Dietary Intake Is Associated with Occlusal Force Rather Than Number of Teeth in 80-y-Old Japanese.

There has been a growing interest in the association between the number of teeth and dietary intake in older populations. However, people around the age of 80 y have frequently lost most of their teeth, and dental prostheses replacing the missing teeth play an important role in masticatory function. Therefore, masticatory function cannot be evaluated by the number of teeth alone. The occlusal force of the complete dental arches is an index of masticatory function, reflecting not only the number of teeth, but the effect of removable dentures. The purpose of this cross-sectional study was to determine the relative importance of the number of teeth and occlusal force in association with dietary intake in 80-y-old Japanese people. This study included 760 community-dwelling Japanese people aged 79 y to 81 y. The authors measured bilateral maximal occlusal force in the intercuspal position using pressure-sensitive sheets. Removable denture wearers kept their dentures in place during the measurements. Energy-adjusted food groups and nutrient intake during the preceding month were assessed by a brief self-administered diet history questionnaire. The authors assessed linear trends in food and nutrient intake in relation to the number of teeth and occlusal force after adjusting for gender and socioeconomic status (education level, financial status, family structure, resident area and BMI). P values of < 0.05 were considered to be statistically significant. The authors found that the number of teeth was not associated with the energy-adjusted intake of any food group examined. In contrast, a decline in occlusal force was significantly associated with a lower intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most vitamins and minerals ( P for trend < 0.05). We conclude that food and nutrient intake was more closely associated with occlusal force than the number of teeth in community-dwelling Japanese people aged 79 y to 81 y. Knowledge Transfer Statement: This cross-sectional study of older Japanese people showed that, after controlling for considerable covariates, occlusal force rather than the number of teeth is positively associated with energy-adjusted intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most of vitamins and minerals. This means that reduced occlusal force may unconsciously lead older people toward a habitual unhealthy dietary intake. Older people have frequently lost most of their teeth and require prosthetics to restore masticatory function. Bilateral occlusal force is therefore a better measure of masticatory function than the number of remaining teeth. Our findings suggest that prosthetic rehabilitation is a significant factor in the prevention and management of chronic diseases and frailty through better dietary intake in older populations.

Longitudinal study of factors affecting taste sense decline in old-old individuals.

The sense of taste plays a pivotal role for personal assessment of the nutritional value, safety and quality of foods. Although it is commonly recognised that taste sensitivity decreases with age, alterations in that sensitivity over time in an old-old population have not been previously reported. Furthermore, no known studies utilised comprehensive variables regarding taste changes and related factors for assessments. Here, we report novel findings from a 3-year longitudinal study model aimed to elucidate taste sensitivity decline and its related factors in old-old individuals. We utilised 621 subjects aged 79-81 years who participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians Study for baseline assessments performed in 2011 and 2012, and then conducted follow-up assessments 3 years later in 328 of those. Assessment of general health, an oral examination and determination of taste sensitivity were performed for each. We also evaluated cognitive function using Montreal Cognitive Assessment findings, then excluded from analysis those with a score lower than 20 in order to secure the validity and reliability of the subjects' answers. Contributing variables were selected using univariate analysis, then analysed with multivariate logistic regression analysis. We found that males showed significantly greater declines in taste sensitivity for sweet and sour tastes than females. Additionally, subjects with lower cognitive scores showed a significantly greater taste decrease for salty in multivariate analysis. In conclusion, our longitudinal study revealed that gender and cognitive status are major factors affecting taste sensitivity in geriatric individuals.

Factors related to taste sensitivity in elderly: cross-sectional findings from SONIC study.

