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Hitoshi Ando

Publications and source records attributed to Hitoshi Ando.

28 records · Page 2Linked to original sources
PubMed2004

The specific p38 mitogen-activated protein kinase pathway inhibitor FR167653 keeps insulitis benign in nonobese diabetic mice.

The p38 mitogen-activated protein kinase (MAPK) pathway is important in Th1 immunity, macrophage activation, and apoptosis. Since they may be associated with beta-cell destruction during the development of type 1 diabetes, we investigated the role of the p38 MAPK pathway in female nonobese diabetic (NOD) mice. Phosphorylated p38 MAPK was observed immunohistochemically in CD4+ cells that had infiltrated into the islets and part of beta-cells, increasing in proportion to the severity of insulitis. Continuous oral administration of 0.08% FR167653, a specific p38 MAPK pathway inhibitor, significantly reduced the ex vivo production of interferon-gamma by splenic Th1 cells without affecting interleukin-4 production by Th2 cells. FR167653 administration from 4-30 weeks of age prevented NOD mice from developing diabetes without affecting the severity of insulitis. Treatment with FR167653 after insulitis had developed (i.e. from 10-30 weeks of age) also prevented diabetes, further suggesting that treatment with the p38 MAPK pathway inhibitor keeps insulitis benign in NOD mice, partly by inhibiting Th1 immunity. These findings suggest that p38 MAPK is a key mediator that switches insulitis from benign to destructive in the development of type 1 diabetes.

Animals↗
PubMed2004

Prostaglandin E1 in lipid microspheres ameliorates diabetic peripheral neuropathy: clinical usefulness of Semmes-Weinstein monofilaments for evaluating diabetic sensory abnormality.

We investigated the effect of Prostaglandin E1 in lipid microspheres (Lipo-PGE1) on diabetic peripheral neuropathy from view of symptoms, neurological examinations including sensory threshold evaluated with Semmes-Weinstein monofilaments (SWM). Type 2 diabetic patients with diabetic peripheral neuropathy were participated in this study. The patients were randomly assigned to two groups, 11 Lipo-PGE1-treated patients and 16 control patients. Lipo-PGE1 at a dose of 10mg in 20ml of saline was injected intravenously as a bolus once daily for 2 weeks. Before and, 1, 2 and 4 weeks after the start of treatment with Lipo-PGE1, sensory threshold was evaluated with Semmes-Weinstein monofilaments at total 18 touch sites on the feet. Administration of Lipo-PGE1 improved subjective symptoms especially in items of numbness and imperception. Such improvement in subjective symptoms correlated well with the improvement in Semmes-Weinstein monofilaments examination, whereas the improvement was not recognized in motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV) and coefficient variation of R-R interval on ECG (CVR-R). The improvement lasted for at least 6 months. This study demonstrated that Lipo-PGE1 has long term amelioration effects on diabetic neuropathy especially in symptoms and sensory threshold, and that Semmes-Weinstein monofilaments examination is a simpler, more valid and quantitative tool for assessing the clinical effect of Lipo-PGE1 on diabetic peripheral neuropathy.

Alprostadil↗
PubMed2004

Beta2-microglobulin adsorption column reduces digoxin trough level during hemodialysis: three case reports.

We have previously reported that a beta2-microglobulin adsorption column for the treatment of dialysis-related amyloidosis decreased serum digoxin concentration in renal failure patients. Because the distribution volume of digoxin is high, it is uncertain whether the repetitive use of this column influences the pharmacokinetics of digoxin in renal failure patients. We have observed 3 renal failure patients whose trough serum digoxin concentrations were significantly reduced by the repetitive use of tandem beta2-microglobulin adsorption columns for treatment of dialysis-related amyloidosis. These patients experienced symptomatic elevation of their heart rates in parallel with a significant reduction in serum digoxin concentrations. Termination of the use of the adsorption column improved the symptoms in 1 patient; however, severe arthritic pain caused by amyloidosis relapsed. Dosage of digoxin was increased in 2 other patients with continuous treatment by the column. Their digoxin concentrations increased, and their heart rates decreased without any deterioration of joint pain. We have demonstrated that the repetitive use of the beta2-microglobulin adsorption column in tandem with standard hemodialysis actually decreases trough digoxin concentration in renal failure patients. Careful monitoring and alteration of digoxin dosage regimens are needed under these circumstances.

Aged↗
PubMed2004

Adsorption of oxacalcitriol by polysulphone haemodialyser in patients with secondary hyperparathyroidism.

