Corrigendum to: cerebroprotective properties of SM-20220, a potent Na(+)/H(+) exchange inhibitor, in transient cerebral ischemia in rats
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Journal Article↗
Biomedical subjects
N Ohashi
Publications and source records attributed to N Ohashi.
Approximate Selection Rules for |K| = 1-0 and 1-1 Tunneling-Rotation Transitions in the Methanol Dimer.
Approximate K = 0 and |K| = 1 tunneling-rotation eigenfunctions for the four A, four E, and one G symmetry species present in the methanol dimer, derived from molecular parameters obtained previously from a least-squares fit to transition frequencies involving K = 0 and 1 levels, are used to clarify some apparent contradictions associated with traditional b- and c-type transition designations in the E and G tunneling-rotational states of this dimer. These approximate eigenfunctions also predict strong and weak line intensities which are consistent with the pattern of strong a-, b-, and c-type transitions observed, thus supporting our previous separate K-state analysis based only on energy level differences. Some of the predicted weaker |K| = 1 a-type transitions should be experimentally observable with more signal averaging. Copyright 2000 Academic Press.
Journal Article↗
Combined therapy utilizing a novel Na+/H+ exchange inhibitor (SM-20220) and THAM for ischemic brain edema.
We investigated in the gerbil model whether the therapeutic effect of a novel Na+/H+ exchange inhibitor SM-20220 on ischemic brain edema could be enhanced by improving the decreased intracellular pH with an alkalizing agent, tris (hydroxymethyl) aminomethane (THAM). The left carotid artery of the animals was occluded twice for 10 min at a 5 hr interval. Ischemia-positive animals were selected and classified into the SM-20220- (0.5 mg/kg, i.p.) THAM- (2.0 ml/kg, i.v., 0.3M-THAM), combination of SM-20220 (0.5 mg/kg, i.p.) and THAM (2.0 ml/kg, i.v.), and vehicle- (0.9% saline, i.p.) treatment groups. Each agent was administered at 0, 6, 12 and 36 hr after recirculation following the 2nd episode of ischemia. The brain water, sodium and potassium contents were measured at 12, 24, and 48 hr after recirculation. The water content of the ischemic hemisphere 12 hr after recirculation was significantly lower in the combination-treated group (79.02%; P < 0.05) than in either the SM-20220- (79.28%) or THAM-treated group (79.32%). At 24 hr after recirculation the water content was significantly lower in the combination-treated group (79.83%, P < 0.05) than in the vehicle group (80.95%). At 48 hr after recirculation there were no significant differences in the water content between the vehicle group and any of the other treatment groups. The changes in brain water (delta H2O) and sodium plus potassium (delta Na + delta K) content in the ischemic hemisphere showed a significant correlation in each group. The combined treatment with the novel Na+/H+ exchange inhibitor SM-20220 and THAM is more effective on ischemic brain edema than treatment with a single agent. The results of this study indicate that improvement of intra- and extracellular acidosis by THAM infusion enhanced the activity of the NHE inhibitor SM-20220.
Amides↗
Pulmonary neuroendocrine cell distribution in sudden infant death syndrome.
The density of pulmonary neuroendocrine cells (PNECs) in 21 sudden infant death syndrome (SIDS) cases, 19 controls, and 25 fetuses was studied morphometrically. Formalin-fixed, paraffin-embedded lung samples were immunostained with antibody against chromogranin A (CGA). The percentage of PNEC-positive airways and the density of PNECs in each airway were calculated in all cases. The density of PNECs was expressed as the number of cells per millimeter of basement membrane. The percentage of PNEC-positive airways reached nearly 100% by term and did not change significantly until 12 months of age in both the SIDS cases and the controls. The density of PNECs also showed a rapid increase in the saccular stage fetus and had its peak of about 4 cells/mm around birth. The density of PNECs, including the standard deviation, was higher in SIDS cases than in controls. The uneven distribution of PNECs may affect respiratory control in SIDS victims.
