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Biomedical subjects

M Imanishi

Publications and source records attributed to M Imanishi.

At least 37 records · Page 2Linked to original sources

Renal production of thromboxane and prostaglandins in a rat model of type 2 diabetes.

In an investigation of the involvement of prostanoids in the pathogenesis of nephropathy in type 2 diabetes, we repeatedly measured the urinary excretion of prostanoids in both diabetic and healthy rats as the rats aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats with a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Otsuka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1alpha, the amounts of which reflect renal production of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glucose and urinary protein excretion also were measured periodically. The mean plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary protein excretion by the diabetic rats was greater than that of the healthy rats, and it increased with age. Urinary excretion of TXB2 by the diabetic rats was higher than that of the healthy rats at 14 weeks (52.4+/-23.5 vs. 27.0+/-2.6 ng/day; mean +/- SD, P = .015) and the difference continued to the end of the experiment. Urinary excretion of 6-keto-PGF1alpha by the diabetic rats was high at 14 weeks (52.3+/-12.8 vs. 26.9+/-4.6 ng/day; mean +/- SD, P<.001) but decreased with age and was the same as that of the healthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered renal production of TXA2 and PGI2 is involved in the pathogenesis of diabetic nephropathy in rats with type 2 diabetes.

6-Ketoprostaglandin F1 alpha↗

A new technique for implanting a fine-wire microelectrode for chronic recording of unit activity from freely-moving mice.

We report here a newly developed chronic implantation technique using an epoxy-coated fine-stainless steel wire (33 microm in diameter) to record single unit activity from the brain of freely-moving mice with as little tissue injury as possible. Since the fine-wire electrode is not capable of staying straight by itself or of penetrating into the brain, a pair of permanent neodymium magnets placed on a micromanipulator as well as below the animal's head was used for stereotaxic implantation to keep the fine-wire straight and strong by the magnetic fields. With those implanted electrodes recording of single units from the hippocampal CA1 of freely-moving mice was performed during sleep and wakefulness.

Action Potentials↗

Relationship of renal histological damage to glomerular hypertension in patients with immunoglobulin A nephropathy.

OBJECTIVE: Studies of experimental animals show glomerular hypertension to be important in the progression of glomerular disease. We evaluated this connection clinically by examining the relationship between glomerular hemodynamics and histological changes in patients with immunoglobulin (Ig)A nephropathy. METHODS: The subjects were 23 patients with IgA nephropathy. All patients underwent renal biopsies. Glomerular hemodynamics, in terms of glomerular capillary hydraulic pressure (PGC) and the whole-kidney ultrafiltration coefficient, were calculated from the renal clearance, plasma total protein concentration, and pressure-natriuresis relationship. The severity of glomerulosclerosis, tubulointerstitial damage and mesangial matrix expansion was evaluated semiquantitatively. RESULTS: PGC ranged from 33-69 mm Hg, and the mean arterial pressure (MAP) from 79-112 mm Hg. Their correlation was not significant (r= 0.29, P= 0.18). PGC was significantly correlated with the glomerulosclerosis score, and also with the score for tubulointerstitial damage (r= 0.65, P < 0.001 and rs = 0.59, P = 0.007, respectively), but not with the score for mesangial matrix expansion (r= 0.08, P= 0.72). MAP was significantly correlated only with the score for tubulointerstitial damage (rs = 0.63, P = 0.004). In multiple linear regression analysis of the histological changes and hemodynamics, the glomerulosclerosis score and the score for tubulointerstitial damage were correlated with PGC, but not with MAP. CONCLUSION: These clinical results support the speculation that glomerular hypertension is involved in the glomerulosclerosis and tubulointerstitial damage that occurs in IgA nephropathy.

Adult↗

Different patterns of renal prostaglandins I2 and E2 in patients with essential hypertension with low to normal or high renin activity.

