Biomedical subjects

M Arita

Publications and source records attributed to M Arita.

At least 37 records · Page 2Linked to original sources

PubMed2001

Absence of Z-chromosome inactivation for five genes in male chickens.

In order to examine if Z-chromosome inactivation, which is analogous to X-chromosome inactivation in mammals, takes place in male birds having ZZ sex chromosomes, five Z-linked genes of chickens which are expressed in both sexes in certain tissues were selected: i.e. genes for growth hormone receptor, nicotinic acetylcholine receptor beta3, aldolase B, beta1,4-galactosyltransferase I, and iron-responsive element-binding protein (also known as cytosolic aconitase). Antisense or sense riboprobe was prepared from an intronic sequence of each gene and subjected to fluorescence in situ hybridization to nascent transcripts of each gene in a nucleus. Each antisense riboprobe hyridized to two spots of nascent RNA which corresponded to its gene loci on the two Z chromosomes in a majority of nuclei in a tissue of the male. The efficiency of detection of two spots per nucleus was comparable to that for the glyceraldehyde-3-phosphate dehydrogenase gene, an autosomal housekeeping gene. These results suggest strongly that Z-chromosome inactivation, i.e. virtual silence of transcription at one of the alleles, does not take place for these five Z-linked genes in male chickens.

Animals↗

PubMed2001

Case report: alternating exit sites in reentry circuit of ventricular tachycardia with nonischemic cardiomyopathy - relationship between ablation site and inner loop.

We present a patient with nonischemic cardiomyopathy who had ventricular tachycardia (VT) with QRS morphology alternans. VTs of two QRS morphologies (VT1 and VT2) exhibiting a right bundle branch block pattern with inferior axis was induced by ventricular pacing. The morphology of the QRS complex during VT1 exhibited more distinctively inferior axis than those during VT2. Induced VTs had similar morphologies to clinically the documented VTs. Pacemapping at anterolateral site of the left ventricle during sinus rhythm produced the same QRS complex of VT1 in a surface 12-lead electrocardiogram. A mapping study was performed with an electrode catheter located at the same site of LV during sustained VT1. The analysis of the local electrograms and postpacing interval during concealed entrainment at the catheter mapping revealed this pacing site was at the inner loop of the reentry circuit. Radiofrequency catheter ablation was performed at this site. The morphology of VT1 changed to different QRS morphology (VT2) during the first delivery of radiofrequency energy and was terminated after 20 seconds of the application. Then VT with alternans of QRS morphology and cycle length of VT1 and VT2 was induced by ventricular pacing, and was abolished by the second application of radiofrequency energy at this same site, suggesting that this site was located in the exit site close to inner loop of the reentry circuit and the alternans of QRS morphology was linked to the change of exit site.

Cardiomyopathy, Dilated↗

PubMed2001

Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis.

IgAN is a common form of primary glomerulonephritis and also a disease of tonsillar focal infection. The comprehensive mechanism underlying this disease remains to be defined. To better understand its pathogenesis, we investigated tonsillar CD5+ B cells (B-1 cells) with respect to IgA synthesis. Germinal centre (GC) B cells were isolated from the tonsils of IgAN patients and the number of B-1 cells in the GC determined by flow cytometry. GC B-1 and B-2 (CD5- B) cells were purified by cell sorter, the cells were incubated with agonist anti-CD40 MoAb and the ability for antibody production by B-1 and B-2 cells determined by ELISPOT assay. GC B-1 cells and B-2 cells were incubated with agonist anti-Fas MoAb, and apoptosis in GC B-1 cells and B-2 cells was analysed by flow cytometry. Although B-1 cells do not usually take part in the GC reaction, an increase in B-1 cell numbers was observed in the GC of tonsils from IgAN patients. These B-1 cells were likely IgA1 antibody-producing cells, since the prominent IgA subclass in IgAN is generally considered to be IgA1. Although Fas-dependent apoptosis is essential for the elimination of activated B cells, these B-1 cells showed a reduced susceptibility to Fas-mediated apoptosis. It is conceivable that activated B-1 cells may survive in the GC due to impaired apoptosis and thus produce abnormal antibodies. These findings suggest that the immune responses of B-1 cells in the tonsillar GC could thus have an impact on the pathogenesis of IgAN.

