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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 325 records · Page 18Linked to original sources

Impaired action of levcromakalim on ATP-sensitive K+ channels in mesenteric artery cells from spontaneously hypertensive rats.

The purpose of the present study was to test the hypothesis that properties of ATP-sensitive K+ channels are altered in arterial smooth muscle cells of hypertensive rats. Using a patch-clamp technique, we compared effects of a K+ channel opener, levromakalim, on membrane currents in mesenteric artery cells from adult Wistar Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR) treated or not treated with hydralazine. Blood pressure was significantly higher in SHR than in WKY or hydralazine-treated SHR. Levcromakalim evoked a time-independent and voltage-insensitive current in a dose-dependent manner in the whole-cell clamp configuration. The reversal potential of the evoked current depended on extracellular K+ concentration. Application of 3 micromol/L glibenclamide, a specific blocker of ATP-sensitive K+ channels, abolished the levcromakalim-evoked current; however, the current was unaffected by either 1 mmol/L tetraethylammonium or 0.3 micromol/L charybdotoxin. These results suggest that the levcromakalim-evoked current was carried through ATP-sensitive K+ channels. In SHR cells, the maximal slope conductance of the levcromakalim-evoked current, normalized by cell capacitance, was decreased, and the dose-response curve was shifted to the right compared with WKY cells. The levcromakalim action was not impaired in cells from hydralazine-treated SHR. In conclusion, the action of levcromakalim on ATP-sensitive K+ channels in SHR mesenteric artery muscle cells was impaired compared with WKY cells. This impairment was corrected by long-term antihypertensive treatment.

Animals↗

Altered cerebrovascular response to a potassium channel opener in hypertensive rats.

We examined whether the effect of Y-26763, an ATP-sensitive potassium channel opener, on cerebral blood flow is altered in stroke-prone spontaneously hypertensive rats (SHRSP) and, if altered, whether long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor, is capable of preventing the change. Cerebral blood flow during intracarotid infusion of Y-26763 was measured in anesthetized SHRSP and normotensive Wistar-Kyoto rats (WKY) as control. Y-26763 increased cerebral blood flow in a dose-dependent manner in WKY, and glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, inhibited the Y-26763-induced increase in cerebral blood flow. In contrast, the response to Y-26763 in SHRSP was significantly impaired compared with that in WKY. Antihypertensive treatment with cilazapril lowered blood pressure toward normal and prevented the impaired response in cerebral blood flow to Y-26763 in SHRSP. These findings suggest that (1) ATP-sensitive potassium channels contribute to the regulation of cerebral blood flow in rats, (2) the response to an ATP-sensitive potassium channel opener is markedly diminished in hypertensive rats, and (3) the altered response to an ATP-sensitive potassium channel opener during chronic hypertension can be prevented by long-term antihypertensive treatment.

Adenosine Triphosphate↗

Angiotensin II increases norepinephrine turnover in the anteroventral third ventricle of spontaneously hypertensive rats.

We evaluated the effect of angiotensin II (Ang II) administered by intracerebroventricular injection on norepinephrine turnover in the anteroventral third ventricle in adult spontaneously hypertensive rats (SHR, n = 35) and age-matched Wistar-Kyoto rats (WKY, n = 38). Ang II (100 ng) or saline (vehicle control) was administered into the cerebral ventricle 30 minutes after injection of alpha-methyl-p-tyrosine (250 mg/kg IP). Norepinephrine turnover was assessed by evaluation of the norepinephrine concentration before and 1 hour after such administration. The pressor response to Ang II administration was significantly greater in SHR than in WKY (+43 +/- 3 versus +23 +/- 2 mm Hg, P < .01). Baseline norepinephrine turnover (response to saline) was reduced in the ventral median preoptic nucleus of SHR. Ang II significantly increased norepinephrine turnover in the organum vasculosum lamina terminalis and ventral median preoptic nucleus of SHR (organum vasculosum lamina terminalis: 40 +/- 5% by Ang II versus 18 +/- 6% by saline, P < .05; ventral median preoptic nucleus: 32 +/- 3% by Ang II versus 21 +/- 2% by saline, P < .05) but not of WKY (37 +/- 5% versus 29 +/- 5%, P = NS, and 30 +/- 2% versus 32 +/- 3%, P = NS, respectively). Thus, norepinephrine turnover in the anteroventral third ventricle region induced by intracerebroventricular administration of Ang II was increased in SHR. This effect may contribute to the enhanced pressor response to central Ang II seen in this model.

