Hiroyuki Sumino

A Novel Adipocytokine, Visceral Adipose Tissue-derived Serine Protease Inhibitor (Vaspin), and Obesity

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an interesting novel adipocytokine with insulin-sensitizing effects. Some studies have suggested that vaspin could play an important role in the development of obesity and metabolic disorders. The induction of vaspin mRNA expression could represent a compensatory mechanism associated with obesity, severe insulin resistance and type 2 diabetes mellitus, however it is unclear whether a correlation exists between human vaspin serum levels and markers of insulin sensitivity and glucose or lipid metabolism. Vaspin serum concentrations have been shown to be lower in lean subjects and competitive sportsmen with long-term physical training, but they are increased with weight loss associated with a physical training programme. In conclusion, there is at present no clear proof of a causal link between vaspin and visceral fat accumulation, or insulin resistance. This article reviews the role of vaspin in obesity-associated diseases and its potential as a new biomarker for obesity and impaired insulin sensitivity.

Effects of hormone replacement therapy on weight, abdominal fat distribution, and lipid levels in Japanese postmenopausal women

OBJECTIVE: To investigate the effects of hormone replacement therapy (HRT) on weight, abdominal fat distribution, and fasting lipid levels in Japanese postmenopausal women (PMW).DESIGN: Prospective, 12-month-controlled clinical comparison of women with and without HRT.SUBJECTS: In all, 35 PMW with HRT (conjugated estrogens, 0.625 mg daily; medroxyprogesterone acetate, 2.5 mg daily; HRT group) and 26 PMW without HRT (control group).MEASUREMENTS: Weight, abdominal fat distribution by computed tomographic measurements, lipid profiles, and sex hormones were determined at baseline and after 12 months of treatment or observation.RESULTS: Weight did not change in any group. Visceral abdominal fat increased in controls, but not in the HRT group. Total and low-density lipoprotein cholesterol decreased, and triglyceride (TG) and high-density lipoprotein cholesterol increased in the HRT group; these did not change in the control group. When we divided women into those with android and gynoid types of abdominal fat distribution. Subjects with an android distribution showed reduced visceral fat with HRT, which also decreased the proportion of patients maintaining an android distribution. HRT did not alter abdominal fat distribution in subjects with a gynoid distribution. HRT increased serum TG in the android and the gynoid subgroups.CONCLUSION: Improved distribution of abdominal fat and fasting lipid levels except for TG may represent beneficial effects of HRT with respect to cardiovascular disease, but caution is warranted concerning TG elevation from HRT performed in PMW.

Chronic Fatigue Syndrome and the Central Nervous System

An increasing amount of neuroimaging evidence supports the hypothesis that chronic fatigue syndrome patients have structural or functional abnormalities within the brain. Moreover, some neurotrophic factors, neurotransmitters and cytokines have also been evaluated in order to elucidate the mechanism of abnormal neuropsychic findings in chronic fatigue syndrome. In this review, we suggest that the focal point of chronic fatigue syndrome research should be transferred to the central nervous system.

Relationship between Carotid Atherosclerosis and Lumbar Spine Bone Mineral Density in Postmenopausal Women

Osteoporosis and increased carotid intima-media thickness (IMT) have been associated with atherosclerosis. We investigated the correlation between carotid IMT and lumbar spine bone mineral density (BMD) in postmenopausal women. We studied the carotid IMT in 175 postmenopausal women, including 43 women (control) with normal spinal BMD, 73 women with osteopenia, and 59 women with osteoporosis. Carotid IMT was assessed by ultrasonography. BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since menopause, and carotid IMT were significantly greater in the osteoporosis group than in the control (all p<0.01) and osteopenia groups (all p<0.01). Estradiol was significantly lower in the osteoporosis group than in the control group (p<0.05). BMD was significantly lower in the osteoporosis group than in the osteopenia or control group (both p<0.01) and in the osteopenia group than in the control group (p<0.01). After adjusting for age, years since menopause, and estradiol, women with osteoporosis had significantly greater carotid IMT than controls (p<0.05). The univariate linear regression analysis revealed that carotid IMT was significantly positively correlated with age, years since menopause, and low-density lipoprotein (LDL) cholesterol (all p<0.05) and was significantly negatively correlated with estradiol and BMD (all p<0.05), but showed no significant association with other clinical variables. In multivariate regression analysis, the carotid IMT was significantly positively correlated with LDL cholesterol (p<0.01) and negatively correlated with BMD (p<0.01), but not with other variables. Carotid atherosclerosis might be associated with lumbar spine bone mass in postmenopausal women, suggesting that postmenopausal women with osteoporosis may have more advanced carotid atherosclerosis than those with a normal bone mass.

Effects of long-term transdermal hormone replacement therapy on the renin–angiotensin– aldosterone system, plasma bradykinin levels and blood pressure in normotensive postmenopausal women

Aim:  This study was designed to investigate the effects of 24‐month long‐term transdermal hormone replacement therapy (HRT) on the circulating levels of components of the renin–angiotensin–aldosterone system (RAAS) and bradykinin, blood pressure (BP) and lipid profile in normotensive postmenopausal women (PMW).

