Effects of intraventricularly administered serotonin, noradrenaline, dopamine and metaraminol on the reserpine-induced spikes recorded from the medial nucleus trapezoides in rabbits.

Effects of intraventricularly administered serotonin (5HT), noradrenaline (NA), dopamine (DA) and metaraminol on the reserpine-induced spikes recorded from the medial nucleus Trapezoides (Trap. m.) in rabbits were investigated. 5HT (30, 50 micrograms) produced marked decreases in the amplitude and discharge rate of the spikes 3 to 5 min after intraventricular administration. NA (30, 50 micrograms) also produced similar effects to those of 5HT, but DA at the same dosage produced no significant changes in the amplitude and discharge rate of spikes. Metaraminol, a metabolite of alpha-methyl-m-tyrosine, produced gradual and long-lasting, potent suppression of spikes. Ninety min later, spikes were completely suppressed, and no recovery was observed within 6 hours after intraventricular administration. These results indicate that NA has a similar suppressing action to that of 5HT on the generation of the reserpine-induced spikes.     

Experimental study on the effects of sclerosants for esophageal varices on blood coagulation, fibrinolysis and systemic hemodynamics.

The effects of five sclerosants used for treating esophageal varices on blood coagulation and fibrinolysis, systemic hemodynamics, and vascular endothelial cells were studied in mongrel dogs. With each sclerosant, hemolysis and a decrease in the platelet count were observed. Changes in the blood coagulation system occurred immediately after sclerosant administration. Prolongation of the PT and APTT and decreases in fibrinogen and alpha 2-PI were seen in the thrombin (TH), sodium tetradecyl sulfate (STS), and ethanolamine oleate (EO) groups. Polidocanol (PO) and absolute ethanol (ET) had less pronounced effects on these systems. A transient decrease in the cardiac index (CI), pulmonary artery pressure (PAP) and pulmonary artery resistance (PAR) was observed with the administration of the sclerosants, especially in the TH and STS groups. Excessive vascular endothelial damage was observed in the ET group, marked damage was seen in the EO and STS groups and slight damage was recorded in the PO and TH groups.     

Interspecies differences and scaling for the pharmacokinetics of xanthine derivatives.

Pharmacokinetic characteristics of the new xanthine bronchodilators, enprofylline and 1-methyl-3-propylxanthine (MPX), were investigated in mice, rats, guinea-pigs, rabbits and dogs. The possibility of an interspecies pharmacokinetic scale was also evaluated. The concentration of these two drugs in plasma and urine was determined by HPLC. Pharmacokinetic parameters were calculated using model-independent methods. The disappearance curves of the two drugs from plasma varied markedly among animal species. Interspecies differences in the plasma protein binding of each drug were observed for all animals in the study. Differences in the biotransformation of enprofylline and MPX were also confirmed among the various animal species: enprofylline is mainly excreted in an unchanged form in urine while MPX follows a non-renal route of elimination. In all animals, the renal clearance for enprofylline was greater than the glomerular filtration rate, indicating active tubular secretion. Significant allometric relationships were seen between the values of total body clearance and steady state volume of distribution for both total and unbound enprofylline and species body weight, but similar correlations could not be recognized for MPX. Renal clearance of enprofylline was also closely correlated with species body weight, suggesting no interspecies difference with relation to affinity and/or capacity for the active tubular secretion mechanism of enprofylline. Our findings suggest that xanthine derivatives, including enprofylline, are mainly eliminated via the kidney, and an estimate of the basic pharmacokinetics in man can be obtained from data in experimental animals.     

Leg lengthening and glycosaminoglycans in the rabbit knee

We investigated the effects of tibial lengthening by callotasis on glycosaminoglycan (GAG) metabolism of the knee articular cartilage in 30 rabbits. The distraction rate was 1 mm per day. On the right side, the daily distraction was in 2 steps, while on the left it was in 120 steps. The animals were divided into 3 subgroups based on length gain; 10, 20, and 30 percent, respectively. The knee joint fluid and medial tibial cartilage were examined by quantitative analysis of the GAG content and/or synthesis. The immunoreactivity for chondroitin sulfate in the cartilage was also examined by immunohistochemistry. For all length gains, the GAG concentration in the synovial fluid was higher on both sides than in controls, with no difference between sides. The GAG content and synthesis in the cartilage on the 2-step side decreased gradually with increasing length. On the 120-step side, the content did not differ from control values in any length gain, and the level of synthesis at 20 and 30 percent lengthening was higher than the control level. Our findings indicate that the alterations in GAG metabolism are attributable to increased mechanical stress on the articular cartilage, suggesting a moderate increase on the 120-step side compared to an excessive one on the 2-step side.     

Clinical studies on panipenem/betamipron in pediatric field]

We have carried out clinical studies on panipenem/betamipron (PAPM/BP, CS-976). The results are summarized as follows. Treatment with PAPM/BP was made in 21 cases of pediatric bacterial infections including 2 cases of tonsillitis, 15 cases of pneumonia and 1 case each of bronchitis, scarlet fever, urinary tract infection and otitis media. Results obtained were excellent in 15 cases, good in 6 cases. No significant side effects due to the drug were observed in any cases.     

A probable common disturbance in the early stage of odontoblast differentiation in Dentinogenesis imperfecta type I and type II

Deciduous teeth from 7 patients with dentinogenesis imperfecta (DI) Type I and Type II were examined by conventional microscopy. A defective layer was found which runs parallel with the dentinal surface in the outer portion of dentin in teeth of both types. Dentinal tubules were interrupted in the vicinity of this layer. When the ground sections were examined after being stained by the phosphophoryn staining method, the DI Type I dentin was found to contain phosphophoryn at the same low level as the DI Type II dentin, suggesting similar deficiency in phosphophoryn concentration. These results suggest that both types of DI have a common primary disturbance in the early stage of odontoblast differentiation.     

Successful resection of a glomus tumor arising from the lower trachea: Report of a case

(Received for publication on Sept. 30, 1996; accepted on Mar. 4, 1997)