Angiotensin II↗

Distribution and physiological roles of ATP-sensitive K+ channels in the vertebrobasilar system of the rabbit.

The effect of an opener (levcromakalim) and a blocker (glibenclamide) of ATP-sensitive K+ (KATP) channels was investigated in the vertebrobasilar system of the rabbit. Arterial tension and membrane potential were measured by the isometric tension recording method and the microelectrode technique, respectively. Glibenclamide (10(-6) mol/L) depolarized the membrane and potentiated the contraction to histamine in vertebral arteries. The sensitivity to the relaxant effects of levcromakalim was in the following descending order: vertebral > proximal basilar > distal basilar > superior cerebellar arteries. Vertebral arteries were approximately 50 times more sensitive to levcromakalim than were superior cerebellar arteries. The relaxation to levcromakalim was abolished by glibenclamide (10(-6) mol/L). Glibenclamide attenuated vasorelaxation to adenosine in proximal arteries (vertebral and proximal basilar) but not in superior cerebellar arteries. Levcromakalim (7 x 10(-8) mol/L) and adenosine (10(-5) mol/L) induced glibenclamide-sensitive membrane hyperpolarization in vertebral arteries but not in distal basilar arteries. These results suggest that KATP channels contribute to the determination of resting membrane potential and resting tone in vertebral arteries. Furthermore, there is a marked heterogeneity in the sensitivity to an opener of KATP channels, and the heterogeneity has a functional link to the mechanism underlying vasorelaxation to adenosine in the vertebrobasilar system of the rabbit.

Animals↗

Simplified model of krypton laser-induced thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: The effects of thrombotic occlusion of the middle cerebral artery on compromised ischemic tissue may be different from and more severe than those of cerebral ischemia induced by mechanical occlusion of the artery. Photothrombosis, which is based on photochemical damage to the endothelium and subsequent platelet aggregation, is an efficient method to induce thrombosis in vivo. This study aimed to improve and simplify this unique method for an ischemia model of middle cerebral artery occlusion in rats. METHODS: Male spontaneously hypertensive rats (5 to 6 months old, 300 to 450 g) were anesthetized with halothane, endotracheally intubated, and mechanically ventilated. A krypton laser operating at 568 nm was used to irradiate the exposed distal middle cerebral artery with an intact dura above the rhinal fissure. The photosensitizing dye rose bengal (20 mg/kg body wt) was administered intravenously over 90 seconds starting simultaneously with 4 minutes of laser irradiation at a power of 20 mW to cause thrombotic occlusion of this artery. RESULTS: The irradiated middle cerebral artery was completely occluded by intraluminal thrombi within 3 minutes after simultaneous laser irradiation and rose bengal infusion. Thrombosed materials were not stained by phosphotungstic acid-hematoxylin stain (ie, aggregated platelets lacked apparent fibrin). The mean volume of 3-day-old infarction, indicated by the lack of staining with 2,3,5-triphenyltetrazolium chloride, was 84.8 +/- 17.4 mm3 (mean +/- SD, n = 6). CONCLUSIONS: We demonstrated a reproducible and minimally traumatic model of brain infarction induced by the thrombotic distal middle cerebral artery occlusion in rats.

Animals↗

Brain ischemia following bilateral carotid occlusion during development of hypertension in young spontaneously hypertensive rats--importance of morphologic changes of the arteries of the circle of Willis.

The present study was designed to examine the effect of morphologic changes of the arteries of the circle of Willis on cerebral blood flow (CBF) and metabolism in young spontaneously hypertensive rats (SHR). CBF in the parietal cortex was measured by the hydrogen clearance method before and during a one-hour bilateral carotid artery occlusion (BCO), and supratentorial brain metabolites were determined by standard enzymatic methods at a one-hour BCO. The internal diameters of the main arteries of the circle of Willis were estimated morphologically. With increase in age, systemic arterial pressure at rest was significantly raised, while cortical CBF tended to decrease and calculated cerebral vascular resistance increased. During BCO, CBF and supratentorial metabolism (adenosine triphosphate and lactate/pyruvate ratio) tended to be better preserved in two-month-old rats as compared with those in one- or three-month-old rats. The internal diameter of the posterior communicating artery (PcomA) was significantly smaller in the one-month-old group than in the other groups, while the diameter of the internal carotid artery was significantly smaller in rats aged three months than those in rats aged one or two months. It is indicated that cortical CBF reduction and impairment of supratentorial metabolism following occlusion of carotid arteries, at least in part, depend on the morphologic changes of the arteries of the circle of Willis associated with age and development of hypertension in young SHR.