Adolescent↗

PubMed2001

More knee joint osteoarthritis (OA) in mice after inactivation of one allele of type II procollagen gene but less OA after lifelong voluntary wheel running exercise.

OBJECTIVE: To investigate the incidence and severity of osteoarthritis (OA) and the effects of voluntary wheel running in normal mice and mice carrying either a targeted inactivation of one allele, heterozygous 'knockout', of Col2a1 gene or both alleles, homozygous 'knockout', of Col11a2 gene. METHODS: Mice lived until 15 months of age in individual cages. Running activity was recorded around the clock. OA changes were evaluated from serial knee joint sections by light microscopy. RESULTS: Heterozygous inactivation of Col2a1 gene coding for type II procollagen made the cartilage more susceptible to OA. At 15 months of age, OA prevalence was 60-90% in knockouts and 20-45% in normal controls (P < 0.01-0.001). Unexpectedly, a reduction of OA due to wheel running was observed in both knockout strains (P< 0.05-0.01). This effect was most evident in the femoral condyles. Incidence of OA in runners was approximately 50-85% of that in sedentary littermates. OA prevalence was higher in normal control and runner mice with high body weight. Running did not affect OA development in normal mice. CONCLUSION: Heterozygous knockout of Col2a1 gene increased the OA prevalence in mice. Lifelong voluntary wheel running had a protective effect against OA in both knockout mice lines. The reason for this remains unknown. Reduction of OA may result from the reorganization and strengthening of the articular cartilage collagen network and/or adjacent muscles due to running, or lower body weight. Increased compliance of the articular cartilage and bones of the knockout mice may also contribute to the reduction of OA in exercised animals.

Aging↗

PubMed2001

Regulation of the yeast Yap1p nuclear export signal is mediated by redox signal-induced reversible disulfide bond formation.

Yap1p, a crucial transcription factor in the oxidative stress response of Saccharomyces cerevisiae, is transported in and out of the nucleus under nonstress conditions. The nuclear export step is specifically inhibited by H(2)O(2) or the thiol oxidant diamide, resulting in Yap1p nuclear accumulation and induction of transcription of its target genes. Here we provide evidence for sensing of H(2)O(2) and diamide mediated by disulfide bond formation in the C-terminal cysteine-rich region (c-CRD), which contains 3 conserved cysteines and the nuclear export signal (NES). The H(2)O(2) or diamide-induced oxidation of the c-CRD in vivo correlates with induced Yap1p nuclear localization. Both were initiated within 1 min of application of oxidative stress, before the intracellular redox status of thioredoxin and glutathione was affected. The cysteine residues in the middle region of Yap1p (n-CRD) are required for prolonged nuclear localization of Yap1p in response to H(2)O(2) and are thus also required for maximum transcriptional activity. Using mass spectrometry analysis, the H(2)O(2)-induced oxidation of the c-CRD in vitro was detected as an intramolecular disulfide linkage between the first (Cys(598)) and second (Cys(620)) cysteine residues; this linkage could be reduced by thioredoxin. In contrast, diamide induced each pair of disulfide linkage in the c-CRD, but in this case the cysteine residues in the n-CRD appeared to be dispensable for the response. Our data provide evidence for molecular mechanisms of redox signal sensing through the thiol-disulfide redox cycle coupled with the thioredoxin system in the Yap1p NES.

Cell Nucleus↗

PubMed2001

Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softer.

