Development of a new perfusion system for pharmacological study on rabbit basilar arteries

We developed a constant-flow perfusion system to measure vascular responses to vasoactive agents applied intraluminally or extraluminally. The intraluminal and extraluminal sides of a cylindrical section of rabbit basilar artery were isolated completely. By loading with 0.75 g of tension, the resting condition of each preparation was made constant. The intraluminal side was perfused at a constant flow of 8 ml/min and under an intraluminal pressure of 8 mm Hg. When 30 mM KCl was administered intraluminally the preparation showed marked contraction, whereas only slight contraction was observed with extraluminal administration. When 2 x 10(-7) M 5-hydroxytryptamine was administered, no significant differences in contraction could be detected between the intraluminal and extraluminal routes. Application of 10(-6) to 10(-4) M acetylcholine after precontraction with 30 mM KCl resulted in much stronger dilatation upon intraluminal application. Thus, it was demonstrated that under certain conditions significant differences exist in the responses of rabbit basilar arteries to vasoactive agents applied intraluminally or extraluminally. This system can detect the effects of vasoactive agents administered intraluminally and extraluminally at a high level of sensitivity and shows good reproducibility as a means of analyzing vascular functions and characteristics.     

Modeling the dependence of hexose distribution volumes in brain on plasma glucose concentration: implications for estimation of the local 2-deoxyglucose lumped constant

The steady-state distribution volumes of glucose, 3-O-methylglucose, and 2-deoxyglucose (2DG) are known to change as the concentration of glucose in plasma ranges from hypo- to hyperglycemic values. Model estimates of the three distribution volumes were compared with distribution volume values experimentally measured in the brains of conscious rats as the concentration of glucose in plasma was varied from 2 to 28 mM. The dependence on plasma glucose concentration of the 2DG lumped constant, the factor that relates the phosphorylation rate of 2DG to the net rate of glucose utilization at unit specific radioactivity in the plasma, had been determined previously in separate series of experiments. The model was extended to incorporate this dependence of the lumped constant. In the model both the transport and the phosphorylation barriers were assumed to be single and saturable. The values of their respective half-saturation concentrations and the ratio of the two maximum velocities for glucose were assumed to be invariant over the entire range of plasma glucose concentration. Good agreement between measured and estimated values for the distribution volumes and the lumped constant was attained over the full range of plasma glucose concentration. The model estimates reflected the progressive transport limitation of the brain glucose content as plasma glucose levels were reduced to hypoglycemic values. The results also indicated that these changes should be evident in the time course of 2DG in brain following administration by bolus or continuous infusion, and thus that indexes of local lumped constant change could be derived from the time course data.     

Mizoribine in steroid-dependent nephrotic syndrome of childhood

We evaluated a 1-year course of a newly developed immunosuppressant, mizoribine (at a dosage of 3 mg/kg body weight per day), in nine children with steroid-dependent nephrotic syndrome. Steroid treatment could be discontinued in two patients and the maintenance dosage of steroid could be reduced to less than half of that given before mizoribine therapy in a third. There were no beneficial effects in the remaining six patients. No adverse effects of mizoribine were observed during the course of therapy. Received September 20, 1996; received in revised form and accepted April 24, 1997     

Downhill esophageal varices due to superior vena cava syndrome

This study examined the incidence of downhill esophageal varices due to SVC syndrome. The presence of downhill esophageal varices was examined by esophagoscopy or autopsy. Downhill esophageal varices were detected in two of nine (22%) patients with SVC syndrome. One case was a 66-year-old male case who and underwent upper lobectomy for lung cancer in September 1985. He developed SVC syndrome due to recurrence in 1986 and died in 1987. Downhill esophageal varices wer in the upper esophagus by esophagoscopy and confirmed by autopsy. The another case was a 61-year-old female who developed carcinoma of the tongue in 1986 and lymph node metastasis to the mediastinum in 1987. Autopsy revealed downhill esophageal varices in the upper and middle esophagus. Eleven cases of downhill esophageal varices due to SVC syndrome reported in Japan were reviewed and discussed.     

Imaging of shifted stimulated echoes and multiple spin echoes

It is shown that a repetitive pulse sequence consisting of two 90° pulses and gradients in a 1:2 ratio around the second 90° pulse generates interscan shifted stimulated echoes (SSTEs) and intrascan multiple spin echoes (MSEs). Separation of these two types of signals is accomplished using specific gradient crusher schemes. The intensity of the SSTEs is an order of magnitude larger than that of the MSEs and determines the signal contrast if both effects are selected simultaneously. The SSTE sequence generates improved contrast between gray and white matter, even at high field, which is explained in terms of increased inverse T₁-weighting for the interscan echo. The MSE image has low signal to noise and no detectable contrast. The effect of interscan diffusion weighting is also discussed.     

Species differences in platelet aggregation induced by platelet-activating factor (PAF).

Species differences in platelet aggregation induced by platelet-activating factor (PAF) were investigated by using the same procedure of platelet preparation and biological assay. Washed platelets of six different species (horses, dogs, rats, rabbits, sheep and guinea pigs) were prepared employing the same method and platelet aggregation was induced by C16-PAF. Horse platelets were most sensitive to PAF (8.0 x 10(-12) M) and rabbit platelets activated by 5.0 x 10(-11) M PAF were also sensitive enough to detect PAF in clinical samples.     

Thoracoscopic esophagomyotomy. Initial experience with a new approach for the treatment of achalasia.

The authors treated 17 patients with achalasia by a thoracoscopic (15 patients) or laparoscopic (2 patients) Heller myotomy. All patients had dysphagia and an upper gastrointestinal series demonstrating a dilated esophagus with a bird-beak deformity at the cardia. Manometry showed a mean lower esophageal sphincter (LES) pressure of 32 +/- 4 mmHg, incomplete sphincter relaxation on swallowing, and no primary esophageal peristalsis. After operation, mean LES pressure was 10 +/- 2 mmHg. Fifteen patients were fed on the second postoperative day. The average hospital stay was 3 days, and there were no deaths or major complications. In three early patients, the myotomy was not carried far enough onto the stomach, and dysphagia persisted until a second myotomy was performed (laparoscopically in two patients). The authors found that having an endoscope in the esophagus during the operation facilitated exposure and was vital to determine the appropriate length of the myotomy. With regard to dysphagia, final results were excellent in 12 patients (70%), good in two patients (12%), fair in two patients (12%), and poor in one patient (6%). Heller myotomy can be safely and reliably performed with minimally invasive techniques. Dysphagia is relieved, postoperative pain is minimal, hospital stay is short, and the patient can return quickly to normal activity.     

Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives.

A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (+/-)-6-[2-Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (+/-)-6-[3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2 (1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39, OPC-18750, and 40, OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.