1.Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model
Satoshi SUGINO ; Ken INOUE ; Reo KOBAYASHI ; Ryohei HIROSE ; Toshifumi DOI ; Akihito HARUSATO ; Osamu DOHI ; Naohisa YOSHIDA ; Kazuhiko UCHIYAMA ; Takeshi ISHIKAWA ; Tomohisa TAKAGI ; Hiroaki YASUDA ; Hideyuki KONISHI ; Yasuko HIRAI ; Katsura MIZUSHIMA ; Yuji NAITO ; Toshifumi TSUJI ; Takashi OKUDA ; Keizo KAGAWA ; Makoto TOMINAGA ; Yoshito ITOH
Journal of Neurogastroenterology and Motility 2022;28(4):693-705
Background/Aims:
Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice.
Methods:
In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725).
Results:
In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice.
Conclusion
For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.
2.Association between Lymphovascular Invasion and Recurrence in Patients with pT1N+ or pT2–3N0 Gastric Cancer: a Multi-institutional Dataset Analysis
Keizo FUJITA ; Mitsuro KANDA ; Seiji ITO ; Yoshinari MOCHIZUKI ; Hitoshi TERAMOTO ; Kiyoshi ISHIGURE ; Toshifumi MURAI ; Takahiro ASADA ; Akiharu ISHIYAMA ; Hidenobu MATSUSHITA ; Chie TANAKA ; Daisuke KOBAYASHI ; Michitaka FUJIWARA ; Kenta MUROTANI ; Yasuhiro KODERA
Journal of Gastric Cancer 2020;20(1):41-49
PURPOSE:
Patients with pathological stage T1N+ or T2–3N0 gastric cancer may experience disease recurrence following curative gastrectomy. However, the current Japanese Gastric Cancer Treatment Guidelines do not recommend postoperative adjuvant chemotherapy for such patients. This study aimed to identify the prognostic factors for patients with pT1N+ or pT2–3N0 gastric cancer using a multi-institutional dataset.
MATERIALS AND METHODS:
We retrospectively analyzed the data obtained from 401 patients with pT1N+ or pT2–3N0 gastric cancer who underwent curative gastrectomy at 9 institutions between 2010 and 2014.
RESULTS:
Of the 401 patients assessed, 24 (6.0%) experienced postoperative disease recurrence. Multivariate analysis revealed that age ≥70 years (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.09–7.23; P=0.030) and lymphatic and/or venous invasion (lymphovascular invasion (LVI): HR, 7.88; 95% CI, 1.66–140.9; P=0.005) were independent prognostic factors for poor recurrence-free survival. There was no significant association between LVI and the site of initial recurrence.
CONCLUSIONS
LVI is an indicator of poor prognosis in patients with pT1N+ or pT2–3N0 gastric cancer.
3.NUTRITIONAL STATUS OF JAPANESE MALE COLLEGIATE ATHLETES
KUMIKO MINATO ; YUKO SATO ; SHUHEI KOBAYASHI ; FUMIHIKO KARIYA ; KEIZO KOBAYASHI ; MITSUO NARUSAWA ; TOSHIO OHMORI
Japanese Journal of Physical Fitness and Sports Medicine 2006;55(Supplement):S189-S192
The purpose of this study was to assess the status of nutrients intake in male Japanese collegiate athletes. Each 20 of baseball (B), soccer (S), volley ball (V), and long distance (L) athletes participated in this study. The B, S, and V athletes lived by themselves, whereas the L athletes lived in an athletes dormitory with provided meal. The nutritional status was assessed for 2 days. Mean energy intakes in the B, S, V, and L groups were 43.6, 53.7, 47.0, and 55.0 kcal/kg body weight, respectively. Mean protein intakes were 1.2, 1.6, 1.3 and 2.4 g/kg, respectively. In B athletes, skipping of breakfast was recognized frequently. Most of micronutrients intakes in the B, S, and V groups were less than the recommended dietary allowances for athletes. We suggest that a provided meal system is a better system for collegiate athletes and more nutritional education is necessary for Japanese male collegiate athletes, in particular, those living by themselves.
