Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 505 records · Page 28Linked to original sources

PubMed1998

Alteration of intracellular Na+ during ischemia in diabetic rat hearts: the role of reduced activity in Na+/H+ exchange against stunning.

To elucidate the contribution of reduced activity of Na+/H+ exchange in streptozotocin-induced diabetic hearts against stunning, intracellular Na+ concentration ([Na+]i) was measured in isolated rat hearts using 23Na-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37 degreesC was significantly better in diabetic ones (102.9+/-2.0% of pre-ischemic level, mean+/-s.e., n=6; P<0.05), and non-diabetic ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 mu mol/l; 93.8+/-2.3%, n=5; *P<0.05) than non-treated, non-diabetic hearts (75.1+/-2.5%, n=8). When diabetic hearts were pre-treated with EIPA, the recovery (101.2+/-2.6%, n=5) was identical to that of non-treated, diabetic hearts. [Na+]i in non-diabetic hearts increased to 329.1+/-8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+]i in diabetic hearts significantly suppressed to 199.8+/-10.3% (P<0.001). EIPA attenuated the increase of [Na+]i during ischemia to 189.1+/-9.0% in non-diabetic hearts ( P<0.001) and to 155.3+/-4.6% in diabetic hearts (P<0.05). Thus, the EIPA-dependent Na+ accumulation during ischemia, i.e. Na+ influx probably mostly via Na+/H+ exchange was smaller in diabetic hearts by 69.7% compared with that in non-diabetic hearts. These results indicate that the cardiac protection against stunning in streptozotocin-induced diabetic hearts is mediated by the attenuation of Na+ accumulation during ischemia, which is caused by the reduced activity in Na+/H+ exchanger.

Adenosine Triphosphate↗

PubMed1998

Effects of gastrointestinal prokinetic agents, TKS159 and cisapride, on the in situ canine heart assessed by cardiohemodynamic and electrophysiological monitoring.

Effects of a novel 5-HT4 receptor agonist TKS159 on the cardiovascular system were assessed in comparison with cisapride using an in vivo canine model. TKS159 in doses of 0.1, 1.0, and 10 mg/kg (n = 6) or cisapride in 1/10 doses of 0.01, 0.1, and 1.0 mg/kg (n = 6) was cumulatively infused over 10 min with a pause of 20 min. The doses of the drugs were determined according to the previous knowledge of their pharmacokinetics. Clinically effective plasma concentrations as a gastrointestinal prokinetic drug were obtained after the infusion of 0.1 mg/kg of the respective drugs. In TKS159-administered animals, no significant change was induced in each cardiovascular parameter by an infusion of 0.1 mg/kg. The blood pressure was decreased, and the effective refractory period and repolarization phase of the ventricle were prolonged after 1.0 mg/kg. The heart rate was decreased, and the atrioventricular, as well as intraventricular, conduction were suppressed after 10 mg/kg, while no significant changes were observed in the cardiac output and the ventricular contraction and the relative refractory period of the ventricle during the study. Meanwhile, in cisapride-administered animals, the repolarization phase and the effective refractory period were prolonged after 0.01 mg/kg. The heart rate and the blood pressure were decreased after 0.1 mg/kg. The cardiac output, the ventricular contraction, and the atrioventricular conduction were suppressed, the relative refractory period was prolonged, and early afterdepolarization was detected after 1.0 mg/kg, while no significant change was observed in the intraventricular conduction during the study. Thus, TKS159 may have a safer cardiovascular profile than cisapride.

Action Potentials↗

PubMed1998

Simultaneous assessment of the hemodynamic, cardiomechanical, and electrophysiological effects of terfenadine on the in vivo canine model.

Prolongation of the QT interval, sometimes leading to torsades de pointes, has been clinically reported during terfenadine treatment. However, information regarding the cardiovascular profile of terfenadine is still limited, particularly in in vivo animal models. In the current study, we examined the cardiovascular effects of terfenadine using halothane-anesthetized, closed-chest in vivo canine models (n = 6) to better simulate the clinical situation. Intravenous infusion of 0.3 mg/kg of terfenadine over 10 min, which would attain the antihistaminic plasma concentration, reduced the heart rate and left ventricular contractility and prolonged the repolarization period as well as the ventricular effective refractory period. An additional infusion of a ten times higher dose of terfenadine over 10 min caused hypotension and increased left ventricular preload and atrioventricular conduction time, in addition to potentiating the changes observed by the lower dose. A reverse use-dependent prolongation of the repolarization period was observed after the higher dose infusion. Moreover, early afterdepolarization-like potential was detected in four out of six experiments. Since each suppressive effect can become deleterious during terfenadine overdose, caution must be taken for those patients with potential cardiac dysfunction and with the risk of elevated plasma drug concentrations.