OBJECTIVE: To evaluate the influence of inactivation of one allele ("heterozygous knockout" or "heterozygous inactivation") of the type II procollagen gene (Col2a1) on the biomechanical properties and structure of the articular cartilage and subchondral bone in 15 month old mice. METHODS: Indentation stiffness of the humerus head articular cartilage was measured by a microindentation method. Cartilage and subchondral bone were prepared for digital densitometry of proteoglycans (PGs), polarised light microscopy (PLM) of collagen, and osteoarthrosis (OA) grading. RESULTS: Heterozygous inactivation of the Col2a1 gene softened articular cartilage (p=0.002) as measured by indentation stiffness ((mean (SEM) 0.50 (0.07) MPa v 0.94 (0.13) MPa in controls). Fibrillar collagen network exhibited lower birefringence in the intermediate (p=0.04) and deep zones (p=0.01) of cartilage by PLM, indicating either decreased collagen content or a lower degree of fibril parallelism in the knockout mice. The total and zonal thicknesses of articular cartilage were unchanged. Zonal PG contents did not differ significantly. In knockout mice, the prevalence of superficial fibrillation-that is, a sign of OA, was higher than in controls (73% v 21%, p=0.002). The collagen induced birefringence of the superficial zone was not reduced. The subchondral bone volume fraction was lower in knockout mice than in controls, 31% v 43% (p=0.01), and optical retardation values in PLM of bone collagen were slightly but significantly lower (p=0.01). CONCLUSION: Heterozygous inactivation of the Col2a1 gene made articular cartilage softer, altered the collagenous network, reduced subchondral bone volume, and altered its microstructure. Changes in the cartilage collagen network probably contributed to increased susceptibility to OA.

Animals↗

PubMed2001

Polymorphic ventricular tachycardia in patients with vasospastic angina--clinical and electrocardiographic characteristics and long-term outcome.

There have been few clinical studies exploring the characteristics of spontaneous polymorphic ventricular tachycardia (VT) during a vasospastic angina attack. During a 4-year recruitment period, Holter ECG recordings were monitored for 42+/-24 h during a drug-free period in 60 consecutive patients with vasospastic angina (VSA) and of these, 8 patients had at least one episode of polymorphic VT during monitoring. Ischemic ST segment elevation was immediately preceded the spontaneous polymorphic VT in all 8 patients, 4 of whom had silent coronary vasospasm. Immediately before the onset of polymorphic VT, both R-on-T and long-short sequences were observed in 4 of the 8 patients and ST wave alternans were recorded in 2 patients. VT exhibited a pattern of torsade de pointes in 4 of the 8 patients. Five patients underwent electrophysiologic testing during a drug-free asymptomatic phase, and polymorphic VT was induced in 2 of the 5 patients, with one developing ventricular fibrillation. During a follow-up period of 73+/-17 months, there was a significant difference in the incidence of sudden death between patients with and without VT (2/8 cases [25%] vs 0/52 [0%]; p<0.01). Thus, vasospastic attacks, even if asymptomatic, that immediately precede the development of polymorphic VT may be associated with a repolarization abnormality and an increased risk of sudden death.

Acetylcholine↗

PubMed2001

Effects of antihypertensive agents on blood pressure during exercise.

The relationship between blood pressure (BP) and cardiovascular morbidity has been appreciated for many years. Casual BP may not be representative of the pressure at other times. It is recognized that BP during exercise may be a more accurate predictor than casual BP. There is, however, little information about the effects of antihypertensive drugs on the BP during exercise. This study was designed to investigate the effects of various antihypertensive agents on BP during exercise. Sixty-four patients (age, 49+/-10 years) with untreated essential hypertension (WHO I, II) were studied during a supine ergometric exercise regimen. A graded exercise test was started at a workload of 50 W, and the load was increased by 25 W every 3 min. The hemodynamic responses to exercise were evaluated by changes in systolic and diastolic BP (SBP, DBP) and heart rate (HR). Plasma norepinephrine (NE) levels were measured at rest and during submaximal exercise, and before and after 4 weeks of treatment with metoprolol (METO), doxazosin (DOXA), trichlormethiazide (TCTZ), nifedipine (NIFE), amlodipine (AMLO) and temocapril (TEMO) between left ventricular mass index (LVMI) and BP values at rest, during exercise, and during the recovery period after exercise were assessed by multiple regression analysis. The stepwise selection (forward conditional) method showed that LVMI was significantly associated with SBP during submaximal exercise and during the recovery period. All antihypertensive treatments decreased SBP and DBP (p<0.01) at rest. METO, AMLO and TEMO significantly lowered SBP (p<0.05) during exercise, whereas DOXA, TCTZ and NIFE induced no change in SBP. The exercise-induced increase of plasma NE was further enhanced by METO and NIFE but not by AMLO, DOXA, or TCTZ, and it was significantly suppressed by TEMO (p<0.01). These results suggest that BP during exercise is more highly associated with the progression of left ventricular hypertrophy (LVH) than is casual BP. Because antihypertensive agents differ in their effects on exercise hemodynamics, we recommend that hemodynamic factors during exercise be considered when selecting the optimal antihypertensive medication for highly active patients.