4.EFFECTS OF PROLONGED VOLUNTARY WHEEL-RUNNING ON TIBIAL BONE-MASS IN GROWING MALE RATS USING pQCT
FUMIHIKO KARIYA ; JUN KITAGAWA ; KEIZO KOBAYASHI ; MITSUO NARUSAWA ; YOSHIBUMI NAKAHARA
Japanese Journal of Physical Fitness and Sports Medicine 2004;53(1):107-114
In this study, we investigated the effects of prolonged voluntary running training on bone mass in the tiba of growing male SD rats. At 5 weeks old, the rats were divided into 4 groups : group 15 VE (n=7) exercised voluntarily on a running wheel for 10 weeks from 5- to 15-weeks old ; group 35 VE (n=7) exercised voluntarily on a running wheel for 30 weeks from 5- to 35-weeks old ; in groups 15SC (n=6) and 35 SC (n=5), rats were housed individually in normal plastic cages for the same periods as groups 15 VE and 35 VE, respectively. At the end of each experimental period, the right tibia from each rat was used for bone- mass analysis using peripheral quantitative cumputed tomography (pQCT) . The evaluated portions were the proximal methaphysis and the diaphysis, with total, cortical, and trabecular data from these portions being obtained as volumetric bone mineral content (vBMC) and volumetric bone mineral density (vBMD) . The results indicated that 1) although voluntary running distance tended to decline during the later period (1635 wk old) in 35 VE rats, some mean values obtained for bone mass parameters using pQCT were significant greater in 35 VE than in 35SC ; 2) the mean values from those parameters in 15 VE were not significantly different from those in 15 SC. These results suggest that the continuation of voluntary exercise may be important for bone- mass enhancement in rat tibia.
5.The effect of running training on regional cardiac myosin isozyme composition in rats.
SHUICHI MACHIDA ; KEIZO KOBAYASHI ; MITSUO NARUSAWA
Japanese Journal of Physical Fitness and Sports Medicine 2000;49(2):247-255
We examined the effect of running training on regional cardiac myosin isozyme composition in rats. Male Sprague-Dawley strain rats (4 weeks old) were used, and divided into two groups: sedentary control (C) and trained (T) groups. The T group was trained by treadmill running (40 m/min, 1h/day, 5 days/week, for 12 weeks) . At 16 weeks old, their hearts were excised. The left ventricle was separated into the subendocardium (Endo) and subepicardium (Epi) by dissecting the ventricle at the mid-wall. The ventricular myosin isozymes were examined by electrophoresis on pyrophosphate gel under non-dissociating conditions. The results showed the following: 1) The relative heart weight of the T group was significantly higher than the C group. 2) Left ventricular myosin isozyme composition showed a region-specific distribution in the C rats, and the proportion of V3 myosin or β-myosin heavy chain in the Endo was significantly higher than that of the Epi. However, the training had no effect on the cardiac myosin isozyme in either portion. 3) The activity of citrate synthase did not show transmural gradient in the ventricle of C animals. Training had no effect on the activities of either portion. 4) The activity of lactate dehydrogenase (LDH) showed transmural gradient in the ventricle of C rats. Training-induced changes in the activity of LDH were found in both portions, therefore, training abolished the transmural gradient in the activity of LDH, suggesting a corresponding redistribution of the myocardial work load.
These results indicate that running training might induce the redistribution of the myocardial work load, whereas the stimulation apparently has no effect on the regional distribution of cardiac myosin isozyme composition.