Analysis of Variance↗

PubMed1998

Effects of antiarrhythmic drugs on the monophasic action potential of the canine isolated, blood-perfused ventricular septum preparation.

The present study was designed to combine the monophasic action potential (MAP) recording technique with a well-established canine isolated, blood-perfused ventricular septum preparation for examining, simultaneously, electrical and mechanical drug-induced changes. A MAP catheter was positioned onto the base of a papillary muscle for recording the local MAP, using a manual micromanipulator together with a commercially available catheter sheath to keep the optimal contact pressure against the ventricular wall. The catheter sheath was filled with saline to eliminate the background electrical noise. Tetrodotoxin, disopyramide, lidocaine, and verapamil were used to clarify the potential utility of the preparation. Tetrodotoxin and lidocaine shortened the MAP duration, while disopyramide prolonged it. Verapamil slightly shortened the MAP duration but not significantly. Each drug showed negative inotropic and coronary vasodilator effects. Sodium channel blockers slowed intraventricular conduction and decreased the maximum upstroke velocity of MAP, while verapamil showed no effects. These results suggest that utilization of the blood-perfused ventricular septum preparation together with MAP recording will become a valuable model for evaluating drugs with multiple sites of action on cardiac muscles.

Action Potentials↗

PubMed1998

[Some techniques for the correction of the congenital heart disease with autologous flap].

14 living flaps in 8 children were used to repair for the congenital heart disease, because artificial material and xeno grafts were shrunk in growing children but living flaps were going to glow with children. It were possible to use the living flaps to reconstruct of pulmonary outflow in truncus arteriosus, for septoplasty in partial anomarous of pulmonary venous return and reconstruction of unloofed coronary sinus in endocardial defect with triatriatum and intraatrial tunnel in TCPC or Fontan type operation.

Cardiac Surgical Procedures↗

PubMed1998

Effects of an antiarrhythmic drug A-2545 on canine ventricular arrhythmia models; comparison with mexiletine and flecainide.

We investigated effects of a new Na+ channel blocking antiarrhythmic drug, A-2545, N-3 (2,2,5,5-tetramethyl-3-pyrroline-3-carboxamido)-propyl-phthalimide-hydro chloride, on various canine ventricular automaticity arrhythmias induced by two-stage coronary ligation, digitalis and adrenaline, and compared them with those of mexiletine. A-2545 showed antiarrhythmic effects, significantly decreasing the arrhythmic ratio of 24-h and 48-h coronary ligation-, digitalis- and adrenaline-induced automaticity arrhythmias. The antiarrhythmic plasma concentrations (IC50) of A-2545, 2 mg kg(-1) 10 min(-1), i.v., for 24-h and 48-h coronary ligation-, digitalis- and adrenaline-induced arrhythmias were 1.8, 1.3, 5.8 and 3.7 microg ml(-1), respectively, and that calculated for oral A-2545 (25 mg kg(-1)) in 24-h coronary ligation-induced arrhythmia was 1.8 microg ml(-1). A-2545 is specifically potent in suppressing coronary ligation-induced arrhythmias, i.e., decreasing the arrhythmic ratio nearly to zero by oral administration, and among the intravenously given experiments A-2545 was effective at lower concentrations than other arrhythmia models; A-2545, 2 mg kg(-1) 10 min(-1), was equipotent to 5 mg kg(-1) 10 min(-1) mexiletine in suppressing 24-h coronary ligation-induced arrhythmia, indicating that A-2545 is more potent than mexiletine. In order to determine whether A-2545 has arrhythmogenic effects, we used programmed electrical stimulation (PES)-induced reentry arrhythmias in dogs with old myocardial infarction and compared effects of A-2545 and flecainide. A-2545, 2 and 5 mg kg(-1) 10 min(-1), significantly suppressed the PES-induced arrhythmias in all six dogs without aggravating them. These arrhythmias were not markedly suppressed by flecainide either with 1 or 3 mg kg(-1) 1O min(-1); moreover even in one out of six dogs aggravation of arrhythmia was noted after 1 mg kg(-1) 10 min(-1). In conclusion, A-2545 suppressed various canine ventricular arrhythmias, and the antiarrhythmic effect of A-2545 was more potent than that of mexiletine, and A-2545 did not show arrhythmogenic effects compared to flecainide.