Age Factors↗

Serial changes in blood pressure and neurohormone levels after the onset of lacunar stroke.

To assess serial changes in blood pressure and its circadian variation following a lacunar stroke, the authors studied 7 patients who developed a single lacunar infarction in either the internal capsule or the corona radiata. Blood pressure and pulse rate were monitored noninvasively for twenty-four hours by an ambulatory blood pressure monitoring device in the acute, subacute, and chronic phases of the strokes. In the acute and chronic phases, the authors also measured urinary excretion of catecholamines every 6 hr, and serum cortisol concentration at 9:00, 17:00, and 21:00 hr. The patients were free from antihypertensive agents during the study. The twenty-four-hour averages of both systolic and diastolic blood pressure in the chronic phase were lower than those in the acute phase (P < 0.05). A nighttime fall in blood pressure was observed in the subacute and chronic phases (P < 0.05), but not in the acute phase. Urinary excretion of epinephrine at night in the acute phase was significantly higher than that in the chronic phase (P < 0.05). Serum levels of cortisol at 17:00 and 21:00 hr in the acute phase also exceeded those in the chronic phase (P < 0.05 and P < 0.01, respectively). The authors conclude that an increased secretion of epinephrine and cortisol might, at least in part, contribute to a high blood pressure and a lack of circadian variation in blood pressure in the acute phase of lacunar stroke.

Acute Disease↗

Acute exacerbation of masked hyperthyroidism after iodine restriction followed by thyrotoxic atrial fibrillation and cerebral embolism. A case report.

The authors present a seventy-two-year-old woman complaining of diffuse and firm goiter. At the first visit, she looked almost euthyroid with regular pulse rate of 78 per minute. After iodine restriction, however, she became severely thyrotoxic and developed cerebral embolism associated with atrial fibrillation due to Graves' hyperthyroidism. In conclusion, sudden withdrawal of dietary iodine might lead to exacerbation of Graves' hyperthyroidism resulting in serious cardiovascular or cerebrovascular complications, especially in elderly patients.

Aged↗

Brain infarction caused by syphilitic aortic aneurysm. A case report.

Neurosyphilis often develops brain infarction. Recently, the authors experienced a case of brain infarction caused by syphilitic aneurysm on the thoracic aorta, and its clinical significance is reported. A seventy-eight-year-old woman with strongly positive serologic tests for syphilis suddenly developed global aphasia and right hemiplegia. Brain computed tomography (CT) showed a large brain infarction in the left middle cerebral artery territory. A huge aneurysm of the ascending aorta eroded the sternum and the second and third ribs. The left common carotid artery was completely compressed by the aneurysm, and blood flow was not demonstrated on enhanced CT. A cerebrospinal fluid examination revealed normal cell counts, and the titer of a syphilis test was very low. She did not have any arrhythmia, ischemic heart disease, or valvular heart disease as an embolic source. Brain infarction may be developed by pressure of an aortic aneurysm on the left common carotid artery. They recommend consideration of syphilis as an etiology of brain infarction when luetic patients are seen in old age.

Aged↗

Risk factors for brain infarction in patients with Cushing's disease. Case reports.

Two women aged 51 and 52 years old, respectively, developed a brain infarction before and after undergoing treatment for Cushing's disease. A biochemical remission was obtained more than ten years after the onset of signs or symptoms of Cushing's disease. The arteriosclerotic changes of the cerebral vessels progressed even during replacement therapy for posttreatment hypopituitarism after they underwent either ablative surgery or radiotherapy. One patient, who showed the signs of Nelson's syndrome, demonstrated severe progressive cerebrovascular sclerotic changes, especially around the irradiated site. It is thus suggested that hypercortisolemia, external pituitary irradiation, and posttreatment hypopituitarism may be risk factors for brain infarction. The early diagnosis and adequate treatment are therefore important to prevent cerebrovascular complications in patients with Cushing's disease.

Cerebral Infarction↗

Medial medullary infarction: analyses of eleven patients.