6.EFFECTS OF SWIMMING ON CARDIAC FUNCTIONS OF RATS AT GROWING STAGE
SATOSHI KURIHARA ; MASATO KONISHI ; KEIZO KOBAYASHI ; NAOKO TOMIZAWA ; YOSUKE MATSUNE ; TAKESHI KAWAMURA ; MASAHIKO YOSHIURA ; TAKEO IWAMOTO ; KEIJI IRIYAMA
Japanese Journal of Physical Fitness and Sports Medicine 1985;34(Supplement):113-120
Long term physical training is known to cause a change of cardiac functions and this effect is observed at various levels of the heart (from whole heart to subcellular level), although its mechanism is not fully understood. It is reported that cardiac hypertrophy and decreased heart rate can be observed as effects of long term physical training, but change of the catecholamine content in heart tissue induced by training is controversial.
In the present experiment, long schedule of short daily swimming episodes was employed to observe the effect of mild physical training on cardiac functions of rats in the growing stage. We measured body weight, heart weight, heart rate under light anesthesia, variation of R-R-interval of electrocardiogram, and catecholamine contents in cardiac muscle.
1) Wister rats were divided into 2 groups 3 weeks after birth. One group rats was kept sedentary in cages, and the other group was required to free swim in a tank containing water at 30°C. At the beginning of the programme, swimming time was 10 min. Swimming was applied 5 days a week for up to 14 weeks, and swimming time was gradually increased to 30 min.
2) Body weight of rats in the trained group was significantly less than that of the controls, and the heart weight to body weight ratio in the trained rats was significantly higher than in the controls.
3) In the exercised rats, the R-R interval of the ECG was longer than that of the controls, and there was a tendency for the variation of R-R interval in the trained group to be larger than that of the controls.
4) At 10 and 17 weeks, rats from each group were sacrificed after or without a 30 min test swim for measurement of catecholamine content of the ventricular muscle. One time swimming for 30 min increased dopamine content, but did not change norepinephrine content except for the trained group at 10 weeks. There was no significant difference in cardiac catecholamine contents in the rested state of the control and trained groups at 10 and 17 weeks.
5) Results were interpreted as follows: One time swimming for 30 min influences the activity of the autonomic nervous system innervating the heart, and catecholamine metabolism at nerve terminals of the sympathetic nervous system. Long term mild swimming does not cause permanent change of catecholamine contents, and the low heart rate in the trained group cannot be soley explained by the decreased activity of the sympathetic nervous system.
8.CHANGES OF PHYSICAL FUNCTIONS DURING “24 HOUR-RELAY”
SUKETSUNE IWAGAKI ; KEIZO KOBAYASHI ; YASUTAKA KOBAYASHI ; AKIRA TAKAHASHI ; MASAHIRO ARIYOSHI
Japanese Journal of Physical Fitness and Sports Medicine 1980;29(1):33-44
Students and general long distance runners carried out 1600m run for 24 hours and their physical functions were measured with lapse of the relay. Following results were obtained.
1) Prolongation of mean running time of student long distance runners in 1600m runs appeared at about 8th-10th runs, 12.8-16.0km, but that of general long distance runners did at 5th-6th runs, 8-9.6km.
2) There was plus correlation between mean of running time and its standard deviation in 1600m runs. It was r=0.55 and its regression equation was Y=0.58X-162.3. But these of general long distance runners were r=0.53 and Y=0.358X-97.3, respectively.
3) Decreased body weight from 1st-8th run was great and succesive, and occupied about 30%-70% of final decreased body weight. Thereafter, increase or decrease of the body weight was repeated and the time course became slow. There were some runners who showed large and succesive decreased body weight with the runs through the competition. The decreased body weight during the competition was influenced by the wind velocity, which supressed it considerably.
4) Heart rate of a student long distance runner during 1600m run reached 180-189 beats per minute every run. Resting heart rate of general and student long distance groups showed circadian rhythm during the competition, but that of student runners was higher through the competition and their systolic pressure shows a tendency to below in later period of the competition.
5) Threshold of knee jerk was low in the initial few runs and thereafter showed circadian rhythm. Reaction time to light was also facilitated in the initial runs and there-after prolonged about 30msec and maintained till the end of the competition. Frequency of subjective symptoms increased with number of the runs. At middle of the competition, it came over Sakai's standard and the A, B and C symptoms at the end of the competition were 33.0%, 20.0% and 25.0%, respectively.