Long-term effects of telmisartan on blood pressure, the renin-angiotensin-aldosterone system, and lipids in hypertensive patients

We prospectively evaluated long-term (12 months) effects of telmisartan on blood pressure (BP), circulating renin-anigiotensin-aldosterone levels, and lipids in hypertensive patients. There were 13 men and 11 women, 59 ± 8.7 years of age (mean ± SEM), with untreated essential hypertension. The 20-60 mg doses of telmisartan were administered once daily in the morning until BP130/85 was obtained. Blood pressure and plasma renin activity, plasma angiotensin (Ang) I and Ang II, serum angiotensin-converting enzyme (ACE) activity, plasma aldosterone concentration, plasma human atrial natriuretic peptide (hANP) concentration, and serum lipids were obtained 6 and 12 months after starting telmisartan administration. Systolic and diastolic BP were significantly (P < 0.001, P < 0.001) decreased from 162 ± 3.3 and 97.7 ± 2.1 mmHg to 128 ± 3.8 and 79.6 ± 2.0 mmHg after 12 months of treatment, respectively. Plasma Ang I and Ang II were unchanged at 12 months. Plasma renin activity and serum ACE activity were significantly (P < 0.001, P < 0.05) increased and plasma aldosterone concentration was unchanged during the study period. Total cholesterol levels were unchanged, but serum triglycerides levels were significantly decreased at 12 months (P < 0.01). Plasma hANP showed no significant alteration throughout the 12-month period. In hypertensive patients, telmisartan is a beneficial antihypertensive drug that also lowers serum triglycerides.

Acupuncture Modifies Immune Cells

Acupuncture, a relief procedure originating in East Asia, has become increasingly popular as a therapy for pain and chronic diseases that are difficult to manage with conventional treatments. The attributive effects of acupuncture have been investigated in various inflammatory disorders including asthma, allergic rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1, and vasculitis. Japan is one of the countries that has done extensive research on the various effects of acupuncture on immunological functions. Recently, we studied acupunctures effect on leukocyte and lymphocyte subpopulations in human peripheral blood. Based on research data and other findings previously published in the literature, this article reviews the ascribed immunomodulation of acupuncture on the immune system, which includes activities of macrophages, neutrophils, natural killer cells, and lymphocytes, immunoglobulin production, and complement systems.

Effects of raloxifene and hormone replacement therapy on forearm skin elasticity in postmenopausal women

OBJECTIVES Hormone replacement therapy (HRT) increases skin elasticity in postmenopausal women. However, the effects of raloxifene, a selective estrogen receptor modulator (SERM), on skin degenerative changes in postmenopausal women remain unknown. We investigated whether raloxifene increases skin elasticity, similar to HRT, in postmenopausal women. METHODS In a 12-month trial, 17 postmenopausal women (mean age, 66.4+/-7.8 years) received continuous raloxifene treatment (60 mg/day), 19 women (56.2+/-6.4 years) received continuous 17-beta estradiol treatment using a patch (0.72 mg/2 days) plus cyclic medroxyprogesterone acetate (2.5mg/day, for 12 days/month), and 11 women (58.1+/-7.3 years) did not receive either therapy. In each subject, the skin elasticity of the forearm was measured using a suction device at baseline and at 12 months after the start of the study. RESULTS Raloxifene and HRT significantly increased skin elasticity from 52.4+/-3.8% and 64.1+/-7.2% at baseline to 55.1+/-4.7% and 67.4+/-7.4% after 12 months, respectively (P<0.05, each), but the untreated subjects did not exhibit any significant change in skin elasticity during the study. The delta value for skin elasticity was significantly higher among the raloxifene and HRT subjects than among the untreated subjects (P<0.05, each). CONCLUSIONS These findings suggest that raloxifene may have a beneficial effect on skin elasticity, which undergoes degenerative changes in postmenopausal women, in addition to its effects on bone metabolism.

Impaired Blood Rheology and Elevated Remnant-like Lipoprotein Particle Cholesterol in Hypercholesterolaemic Subjects

Blood rheology, fasting serum concentrations of remnant-like lipoprotein particle cholesterol (RLP-C) and concentrations of other lipids were compared in 23 hypercholesterolaemic and 69 normocholesterolaemic subjects, and the relationship between red blood cell (RBC) deformability and RLP-C concentrations were studied in a different set of six hypercholesterolaemic and six normocholesterolaemic subjects. Passage time of whole blood and concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and RLP-C were significantly higher in hypercholesterolaemic than in normocholesterolaemic subjects. Passage time of whole blood correlated positively with TC, TG, LDL-C and RLP-C and negatively with high-density lipoprotein cholesterol. Furthermore, the passage time of 10% haematocrit-adjusted RBCs in phosphate-buffered saline, which reflects RBC deformability, correlated positively with the passage time of whole blood and RLP-C. Thus, hypercholesterolaemic subjects had impaired blood rheology and elevated RLP-C concentrations, which may be associated with the pathophysiology of atherosclerosis in hypercholesterolaemic subjects. Impaired RBC deformability may contribute to impaired blood rheology associated with elevated RLP-C in hypercholesterolaemic subjects.

Effects of raloxifene on the renin-angiotensin-aldosterone system and blood pressure in hypertensive and normotensive osteoporotic postmenopausal women.

Aim:  An increase in blood pressure after menopause has been documented. The renin–angiotensin–aldosterone system (RAAS) plays a central role in the regulation of blood pressure and in the pathophysiology of hypertension. This study investigated the effects of raloxifene, a selective estrogen receptor modulator, on components of the RAAS and blood pressure in hypertensive and normotensive osteoporotic postmenopausal women.