Animals↗

PubMed1998

Elimination of neutrophils by apoptosis during the resolution of acute pulmonary inflammation in rats.

We evaluated the apoptosis of neutrophils during the resolution of acute pulmonary inflammation induced by exposure to ozone. The inflammatory response was assessed in rat lungs 0, 1, 3, and 7 days after 4-h exposure to air or 2 ppm ozone. Analysis of bronchoalveolar lavage fluid demonstrated significant increases in albumin concentrations on days 0 and 1 and in the number of lavageable neutrophils on days 0, 1, and 3, indicating the presence of acute pulmonary inflammation. These parameters returned to control values on day 7, which suggests that the acute pulmonary inflammation induced by ozone was reversible. On days 1 and 3, but not on day 0, the neutrophils showed morphologic evidence of apoptosis. Based on morphologic analysis, the proportion of apoptotic neutrophils was 23.3 +/- 2.2% on day 1 and 55.7 +/- 3.2% on day 3. Terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL), in contrast, revealed that the proportion of apoptotic cells was 59.7 +/- 9.1% on day 1 and 68.0 +/- 4.3% on day 3. On day 3, light microscopy and electron microscopy demonstrated engulfment of the neutrophils by macrophages. These findings indicate that the apoptosis of neutrophils followed by their engulfment by macrophages contributes to the clearance of neutrophils from the sites of inflammation. Moreover, TUNEL detected apoptotic neutrophils with greater sensitivity compared with morphologic assessment.

Acute Disease↗

PubMed1998

Perivascular T cells are infected with HTLV-I in the spinal cord lesions with HTLV-I-associated myelopathy/tropical spastic paraparesis: double staining of immunohistochemistry and polymerase chain reaction in situ hybridization.

HTLV-I-infected cells play an important role in pathogenesis HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Our previous studies of quantitative polymerase chain reaction (PCR) and in situ PCR suggested that T cells infiltrating in the spinal cord lesion were infected with HTLV-I. To elucidate the localization of HTLV-I proviral DNA directly, we performed double staining using immunohistochemistry and PCR in situ hybridization (PCR-ISH). Fresh frozen sections of the spinal cord from four HAM patients taken at autopsy were first immunostained with antibodies to pan T cells (UCHL-1), macrophages (KP-1) and helper/inducer T cells (OPD4). Then PCR-ISH was carried out with specific primers and probe for the HTLV-I pX region. UCHL-1-positive cells were noted around perivascular areas and, to some extent, in the parenchyma. Of the UCHL-1-positive cells, 9.4% (case 1), 9.6% (case 2), 1.1% (case 3) and 6.7% (case 4) became positive in HTLV-I PCR-ISH. UCHL-1-negative cells were HTLV-I PCR-ISH negative and almost all KP-1-positive cells were HTLV-I negative. HTLV-I was localized to OPD4-positive cells in examined lesions of cases 2 and 4. These data are a direct demonstration of HTLV-I proviral DNA localizing to infiltrated T cells in HAM/TSP spinal cord lesions.

Aged↗

PubMed1998

Differential expression of SHP2, a protein-tyrosine phosphatase with SRC homology-2 domains, in various types of renal tumour.

SHP2, a widely distributed protein-tyrosine phosphatase with src homology-2 (SH2) domains, is highly expressed in the brain and may play a role in synaptic communications or cellular proliferation. In this study, we examined SHP2 protein expression in 110 renal cell tumours of various histological subtypes, including clear, granular, papillary, chromophobe, collecting duct, and sarcomatoid-type renal cell carcinoma (RCC), and oncocytoma. SHP2 was expressed predominantly in normal distal tubules and collecting ducts, and positivity in various types of renal tumours was as follows: clear cell RCC, 0% (0/77 cases); granular, 7.7% (1/13); papillary, 50% (3/6); sarcomatoid, 0% (0/1); chromophobe, 85.7% (6/7); collecting duct carcinoma, 0% (0/2); oncocytoma, 100% (4/4). Clear and granular-type RCCs showed a very low but positive expression of SHP2. Chromophobe RCC and oncocytoma showed the highest rates and strongest intensities of SHP2 protein on immunostaining. SHP2 may serve as a powerful marker in detecting rare tumours. Estimates of its expression may be useful in histological diagnosis.

