Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.     

Enzymes induced by ethanol differently affect the pharmacokinetics of trichloroethylene and 1,1,1-trichloroethane.

This study was undertaken to clarify the effect of enzymes induced by ethanol consumption on the pharmacokinetics of trichloroethylene (TRI, a highly metabolised substance) and 1,1,1-trichloroethane (1,1,1-TRI, a poorly metabolised substance). Rats maintained on a control liquid diet or a liquid diet containing ethanol (2 g/day/rat) for not less than three weeks were exposed to either TRI (50, 100, 500, and 1000 ppm) or 1,1,1-TRI (50, 100, and 500 ppm) by inhalation for six hours and the concentration of each compound in the blood and the urinary excretion of metabolites (trichloroethanol and trichloroacetic acid) were measured over several hours. Ethanol, which increased the in vitro metabolism of both compounds about fivefold, enhanced the in vivo metabolism of TRI only at high levels of exposure (marginally at 500 and considerably at 1000 ppm), whereas the metabolism of 1,1,1-TRI was enhanced at all concentrations tested. Moreover, there was a definite difference in the effect of induction of enzymes between the two solvents: the enhanced metabolism of TRI in vivo was shown by a decrease in the blood concentration of TRI as well as by an increase in the urinary excretion of its metabolites, whereas that of 1,1,1-TRI was shown by an increase in the urinary excretion of its metabolites alone. These results suggest that the induction of enzymes differentially affects the pharmacokinetics of TRI and 1,1,1-TRI in human occupational exposure: TRI metabolism may be increased only at concentrations much higher than the current occupational exposure limit (mostly 50 ppm), whereas 1,1,1-TRI metabolism may be increased at an exposure similar to occupational exposure.     

Endoscopic observation of pathophysiology of ventricular diverticulum

Background Although there have been reports dealing with ventricular diverticulum (VD) analyzed by cisternography and computed tomography (CT), those focusing on magnetic resonance imaging (MRI) or neuroendoscopic findings are rare. Case report We present a case of noncommunicating hydrocephalus caused by aqueductal stenosis with cystic lesion located in supracerebellar region. Third ventriculostomy was performed on this case. The conventional CT and MRI were compatible with usual VD, but neuroendoscopic examination suggested otherwise. The endoscopic view inside of the cystic lesion demonstrated passing veins and no membrane. We diagnosed this cystic lesion as a unique subtype of advanced VD mimicking spontaneous ventriculostomy. Endoscopic observation of the cyst was very useful for accurate diagnosis and safe treatment.     

Effects of Ageing on the Oral Absorption of d-Xylose in Rats: Analysis of Gastrointestinal Disposition

The effects of ageing on the oral (gastrointestinal) absorption of d -xylose were investigated by analysing the gastrointestinal disposition after oral administration to young (9 weeks) and old (53 weeks) rats. A linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction vs time profiles for the stomach and small intestine to estimate the gastric emptying rate constant (k_g) and the intestinal absorption rate constant (k_a). In young and old rats, k_g values were 0·087 ± 0·008 and 0·070 ± 0·007 min^?1, respectively, and k_a values were 0·020 ± 0·002 and 0·018 ± 0·002 min^?1 suggesting an insignificant effect on ageing on the rate of oral absorption. The average intestinal lumen volume (V_av) was unchanged with ageing, and so was the apparent intestinal membrane permeability clearance (CL_app) as the product of k_a and V_av. However, the small intestinal transit time (T_si) was suggested to be twice that in older rats (171 min) than in young rats (78 min) by the analysis of gastrointestinal disposition of inulin, a non-absorbable marker. It was also shown that our preceding finding of an increase in the fraction absorbed of D-xylose with ageing can be solely ascribable to the delay in intestinal transit. Thus, among various determinants of oral absorption, only T_si was found to be altered with ageing. The CL_a,app and k_a of passively absorbed drugs such as D-xylose may be generally unchanged, and the fraction absorbed may increase with ageing by the delay in intestinal transit.     

Characteristic findings of hepatocellular carcinoma: an evaluation with comparative study of US, CT, and MRI.

The sensitivity, specificity, and accuracy of ultrasonography (US), dynamic incremented computed tomography (CT) with delayed phase imaging, and magnetic resonance imaging (MRI) with or without Gd-DTPA were studied for detecting the characteristic appearances of hepatocellular carcinomas (HCC): fibrous capsules, fibrous septa, and mosaic appearances. Results were prospectively evaluated in 30 patients who subsequently underwent hepatic lobectomies or segmentectomies. Pathologic evaluations of the resected liver specimens demonstrated fibrous capsules in 20 tumors (66.7%), fibrous septa in 13 tumors (43.3%), and mosaic appearances in 19 tumors (63.3%). The accuracies for fibrous capsules were 71.4% (20 of 28) for US, 81.5% (22 of 27) for CT, and 92.3% (24 of 26) for MRI. The accuracies for fibrous septa were 57.1% (16 of 28) for US, 59.3% (16 of 27) for CT, and 73.1% (19 of 26) for MRI. The accuracies for mosaic appearances were 71.4% (20 of 28) for US, 51.9% (14 of 27) for CT, and 69.2% (18 of 26) for MRI. Gd-DTPA administered MRI showed higher accuracies than did conventional MRI for all manifestations. In conclusion, the fibrous capsules of HCCs were readily detected by CT and MRI. Gd-DTPA administration demonstrated an advantage in clarifying fibrous capsules, as well as fibrous septa and mosaic appearances.     

Rotational occlusion of the vertebral artery at the atlantoaxial joint: is it truly physiological?

We present a patient with vertebrobasilar insufficiency, with vertigo and horizontal nystagmus, induced by turning the head to the right. Angiography demonstrated transient occlusion of the left vertebral artery at the atlantoaxial joint during rotation of the head. The pathogenesis and angiographic findings are discussed.     

Effects of Nd:YAG laser irradiation on ventricular myocardium in dogs using an artificial sapphire tip contact laser catheter]

To apply Nd:YAG laser irradiation through a new sapphire tip contact laser method to catheter ablation in treatment of tachy-arrhythmias, effects of laser irradiation on ventricular myocardium were investigated in 10 mongrel dogs. Nd:YAG lase (1064nm) discharges were delivered to different sites on the endomyocardium at power of 5, 10, 15, 20 or 25w with duration of 3, 5, or 10 seconds (sec.) respectively in closed beating hearts. Histopathologically, the lesion irradiated was clearly demarcated from the normal myocardium by the construction band necrosis zone. The depth of injured myocardium was less than 2mm with 3 sec. irradiations, with 5 sec. from 1 mm to 4 mm in proportion to power increase, with 10 sec. from 3mm to 8 mm in proportion to the power from 5w to 15w and could not be measured in cases of more than 20w irradiations. Although with every irradiation duration, the depth of injury increased in proportion to the power increase. With the same total energy, a longer time of irradiation produced deeper injury than a shorter time. This method makes it easier to keep the laser positioned to target than bare laser, and is suitable for use in catheter ablation.     

Reduction by Fentanyl of the Cp sub 50 Values of Propofol and Hemodynamic Responses to Various Noxious Stimuli

Background: Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation.

Results: The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp sub 50loss of consciousness, 4.4 micro gram/ml (range, 3.8-5.0); Cp50tetanus, 9.3 micro gram/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 micro gram/ml (range, 8.9-10.8); Cp50skin incision, 10.0 micro gram/ml (range, 8.1-12.2); and Cp50intubation, 17.4 micro gram/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50 s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion.