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Ehlers-Danlos syndrome (EDS) is a group of disorders caused by abnormalities in the extracellular matrix (ECM). Transforming growth factor-β (TGF-β) plays a crucial role in formation of the ECM by the SMAD (Sma-and Mad-related protein, mothers against decapentaplegic homolog) pathway. It has been reported that loss of function of zinc transporter ZRT/IRT-like protein 13 (ZIP13) is the cause of the spondylocheiro dysplastic form of EDS (SCD-EDS: OMIM 612350). Our previous study suggested that TGF-β1 has a relationship with the skin pathological condition in the Zip13-Knockout (KO) mouse, which is a model of SCD-EDS. Thus far, effective treatment based on modern medicine for this syndrome has not yet been established. According to an approach of traditional Chinese medicine, the present study investigates the medicinal effects of Makomo (Zizania latifolia) on certain aspects of SCD-EDS, such as skin morphology and plasma TGF-β1, in Zip13-KO mice. Increases in densities of collagen fibers and fibrils without a significant change in thickness of the dermal layer were observed in the group of mice fed a Makomo-containing diet. No change in the amount of collagen suggests that Makomo feed does not elevate collagen synthesis, but changes the length of glycosaminoglycan chains and decreases the distance between collagen fibrils. In conclusion, the changes of the skin structure suggest that Makomo can increase the mechanical strength of skin.

Ehlers-Danlos syndrome (EDS) is a group of disorders caused by abnormalities that are identified in the extracellular matrix. Transforming growth factor-β1 (TGF-β1) plays a crucial role in formation of the extracellular matrix. It has been reported that the loss of function of zinc transporter ZRT/IRT-like protein 13 (ZIP13) causes the spondylocheiro dysplastic form of EDS (SCD-EDS: OMIM 612350), in which dysregulation of the TGF-β1 signaling pathway is observed, although the relationship between the dermis abnormalities and peripheral TGF-β1 level has been unclear. We investigated the characteristics of the dermis of the Zip13-knockout (KO) mouse, an animal model for SCD-EDS. Both the ratio of dermatan sulfate (DS) in glycosaminoglycan (GAG) components and the amount of collagen were decreased, and there were very few collagen fibrils with diameters of more than 150 nm in Zip13-KO mice dermis. We also found that the TGF-β1 level was significantly higher in Zip13-KO mice serum. These results suggest that collagen synthesis and collagen fibril fusion might be impaired in Zip13-KO mice and that the possible decrease of decorin level by reduction of the DS ratio probably caused an increase of free TGF-β1 in Zip13-KO mice. In conclusion, skin fragility due to defective ZIP13 protein may be attributable to impaired extracellular matrix synthesis accompanied by abnormal peripheral TGF-β homeostasis.

In order to clarify the roles of endocrine responses to exercise, various hormones and metabolic parameters were determined at the same time. Eleven long distance runners performed treadmill running until exhaustion. Blood samples were obtained before, immediately after, and at 30 and 60 minutes following the exercise. Urine samples were collected before and after the exercise and change in body weight was also determined. Elevations in plasma ACTH, ADH, renin activity, glucagon, GH and serum cortisol were accompanied by a fall of blood pH, and rises in blood lactate concentration and ammonia, suggesting that these metabolic changes induced by strenuous exercise caused a stress reaction. Body weight and urine volume were decreased after the exercise. Increases in Ht and total protein concentration indicate hemoconcentration. The rise in plasma ADH may be induced by elevated osmolarity and reduced plasma volume in addition to stress reaction. The elevation of plasma renin activity may have resulted from reduced plasma volume and stress reaction. Increases in plasma renin activity and ACTH may induce a rise in aldosterone which may have induced a significant decrease in urinary Na/K. Elevations of plasma glucose and serum FFA were accompanied by rises in glucagon and GH. A rise in insulin may be induced by the elevated plasma glucose. A significant rise in plasma testosterone was observed after the exercise, but when the rise was corrected by hemoconcentration the elevation of testosterone was not significant any more. Thus, determinations of various parameters offer a deep insight into endocrine responses., 11, KJ00004196693, 原著論文, Original Article

Effects of different interval jump training on bone mass and bone strength of lower limbs were investigated in female Fischer 344 rats. Rats aged 5 weeks were assigned at random to two jump training groups (n=10, each) or control (n=10). Rats of the training group were made to jump 20 times/day at 3- or 30-second intervals, 5 days/wk for 8 weeks. Following the experimental period, the femur and tibia of the 30-second interval group had significantly greater fat-free dry weights and fat-free dry weights per body weight than the 3-second interval group. There was also a significant difference between the two jump groups in one of the bone strength indexes. The present results suggest that the training with long-interval impacts is more effective for bone hypertrophy than that with short-interval impacts., 9, KJ00004196691, 原著論文, Original Article

The present investigation was carried out to elucidate whether changes in blood pH induced by administrations of alkalinizing or acidifing agents influence aldosterone secretion. Since aldosterone secretion is known to be regulated by various factors such as the renin-angiotensin system, adrenocorticotropin (ACTH) and serum potassium level, these indices were simultaneously measured during manipulation. Oral administration of NaHCO_3 (alkalinization) of 0.3g・body weight^ resulted in a fall of serum aldosterone with an increase in blood pH, whereas serum cortisol and plasma renin activity remained unchanged. NH_4Cl ingestion (acidification) caused an elevation of aldosterone though the increase was not significant statistically, whereas CaCO_3 ingestion (control) resulted in a significant fall in serum aldosterone. In the experiment of NH_4Cl ingestion, both serum cortisol and plasma renin activity decreased significantly. These results suggest that the fall of aldosterone by alkalinization and the rise of aldosterone by acidification are not induced by either renin angiotensin system or ACTH. On the other hand, serum potassium level fell or rose during alkalinization or acidification. The pattern of the change was similar to the change in proton concentration. From these results, it is concluded that changes in blood pH seem to influence aldosterone secretion independent of renin angiotensin system and ACTH, however, possible involvement of serum potassium concentration on aldosterone secretion can not be denied., 8, KJ00004196656, 原著論文, Original article

NaHCO_3を経口投与し運動開始前の血漿カリウム濃度を低下させ, 漸増負荷運動中の換気量に及ぼす血漿カリウム濃度の影響について検討した。運動中の換気量は対照群とアルカローシス群の間に差異はみられず, Ventilation threhold も対照群1.72±0.06L/min, アルカローシス群1.75±0.19L/minと両群間に差異はみられなかった。運動開始前の血漿カリウム濃度はアルカローシス群 (3.42±0.33mM) のほうが対照群 (3.80±0.37mM) と比べて低下しており, 運動中もアルカローシス群のほうが常に1mM程度低値を示していた。以上より血漿カリウム濃度レベルは換気応答に影響しなかった。また血漿カリウム濃度の変化速度は両群間に違いがみられなかったことから血中カリウム濃度の変化速度が換気調節に関与している可能性は否定できなかった。, The present study was designed to test the idea that differences in plasma potassium concentration may have an influence on changes in ventilation during incremental exercise in man. Four healthy males performed two exercise tests in which the power output was increased by 15W each min until exhaustion. Two hours prior to the tests, subjects ingested 0.3g/body weight NaHCO_3 (alkalosis) or CaCO_3 (control) over the two hours. Order of the two tests was randomized. Arterialized venous blood samples were drawn before and after drug ingestion to determine blood pH. In addition, samples for plasma potassium and lactate concentration were obtained before and after drug ingestion, and every min during exercise. As expected, NaHCO_3 ingestion induced an elevation of blood pH and a decrease in plasma potassium concentration. Lactate threshold in alkalosis was higher than that in control since lactate diffusion from muscle can be enhanced by alkalosis. During exercise plasma potassium concentration in alkalosis was slightly lower that in control by about～1mM. VE and ventilation threshold were not different between the two conditions. These results suggest that the differences in potassium concentration by about～1mM have no effect on ventilation during incremental exercise., 15, KJ00004196606, 原著論文, Original article

1993, 【要旨】

1993, 【要旨】