Adult↗

PubMed2001

Hypopituitarism due to pituitary metastasis of lung cancer: case of a 21-year-old man.

A 21-year-old man presented persistent dry cough, general malaise, loss of appetite, decreased sexual desire and double vision. Chest radiograph revealed a mass shadow in the left upper lobe. Histopathological diagnosis of the tumor was squamous cell carcinoma. Brain computed tomography and magnetic resonance imaging revealed a metastasis to the pituitary gland. Hypopituitarism was diagnosed by pituitary function tests. Diabetes insipidus was absent and the function of the posterior lobe of the pituitary gland was preserved. Hypopituitarism due to pituitary metastasis is a rare complication of lung cancer, and has never been reported in a patient as young as 21 years old.

Adult↗

PubMed2001

Efficacy of transthoracic needle aspiration in community-acquired pneumonia.

OBJECTIVE: To evaluate the indications, efficacy, and safety of transthoracic needle aspiration (TNA) in diagnosing community-acquired pneumonia (CAP). METHODS: TNA procedure was performed using an ultrathin needle with ultrasonography and/or computed tomography. The aspirate samples were Gram-stained and sent for cultures. The results were compared with those from conventional microbiological studies. PATIENTS: Sixty patients with CAP who were admitted to the hospital and were studied prospectively between July 1994 and June 1999 were included in the study. RESULTS: TNA culture was positive in 30 cases (50.0%). Streptococcus pneumoniae was the most frequently isolated pathogen, followed by the Streptococcus milleri group, and anaerobes. The results of TNA were consistent with those of quantitative sputum cultures in 9 patients and with those of blood cultures in 4. Complications arose in 3 patients who developed small to moderate pneumothorax. CONCLUSIONS: TNA is a safe procedure with a good diagnostic yield. In particular, anaerobes or microaerophils such as the S. milleri group were highly detectable by TNA. The results obtained by TNA were highly consistent with those obtained by the gold standard methods. Combined with conventional methods, TNA is considered highly useful for determining the etiology of CAP.

Adult↗

PubMed2001

Roles of alpha(1) and alpha(1)/beta subunits derived from cardiac L-type Ca(2+) channels on voltage-dependent facilitation mechanisms.

Strong depolarization pulses facilitate L-type Ca(2+) channels in various cell types including cardiac myocytes. The mechanisms underlying prepulse facilitation are controversial with respect to the requirements for channel subunits, cAMP-dependent protein kinase, and additional anchor proteins. The properties of voltage-dependent facilitation of the L-type Ca(2+) channel was studied in recombinant cardiac alpha(1) subunits with or without cardiac beta subunit, expressed in Chinese hamster fibroblast cells. The magnitude of voltage-dependent I(Ba) facilitation in the alpha(1) subunit channel is dependent on the duration of the prepulse as well as on the interval duration between prepulse and test pulse. The characteristics of this facilitation were not affected by coexpression of the beta subunit. These results indicate that cardiac alpha(1) subunits exhibit voltage-dependent facilitation because of their own intrinsic structure, independent of any other accessory subunit or additional regulatory proteins, and that cardiac beta subunits have no essential regulatory role at the onset or continuance of the voltage-dependent facilitation.

Animals↗

PubMed2001

[Clinical comparison of Chlamydia pneumoniae pneumonia, ornithosis, and Mycoplasma pneumoniae pneumonia].

To elucidate the differences between the clinical aspects of Chlamydia pneumoniae (C. pn) pneumonia and those of two other atypical pneumonias, Chlamydia psittaci (C. ps) pneumonia and Mycoplasma pneumoniae (M. pn) pneumonia, we analyzed the symptoms and laboratory data on the cases of these three types of pneumonia: 46 cases of C. pn pneumonia, 39 cases of C. ps pneumonia, and 131 cases of M. pn pneumonia. C. pn pneumonia was significantly more frequent among the elderly (mean 70 +/- 16 years, p < 0.01) and patients were significantly more likely to be male (76%, p < 0.05). A white blood cell count of over 10,000 was seen in 46% of C. pn pneumonia cases, a higher proportion than those of C. ps pneumonia (15%, p = 0.03) or M. pn pneumonia (18%, p = 0.006) cases. The proportions of patients with these infections who had an elevated GOT or GPT were not significantly different. Maximum body temperature was higher in M. pn pneumonia than in C. pn pneumonia (p = 0.003). Purulent sputa were seen in 44% of C. pn pneumonia cases and 50% of M. pn pneumonia cases, and these rates were higher than that of 13% in C. ps pneumonia cases (p = 0.002, p = 0.004). Dyspnea and anorexia symptoms were the most frequent in C. pn pneumonia cases (24% and 29%, respectively, the highest of all three pneumonias). There were clinical differences between C. pn pneumonia and the other two atypical pneumonias. However, there was some difficulty in differentiating between C. pn pneumonia and typical bacterial pneumonia because mixed infections were common (24%) in C. pn pneumonia cases.

Adult↗

PubMed2000

Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice.

Alpha-tocopherol transfer protein (alpha-TTP), a cytosolic protein that specifically binds alpha-tocopherol, is known as a product of the causative gene in patients with ataxia that is associated with vitamin E deficiency. Targeted disruption of the alpha-TTP gene revealed that alpha-tocopherol concentration in the circulation was regulated by alpha-TTP expression levels. Male alpha-TTP(-/-) mice were fertile; however, placentas of pregnant alpha-TTP(-/-) females were severely impaired with marked reduction of labyrinthine trophoblasts, and the embryos died at mid-gestation even when fertilized eggs of alpha-TTP(+/+) mice were transferred into alpha-TTP(-/-) recipients. The use of excess alpha-tocopherol or a synthetic antioxidant (BO-653) dietary supplement by alpha-TTP(-/-) females prevented placental failure and allowed full-term pregnancies. In alpha-TTP(+/+) animals, alpha-TTP gene expression was observed in the uterus, and its level transiently increased after implantation (4.5 days postcoitum). Our results suggest that oxidative stress in the labyrinth region of the placenta is protected by vitamin E during development and that in addition to the hepatic alpha-TTP, which governs plasma alpha-tocopherol level, the uterine alpha-TTP may also play an important role in supplying this vitamin.

Animals↗

PubMed2000

Exercise BP response in subjects with high-normal BP: exaggerated blood pressure response to exercise and risk of future hypertension in subjects with high-normal blood pressure.

OBJECTIVES: This study was designed to assess the clinical usefulness of an exaggerated blood pressure (BP) response to exercise (EBPR) in predicting the development of hypertension from a high-normal state. BACKGROUND: Exaggerated BP response during both dynamic and isometric exercises are associated with increased risk of future hypertension, while the significance of these responses concerning the identification of individuals with high-normal BP who are prone to develop hypertension is unknown. METHODS: The study population comprised a sample of 239 men with high-normal BP (aged 42.3 +/- 5.9 years) who underwent a symptom-limited bicycle ergometer exercise testing at baseline and then were followed for 5.1 years. RESULTS: The Kaplan-Meier survival analysis showed that the subjects in the upper quartile of BP response to exercise had a significantly higher cumulative incidence of hypertension on follow-up than those in the middle two and lower quartiles (log-rank test, p < 0.05). Multivariate analysis using the Cox proportional hazards survival model showed that the EBPR was significantly and independently associated with the risk of developing hypertension after adjustment for some traditional risk factors for hypertension (RR = 2.31, 95% confidence interval = 1.45 to 6.25). CONCLUSIONS: These findings suggest that an EBPR is an important risk factor for new-onset hypertension from a high-normal state and, thus, exercise testing can provide valid information that may help identify individuals with high-normal BP at a greater risk of future hypertension.

Adult↗

PubMed2000

Synthesis and immunosuppressive activity of 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols.

A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.

Animals↗

PubMed2000

Effects of JTV-519, a novel anti-ischaemic drug, on the delayed rectifier K+ current in guinea-pig ventricular myocytes.