6) Calorie intake per day of the student long distance runners was in the range of 1240-2540Cal. Total energy consumption was estimated 7457Cal. per day.
7) Blood glucose of the student long distance runners mostly unchanged through the competition, but serum triglyceride and total phospholipids significantly decreased and inversely serum free fatty acids prolongly mobilized.
9.QUANTITIVE AND QUALITATIVE STUDIES ON TISSUE TRIGLYCERIDE IN AGING OF RATS
SUKETSUNE IWAGAKI ; KEIZO KOBAYASHI ; KUNIHIKO HARADA ; MANABU YAMADA ; TOSHIO SAKAI
Japanese Journal of Physical Fitness and Sports Medicine 1980;29(2):110-116
Triglyceride contents of liver, heart muscle and skeletal muscles (rectus femoris, tibiaris anterior, soleus, plantaris and extensir digitrum longus) were determined on 1, 3.5, 14, 18 and 21 months-old rats, and especially on 14 and 21 months-old rats composition of triglyceride fatty acids was analyzed and interrelation of these triglyceride contents with aging of rats was studied quantitively and qualitatively. Following results were obtained
1) Changs in liver and muscular triglyceride contents appeared on 14 months-old rats and were significant increase at 21 months-old rats.
2) Liver triglyceride content significantly decreased at 21 months-old rats (p<0.05) .
3) lrriglyceride contents of tibiaris anterior and extensor digitrum longus muscles were mostly unchangeable through the aging of rats.
4) But triglyceride contents of soleus, rectus femoris and plantaris muscles in 21 months-old rats significantly increased (p<0.05) and the individual difference was great.
5) In composition of triglyceride fatty acids, increase of C18, C18-1, C18-2 and C18-3 was observed in epididymal adipose tissue, soleus and rectus femoris muscle on 21 months-old rats, but in extensor digitrum longus and tibiaris anterior muscles.
From these results, changes of tissue triglyceride contents with aging of rats are different in each tissue and increase of triglyceride content is present with qualitative changes in composition of triglyceride fatty acids, increase of long chain and unsaturated fatty acids, and organic specificity, which is related to the functional changes with aging of rats is considered.
10.A STUDY OF LIPOLYTIC ACTIVITY ON EPIDIDYMAL ADIPOSE TISSUE DURING EXERCISE
KEIZO KOBAYASHI ; TAKESHI NAGAI ; TOSHIO SAKAI ; SUKETSUNE IWAGAKI
Japanese Journal of Physical Fitness and Sports Medicine 1979;28(3):265-270
34 male rats (13 weeks old) were used in this experiment. 11 rats were at rest and 23 rats were loaded to run on a treadmill with 2 degree slope at a speed of 25m/min. Relation between quantities of blood substances (plasma glycerol, blood lactate and plasma free fatty acids ; FFA) and lipolytic activity of epididymal adipose tissue was studied to clarify a mechanism of lipolysis of the adipose tissue in the exercise.
1) Plasma FFA and glycerol began to increase in parallel at 30 min after the run, but at exhaustion only plasma glycerol enhanced.
2) Blood lactate increased at 10 min after the run and more at exhaustion.
3) Basal lipolytic activity of epididymal adipose tissue in vitro was not influenced by the run, while norepinephrine induced lipolysis of the adipose tissue decreased with lapse of running time. Relation between plasma FFA and lipolytic activity of epididymal adipose tissue was inverse during the run.
4) There was also inverse relation between blood lactate and lipolytic activity of adipose tissue induced with norepinephrine. From these results, it is assumed that the increase of plasma FFA during the exercise was not resulted from the increase of lipolytic activity of the adipose tissue stimulated with only norepinephrine and effects of other hormones (ACTH, Glucagon, Growth hormone and etc.) and their interactions on the lipolysis might be considered.


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