Akira Kitagawa

The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction

Adiponectin is a new member of adipocyte derived proteins belonging to the soluble defence collagens.1 Plasma adiponectin concentrations in obese subjects are decreased in spite of an adipose specific expression.1 More interestingly, the patients with chronic coronary artery disease exhibited lower plasma adiponectin concentrations compared to body mass index (BMI) matched control subjects.2 On the other hand, adiponectin accumulates in the vascular subendothelial space when the endothelial barrier is damaged.3 In vitro, adiponectin suppresses the expression of adhesion molecules in the vascular endothelial cells and cytokine production from macrophages.2,4 Therefore, the molecule may be involved in the inflammation and tissue repairing processes. Acute coronary syndrome is often precipitated by acute thrombosis.5 It is commonly accepted that the rupture or the erosion of plaques by the inflammatory process leads to coronary thrombosis and acute myocardial infarction (AMI). The C reactive protein (CRP) concentrations in the acute phase are suggested to reflect pre-existing coronary plaque instability associated with the onset of AMI. The significance of adiponectin in acute coronary syndrome has never been investigated. In the present study, we examined the serial change in plasma adiponectin concentrations and its relation to plasma CRP concentration in …

Adiponectin is inversely related to plasminogen activator inhibitor type 1 in patients with stable exertional angina

Adipose tissue is a secretory organ producing a variety of bioactive substances, such as adiponectin. Adiponectin has antiatherogenic properties while plasminogen activator inhibitor type 1 (PAI-1) is closely involved in the development of atherosclerosis. The relationship between adiponectin and PAI-1 in patients with coronary artery disease (CAD) has not been clarified. This study examined plasma levels of adiponectin and PAI-1 in 64 patients with stable exertional angina (SEA) and 65 patients with the chest pain syndrome (CPS). Plasma log-adiponectin levels were significantly lower in patients with SEA (0.62+/-0.08 micro g/dL) compared to those with CPS (0.86+/-0.05 micro g/dL) (p<0.0001). The plasma levels of log-PAI-1 were significantly higher in patients with SEA (1.23+/-0.18 ng/mL) compared to those with CPS (1.15+/-0.22 ng/mL) (p<0.05). Plasma log-adiponectin levels correlated negatively with diabetes mellitus (DM), body mass index (BMI), log-PAI-1 (r=-0.284, p<0.001), triglyceride (TG), and remnant-like particles cholesterol (RLP-C), and positively with high-density lipoprotein cholesterol (HDL-C) levels. Plasma levels of log-PAI-1 correlated positively with DM, BMI,TG and RLP-C levels, and negatively with HDL-C levels. Multiple logistic regression analysis identified sex, angina pectoris, and PAI-1 as independent determinants of hyperadiponectinemia (p<0.05). Adiponectin is inversely related to PAI-1. DM, BMI,TG, HDL-C, and RLP-C are common mediators between adiponectin and PAI-1, and treatment for common mediators may prevent the development of CAD by reducing PAI-1 and increasing adiponectin levels.

Morning home blood pressure may be a significant marker of nephropathy in Japanese patients with type 2 diabetes : ADVANCED-J study 1

A 3-year multicenter, prospective, randomized, open-label trial (ADVANCED-J) compared the effect of an increased dose of angiotensin-II receptor blocker (ARB) with that of a maintenance dose of ARB plus calcium channel blocker (amlodipine) on blood pressure (BP) control, nephropathy and atherosclerosis in patients with type 2 diabetes and hypertension in whom the usual ARB dose failed to control BP. A cross-sectional analysis using baseline data was conducted. Of 316 patients (recruited between September 2004 and December 2005), 228 patients were evaluated by multiple regression analysis using two models after randomization and exclusions. Model 1 assessed 13 baseline variables (age, sex, estimated diabetes duration, estimated hypertension duration, HbA1c, brain natriuretic peptide (BNP), high-sensitive C-reactive protein (hsCRP), triglycerides (TGs), total cholesterol (TCHO), diabetic retinopathy (DMR), systolic morning home BP (HBP), diastolic morning HBP and brachial-ankle pulse wave velocity (baPWV)) for correlation with the urinary albumin creatinine excretion rate (UACR). In model 2, systolic and diastolic morning HBP was replaced by systolic and diastolic office BP. The systolic morning HBP and systolic office BP or diastolic morning HBP and diastolic office BP correlations were weak, but significant (r=0.43 and 0.48, respectively). BNP, HbA1c, DMR and estimated diabetes duration were significantly correlated with UACR in both models 1 and 2. Although systolic office BP did not show a significant correlation with UACR in model 2, systolic morning HBP showed a significant correlation with UACR in model 1. Morning HBP, but not office BP, may be a significant marker of nephropathy in Japanese patients with type 2 diabetes.