Journal Article↗
Patterns and mechanisms of pedestrian injuries induced by vehicles with flat-front shape.
To clarify the difference between flat-front vehicles and bonnet-front vehicles with regard to the patterns and mechanisms of vehicle-induced pedestrian injuries, we investigated 101 cases of pedestrians who were struck by the front of a vehicle. There were 33 flat-front vehicle collision cases and 68 bonnet-front vehicle collision cases. The frequency of chest injuries in flat-front vehicle collisions (30.3%) was significantly higher than that in bonnet-front vehicle collisions (11.8%). Lower leg fractures were more common in bonnet-front vehicle collisions than in flat-front vehicle collisions. Although head injuries were common in both cases, the mechanisms of these injuries differed. The pedestrians who were struck by flat-front vehicles tended to sustain more severe injuries at lower impact speeds. All of these results stem from the difference in the front shape of the two types of vehicle. Pedestrians who are struck by the front of flat-front vehicles receive the impact force to the trunk, particularly the chest, at the initial impact and are thrown out forward after the impact, because the front of these vehicles is perpendicular to the road.
Journal Article↗
Fatal cardiovascular injuries to the unbelted occupant associated with airbag deployment: two case-reports.
We present two forensic autopsy cases of unbelted occupants associated with the airbag deployment in motor vehicle collisions. Both victims suffered from cardiovascular injuries which were the cause of death. Case 1: A 50-year-old man sustained a contusion on the left anterior chest with rib fractures and laceration of the intrapericardial inferior vena cava, the right ventricle, and the right pleuropericardium. Case 2: A 40-year-old man sustained multiple rib fractures, sternal fracture, and the rupture of the right ventricle. Autopsies and vehicle examinations revealed that both victims' chest seemed to strike the steering wheel through the deployed airbag. Therefore, we determined that the source of blunt impact force is the steering wheel through the airbag rather than airbag deployment only. In light of these two cases, we learned that the steering wheel should be considered as the blunt impact force inducing cardiovascular injuries even in cases in which the airbag has been deployed.
Journal Article↗
Renal arteriovenous malformation with thrombus in the inferior vena cava.
BACKGROUND: Thrombus formation in the inferior vena cava (IVC) is usually seen in cases with malignancy. In contrast, vascular anomalies hardly ever accompany this disorder. Herein, a case of thrombus formation in the IVC associated with renal arteriovenous malformation (AVM) is reported. METHODS/RESULTS: A 50-year-old woman who received transarterial embolization (TAE) for AVM in the right kidney noticed right flank pain with macrohematuria 12 months later. Because radiographic evaluation could not rule out malignancy in the kidney, nephrectomy was performed. During nephrectomy, a palpable thrombus was found in the IVC, so thrombectomy was performed simultaneously. Histopathologic examination revealed an old infarction due to the TAE, circumferential arteriovenous thrombi and a large organized thrombus up to the IVC, but neither renal cell carcinoma nor transitional carcinoma in the kidney. CONCLUSIONS: Careful observation may be required, even after treatment for renal AVM, such as TAE, to avoid the formation of an IVC thrombus.
Angiography↗
SM-20550, a new Na+/H+ exchange inhibitor and its cardioprotective effect in ischemic/reperfused isolated rat hearts by preventing Ca2+-overload.
