Shinrin-yoku (forest-air bathing and walking) effectively decreases blood glucose levels in diabetic patients.

The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.

Involvement of Ras in the expression of glycolipid sulfotransferase in human renal cancer cells.

Glycolipid sulfotransferase activity in a human renal cell carcinoma cell line, SMKT-R3, is enhanced by epidermal growth factor (EGF); tyrosine kinase inhibitors suppress this enhancement. To investigate the involvement of Ras in the signal transduction pathway from the EGF receptor to the expression of glycolipid sulfotransferase, we introduced v-H-ras into SMKT-R3 cells. In a quiescent state, the percent GTP bound to Ras in v-H-ras-expressing cells increased about 2.5-fold compared with control cells, suggesting that v-Ras introduced into the renal cancer cells is in an active form without EGF stimulation. Glycolipid sulfotransferase activity in v-H-ras-expressing cells was higher than in control cells. The sulfotransferase activity was affected neither by EGF nor by genistein, a tyrosine kinase inhibitor, in v-H-ras-expressing cells, whereas it was enhanced by EGF and reduced by genistein in control cells. Our observations suggest that Ras mediates the regulation pathway of glycolipid sulfotransferase activity in SMKT-R3 cells.

Balneotherapy and platelet glutathione metabolism in type II diabetic patients.

Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r = 0.692, P < 0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG < 150 mg/dl), the level increased (P < 0.01) and in poorly controlled patients (FPG > 150 mg/dl), the value decreased (P < 0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG (r = -0.430, P < 0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within +/- 3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

Continuous measurement of blood pressure, heart rate and left ventricular performance during and after isometric exercise in head-out water immersion.

Experiments were performed to determine the changes in blood pressure (BP), heart rate (HR) and left ventricular function during and after isometric knee extension during thermoneutral (35 degrees C) head-out water immersion (HWI) or in air. Seven healthy male subjects mean age 24 (SD 3) years kept their knees extended (60% maximal voluntary extension) until they reached exhaustion. The mean BP at rest was 80 (SD 10) and 78 (SD 8) mmHg [10.7 (SD 1.33) and 10.4 (SD 1.07)kPa] in air and during HWI, respectively, (NS). They increased progressively (P < 0.01) during contraction and reached maximal values of 148 (SD 22) and 143 (SD 26) mmHg [19.7 (SD 2.93) and 19.1 (SD 3.47)kPa] in air and in HWI, respectively, (NS). The mean HR at rest was 74 (SD 8) and 70 (SD 11) beats.min-1 in air and in HWI, respectively, (NS). They also increased progressively, (P < 0.01) and reached 126 (SD 14) and 118 (SD 17) beats.min-1 in air and in HWI, respectively, (NS). The changes in BP and HR during contraction in HWI tended to be smaller than those in air (NS). Left ventricular end diastolic diameters (dd) at rest in HWI were greater than those in air and were maintained at higher values during and after isometric contraction. In contrast, dd decreased during isometric contraction in air (P < 0.01). The change of left ventricular systolic diameters (ds) in HWI was no different to those in air. From these findings, isometric exercise in thermoneutral HWI would seem to be characterized by a greater dd than in air and this could be useful for patients with deconditioning effects such as orthostatic hypotension.

Elevated levels of heat-shock protein 70 (HSP70) in the mononuclear cells of patients with non-insulin-dependent diabetes mellitus.

Increased free radicals and reduced levels of antioxidants have been reported in diabetes mellitus. Since heat-shock protein 70 (HSP70) is a stress-induced protein and is suggested to play a protective role against oxidative stress, we have investigated whether HSP7O acts as one of the defense systems against this stress. We separated mononuclear cells from diabetic patients (N=12) and age- and sex-matched healthy controls (N =12), and detected HSP70 by western blot analysis. The results were expressed by the ratio of the density determined by laser densitometry, to that of 10 mu g of purified HSP70. HSP70 levels in the mononuclear cells of diabetic patients (0.78 + or- 0.56) were significantly high, compared with healthy subjects (0.43 + or - 0.23) (P < 0.05). No correlation was found between HSP7O and hemoglobin A1c, fasting plasma glucose, duration of diabetes or diabetic complications except age. A negative correlation was found between HSP70 and age (r = -0.658, P < 0.05). These results suggest that HSP70 levels in the mononuclear cells are elevated reflecting increased oxidative stress in patients with diabetes.

[Study of the interrelation between variation of blood pressure and pulse rate under various respiratory conditions].

By means of non-invasive continuous blood pressure measurement (Finapres method), coefficient of variation for pulse rate (CV-PR) and coefficient of variation for blood pressure (CV-BP) under various respiratory conditions were calculated simultaneously to examine the interrelation between them. The subjects were 148 healthy normal adults and 75 patients with diabetes mellitus (DM). Both coefficients of variation for healthy normal adults showed significantly (p < 0.01) positive correlations: correlation coefficients tended to be greater during deep breathing than that during resting breathing. The case was the same for the ratio of CV-PR to CV-BP (CV-PR/CV-BP): the ratio for deep breathing was approximately 1.0. The ratio showed a significant decrease for DM patients compared with that for healthy normal group. The examination of the interrelation between these coefficients of variation under various respiratory conditions, which reflected the sensitivity of cardiovascular vagal reflex was considered to be also useful for the judgment of the degree of progress of DM-complications.