The sense of taste is important, as it allows for assessment of nutritional value, as well as safety and quality of foods, with several factors suggested to be associated with taste sensitivity. However, comprehensive variables regarding taste and related factors have not been utilised in previous studies for assessments of sensitivity. In the present study, we performed cross-sectional analyses of taste sensitivity and related factors in geriatric individuals who participated in the SONIC Study. We analysed 2 groups divided by age, 69-71 years (young-old, n = 687) and 79-81 years (old-old, n = 621), and performed a general health assessment, an oral examination and determination of taste sensitivity. Contributing variables were selected by univariate analysis and then subjected to multivariate logistic regression analysis. In both groups, females showed significantly better sensitivity for bitter and sour tastes. Additionally, higher cognitive scores for subjects with a fine taste for salty were commonly seen in both groups, while smoking, drinking, hypertension, number of teeth, stimulated salivary flow salt intake and years of education were also shown to be associated with taste sensitivity. We found gender and cognitive status to be major factors affecting taste sensitivity in geriatric individuals.

Association of Occlusal Force with Cognition in Independent Older Japanese People.

Recent longitudinal studies have shown the influence of multiple tooth loss on cognitive impairment, and earlier studies suggested that periodontal disease was related to cognitive decline. Tooth loss is associated with reduced masticatory function, which may affect stimulation of the central nervous system and dietary intake. Although some studies have reported a relationship between chewing ability and cognitive function, no studies have examined this area in terms of objective oral function. The aim of this study was to examine the association of occlusal force with cognitive decline in the preclinical stage among older people with higher-level functional capacity. This cross-sectional study for community-dwelling older people living in urban and rural areas in Japan examined 994 persons in the 70-y group (age range, 69-71 y) and 968 persons in the 80-y group (age range, 79-81 y). Retention of higher-level competence was defined according to the Tokyo Metropolitan Institute of Gerontology Index of Competence. Cognitive function was measured with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Oral status and function were assessed by the number of remaining teeth, periodontal pocket depth, and maximal occlusal force. Associations between the MoCA-J score and occlusal force were examined by bivariate and multivariate analysis. Approximately one-half of the participants retained higher-level functional capacity and were included in the analysis. Multiple regression analysis showed that occlusal force was significantly related to cognitive function after controlling for possible predictors including age, sex, socioeconomic status, medical condition, and handgrip strength. The number of remaining teeth and periodontal pocket depth were not significantly associated with cognitive function. Among community-dwelling older people with retained competence, maximal occlusal force was positively associated with their cognitive function. These results suggest that oral function might be a predictor for preclinical cognitive decline. Knowledge Transfer Statement: Multiple regression analysis showed that occlusal force was significantly related to cognition after controlling for possible predictors including handgrip strength as an indicator of general muscle strength, suggesting the independence of oral function. The number of remaining teeth did not have this association. The majority of older people have lost teeth and have received prosthodontic treatment, and their occlusal force is determined not only by the number of remaining teeth but also by prosthetic rehabilitation. These results can be used by clinicians focusing on prevention of tooth loss among the entire population, as well as to encourage partially edentulous and fully edentulous patients to restore their oral function with prostheses in order to eliminate a possible risk factor for cognitive impairment.

Role of Renin-Angiotensin-Aldosterone System in Metabolic Syndrome and Obesity-related Hypertension.