We investigated the effect of a newly synthesized compound, SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid] on Na+/H+ or Na+/Ca2+ exchange activity in rat cardiomyocytes, and on radioligand binding with several channels or receptors in membrane preparations, and ischemia/reperfusion injury in isolated perfused rat hearts. In myocytes, SM-20550 concentration-dependently inhibited the recovery from acidosis induced by an NH4Cl prepulse in HCO3(-)-free solution. Its IC50 was 10(-8) M, which was 10 times lower than that of ethylisopropyl amiloride (EIPA). SM-20550 (10(-6) M) did not affect the Na+-dependent Ca2+ influx (Na+/Ca2+ exchange activity) in cardiomyocytes. In the radioligand binding assay, SM-20550 did not have affinity for K+ channel, beta-adrenoceptor, adenosine, angiotensin, or endothelin receptors, and had low affinity for Na+ and Ca2+ channels and alpha-adrenoceptors, only at the concentrations of 10(-6)-10(-5) M. In perfused hearts exposed to 40 min of global ischemia and 20 min of reperfusion, SM-20550 (10(-8)-10(-7) M) significantly reduced the elevation of left ventricular end-diastolic pressure during reperfusion, improved the postischemic recovery of developed pressure, and prevented coronary perfusion pressure increase after reperfusion. Furthermore, SM-20550 reduced creatine phosphokinase release during reperfusion and prevented the abnormal gain of tissue Na+ and Ca2+ at the end of reperfusion. These results suggest that SM-20550 is a potent, highly specific Na+/H+ exchange inhibitor, which exerts a protective effect against myocardial ischemia/reperfusion injury. In addition, our data strongly support the hypothesis that Na+/H+ exchange plays an important role in the development of postischemic cardiac dysfunction, most likely by inducing Na+ and Ca2+ overload.
Amidines↗
Analysis of 16S rRNA and 51-kilodalton antigen gene and transmission in mice of Ehrlichia risticii in virgulate trematodes from Elimia livescens snails in Ohio.
Operculate snails (the family Pleuroceridae: Elimia livescens) were collected between June and October 1998 from a river in central Ohio where repeated cases of Potomac horse fever (PHF) have occurred. Of collected snails, consistently 50 to 80% carried a combination of cercariae and sporocysts of digenetic virgulate trematodes. The trematodes obtained from each snail were pooled and tested for Ehrlichia risticii, the agent of PHF, by nested PCR using primers specific to the 16S rRNA gene. Out of a total of 209 trematode pools, 50 pools were found to be positive by PCR. The DNA sequence of the 16S rRNA gene identified in one trematode pool was identical to that of the type strain of E. risticii, and the sequence of the gene identified in another pool differed from that of the type strain by 1 nucleotide. Comparison of the deduced amino acid sequence of the partial 51-kDa antigen gene from various sources revealed that Maryland, Ohio (except Ohio 081), and Kentucky strains are in a cluster distinct from the sequences obtained from sources in California and Oregon. Ohio 081 was shown previously by antigenic composition analysis to be distinct from other groups. However, all sequences examined were not segregated according to their sources: horse blood or infected trematodes. E. risticii was found to be transmittable from trematodes to mice and was subsequently passaged from infected mice to additional mice, as determined by PCR analysis. Our findings suggest the evolution of E. risticii in the natural reservoir in separate geographic regions and persistent infection of trematode populations with E. risticii during summer and early fall. The study also suggests that the mouse can be used to isolate E. risticii from the infected trematode.
Amino Acid Sequence↗
Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury.
p38 mitogen-activated protein kinase (MAPK) is involved in intracellular signals that regulate a variety of cellular responses during inflammation. However, the role of p38 MAPK in atherosclerosis, a chronic inflammatory disorder, remains uncertain. The aim of the present study was to examine the role of p38 MAPK in the development of neointimal hyperplasia in balloon-injured rat carotid arteries. Immunohistochemical studies indicated that p38 MAPK was rapidly activated in the majority of medial cells in injured arterial walls. Rats treated with FR167653, a selective inhibitor of p38 MAPK, at a dosage of 10 mg x kg(-1) x d(-1), had a 29.4% lower intima-to-media ratio than the untreated controls at 14 days after balloon injury (P:<0.05). The percentage of proliferating nuclear antigen-positive cells in the media at 48 hours was significantly lower in the FR167653-treated group than in the control group. Quantitative competitive reverse transcription-polymerase chain reaction analysis revealed that interleukin-1beta mRNA expression in arteries was significantly inhibited by FR167653 (to 18.1% of control, P:<0.05) at 8 hours after balloon injury. Moreover, p38 MAPK activation and interleukin-1beta production by lipopolysaccharide-stimulated vascular smooth muscle cells were inhibited by FR167653 in a concentration-dependent manner in vitro. These results indicate that p38 MAPK is activated in vascular walls after injury and promotes neointimal formation and suggest that selective inhibition of p38 MAPK may be effective in the prevention of restenosis after percutaneous transluminal coronary angioplasty.
