Effects of Pyridoxalated Hemoglobin Polyoxyethylene Conjugate and Stroma-free Hemoglobin on Renal Vascular Responsiveness to Vasoactive Substances in Isolated Perfused Rat Kidney

Abstract: The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma-free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances were examined in isolated perfused rat kidneys. The kidneys isolated from rats were perfused with 6% PHP, 6% SFH, and 6% hydroxyethylstarch (HES) solution at a constant flow rate. Vascular responsiveness to acetylcholine (ACh), nitroglycerin (NG), norepinephrine (NE), and angiotensin-II (ANG-II) was examined by measuring the perfusion pressure (PP). Effects of inhibition of endothelium-derived relaxing factor (EDRF) by N^G-monomethyl L-arginine (L-NMMA) on NE-induced and ANG-II-induced renal vascular responses were examined. ACh and NG induced a dose-dependent decrease in perfusion pressure (PP) in all groups. NE and ANG-II induced an increase in PP in all groups, but NE-induced and ANG-II-induced responses in the PHP-perfused and SFH-perfused groups were significantly larger than those in the HES-perfused group. L-NMMA did not alter vascular responsiveness to NE and ANG-II. These results indicate that PHP and SFH do not inhibit EDRF induced by ACh, but hemoglobin moiety per se does augment the vascular responsiveness to NE and ANG-II in the isolated perfused rat kidney.     

I.m. midazolam as premedication produces a concentration-dependent decrease in core temperature in male volunteers

We tested the hypothesis that premedication with i.m. midazolam decreases core temperature dose-dependently. We studied six male volunteers, in random order, on 3 days: (1) no midazolam administration (control day), (2) midazolam 0.025 mg kg-1 i.m., (3) midazolam 0.075 mg kg-1 i.m. On the first day, subjects were maintained alert during a 30- min control period. On the second and third days, midazolam 0.025 or 0.075 mg kg-1 was administered i.m. Core temperatures were measured at the right tympanic membrane. Four adhesive skin surface probes were fixed on the chest, upper right arm, lateral calf and thigh. Finger tip perfusion was evaluated using forearm minus fingertip and calf minus toe, skin surface temperature gradients. Thirty minutes after midazolam i.m., the level of sedation in the volunteers was assessed. Peripheral venous blood was obtained immediately after the assessment of the level of sedation. Tympanic membrane temperatures after administration of midazolam 0.075 mg kg-1 i.m. were significantly lower than those on the control and midazolam 0.025 mg kg-1 i.m. days at 20 and 30 min. The decreases in tympanic membrane temperatures at 30 min after midazolam i.m. became larger as the volunteers were more deeply sedated. i.m. midazolam produced a concentration-dependent decrease in tympanic membrane temperature at 30 min after midazolam 0.025 and 0.075 mg kg-1 i.m. We conclude that midazolam impaired tonic thermoregulatory vasoconstriction, allowing core-to-peripheral heat redistribution in a dose-dependent manner after i.m. administration.      

Antihypertensive effect of bopindolol on stroke-prone spontaneously hypertensive rats (SHRSP)

The antihypertensive effect of bopindolol, a long-acting beta-adrenoceptor blocking agent, was investigated in stroke-prone spontaneously hypertensive rats (SHRSP). One group received tap water during the period of 8 to 32 weeks of age. The average dose of bopindolol administered was calculated from water intake to be approximately 1.4 mg/kg/day. The lowering effect in blood pressure of bopindolol was apparent at the age of 14 weeks, and this continued up to the end of the experiment. Bopindolol significantly reduced the heart rate. Plasma levels of urea nitrogen (BUN), triglyceride, and phospholipid of SHRSP treated with bopindolol were lower than those of the control SHRSP. One of the 8 control SHRSP died, and no rats treated with bopindolol died during the experiment. The histopathological study revealed that three of the control SHRSP had cerebral apoplexy, whereas there was no evidence of cerebral apoplexy in the treated SHRSP. Chronic treatment of bopindolol clearly alleviated myocardial fibrosis and hypertrophic changes in the left ventricular wall of the heart. Decreases in the incidence of proliferative arteritis and malignant nephrosclerosis in the kidney and necrotizing arteritis of the mesenteric arteries were observed in SHRSP treated with bopindolol. The data presented indicate that bopindolol is a powerful antihypertensive agent.     