Several recent clinical trials show that blocking agents of the renin-angiotensin-aldosterone system (RAAS) reduce cardiovascular events in patients with metabolic syndrome based on insulin resistance and obesity, especially accumulated visceral fat. Our laboratory has focused on the relationship between the vascular RAAS and the action of insulin on the vasculature. We first revealed that the addition of insulin to cultured vascular smooth muscle cells (VSMC) markedly increases angiotensinogen and angiotensin II (Ang II) expression and production. Insulin addition also induces VSMC growth that is inhibited by the blockade of the RAAS by either ACEI or ARB which suggests a role for the RAAS in insulin-mediated growth. Insulin has a quite different effect on cultured vascular endothelial cells (EC) as it reduces angiotensinogen and renin expression. However, insulin added to EC induces a marked activation of ACE and the activated ACE promotes the conversion of Ang I to Ang II and cell growth under conditions of high insulin concentration. Ang II induces the progression of atherosclerosis through the production of oxidative stress that blocks insulin signaling and accelerates atherosclerosis. In this paper, we attempt to clarify the relationship between insulin resistance, the RAAS, and oxidative stress in vascular tissues to mimic in vivo conditions found in patients with metabolic syndrome and obesity-related hypertension as previously I reviewed in "Current Hypertension Reviews" in 2010 [1]. In addition, I update the relationships between vascular RAAS and insulin resistance for the last 4 years. JSH-2014 [2] states that the target goals of blood pressure (BP) for diabetes patients is lower than 130/80 mmHg, whereas updated JNC 8 [3] and ESH-ESC 2013 [4] recommends the target BP was changed to <140/90 mmHg for hypertensive patients with diabetes. Patients with diabetes and hypertension have reduced mortality as well as improved cardiovascular and cerebrovascular outcomes with treatment to a goal SBP <150 mm Hg, but no randomized controlled trials support a goal <140/90 mm Hg. Despite this, the panel opted for a conservative recommendation in patients with diabetes and hypertension, opting for a goal level of <140/90 mm Hg in adult patients with diabetes and hypertension rather than the evidence based goal of <150/90 mm Hg [3, 5]. JSH-2014 recommends that the first choice of antihypertensive medication should be RAAS blockers such as ACE inhibitor or ARB. For the last several years, several large cohort clinical studies using ACEI and ARB have shown more favorable effects, but aldosterone receptor inhibitor (mineral corticoid receptor inhibitors; MR inhibitors) and Renin Inhibitors have been withdrawn. Some studies showed the strong support to use these medications for diabetic patients. This review will discuss the relationships between vascular RAAS and insulin resistance in patients with hypertension and diabetes as previously reviewed with new updated findings for the last 4 years, and clinical implications based on updated JNC-8, ESH-ESC2013 and JSH-2014.

Association of periodontal status with occlusal force and food acceptability in 70-year-old adults: from SONIC Study.

This cross-sectional study aimed to investigate the association of periodontal status with occlusal force and food acceptability. We hypothesised that mastication deteriorated with reduced periodontal support, even when posterior occlusal contacts with natural teeth were maintained and the patients remained clinically asymptomatic. Participants were 482 independently living 69-71-year-olds, classified as Eichner's group A, having no mobile teeth and no periodontal symptoms. The periodontal probing depth (PPD) and restoration status of each tooth were examined. Occlusal force in the intercuspal position was measured with pressure-sensitive films. Food acceptability was evaluated from the difficulty experienced in chewing apples, grilled beef, and hard rice crackers. Multivariate regression analysis was performed to investigate the association of periodontal status with occlusal force and food acceptability. A P-value of <0.05 was considered statistically significant. Multiple linear regression analysis showed that occlusal force had significant negative associations with maximal PPD (standardised partial regression coefficient (ß) = -0.121) after controlling for gender, handgrip strength, number of teeth, and percentage of restored teeth. Approximately 15% of participants were included in the compromised food acceptability group. Logistic regression analyses showed that compromised food acceptability was significantly associated with PPD, after controlling for gender, number of teeth, and percentage of restored teeth. Periodontal probing depth (PPD) was significantly correlated with occlusal force and self-rated food acceptability after controlling for the possible confounding factors in septuagenarians, even those with complete posterior occlusal contacts and no tooth mobility.

Association of insulin-like growth factor-1 receptor gene polymorphisms with left ventricular mass and geometry in essential hypertension.

Stimulation of insulin-like growth factor (IGF)-1 receptor by IGF-1 and insulin strongly induces cardiomyocyte hypertrophy. In this study, we assessed the hypothesis that genetic variations of the IGF-1 receptor may be linked to the diversity of left ventricular (LV) structure in hypertensive patients. Genotypes in 12 single nucleotide polymorphisms (SNPs) of the IGF-1 receptor gene identified by direct sequencing were determined in 795 Japanese patients with essential hypertension. In echocardiographic examinations, LV mass index (LVMI) and relative wall thickness (RWT) were measured. Among 12 SNPs, promoter -328C>T and intron-13 275124A>C polymorphisms were significantly associated with LV hypertrophy (LVMI> or =125 g m(-2)) and concentric change (RWT> or =0.44), respectively. In allele frequencies, the C allele of -328C>T was related to LV hypertrophy, and the A allele of 275124A>C was related to LV concentric change. In fact, LVMI and prevalence of LV hypertrophy increased in CC genotype of -328C>T. RWT and prevalence of LV concentric change increased in AA genotype of 275124A>C. A multiple logistic regression analysis revealed that the presence of CC genotype of -328C>T or AA genotype of 275124A>C was an independent determinant for LV hypertrophy or concentric change, respectively. Furthermore, the combination of CC of -328C>T and AA of 275124A>C genotypes was significantly associated with abnormal LV geometry, especially concentric hypertrophy. Our findings show that two SNPs of the IGF-1 receptor gene are related to LV hypertrophy in patients with essential hypertension, suggesting that the genetic variation of the IGF-1 receptor may be involved in the diversity of LV structure in hypertensives.

Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide and its activity is mediated by the receptors ET type A (EDNRA) and ET type B (EDNRB). Although ET-1 is thought to play an important role in the development of atherosclerosis, it remains unclear whether polymorphisms of ET-1 family genes, including the ET-1 gene (EDN1), EDNRA, EDNRB and the genes for endothelin converting enzymes 1 and 2 (ECE1 and ECE2), are associated with the progression of atherosclerosis. We investigated the relationship between 11 single nucleotide polymorphisms (SNPs) of ET-1 family genes (including three in EDN1, one in EDNRA, two in EDNRB, four in ECE1 and one in ECE2) and atherosclerotic changes assessed using pulse wave velocity (PWV) and carotid ultrasonography in 630 patients with essential hypertension (EHT). In male subjects, we found significant differences in brachial-ankle PWV (baPWV) in additive and recessive models in EDNRB-rs5351 after Bonferroni correction. Also in male subjects, there were significant differences in mean intima-media thickness (IMT) in additive and recessive models in EDNRA-rs5333 after Bonferroni correction. We found no significant correlation between any SNPs in the ET family genes and baPWV, IMT and Plaque score (PS) in female subjects. Furthermore, after multiple logistic regression analysis, only EDNRB-rs5351 indicated as an independent risk of atherosclerosis in male hypertensive subjects. Of the endothelin-related genes, EDNRB-rs5351 was the most susceptible SNP associated with atherosclerosis in male hypertensives, and the genetic background may be involved in the progression of atherosclerosis in EHT patients.

Reverse white-coat effect as an independent risk for left ventricular concentric hypertrophy in patients with treated essential hypertension.

Recent studies have shown that the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' is associated with poor cardiovascular prognosis. We assessed the hypothesis that this phenomenon may specifically influence left ventricular (LV) structure in treated hypertensive patients. A total of 272 outpatients (mean age, 65 years) with chronically treated essential hypertension and without remarkable white-coat effect were enrolled. Patients were classified into two groups according to office and daytime ambulatory systolic blood pressure (SBP); that is subjects without (Group 1: office SBP > or =daytime SBP, n=149) and with reverse white-coat effect (Group 2: office SBP

Microalbuminuria and deterioration of renal function after elective repair of infrarenal abdominal aortic aneurysm.

AIMS: Renal dysfunction affects the prognosis of patients after aortic surgery. However, the factors associated with the postoperative deterioration of renal function has not been clarified precisely. METHOD: We prospectively examined renal function in 80 patients (age: 73 +/- 7 years, 66 males) who required the elective repair of infrarenal abdominal aortic aneurysm (AAA). Serum creatinine (Scr) was measured. 24-h-creatinine clearance (Ccr) and urinary albumin excretion (UAE) were determined. Renal volume and mean renal length were calculated using the data obtained by ultrasonography. 48 patients showed normal UAE (< 30 mg/day), and 24 had microalbuminuria (30-300 mg/day) and 8 had overt proteinuria (> 300 mg/day). Scr were 0.9 +/- 0.4, 1.0 +/- 0.3 and 2.1 +/- 1.3 mg/dl, respectively. RESULTS: On Day 5 after surgery, 12 patients (15%) showed deterioration of renal function as defined either by an increase in Scr (> or = 0.5 mg/dl) or by a decrease in Ccr > or =20%). The acute deterioration of renal function was related to mean renal volume, mean renal length, duration of operation and the use of antibiotics. At Month 12 after surgery, Scr increased in the overt proteinuria group. The deterioration of renal function at Month 12 was found in 8 patients (10%) with microalbuminuria or overt proteinuria, and related to preoperative Ccr, UAE, mean renal volume, mean renal length, smoking status and blood pressure. CONCLUSION: We conclude that the deterioration of renal function occurred in considerable number of patients with AAA after elective operation on acute and chronic phase, although the development of end-stage renal failure is rare. Factors related to the acute and late deterioration appears to be different. UAE and renal size should be measured, even if Scr is in normal range at preoperative observation.