Adenoma, Oxyphilic↗

PubMed1998

Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene.

In the course of investigations of familial coronary artery disease in Hokkaido, the northern island of Japan, we identified five families in which multiple members showed elevated plasma levels of low-density lipoprotein (LDL) cholesterol. To determine the genetic etiology of their lipoprotein abnormalities, we screened DNA samples from these families for mutations in all 18 exons and the exon-intron boundaries of the LDL receptor (LDLR) gene. Novel point mutations were identified in each family: (1) a C-to-A transversion at nucleotide 285, causing a nonsense mutation at codon 74, in eight members of family A; (2) a G-to-A transition at nucleotide 1136, causing substitution of Tyr for Cys at codon 358, in six members of family B; (3) a C-to-T transition at nucleotide 1822, causing substitution of Ser for Pro at codon 587, in five members of family C; (4) a one-base insertion of G to a five-G stretch at nucleotides 1774-1778 (codons 571-572), causing a frameshift, in six members of family D; and (5) a one-base deletion of T at nucleotide 1963-1964 (codon 634), causing a frameshift, in three members of family E. Through the molecular genetic approach a total of 28 individuals in these families were diagnosed unequivocally as heterozygous for the respective LDLR mutations. This method also helped us to diagnose familial hypercholesterolemia, or to exclude from carrier status, 11 children with borderline high cholesterol levels.

Adolescent↗

PubMed1998

Effect of sexual intercourse on fetal fibronectin concentration in cervicovaginal secretions.

An investigation was performed evaluating persistence of fetal fibronectin in cervicovaginal secretions after sexual intercourse. Fetal fibronectin samples were positive at 12 to 24 hours, 24 to 48 hours, and 48 to 72 hours after coitus in 22.2%, 11.8%, and 5.6% of samples, respectively. A history of vaginal intercourse should be obtained before sampling for fetal fibronectin to eliminate this potential source of false-positive fibronectin test.

Adult↗

PubMed1998

Preferential inhibition of Ikr by MCI-154, a putative cardiotonic Ca2+ sensitizer, in guinea pig atrial cells.

OBJECTIVE: To define the electrophysiologic mechanism(s) by which MCI-154, a putative Ca2+ sensitizer, produces a positive inotropic response without a positive chronotropic response, we examined effects of MCI-154 on the action potential of atrial preparations and the membrane currents of atrial myocytes. METHODS: The action potentias were recorded from left atrial and sinoatrial node preparations of guinea pigs by the use of standard microelectrode techniques. The whole-cell membrane currents were recorded from enzymatically-dissociated guinea pig atrial myocytes using conventional patch clamp techniques. RESULTS: In isolated left atria, MCI-154 increased the developed tension in a concentration-dependent manner. MCI-154 at concentrations of 10 and 100 microM increased the action potential duration (APD) in left atria stimulated at 0.5 Hz. In sinoatrial node preparations MCI-154 at a concentration of 100 microM produced a negative chronotropic response and prolonged APD. In single right atrial myocytes, MCI-154 at concentrations of 10 and 100 microM failed to increase the inward L-type Ca2+ current, but decreased the delayed rectifier K+ current (IK) in a concentration-dependent manner. MCI-154 decreased IK elicited by short depolarizing pulses more markedly than that induced by long depolarizing pulses. In addition, MCI-154 produced only a little inhibition of IK in the presence of E-4031, a specific blocker of rapidly activating component of IK (IKr). CONCLUSIONS: MCI-154 preferentially blocks IKr and the inhibitory action on IKr may be partly involved in the negative chronotropic and positive inotropic responses in atrial preparations.

Action Potentials↗

PubMed1998

Differential time-related effects of conjugated equine estrogen on bone metabolism in oophorectomized women.