Angioplasty, Balloon, Coronary↗
SM-20220, a potent Na+/H+ exchange inhibitor, improves consciousness recovery and neurological outcome following transient cerebral ischaemia in gerbils.
We studied the cerebroprotective effect of SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulphonate), a newly synthesized Na+/H+ exchanger (NHE) inhibitor, in Mongolian gerbil global ischaemia. Transient cerebral ischaemia was induced by clipping both common carotid arteries for 30 min followed by 24h reperfusion. Intravenous administration of SM-20220 (0.3 or 1.0 mg kg(-1)) immediately after reperfusion significantly shortened the consciousness recovery time (P < 0.01). SM-20220 also improved the neurological outcome (McGraw's scale) after reperfusion. At the dose of 1.0 mg kg(-1), the mortality rate was significantly reduced at 24 h after reperfusion (P < 0.01). This study shows that NHE is involved in the aggravation of cerebral function, represented by consciousness recovery, and neurological outcome following transient forebrain ischaemia, and that its inhibitor may exert protective effects on post-ischaemic brain damage.
Amides↗
Hypertrophic cardiomyopathy as a manifestation of cardiac sarcoidosis.
The present study aimed to clarify whether cardiac sarcoidosis causes changes that mimic hypertrophic cardiomyopathy. Eighty-two consecutive patients (35 men, 47 women), who were referred to the Department of Cardiovascular Medicine, with a diagnosis of pulmonary and/or ocular sarcoidosis (average age, 49.5 years, range 20-74), underwent detailed clinical, electrocardiographic, and echocardiographic evaluations; in some patients, right and left heart catheterization, selective coronary artery cineangiography, and right and left endomyocardial biopsies were performed. Over a 15-month period of observation, 6 of these 82 patients (7.3%) were found to have echocardiographic abnormalities: increased thickness of the interventricular septum was found in 4 patients, asymmetric septal hypertrophy in 2, localized septal hypertrophy in 1 and apical hypertrophy in 1 patient. One patient had an 'ace-of-spades' deformity of the left ventricle. Cardiac sardoidosis can mimic, and even present as, hypertrophic cardiomyopathy.
Adult↗
Protective effect of SM-19712, a novel and potent endothelin converting enzyme inhibitor, on ischemic acute renal failure in rats.
Effects of SM-19712 (4-chloro-N-[[(4-cyano-3-methyl- 1-1-phenyl- 1H-pyrazol-5-yl)amino]carbonyl] benzenesulfonamide, monosodium salt), a novel endothelin converting enzyme (ECE) inhibitor, on ischemic acute renal failure (ARF) in rats were examined in comparison with those of phosphoramidon, a conventional ECE inhibitor. ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in ARF rats markedly decreased at 24 h after reperfusion. Intravenous bolus injection of SM-19712 (3, 10, 30 mg/kg) prior to the occlusion attenuated dose-dependently the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damages such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were dose-dependently attenuated by SM-19712. Protective effects of phosphoramidon (10 mg/kg) on ARF-induced functional and tissue damages were less potent than that of the same dose of SM-19712. Endothelin-1 (ET-1) content in the kidney after the ischemia/reperfusion was significantly increased, being the maximum level at 6 h after reperfusion, and this elevation was completely suppressed by the higher dose of SM-19712. Our findings support the view that renal ET-1 plays an important role in the development of ischemia/reperfusion-induced renal injury. SM-19712 may be useful in the treatment of ischemic ARF.
