Effects of turpentine oil pretreatment on β-blocker pharmacokinetic parameters in rats

Abstract— Turpentine oil treatment (0·2 mL kg^?1, s.c.) was used to increase the plasma concentration of α₁-acid glycoprotein (0·13 mg mL^?1 in control rats) to 1·72 mg mL^?1 after 2 days, and allow assessment of its effects on the pharmacokinetics and stereoselective binding of three β-blockers. Racemates (5 mg kg^?1) were administered intravenously to control and turpentine oil-pretreated rats and the plasma concentrations were determined up to 90 min. Stereoselective analysis showed the apparent distribution volume and the area under plasma concentration-time curves (AUC) of R-(+)-propranolol to be, respectively, one-quarter and twice those of the S-(–)-enantiomer and differences in pharmacokinetic parameters between the two were magnified by turpentine oil pretreatment. Pharmacokinetic parameters of oxprenolol enantiomers were essentially similar for the controls but after turpentine oil pretreatment, a higher affinity of the R-(+)-enantiomer for plasma was observed. Acebutolol enantiomers behaved non-stereospecifically throughout. These results were consistent with predictions from the in-vitro stereospecific binding properties of these agents to purified rat α₁-acid glycoprotein.     

Rare case of aggressive angiomyxoma presenting as a retrovesical tumor

Aggressive angiomyxoma (AAM) is a rare mesenchymal benign tumor that preferentially involves the pelvic and perineal regions in relatively young females. We report here a rare case of AAM presenting as a retrovesical tumor in a male patient. A 59-year-old man undergoing abdominal ultrasound examination because of benign prostatic hyperplasia was found to have a retrovesical mass. Computed tomography and magnetic resonance imaging of the pelvis showed the retrovesical tumor to be 7.4 x 6.7 cm. The tumor was resected, and diagnosed histopathologically as AAM. The patient showed no recurrence 26 months after resection. Although the majority of retrovesical tumors are considered to be sarcoma or neurogenic tumor, AAM should also be recognized as a differential diagnosis.     

Tissue- and subcellular-distribution of the binding site of [3H]9-methyl-7-bromoeudistomin D,a potent caffeine-like Ca2+ releaser,in rabbits

Abstract— Tissue and subcellular distribution of the binding site of ³H-labelled 9-methyl-7-bromoeudistomin D ([³H]MBED), a powerful caffeine-like Ca²⁺ releaser, were investigated in rabbits. The order of specific activities of total homogenates was liver > brain > other tissues. All binding was completely suppressed by 10 Mm caffeine, indicating that all [³H]MBED binding sites are modulated by caffeine. [³H]MBED binding sites distributed mainly in membrane fractions rather than soluble fractions in most tissues. In lung and liver, [³H]MBED binding was enriched in microsomes. [³H]MBED may be useful as a probe to investigate the actions of caffeine at the molecular level not only in muscles but also in a variety of tissues including liver, kidney and lung.     

Influence of Age on the Disposition and Renal Handling of Enprofylline in Rats

Abstract— The effects of ageing on the pharmacokinetics, renal handling and protein binding of enprofylline were investigated in 6-, 13- and 18-month-old male Fischer 344 rats. Concentrations of enprofylline in plasma and urine were determined by HPLC, and pharmacokinetic parameters were estimated by model-independent methods. No significant differences in the volume of distribution, systemic clearance of enprofylline or urinary recovery of unchanged enprofylline (> 85%) were observed among any of the groups of rats. The dissociation constant and free fatty acid concentration in plasma increased with age. Age-dependent decreases in the systemic clearance for unbound drug were observed, and the volume of distribution for unbound drug tended to decrease with age. The ratio of systemic clearance for unbound drug to the glomerular filtration rate (GFR) decreased with ageing. Ageing was associated with decreases in the apparent maximum capacity of transport (V_max) (223·33,160·24 and 142·98 μg min^?1 kg^?1 for 6-, 13- and 18-month-old rats, respectively) and in the tubular secretory intrinsic clearance (V_max/K_m) of enprofylline (75·45, 51·03 and 44·13 mL min^?1 kg^?1, respectively), while a slight change in the Michaelis-Menten constant (K_m) was observed. These results indicate that the mechanism responsible for age-related changes in the disposition and renal handling of enprofylline may be responsible for a decrease in the ability of the tubular anion transport system.     

The effect of sodium cromoglycate on the antigen-induced nasal reaction in allergic rhinitis as measured by rhinomanometry and symptomatology

The protective effect of sodium cromoglycate (DSCG) on the allergic reaction in the nose was compared with placebo in a double blind crossover study of sixteen patients diagnosed as allergic rhinitis. The drug effect was assessed by both a rhinomanometric method and by symptom scores in all patients. DSCG protected the nasal mucosa against antigen challenge and was significantly better than placebo. There was a correlation between the objective and subjective assessments.     

AETIOPATHOGENESIS OF HEPATOCELLULAR CARCINOMA

Abstract Most patients with hepatocellular carcinoma (HCC) in Japan have hepatitis B virus (HBV)-or hepatitis C virus (HCV)-associated cirrhosis. In the present study, the risk of HCC in patients with cirrhosis was analysed by the levels of serum alanine aminotransferase (ALT). One hundred and one (78%) of 129 patients with cirrhosis registered from April 1979 were followed at monthly intervals with the measurement of serum ALT. Of 101 patients, 38 tested positive for hepatitis B surface antigen (HBsAg) but negative for antibody to HCV (anti-HCV; HBV group), 47 tested negative for HBsAg but positive for anti-HCV (HCV group) and nine tested positive and seven tested negative for both. Mean serum ALT during follow-up was calculated on the basis of monthly values during the observation period that started at enrolment and ended with the detection of HCC or at the end of March 1994. By the end of March 1994, 37 (37%) patients developed HCC; 12 were in the HBV group, 21 in the HCV group and four were in the group positive for both. Mean serum ALT during the observation period was similar in patients who developed HCC and those who did not develop HCC in the HBV group. In contrast, the value was significantly higher in patients who developed HCC than in patients who did not develop HCC in the HCV group (P < 0.05).     

Stage Differences in Developmental Disorders in ICR Mouse Embryos Irradiated with Gamma-Rays

This study was designed to determine precisely the radiosensitive period in the development of ICR mouse embryos during which external malformations and growth retardation tend to occur. Female and male mice were placed together for only three hours to allow fairly precise identification of the time of conception. The pregnant mice were divided into 31 groups, which were irradiated in turn with 1.5 Gy gamma radiation at 6-hour intervals during the period of organogenesis. They were then observed on day 18 of gestation. Items recorded were intrauterine death, external malformations, sex ratio and fetal body weight. Death of the embryo/fetus, especially death in the early period of organogenesis, was most frequent in mice irradiated between days 6.75 and 8.25 of gestation, but there was no statistically significant difference in the frequency of early- and late-period deaths between irradiated and control groups. The types and frequencies of external malformations observed differed according to the exposure period. The most highly sensitive period for each malformation lasted no more than 12 hours. Reduction of fetal body weight was a good indicator of radiation effects, and was observed mostly in the groups irradiated between days 9.75 and 11.00 of gestation. The sex ratio was not affected by the period in which irradiation was performed.