The effect of methamphetamine on serotonin and its metabolite in the suprachiasmatic nucleus: A microdialysis study

Summary The suprachiasmatic nucleus (SCN) has been identified as a major circadian pacemaker. Methamphetamine has been shown to modify the behavior of circadian rhythms. We detected extracellular serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the SCN in freely moving rats, using a microdialysis method, to investigate biochemical effects of methamphetamine in the SCN. Methamphetamine infusion into the SCN dose-dependently increased extracellular 5-HT and decreased extracellular 5-HIAA.     

Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome.

The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65+/-2.7 years) and non-metabolic syndrome (n=70, age: 66+/-2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the EIA and Tei index were significantly different between the metabolic syndrome (0.66+/-0.14 and 0.36+/-0.07, respectively) and non-metabolic syndrome (0.88+/-0.25 and 0.29+/-0.09) groups (p<0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction.     

Urinary dysfunction and autonomic control in amyloid neuropathy

Abstract Uro-neurological assessment was performed in four patients with small-fiber neuropathy due to amyloidosis (2 transthyretin-type/2 immunoglobulin light-chain-type). Voiding difficulties were due to detrusor weakness and impaired bladder sensation. In two patients cholinesterase inhibition treatment caused urge incontinence, indicating detrusor denervation supersensitivity. The underlying mechanisms of urinary dysfunction seem to involve postganglionic cholinergic and afferent somatic nerves.     

Body temperature monitoring in subjects with delayed sleep phase syndrome

To clarify the circadian aspects of delayed sleep phase syndrome (DSPS) in 4 patients with DSPS, we recorded polysomnograms and rectal temperature before and after chronotherapy. The time interval (2.7 h) between sleep onset and rectal temperature minimum before chronotherapy was shorter than the time interval after chronotherapy (5.3 h). Before chronotherapy, the period of rectal temperature rhythm was 24.7 h. After chronotherapy, the period of rectal temperature rhythm was 24.0 h. These findings lead to the conclusion that in DSPS there is a weakened mechanism of entrainment similar to that in non-24-hour sleep-wake syndrome.     

Enhanced clearance of lactic dehydrogenase-5 in severe combined immunodeficiency (SCID) mice: effect of lactic dehydrogenase virus on enzyme clearance.

The lactic dehydrogenase (LDH) level in plasma and the clearance of LDH in C.B-17 scid (severe combined immunodeficiency; SCID) mice were compared with those in C.B-17 or BALB/cCrSlc mice with or without lactic dehydrogenase virus (LDV) infection. The resting enzyme level in SCID mice showed little difference from that in C.B-17 or BALB/cCrSlc mice. The degree of increased plasma LDH level in SCID mice was lower than that in C.B-17 and BALB/cCrSlc mice after LDV infection. To assess the mechanisms of decrease in LDH elevation in SCID mice infected with LDV, virus replication was compared in SCID and BALB/cCrSlc mice. The infectivity titre of plasma in SCID mice was higher (more than 10 times) than that in BALB/cCrSlc mice. Moreover, the percentage of virus antigen positive Kupffer cells was higher in SCID mice than that in BALB/cCrSlc mice. The level of endogenous LDH release as a result of carbon tetrachloride treatment was similar in the SCID and BALB/cCrSlc mice. The clearance rate of endogenous LDH was greater in SCID mice than in BALB/cCrSlc mice with or without LDV infection. The rate of clearance of intravenously injected porcine LDH-5, but not porcine LDH-1, was enhanced in SCID mice as compared with that in BALB/cCrSlc mice. Furthermore, carbon clearance was higher in SCID mice than that in BALB/cCrSlc mice. These results suggest that the smaller increase of plasma LDH after infection might be due, at least in part, to the enhanced LDH-5 clearance function by macrophages in SCID mice.     

Surgical repair of discrete subaortic stenosis complicated with prosthetic valve endocarditis--a case report]

A 46-year-old man was referred to our hospital because of prosthetic valve regurgitation. Eight years previously he had undergone aortic valve replacement because of aortic regurgitation due to infective endocarditis. At reoperation, we found prosthetic valve endocarditis and discrete subaortic stenosis. The obstructing fibrous tissue was resected and the aortic valve was replaced. Because discrete subaortic stenosis is usually located just below the aortic valve, the aortic valve cusps are liable to become thickened by the jet through the discrete stenosis and thus are vulnerable to infective endocarditis. It is pointed out that care must be taken not to overlook discrete subaortic stenosis in the presence of other associated cardiac disorders.