Acute Kidney Injury↗
Effect of SMP-300, a new Na+/H+ exchange inhibitor, on myocardial ischemia and experimental angina models in rats.
We evaluated the effects of SMP-300 (N-(aminoiminomethyl)-11-chloro-5,6,7,8-tetrahydro-8-oxo-4H-pyrrolo[3,2,1-kl][1]benzazocine-2-carboxamide monomethanesulfonate monohydrate), a newly synthesized compound, on Na+/H+ exchange activity in rat cardiomyocytes and on other ion transporters, channels and receptors. We also investigated the protective effects of SMP-300 in isolated ischemic rat hearts and rat isoproterenol- or vasopressin-induced experimental angina models. SMP-300 concentration-dependently inhibited recovery from acidosis in rat myocytes, and its IC50 for Na+/H+ exchange was 6 nM. In comparison, its IC50s for Na+/Ca2+ exchange and for the Na+ channel were >1000 nM, and those for other channels or receptors tested were >10,000 nM. In rat isolated perfused hearts, SMP-300 (10(-8)-10(-7) M), administered only at preischemia and not during reperfusion, significantly improved the postischemic recovery of cardiac function. SMP-300 (0.03-0.3 mg/kg, i.v.) or 5-(N-ethyl-N-isopropyl)-amiloride (1 mg/kg, i.v.) prevented the isoproterenol-induced ST-segment depression in the ECG of anesthetized rats, in a dose-dependent manner. SMP-300 (0.1 mg/kg, i.v.) and 5-(N-ethyl-N-isopropyl)-amiloride (1 mg/kg, i.v.) also inhibited the vasopressin-induced ST-segment depression in the ECG of anesthetized rats. This is the first report presenting the protective effect of Na+/H+ exchange inhibitors on isoproterenol- or vasopressin-induced ECG changes in rats, providing the future perspective of SMP-300, a potent Na+/H+ exchange inhibitor, as an anti-anginal drug.
Amiloride↗
Pharmacological characterization of a novel sulfonylureid-pyrazole derivative, SM-19712, a potent nonpeptidic inhibitor of endothelin converting enzyme.
We describe the pharmacological characteristics of SM-19712 (4-chloro-N-[[(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl)amino]carbonyl] benzenesulfonamide, monosodium salt). SM-19712 inhibited endothelin converting enzyme (ECE) solubilized from rat lung microsomes with an IC50 value of 42 nM and, at 10 - 100 microM, had no effect on other metalloproteases such as neutral endopeptidase 24.11 and angiotensin converting enzyme, showing a high specificity for ECE. In cultured porcine aortic endothelial cells, SM-19712 at 1 - 100 microM concentration-dependently inhibited the endogenous conversion of big endothelin-1 (ET-1) to ET-1 with an IC50 value of 31 microM. In anesthetized rats, either intravenous (1-30 mg/kg) or oral (10-30 mg/kg) administration of SM-19712 dose-dependently suppressed the pressor responses induced by big ET-1. In acute myocardial infarction of rabbits subjected to coronary occlusion and reperfusion, SM-19712 reduced the infarct size, the increase in serum concentration of ET-1 and the serum activity of creatinine phosphokinase. The present study demonstrates that SM-19712 is a structurally novel, nonpeptide, potent and selective inhibitor of ECE, and SM-19712 is a valuable new tool for elucidating the pathophysiological role of ECE.
Acute Disease↗
[Evaluation of cardiac autonomic nerves by iodine-123 metaiodobenzylguanidine scintigraphy and ambulatory electrocardiography in patients after arterial switch operations].