Of 2,130 consecutive patients admitted to two hospitals with acute brain infarction, we examined 11 patients (0.52%) with medial medullary infarction. The infarcts documented by MRI were unilateral in 9 patients and bilateral in 2 patients, and located in the anteromedial arterial territory of the upper or middle part of the medulla. Atherosclerosis of the vertebral arteries was the predominant vascular pathology. The vertebral artery was occluded at its terminal portion in 7 patients. Nine patients had hypertension, and 8 of these had additional risk factors. Male gender (10 patients) and smoking habits (7 patients) were more prevalent compared with patients with pontine infarction. One patient had a medial medullary infarction attributed to dissection of the vertebral arteries following blunt head injury. Limb weakness was the major symptom in all patients, and gaze-evoked nystagmus was also frequent (6 patients). Tongue weakness ipsilateral to the infarct, the classic sign of medial medullary syndrome, was evident in only 3 patients. The outcome was usually excellent.

Adult↗

Blood pressure response during dental surgery.

To investigate blood pressure and pulse rate responses to dental surgery, 21 patients 18 to 73 years of age (mean age, 42 +/- 4 years) who visited our hospital for tooth extraction were studied. Before dental treatment, the patients underwent a mental arithmetic stress test, electrocardiography, and an anxiety evaluation with the State-Trait Anxiety Inventory. Baseline blood pressure and pulse rate were 118 +/- 4/70 +/- 3 mmHg and 69 +/- 2 beats/min, respectively. Blood pressure rose by 24 +/- 3/17 +/- 2 mmHg during the mental stress test, and the magnitude of the rise in systolic blood pressure was significantly correlated with age (r = 0.81, p < 0.001) and baseline blood pressure (r = 0.56, p < 0.01). After the topical injection of local anesthetic containing 1: 80,000 epinephrine, a transient increase in systolic blood pressure was observed. The maximum blood pressure and pulse rate increases during dental surgery were 24 +/- 4/13 +/- 2 mmHg and 17 +/- 3 beats/min, respectively. Similarly, the rate pressure product increased from 8,196 +/- 486 to 11,802 +/- 682. The magnitude of the blood pressure increase during dental surgery was not correlated with age, sex, family history of hypertension, baseline blood pressure, anxiety score, or response to mental stress. On the other hand, when the subjects were divided into two subgroups according to the blood pressure response during dental surgery, the larger response group (increase in mean blood pressure greater than 15 mmHg, n = 9) required a significantly larger dose of local anesthetic than did the smaller response group. The number of cases of pericoronitis of the third molar tended to be greater in the larger response group. These results indicate that an increase in blood pressure during dental surgery cannot be predicted on the basis of baseline blood pressure or the response to mental stress, but is related to the cause of tooth extraction and the volume of local anesthetics required to control the pain.

Adolescent↗

Transforming growth factor-beta 1 in hypertensive renal injury in Dahl salt-sensitive rats.

The expression of transforming growth factor-beta 1 (TGF-beta 1) for hypertensive renal injury was investigated in Dahl salt-sensitive (Dahl-S) rats fed a high-salt (HS; 8% NaCl) diet or a low-salt (LS; 0.3% NaCl) diet for 4 wk. The HS rats developed severe hypertension and renal damage, including glomerulosclerosis and arteriosclerosis. TGF-beta biosynthesis by isolated glomeruli, the TGF-beta localization, and the gene expression of TGF-beta 1, latent TGF-beta binding protein (LTBP), and TGF-beta receptors (Types I, II, and III) were compared between the HS rats and LS rats. A TGF-beta bioassay revealed that the isolated glomeruli from the HS rats secreted a larger amount of latent TGF-beta than those from the LS rats. Northern blotting analysis demonstrated that the HS diet led to the increases in cortical gene expression of TGF-beta 1, LTBP, and TGF-beta receptors, compared with the LS diet. The glomerular biosynthesis of fibronectin and plasminogen activator inhibitor-1 (PAI-1), and cortical mRNA expression for fibronectin, collagen I, and PAI-1 (which may be affected by TGF-beta) in the HS rats were elevated, compared with the LS rats. The latent TGF-beta immunostained by anti-LTBP antibody was localized on the sclerosing glomeruli and vascular walls. Furthermore, fibronectin, collagen I, and PAI-1 were also localized in the sclerotic area. The TGF-beta 1-positive cells, immunostained by antibody for latency-associated peptide of TGF-beta 1, increased in the glomeruli and vascular walls in the HS rats. These results thus suggested that TGF-beta 1 may be related to hypertensive renal injury in this model.