Evaluation of intrarenal hemodynamics by Doppler ultrasonography for renoprotective effect of angiotensin receptor blockade.

AIMS: It has been shown that both angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB) have renoprotective effects via mechanisms that are independent of blood pressure reduction. The aim of this study was to evaluate the intrarenal hemodynamic change with ARB by renal Doppler ultrasonography (RDU) and to assess the mechanism of ARB in patients with hypertension. METHODS: Thirty hypertensive patients with renal insufficiency caused by glomerular diseases, diabetes and hypertensive nephrosclerosis were included in this study. RDU was performed before and one week after taking ARB. Resistance index (RI) (peak systolic velocity - end diastolic velocity/peak systolic velocity) in the intrarenal segmental artery were calculated, and the amounts of urinary protein or albumin were determined. RESULTS: We defined patients whose microalbuminuria or proteinuria was reduced by greater than 30% by ARB as responders (n = 22) and defined other patients as non-responders (n = 8). There were no significant differences between the responder and non-responder groups in baseline characteristics. RI was significantly improved by ARB in the responder group, but not in the non-responder group. The reduction of RI after ARB treatment was most prominent in patients with hypertensive nephrosclerosis. CONCLUSIONS: Improvement in intrarenal hemodynamics might play an important role in the mechanisms of the renoprotective effect of ARB in patients with hypertension.

Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus.

AIMS: Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients. METHODS: In 67 patients with non-dialysis CRF as a result of chronic glomerulonephritis (n = 33) or diabetic nephropathy (n = 34), and 134 hypertensive patients with normal renal function, two-dimensional and Doppler echocardiographic examinations were performed, and LV dimension, mass, systolic function, and diastolic function were evaluated. RESULTS: LV mass was increased and LV diastolic dysfunction was advanced in subjects with CRF compared with hypertensive controls. In the comparison of echocardiographic parameters between the two groups of CRF patients, i.e. chronic glomerulonephritis and diabetic nephropathy groups, all indices of LV diastolic function were more deteriorated in the diabetic nephropathy group than in the chronic glomerulonephritis group, although LV structure including hypertrophy and systolic function did not differ between the groups. In a multiple regression analysis, the presence of diabetes (i.e. diabetic nephropathy group) was a significant predictor of LV diastolic dysfunction in CRF subjects, independent of other influencing factors such as age, blood pressure, renal function, anaemia and LV hypertrophy. CONCLUSION: The present findings suggest that LV diastolic dysfunction, independent of LV hypertrophy, is specifically and markedly progressed in patients with CRF as a result of diabetic nephropathy.

Diagnostic value of carotid intima-media thickness and plaque score for predicting target organ damage in patients with essential hypertension.