OBJECTIVE: The effects of conjugated equine estrogen (CEE) on bone mineral density (BMD) and biochemical indices of bone remodeling in oophorectomized women were studied for 3 years during estrogen replacement therapy (ERT) to investigate whether 0.625 mg/day of CEE alone prevent acute bone loss in the early stage of surgical menopause. METHODS: We divided the subjects into three groups according to interval between oophorectomy and the start of ERT (group 1: less than 2 years after surgery, n = 31; group 2: 2-5 years after surgery, n = 29; and group 3: more than 5 years after surgery, n = 27). Vertebral BMD was measured using dual energy X-ray absorptiometry (DEXA). Two biochemical indices of bone metabolism, urinary deoxypyridinoline (DPyr) and serum intact human osteocalcin (hOC) were also measured. RESULTS: In group 1, continuous ERT with 0.625 mg/day of CEE could not prevent a BMD decrease within the first year. However, by the end of the second year, BMD was restored to the pre-ERT. The same dosage of CEE significantly increased BMD in groups 2 and 3 by the end of the first year. DPyr and hOC levels both decreased dramatically in the initial 6 months of therapy and were stable thereafter. CONCLUSION: In the initial 2-year period after oophorectomy, 0.625 mg/day of CEE alone could not prevent acute bone loss suggesting that additional therapy for the prevention of osteoporosis may be needed.

Absorptiometry, Photon↗

PubMed1998

Treatment of bone loss in oophorectomized women with a combination of ipriflavone and conjugated equine estrogen.

OBJECTIVE: We previously reported that 0.625 mg/day of conjugated equine estrogen (CEE) could not prevent acute bone loss in the first year after oophorectomy. The effect of additional administration of ipriflavone on bone mineral density (BMD) and biochemical indices of bone remodeling were studied to investigate whether concurrent use of CEE and ipriflavone prevent acute bone loss in the early stages following surgical menopause. METHODS: One-hundred and sixteen oophorectomized women were randomly divided into four groups according to treatment; group 1: placebo, n = 30; group 2: CEE (0.625 mg/day), n = 29; group 3: ipriflavone (600 mg/day), n = 30; group 4: CEE (0.625 mg/day) plus ipriflavone (600 mg/day), n = 27. Vertebral BMD was measured using dual energy X-ray absorptiometry (DEXA) and two biochemical indices of bone metabolism, urinary pyridinoline (Pyr) and serum intact human osteocalcin (hOC), were also measured before, 24 weeks, and 48 weeks after initiation of treatment. RESULTS: BMD was reduced 48 weeks after treatment by 6.1, 3.9 and 5.1% in groups 1-3, respectively, but by only 1.2% in group 4. Pyr decreased by 49.5, 32.0 and 41.5% in groups 2-4, respectively. hOC also decreased by 45.2 and 21.6% in groups 2 and 4, but increased by 40.5% in group 3, suggesting an inhibitory action of CEE and ipriflavone on the turnover of bone metabolism and stimulatory action of ipriflavone on bone formation. CONCLUSION: Concomitant use of ipriflavone with CEE from an early stage after oophorectomy inhibited bone loss and was considered to be effective in maintaining bone mass after oophorectomy.

Absorptiometry, Photon↗

PubMed1998

Type 2 corticotropin-releasing hormone receptor mRNA expression in the heart in hypertensive rats.

Novel subtype of corticotropin-releasing hormone receptor (CRHR), designated type-2 CRHR (CRHR-2), mRNA was expressed not only in the central nervous system but also in the peripheral tissues such as the heart and skeletal muscle. The previous finding that type-1 CRHR mRNA is not detected in heart leads us to speculate that systemic administration of CRH induces hypotensive effects through CRHR-2, and that alterations in CRHR-2 in the heart may be implicated in blood pressure regulation. Therefore we examined CRHR-2 mRNA expression in the heart (at the level of ventricle) in spontaneously hypertensive rats (SHR) or DOCA-salt hypertensive rats (DOCA) using in situ hybridization histochemistry, compared to age-matched normotensive control rats. CRHR-2 mRNA levels in the heart were significantly higher in 7-week-old SHR than in 12-week-old SHR. Furthermore, CRHR-2 mRNA levels in SHR heart were significantly higher than those in normotensive controls, Wistar-Kyoto rats (WKY), at both 7 and 12 weeks of age. In contrast, CRHR-2 mRNA levels in DOCA heart were significantly lower than that of sham-operated controls after 6-weeks of treatment. Thus, alterations of CRHR-2 mRNA are dependent on the strain or experimental condition rather than as a consequence of hypertension. Plasma CRH levels in SHR or DOCA were not different from their normotensive control rats. CRH content in the ventricular heart of SHR or DOCA were also similar to normotensive controls. These results suggest that heart CRHR-2 mRNA levels are not influenced by circulating or locally existing CRH. Since alterations in heart CRHR-2 mRNA, as seen in SHR and DOCA, were bi-directional, the role of heart CRHR-2 in the regulation of hypertension remains to be elucidated.