OBJECTIVE: Differences in renal synthesis between prostaglandins I2 and E2, and the relationships of the amounts synthesized to renin release were investigated in patients with essential hypertension. METHODS: Of 12 inpatients, six had low to normal plasma renin activity and six had high renin activity. Before and 30 min after intravenous injection of aspirin D,L-lysine (18 mg/kg), abdominal aortic and renal venous plasma was sampled and assayed for renin activity, 6-ketoprostaglandin F1alpha (as an index of prostaglandin I2), and prostaglandin E2. RESULTS: In patients with low to normal renin activity, mean +/- SD plasma levels of 6-keto-prostaglandin F1alpha were lower in the right and left renal veins (3.6 +/- 1.4 and 4.1 +/- 1.5 pg/ml, respectively) than in the aorta (5.5 +/- 2.0 pg/ml), but in the other patients, the levels in these veins (7.0 +/- 2.4 and 6.5 +/- 1.5 pg/ml) were higher than in the aorta (5.4 +/- 0.9 pg/ml). Plasma prostaglandin E2 levels in both veins were higher than in the aorta in both groups and, at each site, the levels were similar in the two groups. Aspirin suppressed renin release in the patients with high renin activity. CONCLUSIONS: In patients with essential hypertension with low to normal renin activity, either less prostaglandin I2 than prostaglandin E2 is produced in the kidney or else more is metabolized there, and in such patients with high renin activity, the renal synthesis of prostaglandin I2, more than that of prostaglandin E2, seems to be related to the increased renin release.

6-Ketoprostaglandin F1 alpha↗

Genistein potentiates the relaxation induced by beta1- and beta2-adrenoceptor activation in rat aortic rings.

In rat aortic rings, genistein, an inhibitor of tyrosine kinase, but not daidzein, an inactive analogue of genistein, potentiated the relaxation induced by isoproterenol. Atenolol, a beta1-adrenoceptor antagonist, or ICI-118,551, a beta2-adrenoceptor antagonist, inhibited the relaxation induced by isoproterenol. The potentiating effect of genistein on the relaxation induced by isoproterenol in the presence of ICI-118,551 was apparently greater than that in the presence of atenolol. In the presence of ICI-118,551, theophylline, an inhibitor of cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE), markedly inhibited the potentiating effect of genistein on the isoproterenol-induced relaxation, whereas in the presence of atenolol, theophylline only partly inhibited the potentiating effect of genistein. The relaxation induced by forskolin, an activator of adenylyl cyclase, was potentiated by genistein or theophylline. In the presence of theophylline, the relaxation induced by forskolin was not further affected by genistein. Genistein also inhibited the activities of cAMP-PDE. In the presence of atenolol, but not ICI-118,551, iberiotoxin, an inhibitor of Ca-activated K channels, inhibited the relaxation induced by isoproterenol and the potentiating effect of genistein. In the presence of atenolol, quinacrine, an inhibitor of phospholipase A2, and metyrapone, an inhibitor of P-450 enzymes, but not alpha-naphthoflavone, an inhibitor of P-450 enzymes, indomethacin, a cyclooxygenase inhibitor, or AA861, a 5-lipoxygenase inhibitor, inhibited the potentiating effect of genistein. These results suggest that the potentiation of the beta1-adrenoceptor-induced relaxation by activation of genistein may mostly be due to inhibition of cAMP-PDE activities. In addition, the potentiation of the relaxation induced by activation of beta2-adrenoceptors by genistein may be related to the inhibition of arachidonic acid metabolism and cAMP-PDE activities.

Adrenergic beta-Agonists↗

The inhibitory effect of KT3-671, a nonpeptide angiotensin-receptor antagonist, on rabbit and rat isolate vascular smooth muscles: a possible involvement of K(ATP) channels.

The vasoinhibitory effect of KT3-671, a recently synthesized nonpeptide angiotensin II (Ang II), AT1-receptor antagonist, and the factors affecting insurmountable antagonism of Ang II were examined in rabbit and rat isolated vascular smooth muscle preparations. In rabbit and rat aortic rings, KT3-671 caused insurmountable antagonism of Ang II. In addition, KT3-671 inhibited contractile responses to angiotensin III (Ang III). In rabbit isolated smooth muscles, KT3-671 was most effective in reducing the maximal contraction induced by Ang II in the renal artery followed by the basilar artery and the aorta. In rat renal arterial rings, KT3-671 (10(-5) M) inhibited the concentration-response curves of prostaglandin F2alpha and STA2. In rabbit and rat aortic rings without endothelium, the insurmountable antagonisms of Ang II by KT3-671 and EXP 3174 were changed to surmountable antagonism by pretreatment with DuP 753 and KT3-671, respectively. In addition, KT3-671 abolished the inhibitory effect of CV- 11974 in the rat aorta but not in the rabbit aorta. Indomethacin (10(-5) M) or the removal of endothelium did not affect the inhibitory effect of Ang II by CV-11974 or EXP 3174 but enhanced the insurmountable antagonism by KT3-671. ODQ (3 x 10(-6) M), N(G)-nitro-L-arginine (3 x 10(-4) M), 4-aminopyridine (3 x 10(-3) M), tetraethylammonium (TEA; 10(-3) M), or iberiotoxin (10(-7) M) did not affect the inhibitory action of KT3-671 or CV-11974. Methylene blue (3 x 10(-6) M), KCl (10(2) M), TEA (10(-2) M), or BaC12 (10(-4) M) changed the insurmountable antagonism by KT3-671 to surmountable antagonism and abolished the inhibitory effect of CV-11974. However, glibenclamide (3 x 10(-6) M) did not affect the inhibitory action of KT3-671 but reduced the insurmountable antagonism by CV- 11974. These results indicate that KT3-671 is an insurmountable antagonist of Ang II in the rabbit and rat aorta. The results in the rat aorta also suggest that K(ATP) channels may be involved in insurmountable antagonism of Ang II by KT3-671 and CV-11974. Key Words: KT3-671-Rabbit-Rat-Vascular smooth muscle-Angiotensin II-Insurmountable antagonist-K(TP)channels.

Angiotensin Receptor Antagonists↗

Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the monkey.

How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. In the present study, by using awake monkeys, the polysynaptic effects of electrical stimulation in the forelimb regions of the primary motor and primary somatosensory cortices on the activity of globus pallidus (GP) neurons, especially mediated by the subthalamic nucleus (STN), have been characterized. Cortical stimulation induced an early, short-latency excitation followed by an inhibition and a late excitation in neurons of both the external and internal segments of the GP. It also induced an early, short-latency excitation followed by a late excitation and an inhibition in STN neurons. The early excitation in STN neurons preceded that in GP neurons. Blockade of STN neuronal activity by muscimol (GABA(A) receptor agonist) injection resulted in abolishment of both the early and late excitations evoked in GP neurons by cortical stimulation. At the same time, the spontaneous discharge rate of GP neurons decreased, pauses between the groups of spikes of GP neurons became prominent, and the firing pattern became regular. Injection of (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) [N-methyl-D-aspartate (NMDA) receptor antagonist], but not 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX (non-NMDA receptor antagonist)], into the STN attenuated the early and late excitations in GP neurons, suggesting that cortico-subthalamic transmission is mediated mainly by NMDA receptors. Interference with the pallido-subthalamic transmission by bicuculline (GABA(A) receptor antagonist) injection into the STN made the inhibition distinct without affecting the early excitation. The present results indicate that the cortico-subthalamo-pallidal pathway conveys powerful excitatory effects from the motor-related cortical areas to the GP with shorter conduction time than the effects conveyed through the striatum.

Animals↗

[1-11C]Octanoate as a PET tracer for studying ischemic stroke: evaluation in a canine model of thromboembolic stroke with positron emission tomography.

