Effects of bromocriptine on hepatic cytochrome P-450 monooxygenase system

We have evaluated the in vitro effects of bromocriptine (Br), on the hepatic cytochrome P-450 monooxygenase system of rats pretreated with saline phenobarbitone (PB) and beta-naphthoflavone (BNF). Br inhibited ethoxyresorufin O-dealkylase (EROD) activity in liver microsomes of rats pretreated with saline and PB but not in BNF pretreated animals. Maximum inhibition of EROD activity by Br in the microsomes of saline and PB pretreated rats were 50%-60% of the control. In contrast, a dual effect was observed on aminopyrine N-demethylase activity (APD) by Br in microsomes of saline, PB and BNF pretreated rats. At a low concentration (25 microM), Br inhibited the activity of APD to a similar extent in all pretreatment groups; however, with higher concentrations of Br (50 microM to 300 microM), enhancement of APD activity was observed. Br (300 microM) increased the APD activity to 2-3 times the control level in microsomes of rats pretreated with saline, PB or BNF. Spectral studies revealed a Type II binding of Br to cytochrome P-450 from microsomes of saline and PB pretreated rats. A reverse type I binding was observed for BNF induced microsomes. In addition, Br also enhanced NADPH cytochrome c (P-450) reductase activity to a similar extent in all pretreatment groups. These results suggest that the inhibition of EROD activity may be due to direct binding by Br to certain isozymes of cytochrome P-450 and that the enhancing effect of Br on APD activity may be in part due to the activation of the NADPH cytochrome c reductase component of the cytochrome P-450 monooxygenase system.     

Retained intrahepatic stones: treatment with piezoelectric lithotripsy combined with stone extraction

Extracorporeal shock wave lithotripsy (ESWL) was performed in 11 patients with oriental cholangiohepatitis and intrahepatic stones associated with segmented strictures of intrahepatic ducts. All patients had previously undergone biliary surgery and basket extraction via a T-tube tract at the time of lithotripsy. The indication for ESWL was failure of, or anticipated difficulty with, basket extraction of the stones via a T-tube tract. A piezoelectric lithotriptor was used in all procedures. The average total number of shock waves administered was 29,756 (range, 10,000-61,395). The average number of treatment sessions was 3.1 (range, 1-6); the number of shock waves used in a single session ranged from 10,000 to 15,000 with a frequency of five shots per second and 30%-50% power. In six patients, the stones were successfully fragmented and completely removed; in three of the others of the stones were fragmented and removed. The overall success rate, including complete (54%) and incomplete (27%) success, was 82%. Difficulty in targeting stones, and severe strictures and deformities of intrahepatic ducts, were the factors responsible for failure. No significant complications were observed.     

Environmental temperature and stroke in a subtropical climate.

The effect of environmental temperature on stroke occurrence in a subtropical climate was studied over a 1-year period by documenting the number of strokes (subdivided into cerebral infarct and intracerebral hemorrhage) admitted into a district hospital in Hong Kong at different temperatures. There was no significant correlation between the number of strokes (or its subtypes) per day per temperature category and the environmental minimum or maximum temperature. However, an association was present between the occurrence of cerebral infarcts and maximum temperature on the day of onset in elderly patients aged 70 years and above. Environmental temperature is not a strong risk factor for the occurrence of stroke in a subtropical climate.     

Presence of circulating suppressive factor for muscarinic acetylcholine receptor in senile dementia

Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.     

In situ forces in the anterior cruciate ligament and its bundles in response to anterior tibial loads

The anterior cruciate ligament has a complex fiber anatomy and is not considered to be a uniform structure. Current anterior cruciate ligament reconstructions succeed in stabilizing the knee, but they neither fully restore normal knee kinematics nor reproduce normal ligament, function. To improve the outcome of the reconstruction, it may be necessary to reproduce the complex function of the intact anterior cruciate ligament in the replacement graft. We examined the in situ forces in nine human anterior cruciate ligaments as well as the force distribution between the anteromedial and posterolateral bundles of the ligament in response to applied anterioi tibial loads ranging from 22 to 110 N at knee flexion angles of 0–90°. The analysis was performed using a robotic manipulator in conjunction with a universal force-moment sensor. The in situ forces were determined with no device attached to the ligament, while the knee was permitted to move freely in response to the applied loads. We found that the in situ forces in the anterior cruciate ligament ranged from 12.8 ± 7.3 N under 22 N of anterior tibial load applied at 90° of knee flexion to 110.6 ± 14.8 N under 110 N of applied load at 15° of flexion. The magnitude of the in situ force in the posterolateral bundle was larger than that in the anteromedial bundle at knee flexion angles between 0 and 45°, reaching a maximum of 75.2 ± 18.3 N at 15° of knee flexion under an anterior tibial load of 110 N. The magnitude of the in situ force in the posterolateral bundle was significantly affected by knee flexion angle and anterior tibial load in a fashion remarkably similar to that seen in the anterior cruciate ligament. The magnitude of the in situ force in the anteromedial bundle, in contrast, remained relatively constant, not changing with flexion angle. Significant differences in the direction of the in situ force between the anteromedial bundle and the posterolateral bundle were found only at flexion angles of 0 and 60° and only under applied anterior tibial loads greater than 66 N. We have demonstrated the nonuniformity of the anterior cruciate ligament under unconstrained anterior tibial loads. Our data further suggest that in order for the anterior cruciate ligament replacement graft to reproduce the in situ forces of the normal anterior cruciate ligament, reconstruction techniques should take into account the role of the posterolateral bundle in addition to that of the anteromedial bundle.     

Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats

We have studied the effect of intrathecal administration of N-methyl-D- aspartate (NMDA) receptor antagonists on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after administration of a competitive NMDA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 micrograms), a non-competitive NMDA receptor antagonist, MK801 (0.1, 1.0, 10, 30 micrograms). NMDA (0.01, 0.1, 1.0, 10, 30 micrograms) and saline. APV at all doses except 0.01 micrograms decreased MAC by 17.1-32% (P < 0.001 and P < 0.0001). Although MK801 at 10 and 30 micrograms reduced MAC by 24.3-31.7% (P < 0.001 and P < 0.0001), lower doses did not affect MAC. Intrathecal administration of NMDA reversed these decreases in MAC, but not to control values with APV 10 and 30 micrograms and MK801 30 micrograms. We suspect that NMDA and NMDA receptor antagonists play important roles in the spinal cord in determining the MAC of isoflurane.      

Effect of tissue inhomogeneity on beta dose distribution of 32P

In a homogeneous medium of soft tissue the radiation dose distribution due to a nonuniformly distributed beta source can be calculated by convolution of the beta dose point kernel of the nuclide with the source distribution. A possible extension of the technique to the calculation of the dose distribution in heterogeneous media involving relatively simple geometric interfaces requires the knowledge of the resulting perturbation to the beta point kernels in individual media. We simulated a soft-tissue-bone planar interface by a polystyrene (PST)-aluminum junction and measured the change in beta dose from the dose value in homogeneous PST due to a point source of 32P using 7LiF thermoluminescent dosimeters. With the point source at the interface, the dose rates at 0-31, 125-156, and 283-314 mg/cm2 separations from the interface were increased by (12 +/- 3)%, (8 +/- 2)%, and (3 +/- 2)%, respectively, compared with homogeneous PST. With the point source at a PST-air planar interface to simulate a soft-tissue-air junction, the dose rates at 0-31, 139-170, and 283-314 mg/cm2 from the interface were decreased by (25 +/- 4)%, (11 +/- 7)%, and (5 +/- 2)%, respectively. The changes in dose rates for these two interfaces have also been measured with degraded spectra of 32P. Comparison of the experimental data with Monte Carlo calculation for a point source and the two-group method of calculation for a plane source is also presented.     

Alkaloidal components ofPanax ginseng

Over twelve alkaloids were delected in the roots ofPanax ginseng C.A. Meyer. Among them three alkaloids were isolated and were identified as N₉-formylharman, ethyl β-carboline-1-carboxylate and perlolyrine on the basis of spectroscopic studies.     

Cyclin E, p27 and mutant p53 do not predict the prognosis in AJCC stage II colorectal carcinomas.

BACKGROUND/AIMS: Carcinogenesis is characterized by the abnormal regulation of cell cycle. The abnormal expression of the regulators of cell cycle may be related to the prognosis. Since the clinical significance of the expression of the three proteins in colorectal carcinomas is still controversial, we evaluated the prognostic value of the expression of cyclin E, p27 and mutant p53 in stage II colorectal cancer. METHODS: The expression levels of cyclin E, p27 and mutant p53 proteins in 41 patients with stage II colorectal carcinomas were analyzed by immunohistochemistry. RESULTS: In the univariate analysis, the level of CEA at diagnosis was associated with disease relapse. In the multivariate analysis, the clinicopathological variables such as age, gender, site of primary tumor, tumor size, state of tumor differentiation and preoperative plasma CEA level were not associated with disease relapse. When Kaplan-Meier survival curves were constructed to determine the prognosis, cyclin E, p27 and mutant p53 expressions did not predict poor prognosis. CONCLUSIONS: Our results suggested that the expression of cyclin E, p27 and mutant p53 proteins did not predict the clinical outcome in the stage II colorectal carcinomas.     

Recombinant tissue-plasminogen activator (rt-PA) in acute myocardial infarction in the Chinese in Hong Kong.

Eighty-nine consecutive Chinese patients (69 males, 20 females) with acute myocardial infarction treated by 100 mg recombinant tissue-plasminogen activator (rt-PA) (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 hours after onset, and intravenous heparin or dipyridamole therapy started at 3 hours, were studied prospectively. Their mean age was 59.6 +/- 10.6 years. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion was seen in 63 patients (72.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%), hematoma around vascular access sites (23.6%), melena (2.2%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 hours, including a decrease in fibrinogen (by 64.2%), an increase in FDP by 11.7 times and D-dimers by 4.4 times. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure (5) and reinfarction (1). Angiogram at 14 days confirmed TIMI (2 or 3) patency of infarct related arteries in 62/81 (76.5%) patients, with a mean global ejection fraction of 52.5 +/- 12.4%. Nearly all survivors could maintain class I-II functional status after discharge. The safety and promises of rt-PA for acute myocardial infarction in the Chinese were confirmed.