Carotid intima-media thickness (IMT) assessed by ultrasonography is regarded as an early predictor of general arteriosclerosis in patients with essential hypertension. However, the methods of measuring IMT have not been globally standardized, and it remains unclear whether conventional measurement of IMT represents the prevalence of hypertensive target organ damage. In this study, we verified the association between several commonly used carotid ultrasonographical parameters and the severity of hypertensive target organ damage (retinal arteriosclerosis, microalbuminuria, left ventricular hypertrophy (LVH)). Carotid ultrasonography, echocardiography, urinalysis, and funduscopy were performed in 184 patients (64 +/- 12 years, 96 males and 88 females) with various stages of essential hypertension. Carotid arteriosclerosis was assessed using four methodologically different methods: conventional-IMT, maximum-IMT (Max-IMT), Mean-IMT, and Plaque Score (the sum of all plaque thicknesses). Age and all carotid ultrasonographical parameters were significantly associated with albuminuria, retinal arteriosclerosis, and left ventricular mass index. High-sensitivity CRP was significantly correlated with retinopathy and LVH. Carotid parameters in patients with histories of cardiovascular events were significantly greater in those without events. Among all carotid parameters, Max-IMT showed the highest correlation coefficient of the severity of target organ damage, and showed significant association with CRP. Stepwise regression analysis revealed that Max-IMT was the independent factor for predicting target organ damage. Max-IMT is suggested to be the most reliable and simplest parameter for predicting hypertensive target organ damage including microangiopathy in patients with essential hypertension.

Insulin and insulin-like growth factor-I promotes angiotensinogen production and growth in vascular smooth muscle cells.

BACKGROUND: Circulating insulin and insulin-like growth factor-I (IGF-I) levels are increased in patients with hypertension and insulin resistance. Since both hormones are known to have cell growth-promoting effects, they may contribute to the progression of vascular hypertrophy in patients with insulin resistance. Insulin-mediated activation of the vascular renin-angiotensin system (RAS) stimulates growth in cultured rat vascular smooth muscle cells (VSMC). OBJECTIVE: In order to evaluate the role of IGF-I-mediated activation of components of the tissue RAS, we examined the effect of IGF-I receptor stimulation on cell proliferation, and production of angiotensinogen in cultured VSMC. STUDY DESIGN: Aortic VSMC were derived from male Sprague-Dawley rats. IGF-I and insulin-mediated DNA synthesis were estimated by 3H-thymidine uptake (3H-TdR) with or without the angiotensin I converting enzyme inhibitor, captopril. Moreover, angiotensinogen released by the cells to the culture medium was determined by radioimmunoassay with or without the anti-IGF-I receptor antibody alphaIR3 or captopril. RESULTS: Both IGF-I and insulin increased 3H-TdR uptake by cultured rat VSMC (P < 0.05). Captopril blocked IGF-I and insulin-mediated 3H-TdR uptake (-34.4 +/- 1.9% and -32.7 +/- 1.8%, P < 0.05, respectively). IGF-I increased the angiotensinogen level in the medium by 30.6 +/- 2.9% (P < 0.01). Insulin also stimulated angiotensinogen synthesis by 26.3 +/- 2.2% (P < 0.01). Captopril and alphaIR3 significantly suppressed angiotensinogen production stimulated by both IGF-I and insulin. CONCLUSIONS: These results indicate that IGF-I as well as insulin stimulates angiotensinogen production and growth in VSMC. Thus, both hormones may independently play a role in progression of the vascular hypertrophy and atherosclerosis in patients with hypertension and insulin resistance through activation of the tissue RAS.

Deletion polymorphism of angiotensin-converting enzyme gene is associated with postprandial hyperglycaemia in individuals undergoing general check-up.

1. Deletion polymorphism, DD, of the angiotensin-converting enzyme (ACE) gene is reported to be related to cardiovascular disease, which is frequently based on insulin resistance. 2. To clarify the relationship between the ACE genotype DD and plasma glucose increases after an oral glucose load, we performed 75 g oral glucose tolerance test (OGTT) in 301 nondiabetic men (age range 30-60 years) undergoing general check-up. 3. Insertion/deletion (I/D) polymorphism of the ACE gene was explored using a polymerase chain reaction. The frequency of the II, ID and DD genotypes was 0.43, 0.43 and 0.14, respectively. 4. There were no differences in baseline clinical characteristics between subjects with each ACE genotype. 5. The mean (+/- SEM) plasma glucose level at 60 min of the OGTT was significantly higher in subjects with the DD genotype (170.8 +/- 6.9 mg/dL) than in subjects with either the II or ID genotype (mean value for two groups 156.6 +/- 2.7 mg/dL; P < 0.05). Moreover, the mean percentage change of plasma glucose after 60 min of the OGTT, a marker of plasma glucose increase, was significantly higher in individuals with the DD genotype than in individuals with either the II or ID genotypes. 6. In contrast, the mean fasting plasma glucose level, the plasma glucose level at 120 min, the glucose response area and the fasting insulin level were not different between individuals with the DD genotype and individuals with other genotypes. 7. In conclusion, subjects with the DD genotype showed transiently higher levels of plasma glucose after an oral glucose load than subjects with other genotypes. Further studies are required to determine whether the association between ACE genotype and postprandial hyperglycaemia influences the incidence of cardiovascular disease and diabetes mellitus.