Octanoate is taken up by the brain and converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. Consequently, [1-11C]octanoate might serve as a useful positron emission tomography (PET) probe for studying cerebral oxidative metabolism and/or astroglial functions. The present study attempted to evaluate the utility of using [1-11C]octanoate as a PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. We used a canine model of thromboembolic stroke. Five male beagle dogs were implanted with an indwelling catheter in the left internal carotid artery. A single autologous blood clot was injected into the left internal carotid artery through the catheter. The brain distribution of [1-11C]octanoate and cerebral blood flow (CBF) were determined 24 h after insult using a high resolution PET scanner. Post mortem brain regions unstained with 2,3,5-triphenyltetrazolium chloride (TTC) were defined as infarcts. In the region of an infarct, accumulation of [1-11C]octanoate decreased concurrently with CBF reduction. In contrast, normal accumulation of [1-11C]octanoate was observed in ischemic but vital regions, suggesting that an increased accumulation of [1-11C]octanoate relative to CBF takes place in these regions. In conclusion, [1-11C]octanoate accumulated in ischemic but vital regions, indicating that [1-11C]octanoate is a potentially useful PET tracer for imaging and evaluating the pathophysiology of ischemic stroke.

Animals↗

Effects of nitric oxide scavenger, carboxy-PTIO on endotoxin-induced alterations in systemic hemodynamics in rats.

The present experiments were conducted to clarify the mode of cardiovascular action of carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a nitric oxide (NO) scavenger, during rat endotoxic shock by determining cardiac output and systemic arterial tone simultaneously. Lipopolysaccharide (LPS) (10 mg/kg, i.v.) decreased systemic blood pressure and cardiac output with transient increases in hematocrit and total vascular resistance. Administration of carboxy-PTIO (1.7 mg x kg(-1) x min(-1), i.v. for 60 min) at 90 min after LPS attenuated further decline in blood pressure and cardiac output without affecting changes in hematocrit or total vascular resistance. It is concluded that carboxy-PTIO attenuates endotoxin-induced hypotension predominantly by maintaining cardiac output in rat experimental endotoxic shock.

Animals↗

Flow cytometric detection and analysis of tailless sperm caused by sonication or a chemical agent.

Flow cytometric analysis has been developed to detect tailless sperm with heads detached from the tails at the neck position. When isolated tailless sperm suspension was subjected to flow cytometry, a second sperm population appeared alongside the normal sperm population on light scatter-histogram. The percentage of this second sperm population (85.2%) was in good agreement with that for the tailless sperm (88.7%) determined microscopically, indicating that the second sperm population would correspond to tailless sperm population in the light scatter-histogram. Rates for tailless sperm determined by flow cytometry significantly correlated with those estimated microscopically following exposure of sperm to either sonication (r = 0.94, P < 0.01), or nitrobenzene (r = 0.80, P < 0.01). The results indicated the utility of the light scatter-histogram in flow cytometry as a simple and convenient procedure for the detection of tailless sperm induced by chemical compounds.

Animals↗

[Surgical treatment for spontaneous hemopneumothorax complicated by delayed re-bleeding: a case report].

A 34-year-old man was admitted to the hospital due to spontaneous hemopneumothorax. A chest tube drainage was performed, and hemorrhagic plueral effusion of 1,600 ml was drained. Because of this, the patient was transferred to the emergency center of our hospital. Following a blood transfusion, we continued to treat conservatively for nine days, because no more bleeding was recognized. On day ten, the patient suddenly started bleeding again, thus, an emergency operation was performed. At the operation under a thoracoscope, a bleeding point was ligated with surgical clip, however, it was difficult to remove blood clots that were attached with the lung surface, it was impossible to continue the thoracoscopic surgery. If re-bleeding occurs after the acute phase, problems may arise from conservative treatment. So, early surgical treatment should be considered.

Adult↗

[Penetrating lung and diaphragmatic injuries with no abnormal finding of chest X-ray: a case report].

