Isolation of a renal function-facilitating constituent from the Oriental drug, salviae miltiorrhizae radix

An attempt was made to isolate the active component which exhibits an improving effect on renal function from Salviae Miltiorrhazae Radix (Chinese crude drug). Systematic isolation from aqueous extract of Salviae Miltiorrhizae Radix was carried out, and Compound 1 was found to be more effective than any of the other constituents in improving renal functional parameters; that is, a marked reduction of glomerular filtration rate following adenine ingestion was improved by administration of this substance. The renal plasma flow and renal blood flow were also increased in renal failure rats. On the basis of chemical and spectroscopic data, Compound 1 was shown to be identical with magnesium lithospermate B.     

Effect of meal on the physiological and physicochemical actions of potassium citrate

The effect of meals on the physiological and physicochemical actions of potassium citrate was examined in 8 patients with nephrolithiasis maintained on a constant metabolic dietary regimen. Potassium citrate (20 mEq. 3 times per day), whether given with food or on an empty stomach, significantly increased urinary pH, citrate and potassium, and decreased urinary calcium and ammonium. Moreover, potassium citrate decreased urinary saturation of calcium oxalate and uric acid, although it slightly increased that of brushite. However, there was no significant difference in these measures when the drug was given with meals from the time when it was given on an empty stomach. Thus, the effect of potassium citrate on urinary risk factors is unaffected by food.     

The physical dependence liability of butorphanol: a comparative study with morphine.

In these studies, the physical dependence liability of butorphanol, a mixed 'agonist/antagonist' opioid analgesic, was compared to that of morphine. Male, Sprague-Dawley rats received i.c.v. infusions of saline (1 microliter/h), or an equimolar dose of butorphanol or morphine (52.3 nmol/h) for 3 days. The physical dependence liabilities of these two compounds were then compared by assessing both behavioral withdrawal signs and weight loss following naloxone-precipitated withdrawal. Body weight loss was also evaluated following abrupt (cessation of infusion) withdrawal from butorphanol or morphine. In animals receiving i.c.v. infusions of butorphanol or morphine, naloxone administration (5 mg/kg s.c.) induced an equivalent degree of body weight loss compared to saline-treated animals. In addition, the ED50 of naloxone to produce wet shakes, escape behavior, teeth chattering, urination and defecation was equivalent in rats receiving butorphanol or morphine. Infusions of butorphanol or morphine also produced an equivalent degree of weight loss in animals undergoing abrupt withdrawal. These results demonstrate then that a substantial degree of physical dependence had developed in rats which received a large dose of butorphanol.     

Effects of haloperidol on motor and cognitive functioning in aged mice

The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging-induced changes in the behavioral effects of neuroleptic agents.     

Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.