostic value in the preoperative staging of colorectal cancer was comparable to that of the CEA assay. The measurement of the preoperative DD level is thus considered to be useful for the preoperative staging of colorectal cancer.

Adult↗

Expression of G1-->S transition regulatory molecules in human urothelial cancer.

Growth of cancer cells is characterized by accelerated passage through the cell cycle, which is often caused by deregulation of the G1-->S transition. In this study the expression of G1-->S transition regulatory molecules was analyzed in 32 transitional cell carcinoma specimens and fifteen normal tissues obtained by cystectomy or nephroureterectomy of mainly locally advanced tumors, as well as six bladder cancer cell lines. Expression of mRNAs for cyclins D1 and D2 and cyclin-dependent kinases (CDK) 2 and 4 was investigated by quantitative reverse transcription-polymerase chain reaction. Overexpression of cyclin D1 compared to normal mucosa was observed in 3 tumors (9.4%), but in neither of the cell lines. All tumors with overexpression were moderately differentiated (G2) pT1 or pT2 tumors, and thus among the less advanced specimens. Cyclin D2 was not expressed in normal bladder mucosa or in tumors. The expression of CDK4 mRNA varied within the same range in mucosa, tumors, and cell lines. CDK2 mRNA expression varied more strongly and was diminished in individual tumors and in four cell lines. It is concluded that cyclin D1 overexpression can play an important role in the early stage of urothelial tumorigenesis, driving cell proliferation. Ectopic expression of cyclin D2 or amplification of CDK4 does not occur at a significant frequency in urothelial carcinomas. Different expression patterns of cyclin D1 and CDK2 indicate heterogeneity in the mechanisms of G1-->S transition deregulation in individual bladder tumors which may elicit differences in their biological and clinical behavior.

Aged↗

Efficacy of oral magnesium administration on decreased exercise tolerance in a state of chronic sleep deprivation.

We have previously reported that chronic sleep deprivation causes a deficiency of intracellular magnesium (Mg) and decreased exercise tolerance. The aim of this study was to clarify whether oral administration of Mg could be effective in restoring the exercise tolerance that is decreased by chronic sleep deprivation. A bicycle ergometer cardiopulmonary exercise test was performed by 16 healthy volunteers (mean age 21.9 years). They were divided into 2 groups: 8 received doses of 100 mg of Mg orally per day for 1 month (Mg group) and the remaining 8 received no Mg and served as the control group. The study conditions were designed as follows: (1) the usual state (good sleep); and (2) the sleep-deprived state (sleeping time up to 60% less than the usual state for 1 month). The ratio of intracellular Mg content of the sleep-deprived state to the usual sleep state was significantly higher in the Mg group (p<0.05) than the untreated control group. There was no difference between the sleep-deprived state and the usual state with regard to anaerobic threshold and peak oxygen uptake in the Mg group, whereas both of these decreased in the sleep-deprived state in the control group. These results indicate that decreased exercise tolerance observed in the sleep-deprived state could be improved by oral Mg administration.

Administration, Oral↗