A case of penetrating lung and diaphragmatic injuries with no abnormal findings of chest X-ray is reported. A 76-year-old man was admitted to our hospital due to penetrating chest trauma. A simple X-ray film of the chest on admission revealed no abnormal finding. An emergency operation was performed. On exploring the back open wound, we found a laceration of 7 cm in diameter in the right diaphragm and lung laceration. Then we repaired primarily with absorbable material. The postoperative course was uneventful, and the patient was discharged 12 days later. Penetrating truncal traumas can result in diaphragmatic injury. Sometimes the clinical and roentgenographic findings are unreliable. If the diagnosis is missed, a diaphragmatic injury may occur delayed diaphragmatic hernias within hours to years. Accordingly, initial wound exploration are important for the diagnosis of diaphragmatic injury in avoiding serious complications.

Aged↗

Increased nitroglycerin-induced relaxation by genistein in rat aortic rings.

The effect of genistein, a tyrosine kinase inhibitor, on nitroglycerin-induced relaxation was examined in rat aortic rings contracted by phenylephrine. In rat aortic rings, genistein (10(-5) M and 3x10(-5) M), a tyrosine kinase inhibitor, but not daidzein, an analogue of genistein, increased relaxation induced by nitroglycerin in a concentration-dependent manner. Iberiotoxin, an inhibitor of Ca2+ -activated K+ channels, inhibited the relaxation induced by nitroglycerin, but it did not affect the effect of genistein. Glibenclamide, an inhibitor of ATP-sensitive K+ channels, did not affect the relaxation induced by nitroglycerin. Theophylline, an inhibitor of cyclic AMP-dependent phosphodiesterase, increased the relaxation induced by nitroglycerin, and genistein (10(-5) M) failed to affect the relaxation induced by nitroglycerin in the presence of theophylline. Genistein also inhibited the activity of cyclic AMP-dependent phosphodiesterase. In addition, 6-[4-(4'-pyridyl)amino phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, an inhibitor of cyclic GMP-inhibitable cyclic AMP phosphodiesterase, inhibited the relaxation induced by nitroglycerin. These results suggest that, in the rat aortic rings, genistein inhibits cyclic AMP-dependent phosphodiesterase activities, resulting in the increase of the relaxation induced by nitroglycerin.

Animals↗

Posttraumatic intestinal stenosis presenting as a perforation: report of a case.

A 78-year-old woman was admitted to the hospital after falling into a ditch approximately 1 m deep and sustaining a blunt abdominal trauma with a left femur fracture. On the tenth day after admission, symptoms of a small bowel obstruction occurred. A nasogastric tube was inserted, and the symptoms thus improved. She sometimes complained of abdominal pain during the 12 months after the fall, but recovered with conservative management. The next year, she was readmitted to the hospital for a pin extraction of the left femur bone. During this admission, 15 months since her admission after her fall, she again complained of abdominal pain. Abdominal pain increased with a muscular defense, and abdominal X-rays revealed free air. She was referred to our hospital with a diagnosis of perforative peritonitis, and emergency surgery was performed. Upon laparotomy, circumferential stenoses of the small bowel were recognized in the proximal segments about 40cm, 80cm, and 100cm from the ileocecal region. In addition, a perforation and prominent dilatation of the bowel segment was observed just proximal to the stenosis about 100cm from the ileocecal region. She underwent a small intestinal resection at two sites. There were no findings of an intestinal specific ulcer, such as Crohn's disease, intestinal tuberculosis, or malignancy, based on the results of a histopathological examination.

Abdominal Injuries↗

Glomerular hypertension as one cause of albuminuria in type II diabetic patients.