Amlodipine versus angiotensin II receptor blocker; control of blood pressure evaluation trial in diabetics (ADVANCED-J)

BackgroundThe coexistence of type 2 diabetes mellitus and hypertension increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes Study has shown that blood pressure control as well as blood glucose control is efficient for prevention of complications in hypertensive patients with diabetes mellitus. However, some reports have shown that it is difficult to control the blood pressure and the concomitant use of a plurality of drugs is needed in hypertensive patients with diabetes mellitus. In recent years renin-angiotensin system depressants are increasingly used for the blood pressure control in diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are increasingly used. However, there is no definite evidence of the point of which is efficient for the control, the increase in dose of A II antagonist or the concomitant use of another drug, in hypertensive patients whose blood pressure levels are inadequately controlled with A II antagonist.Methods/DesignHypertensive patients of age 20 years or over with type 2 diabetes mellitus who have been treated by the single use of AII antagonist at usual doses for at least 8 weeks or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks are included.DiscussionWe designed a multi-center, prospective, randomized, open label, blinded-endpoint trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in hypertensive patients with diabetes mellitus, whose blood pressure levels were inadequately controlled with A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure. The ADVANCED-J study may have much influence on selection of antihypertensive drugs for treatment in hypertensive patients with diabetes mellitus. It is expected to give an important hint for considering the validity of selection of antihypertensive drugs from the aspects not only of the antihypertensive effect but medical cost-effectiveness.

Protective Effect of N-Benzoyl-β-Alanine Against Cisplatin Nephrotoxicity in Rats

Prophylactic effects of N-benzoyl-beta-alanine (betamipron, BP), one of a series of N-acyl amino acids, were examined against cisplatin-induced nephrotoxicity. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with an i.p. BP dose given at various times and various doses. Rats were sacrificed 5 days after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Preliminary results suggest that treatment with BP is an effective means of protection against cisplatin-induced nephrotoxicity. Combination with BP reduced the weight loss following treatment with cisplatin. The ratios of the kidney and liver weights to the body weight in the animals treated with cisplatin followed later with BP are significantly different (p < 0.05) from those in the animals that received only cisplatin. The BUN and serum Cr levels in the animals treated with cisplatin followed from -1 to 4 hr, and from -4 to 4 hr later with 250 mg/kg BP dose and followed 1 hr later with from 250 to 1000 mg/kg, and from 250 to 2000 mg/kg BP doses differed significantly (p < 0.05) from those in the animals that received only cisplatin. Histological analysis of the kidneys confirmed the protective effect of BP.

Protective Effects of Betamipron on Renal Toxicity During Repeated Cisplatin Administration in Rats and Protective Mechanism

The protective effects of betamipron (BP, N-benzoyl-beta-alanine) against nephrotoxicity induced by repeated cisplatin injections were examined. The ratio of the kidney weight to body weight and the lipid peroxide level after treatment with cisplatin plus BP tended to be larger and lower than those after treatment with cisplatin plus alkaline solution, respectively. The blood urea nitrogen, serum creatinine and glutathione levels in the animals treated with cisplatin plus BP differed significantly from those in the animals treated with cisplatin plus alkaline solution. Furthermore, the mechanism of the preventive effects of BP was analyzed for cisplatin-induced nephrotoxicity. The concentration of cisplatin in the renal cortex significantly decreased with concomitant BP. BP inhibited the uptake of cisplatin into the renal cortex in a competitive manner in the same way as an anionic transport inhibitor, probenecid. The treatment with BP appears to be useful for the renal toxicity induced by repeated cisplatin administration.

Betamipron reduces cisplatin nephrotoxicity in rodents without modifying its antileukemic activity in mice.

Protective effects of betamipron (BP, N-benzoyl-beta-alanine), one of a series of N-acyl amino acids, on cisplatin-induced nephrotoxicity were examined. Since the damage observed in the kidney is localized to the proximal tubule cells, we investigated the influence of BP on urinary enzymes and excreta. Male Wistar rats and ddY mice were injected i.p. with 6 mg/kg and 16 mg/kg, respectively, of cisplatin combined with an i.p. 250 mg/kg BP dose. The toxicity of cisplatin as indicated by body weight gain, blood urea nitrogen, and serum creatinine levels was significantly (p < 0.05) suppressed by administration of BP after cisplatin treatment. The increase in urinary N-acetyl-beta-D-glucosaminidase activity, increase and subsequent decrease in gamma-glutamyl transferase activities, and increase in beta 2-microglobulin level observed after treatment with cisplatin were suppressed by administration of BP after cisplatin treatment. The combination of cisplatin and BP had no apparent effect on the efficacy of cisplatin against P388 leukemic cells in mice.

Analysis of Waiting Time of Outpatients.

In order to increase our service for outpatients, characteristics of waiting time at pharmacy was investigated on the number of prescriptions, dispensing cases, and drug items every 30minutes, and was imvestigated on the number of pharmacists with weight in experiences and of clinical departments for outpatients. Multiple regression analysis using 3 factors was carried out.The obtained standard partial regression coefficients showed that waiting time depended on the number of prescriptions every 30 minutes and of pharmacists with weight in experiences. The number of patients who failed to receive medicines was independent of waiting time.As the result that we inquired of outpatients how about waiting time at pharmacy, many outpatients voiced their discontent.The source of their discontent was, however, not their waiting time in itself, but it was revealed that they had been discontented because of the lack of understanding of dispensing.