Characterization of liposomes carrying von Willebrand factor-binding domain of platelet glycoprotein Ibalpha: a potential substitute for platelet transfusion.

Platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor (vWf), which plays a crucial role in primary hemostasis by mediating platelet adhesion to injured blood vessels. We have expressed in CHO cells a fragment of GPIba that retained a vWf-binding function. The recombinant fragment (rGPIba) was incorporated into liposomes and evaluated their functions in vitro. rGPIba on the liposome surface was detectable by flow cytometric analysis. Addition of vWf and ristocetin caused specific agglutination of rGPIbalpha-liposomes, as evaluated by an aggregometer or a fluorescent microscopy. When ristocetin was added to platelet-rich plasma (PRP) pre-mixed with rhodamine-labeled rGPIbalpha-liposomes, platelets aggregated and rhodamine-fluorescence was strongly positive in the platelet thrombi, suggesting that heterologous aggregation (attachment of liposomes to platelets) occurred. Platelet aggregation in PRP at low platelet concentration (20-80 x 10(6)/ml) was enhanced by rGPIbalpha-liposomes in a dose-dependent manner. Thus, rGPIbalpha-liposomes may accumulate on vWf-exposed subendothelial tissues and enhance platelet function in vivo, supporting hemostasis in thrombocytopenic individuals.

Insulin-mediated growth in aortic smooth muscle and the vascular renin-angiotensin system.

Insulin has been shown to directly affect blood vessel tone and to promote vascular hypertrophy, but the mechanism of these actions remains uncertain. Because angiotensin I (Ang I)-converting enzyme inhibitors have been shown to improve insulin action and to impede the progression of vascular hypertrophy in hypertensive animal models, it is possible that the vascular properties of insulin may be mediated through the tissue renin-angiotensin system (RAS). To evaluate this relationship, we first investigated the effect of insulin on components of the RAS using cultured rat vascular smooth muscle cells (VSMCs). Insulin treatment (1000 microU/mL) markedly increased angiotensinogen mRNA expression and angiotensinogen production. We next investigated the role of the RAS in insulin-mediated cell proliferation, using [3H]thymidine uptake. Studies were done both with insulin alone and in the presence of captopril (1x10(-7) to 10(-5) mol/L) and losartan (1x10(-9) to 10(-7) mol/L). [3H]Thymidine uptake was increased significantly by 1000 microU/mL insulin, and this stimulation was reduced by 1x10(-6) mol/L captopril (-38.8%, P<0.05) and by 1x10(-8) mol/L losartan (-37. 5%, P<0.05). Further studies showed that the degree of insulin-mediated [3H]thymidine uptake in VSMCs could be duplicated by 4x10(-10) mol/L Ang II. Losartan reduced the effects of both Ang II and insulin on [3H]thymidine uptake by about 40% to 45% of baseline (P<0.05). Captopril reduced insulin-mediated [3H]thymidine uptake but did not affect Ang II-mediated [3H]thymidine uptake. In summary, insulin induced significant stimulation of angiotensinogen expression and production and stimulated growth similar to that seen with Ang II in cultured rat VSMCs. Inhibition of Ang II production or its binding to the Ang II type 1 (AT1) receptor inhibited insulin-mediated growth in a fashion similar to that seen with inhibition of Ang II-mediated growth. Thus, insulin can modulate the vascular RAS, and the effect of insulin on vascular growth may be via direct effects on angiotensinogen expression and translation operative through both the AT1 receptor and the conversion of Ang I to Ang II.