Animals↗

PubMed1998

Human urinary trypsin inhibitor inhibits the activation of pro-matrix metalloproteinases and proteoglycans release in rabbit articular cartilage.

Treatment of primary cultured chondrocytes from rabbit articular cartilage with interleukin-1 (IL-1)alpha and plasminogen induced the production of pro-matrix metalloproteinase 1 (proMMP-1/interstitial collagenase), proMMP-3 (stromelysin 1) and proMMP-9 (gelatinase B), as well as their active forms. Human urinary trypsin inhibitor (UTI), a multipotent inhibitor of serine proteases, including plasmin inhibited the activation of proMMP-1, proMMP-3 and proMMP-9 when added to the culture medium together with IL-1alpha and plasminogen, in a dose-dependent manner. Moreover, UTI inhibited the release of proteoglycans induced by IL-1alpha and plasminogen from rabbit articular cartilage explants. These findings strongly suggest that UTI inhibits the destruction of articular cartilage induced by plasmin and/or MMPs. Thus, UTI probably exert an anti-osteoarthritic action via inactivation of proMMPs.

Animals↗

PubMed1998

Inhibition of signal transduction by a splice variant of the growth hormone-releasing hormone receptor expressed in human pituitary adenomas.

We have previously shown that some of human growth hormone (GH)-producing pituitary adenomas preferentially express a larger transcript of GH-releasing hormone (GHRH) receptor (GHRH-R). This transcriptional variant is presumed to be produced by alternative messenger RNA splicing and contains premature stop codon in frame, predicted to yield a truncated GHRH-R. Functional expression study indicated that the variant receptor was unable to transduct GHRH signals. To determine the functional relationship between the splice-variant and the wild-type GHRH-R, the expression vector for the variant GHRH-R transcript was transfected into COS-7 cells together with or without that for the wild GHRH-R transcript. In cells transfected with both GHRH-R expression vectors, GHRH-dependent cyclic adenosine monophosphate (cAMP) induction was decreased to 39% of that in the cells transfected with the wild-type GHRH-R expression vector alone. This inhibition was found to be irrespective of the concentration (10(-8) to 10(-5) mol/L) of GHRH. These findings suggest that the splice variant form of GHRH-R functions as a dominant-negative modulator in GHRH-induced cellular signaling.

Adenoma↗

PubMed1998

Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus.

Paraoxonase (PON) is an esterase associated with high-density lipoprotein (HDL). Serum PON activity is affected by PON gene polymorphism (L/M, Leu-Met54, and Q/R, Gln-Arg191). We investigated PON activity and polymorphism in 108 patients (53 men and 55 women) with non-insulin-dependent diabetes mellitus (NIDDM) and 161 control subjects (82 men and 79 women) matched to the patients by age and gender. Serum PON activity was determined using paraoxon as a substrate. PON gene polymorphisms were detected by the restriction fragment length polymorphism method after a polymerase chain reaction. The mean PON activity in the patients was significantly lower than in the controls (116+/-55 and 162+/-57 U/L, respectively, P < .001). The distribution of each genotype showed no difference between the patient and control groups, and PON activity increased in the order of the QQ < OR < RR genotype and MM < LM < LL genotype in both groups. However, among each genotype subgroup, the activity was lower in patients than in controls. Forty-one patients with retinopathy had lower PON activity than those without the complication (94+/-36 and 129+/-61 U/L, respectively, P < .002). There was also a significant difference in PON activity between patients with and without overt proteinuria (93+/-38 and 122+/-58 U/L, respectively, P < .05). Logistic analysis showed that serum PON activity was one of the significant factors for retinopathy. These results suggest that decreased PON activity in patients with NIDDM is involved in diabetic vascular complications.

Adult↗