The autonomic cardiac nerves reach the heart after passing through the vicinity of the aortic root and the pulmonary trunk. The arterial switch operation (ASO) completely transects the ascending aorta and the pulmonary trunk. Therefore, this surgical procedure virtually denerves the heart. Cardiac sympathetic denervation and reinnervation were evaluated in patients after ASO using iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and parasympathetic denervation and reinnervation using ambulatory electrocardiography [Holter electrocardiogram (ECG)]. MIBG scintigraphy was performed in 14 patients who underwent ASO (ASO group) and 3 patients who underwent other open heart surgery (control group). All patients in the ASO group underwent the operation in the neonatal or infantile period. Planar and single photon emission computed tomography (SPECT) images of the myocardium were obtained. Defect score was determined by the SPECT images as a semi-quantitative index. The mean interval between ASO and MIBG scintigraphy was 25.6 +/- 14.6 months. Holter ECG was also performed in 14 patients in the ASO group and 19 age-matched normal children. The Holter ECGs were plotted on a Lorenz plot. The H index, which is related to vagal tone for the cardiovascular system, was calculated from the R-R intervals. The mean interval between the ASO and Holter ECG was 8.3 +/- 9.7 months. MIBG scintigraphy in the control group demonstrated an almost normal homogeneous tracer uptake, but showed extremely reduced tracer uptake and significantly higher defect score in the ASO group. The extent and degree of the reduction of MIBG uptake improved with time after the ASO. The heart-to-mediastinum MIBG count ratio tended to increase with time. The H index of the ASO group was lower than that of normal children (< 12 months: Control group 0.0280 +/- 0.0068 vs ASO group 0.0219 +/- 0.0083), and gradually increased with time (1-3 years: 0.0470 +/- 0.0157 vs 0.0314 +/- 0.0124). These results indicate that MIBG scintigraphy reflects the presence of sympathetic denervation and the possibility of reinnervation after ASO, and that H index reflects the presence of parasympathetic denervation and the possibility of reinnervation after ASO. These are simple and useful methods for assessing the extent and degree of autonomic denervation and reinnervation.
3-Iodobenzylguanidine↗
[A case of docetaxel-resistant lung cancer effectively treated with chemotherapy of gemcitabine and vinorelbine].
We report a NSCLC patient effectively treated with anti-cancer agents on an outpatient basis despite chemotherapy with carboplatin and docetaxel, he relapsed after achieving a transient response. Combination chemotherapy with gemcitabine and vinorelbine administered every three weeks in an outpatient clinic caused the lung cancer volume to reduce remarkably. This regimen was well tolerated and suitable for outpatients. Its usefulness as a second line chemotherapy in the treatment of NSCLC should be investigated.
Adenocarcinoma↗
Na+/H+ exchange inhibitor reduces vascular injury caused by ischemia-reperfusion in the rat hind limb.
This study was designed to evaluate the effects of an Na+/H+ exchange inhibitor, SM-20550, on ischemia-reperfusion injury in the skeletal muscle. Male Sprague-Dawley rats were exposed to ischemia and reperfusion by clamping and releasing clamps both at the abdominal aorta and the bilateral femoral arteries. Rats were divided into three groups; the sham, the SM-20550 treated (SM), and the untreated control (Control) groups. In the SM and control groups, rats were exposed to 5-hr ischemia and 5-hr reperfusion. In the sham group, vessel isolation only was performed. SM-20550 (2.8 mg/kg/hr) in the SM group or vehicle in the sham and control group was continuously administered during ischemia and reperfusion periods. The wall thickness of the vessels were significantly (p<0.01) decreased in the control group than any other group. The internal diameter was significantly (p<0.01) higher in the control and SM group than in the sham group. The wall thickness/internal diameter ratio was significantly (p<0.05) lower in the control group than in the SM group. Thus, an Na+/H+ exchange inhibitor, SM-20550, ameliorated the morphological change due to ischemia reperfusion. These findings provide a clue into the mechanism of ischemia reperfusion injury.
Animals↗