[Studies on the regulation of glycolipid sulfotransferase activity in human renal cancer cells].

In the previous studies, epidermal growth factor (EGF) was found to elevate glycolipid sulfotransferase activity in a human renal cell carcinoma cell line, SMKT-R3. To elucidate whether Ras is involved in the signal transduction pathway from EGF to the expression of the sulfotransferase, effects of EGF and a tyrosine kinase inhibitor on the sulfotransferase activity were investigated in renal cancer cells stably expressing activated Ras. SMKT-R3 cells were transfected with a plasmid carrying v-H-ras (pv-H-ras). As a control, SMKT-R3 cells transfected with a mutant v-H-ras, in which glycine at position 15 was replaced by valine (pG15V), was used. The expression of v-H-ras in transfected cells was examined by RT-PCR analysis. Two clones transfected with pv-H-ras, named A1 and A6, and two clones transfected with pG15 V, termed B1 and B4, were found to express v-H-ras and G15V genes, respectively, and employed in the following experiments. Though EGF elevated the activity of glycolipid sulfotransferase in B1, B4 and SMKT-R3 cells, it did not change the activity levels in A1 and A6 cells. This result suggested that since the signal from Ras was saturated in the cells expressing activated Ras, the cells did not respond to the stimulation by EGF. To know the association between tyrosine kinase of EGF receptor and Ras, the effect of Genistein, a specific inhibitor of tyrosine kinase, on the sulfotransferase activity was examined in these cell lines. Genistein reduced the activity of glycolipid sulfotransferase in B1, B4, and SMKT-R3 cells, whereas it hardly affected the sulfotransferase activity in A1 and A6 cells. This result indicated that the signal from tyrosine kinase was dissociated from the regulation of the sulfotransferase activity in the cells expressing activated Ras. These observations suggest that Ras is involved in the signal transduction from EGF to the expression of glycolipid sulfotransferase activity in SMKT-R3 cells and acts in the downstream of tyrosine kinase of EGF receptor.

Thermal stress and diabetic complications.

Activities of erythrocyte aldose reductase were compared in 34 normal subjects, 45 diabetic patients, and nine young men following immersion in water at 25, 39, and 42 degrees C. Mean basal enzyme activity was 1.11 (SEM 0.12) U/g Hb and 2.07 (SEM 0.14) U/g Hb in normal controls and diabetic patients, respectively (P < 0.0001). Activities of the enzyme showed a good correlation with hemaglobin A1 (HbA1) concentrations (P < 0.01) but not with fasting plasma glucose concentrations. After immersion at 42 degrees C for 10 min, enzyme activity was increased by 37.6% (P < 0.01); however, the activity decreased by 52.2% (P < 0.005) after immersion for 10 min at 39 degrees C and by 47.0% (P < 0.05) at 25 degrees C. These changes suggest that heat stress might aggravate diabetic complications, and body exposure to hot environmental conditions is not recommended for diabetic patients.

Effect of thermal stress on glutathione metabolism in human erythrocytes.

This is the first experiment to investigate the effect of heat and cold stress on glutathione metabolism in human erythrocytes. We immersed men at three different water temperatures for 10 min. At 39 degrees C, no remarkable changes were observed. Levels of glutathione (GSH) decreased from 2.44 (0.14) to 1.80 (0.10) mumol.ml red blood cells-1 [mumol.ml RBC-1; mean (SEM); P < 0.0005] and those of lipid peroxides increased from 1.87 (0.03) to 2.06 (0.04) nmol.ml RBC-1 (P < 0.01) after the immersion at 42 degrees C. In contrast, levels of GSH increased from 2.46 (0.17) to 2.91 (0.17) mumol.ml RBC-1 (P < 0.05) and those of lipid peroxides did not change after the immersion at 25 degrees C. The activities of glutathione peroxidase decreased from 35.90 (1.83) to 34.33 (1.66) IU.g Hb-1 (P < 0.01) after the immersion at 42 degrees C; however, these activities did not change after the immersion at 25 degrees C. The activities of glutathione reductase (both active and inactive forms) showed no changes at any temperatures. These changes indicate that heat stress causes oxidative stress in the human body; however, cold stress is thought to augment the activity of the antioxidative defence system. It is suggested that body exposure to hot environmental conditions should not be recommended for patients suffering from a damaged antioxidative defence system.

[Hypertrophic cardiomyopathy with rapid development of giant negative T-wave within a year: a case report].

A 61-year-old female was admitted to our hospital, presenting hypertension and giant negative T-wave (GNT) on an electrocardiogram (ECG). The ECG taken one year prior to the admission showed left ventricular hypertrophy (LVH) without GNT. Hypertension had been poorly treated during the year previous to her admission. These had been almost no administration of antihypertensive drugs. Echocardiograms, left ventriculograms and magnetic resonance imaging revealed concentric and diffuse LVH. Endomyocardial biopsy of bilateral ventricles disclosed a degeneration of myocytes and their bizarre hypertrophy with disorganization. This pathologic finding was compatible with that of hypertrophic cardiomyopathy (HCM). Although GNT has frequently been noted in apical type of HCM, the alteration from normal T-wave to GNT within a year has rarely been reported. The present case exhibited GNT on an ECG which showed no apical hypertrophy. Since GNT had developed within a year while hypertension was poorly treated, the rapid development of GNT might have been precipitated by hypertension, which possibly altered the hypertrophic pattern of the left ventricle.