AIMS: This study was undertaken to evaluate removal of 22-oxacalcitriol (OCT), an active and intravenously used vitamin D3 analogue with less calcaemic activity, by polysulphone haemodialyser in vivo and in vitro. We further compared the pharmacodynamic efficacy [suppression of intact parathyroid hormone (iPTH)] when given intravenously either during or at the end of the haemodialysis. METHODS: (i) Drug clearance by the polysulphone dialyser was measured during a single continuous infusion (5 microg) for 30 min into the arterial side of the dialyser in end-stage renal failure patients with secondary hyperparathyroidism (n = 7). (ii) The drug adsorption by the hollowfibre membrane during incubation for 30 min was measured in vitro. (iii) To evaluate efficacy, the drug was given (i.v. bolus) during or at the end of haemodialysis for 4 weeks in a cross-over fashion with a washout period of 8 weeks (n = 9). Serum Ca(2+), phosphate (P) and iPTH concentrations just before the initiation of the dialysis were monitored every week. RESULTS: (i) OCT was significantly cleared by the polysulphone haemodialyser, but the clearance declined in a time-dependent manner to approach zero at 30 min. Arterial (at the place between the drug infusion site and the haemodialyser column) drug concentrations did not change during the infusion (mean = 2064 +/- 233 pg ml(-1)). Venous (just after the dialyser) drug concentrations at 10 min after the infusion were significantly lower than those of the arterial side (mean = 784 +/- 84 pg ml(-1)); however, they increased with time and reached those of the arterial side at 30 min. (ii) In vitro, OCT was adsorbed by the membrane. The amount of adsorption was concentration-dependent and was lower in the presence of human serum (55 +/- 4% without and 23 +/- 4% with serum at 600 pg ml(-1) of OCT). (iii) Although serum Ca(2+) and P increased and iPTH decreased by both treatment regimens (i.e. OCT administered either during or at the end of haemodialysis), these changes did not significantly differ. Mean differences (and 95% confidence interval) of Ca(2+), P, and iPTH at the end of the trial were 0.03 (-0.04, 0.09) mm, 0.41 (-0.43, 1.26) mg dl(-1) and 38 (-42, 88) pg ml(-1), respectively. CONCLUSION: OCT is adsorbed by polysulphone dialyser in vitro and in vivo. However, the pharmacodynamic effectiveness was largely independent of the administration regimen of OCT given either during or at the end of haemodialysis.

Adsorption↗
PubMed2003

Fulminating onset type 1 diabetes with positivity for anti-GAD antibody and elevated pancreatic exocrine enzyme concentrations.

A 52-year-old man was admitted to our hospital for diabetic ketoacidosis. On admission, Hb(A1c) was 6.5%, anti-GAD antibody 10.3 U/ml, serum amylase 144 IU/l, lipase 169 U/l and elastase-I 1,000 ng/dl. There were no abdominal symptoms, and abdominal CT showed unremarkable findings. He was treated with intensive insulin therapy. After 1 month, urinary excretion of C-peptide was 3.8 microg/day. Serum pancreatic exocrine enzyme concentrations returned to normal after 3 months. After 10 months, anti-GAD antibody had become negative, but insulin therapy was still needed for glycemic control. This report concerns a case of autoimmune fulminating onset type 1 diabetes.

Aspartate Aminotransferases↗
PubMedDate not supplied

Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy.

The relationship between the effect of aldose reductase inhibitors (ARIs) on the activation of the polyol pathway and on diabetic neuropathy has not been fully established. To address this issue, we investigated the effect of epalrestat (150 mg/day), an ARI, on erythrocyte sorbitol levels as an index of polyol activation and on nerve function test results in 43 patients with diabetic peripheral polyneuropathy. After 6 months of epalrestat administration, erythrocyte sorbitol levels did not decrease in patients as a whole. However, a decrease in erythrocyte sorbitol levels during epalrestat administration was significantly correlated with baseline erythrocyte sorbitol levels (rho=-.47, P<.01): The higher the level at baseline, the greater the decrease after epalrestat treatment. Moreover, the mean sorbitol level during epalrestat treatment was associated with the beneficial effect of epalrestat on vibration sensitivity as measured with a C-128 tuning fork (rho=-.66, P<.01) and/or a pallesthesiometer TM-31A (rho=.53, P<.05). On the other hand, erythrocyte sorbitol levels did not reflect the prognosis of nerve conduction velocity. These findings at least partly suggest a causal relationship between polyol activation and the development of diabetic neuropathy. Aldose reductase inhibitor treatment may be clinically useful in the control of polyol activation, especially in patients with excessive accumulation of sorbitol.

Aged↗