We studied the effects of a newly synthesized anti-ischaemic agent, 4-[3-(4-benzylpiperidin-1-yl) propionyl]-7-methoxy-2, 3, 4, 5-tetrahydro-1, 4-benzothiazepine monohydrochloride (JTV-519) on the delayed rectifier potassium current (IK), using guinea-pig ventricular myocytes and whole-cell voltage-clamp techniques, under blockade of the L-type calcium current (ICa,L) by D600 (1 microM) or nitrendipine (5 microM). The IK in guinea-pig ventricular cells consists of two different components; the rapidly activating, E4031-sensitive component (IKr) and the slowly activating E4031-resistant component (IKs). Under steady-state conditions, JTV-519 (1 and 5 microM) did not change the amplitude of IKs remaining after blockade of IKr with 5 microM E4031. The effect of JTV-519 on IKr was assessed using short (50 ms) pulses which evoked a tail current that was sensitive to E4031 but not to chromanol 293B, a specific blocker of IKs. JTV-519 suppressed the IKr with a half-maximal inhibitory concentration of 1.2 microM. Selective inhibition of IKr by this agent was confirmed by using the "envelope of tails" test. These results suggest that the blockade of IKr may underlie the prolongation of action potential duration in ventricular muscle and QT-intervals alleged to occur in animal as well as human hearts.

Action Potentials↗

PubMed2000

Nicorandil increases adenosine 5'-monophosphate-primed interstitial adenosine via activation of ecto-5'-nucleotidase in rat hearts.

With the use of microdialysis techniques, we examined the effects of nicorandil, a hybrid of an ATP-sensitive K+ (K ATP) channel opener and a nitrate compound, on the production of interstitial adenosine in rat hearts in situ. The level of dialysate adenosine measured under a constant supply of adenosine 5'-monophosphate (AMP) reflected the activity of endogenous ecto-5'-nucleotidase. Nicorandil (0.3-3mM) increased the level of AMP (100 microM)-primed dialysate adenosine in a concentration-dependent manner, and this effect was completely abolished by the guanylate cyclase inhibitor, methylene blue (100 microM), but not by the K ATP channel blocker, glibenclamide (10 microM). Another K ATP channel opener, cromakalim (0.1-1mM), did not increase the production of AMP-primed dialysate adenosine. These results suggest that nicorandil increases the level of interstitial adenosine via cyclic guanosine monophosphate-mediated activation of ecto-5'-nucleotidase.

5'-Nucleotidase↗

PubMed2000

Hypoglycemic effect of cibenzoline in patients with abnormal glucose tolerance and frequent ventricular arrhythmias.

While some antiarrhythmic agents have potential hypoglycemic effects and indeed some reports of hypoglycemic adverse effect of those drugs, no systematic reports have been issued. We studied the hypoglycemic effects of cibenzoline, a class I antiarrhythmic agent. Cibenzoline succinate (150-300 mg/day) was given orally for 12 weeks to 10 patients who had ventricular premature complexes (VPCs) of >1000 per 24 hours and abnormal glucose tolerance before treatment with cibenzoline. Abnormal glucose tolerance, judged by a 75-g oral glucose tolerance test (OGTT), was defined as the response designated as "diabetic" or "borderline" type according to the criteria specified by the Japan Diabetes Society. In OGTT, the insulinogenic index (defined as the ratio of the increment of IRI [immunoreactive insulin] to that of plasma glucose at 30 minutes after a glucose load) and the sum of IRI (sigma IRI) were also determined. Holter ECG recordings, OGTT, and measurements of fasting plasma glucose IRI, and HbA(1c) were performed before and during cibenzoline treatment. Cibenzoline caused VPC reduction of >70% in 6 of the 10 patients. The drug significantly decreased fasting plasma glucose and HbA(1c) (mean +/- SD) 12 weeks after treatment, from 6.18 +/-0.92 mM/L to 5.54 +/- 1.08 mM/L and from 6.17 +/- 1.03% to 5.83 +/- 0.96%, respectively (P < 0.05). While it significantly increased fasting IRI from 4.99 +/- 1.50 to 6.51 +/- 1.47 microU/mL (P < 0.01), the insulinogenic index from 0.33 +/- 0.26 to 0.65 +/- 0.38 (P < 0.05), and sigma IRI from 168 +/- 67 microU/mL to 199 +/-46 (P < 0.05). Cibenzoline exerted a hypoglycemic effect, facilitating insulin secretion in patients with abnormal glucose tolerance and ventricular arrhythmias.

Aged↗