Animals↗

Hypopituitarism associated with transient diabetes insipidus followed by an episode of painless thyroiditis in a young man.

A 16-year-old male complained of a headache and a high fever followed by polyuria. The endocrinological studies showed he had hypopituitarism and central diabetes insipidus, and magnetic resonance imaging (MRI) revealed a pituitary mass. Diabetes insipidus gradually improved and hydrocortisone treatment was begun at three months after onset, but a month later painless thyroiditis developed. An MRI demonstrated a spontaneous shrinkage of the pituitary mass nine months after onset. Lymphocytic hypophysitis followed by painless thyroiditis was the most probable diagnosis, although it is very uncommon especially among men.

Adolescent↗

Hypercholesterolemia and the progression of the renal dysfunction in chronic renal failure patients.

The effect of hyperlipidemia on the progression of chronic renal failure was investigated in 104 chronic renal failure patients, aged 39.3 +/- 2.9 years. The follow up period was 4.1 +/- 2.9 years. The serum creatinine level was 2.1 +/- 1.1 (mean +/- SD) mg/dl at the beginning of study and increased to 8.7 +/- 4.4 mg/dl at the end of the study. The reciprocal serum creatinine concentration (1/Cr) was plotted against the observation time, and the slope was calculated. The absolute value of the slope was used as the progression rate of renal impairment. The progression rate was positively related to total cholesterol level or urinary protein score, while it was negatively related to total protein level. Without the influence of urinary protein score, the progression rate correlated with total cholesterol level. The result suggests that hypercholesterolemia may be an independent aggravating factor in the progression of renal dysfunction in chronic renal failure patients.

Adolescent↗

Incidence of methicillin-resistant Staphylococcus aureus (MRSA) isolation in a skilled nursing home: a third report on the risk factors for the occurrence of MRSA infection in the elderly.

A case control study was carried out in order to evaluate the various factors which may influence the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) infections in a skilled nursing home. From April 1991 to March 1994, bacterial cultures were performed in 55 out of 102 residents in a nursing home based on various clinical aspects. We divided 102 residents into following three groups; (1) the MRSA group (n = 10), residents whose materials for bacterial culture were positive for MRSA, (2) the non-MRSA group (n = 45), residents whose specimens were negative for MRSA but positive for other bacteria, (3) the control group (n = 47), residents who did not have to undergo a bacterial culture because they were free from moderate and severe infectious diseases. Compared with the control group, the activities of daily living score and the serum albumin level were significantly lower in the MRSA group and the non-MRSA group at the beginning of the study. In contrast, the number of antibiotics used prior to the bacterial culture and the proportion of hospitalization within 6 months prior to the bacterial culture were significantly larger in the MRSA group than in either the non-MRSA group, or the control group. These results thus suggest that a low activities of daily living score, the use of many kinds of antibiotics and a recent previous hospitalization may be risk factors of MRSA infection in a nursing home environment.

Aged↗

Diabetes and cardiovascular disease in a prospective population survey in Japan: The Hisayama Study.

To elucidate the effect of glucose intolerance on cardiovascular disease in the current Japanese population, we performed a 75-g oral glucose tolerance test in 2,427 Hisayama residents aged 40-79 years in 1988, who were free from a previous history of stroke or myocardial infarction, and followed them prospectively for 5 years. The prevalence of diabetes (NIDDM) among men was 13% and that of impaired glucose tolerance (IGT) was 20%; the corresponding values for women were 9 and 19%, respectively. The age- and sex-adjusted incidence of cerebral infarction (6.5 per 1,000 person-years, P < 0.01) and coronary heart disease (5.0 per 1,000 person-years, P < 0.05) was significantly higher in subjects with NIDDM than in those with normal glucose tolerance (1.9 and 1.6 per 1,000 person-years, respectively). In addition, subjects with IGT and NIDDM had a higher risk of cardiovascular disease including stroke and coronary heart disease than did those with normal glucose tolerance after adjustment for age and sex, namely the relative risk for IGT was 1.9 (95% CI 1.2-3.2), and the relative risk for NIDDM was 3.0 (95% CI 1.8-5.2). These associations remained significant even after controlling for six other risk factors including hypertension in multivariate analysis. Our data suggest that NIDDM is a significant risk factor for both cerebral infarction and coronary heart disease and also that IGT itself is a risk factor for cardiovascular disease in the general Japanese population today.

Adult↗