AIMS/HYPOTHESIS: Results from animal models of glomerular hypertension have suggested that this disorder is one cause of albuminuria in diabetic nephropathy. We evaluated this hypothesis clinically. METHODS: The subjects were 20 patients with Type II (non-insulin-dependent) diabetes mellitus but without uraemia or hypertension: 8 had normoalbuminuria and 12 had albuminuria (> or = 20 micrograms/min). In the 2-week study, patients were on a diet with ordinary amounts of sodium for 1 week and on a sodium-restricted diet for 1 week. Urinary excretion of sodium and albumin and the systemic blood pressure were measured daily. Intrarenal haemodynamics, in terms of the glomerular pressure and resistance of afferent and efferent arterioles, were calculated from renal clearance, the plasma total protein concentration, and the pressure-natriuresis relation. In 8 of the 12 patients with albuminuria, an angiotensin-converting enzyme inhibitor, cilazapril, was given orally (2 mg/day) and the 2-week study was repeated. RESULTS: In patients with albuminuria, resistance of efferent arterioles and the glomerular pressure were higher than in patients with normoalbuminuria (glomerular pressure, 53 +/- 5 vs 43 +/- 5 mmHg, means +/- SD, p < 0.001). Urinary excretion of albumin correlated (n = 20, r = 0.675, p < 0.001) with the glomerular pressure but not with systemic pressure. The increased glomerular pressure and the albuminuria were decreased by cilazapril but systemic pressure was not. CONCLUSIONS/INTERPRETATION: These findings are consistent with the hypothesis that glomerular hypertension is present in Type II diabetic patients with early nephropathy and can cause albuminuria.

Adult↗

Creatinine clearance as a substitute for the glomerular filtration rate in the assessment of glomerular hemodynamics.

A method for the clinical assessment of glomerular hemodynamics has been published previously. We here examined whether, when using this method, renal creatinine clearance (Ccr) can be substituted for the glomerular filtration rate (GFR). The study subjects comprised 57 inpatients from Osaka City General Hospital: 30 with type 2 diabetes mellitus and 27 with chronic glomerulonephritis. During the 2-wk study, patients received a high-salt diet for 1 wk and a low-salt diet for 1 wk. Urinary sodium excretion and systemic blood pressure were measured daily. The renal plasma flow, Ccr, and plasma total protein concentration were also evaluated simultaneously on the last day of the high-salt diet. The GFR was also calculated from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid (DTPA). Glomerular hemodynamics, represented by the glomerular capillary hydraulic pressure and the resistance of afferent and efferent arterioles, were calculated using the renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Values for renal hemodynamics with the Ccr-derived GFR were compared with those from the 99mTc-DTPA-derived GFR. Ccr values of 53 to 169 ml/min correlated with the 99mTc-DTPA-derived clearance of 39 to 179 ml/min (n=57, r=.71, p<.001). Values for the glomerular pressure and the resistances of afferent and efferent arterioles calculated using the Ccr-derived GFR correlated significantly with those calculated using the 99mTc-DTPA-derived GFR (r=.99, p<.001 and r=.99, p<.001, respectively). These results indicate that the Ccr is an accurate representation of the GFR for use in glomerular hemodynamic analysis of the pressure-natriuresis relationship.

Chronic Disease↗

[Thoraco-abdominal impalement injury with diaphragmatic injury: a case report].

A 60-year-old man was admitted to our hospital because of impalement injury due to traffic accident. Chest X-ray on admission revealed normal lung field. CT scans of the chest and abdomen revealed slight pneumothorax and intra-abdominal organ protruding from abdominal cavity. An emergency operation was performed. Diaphragmatic injury was not detected during the abdominal procedure. On exploring the back wound, we found a laceration of 8 cm in diameter in the diaphragm and repaired it. Impalement injuries which have aspects of both blunt and penetrating trauma are uncommon. Accordingly, wound exploration and debridement of fistulous tract are necessary. In the case of thoraco-abdominal injuries by impalement, one should bear in mind the existence of diaphragmatic injury even with normal diaphragmatic shadow on chest X-ray.

Abdominal Injuries↗