Reperfusion of ischemic liver results in the generation of oxygen radicals, nitric oxide (NO) and their reaction product peroxynitrite, all of which may cause strand breaks in DNA, which activate the nuclear enzyme poly(ADP ribose)synthase (PARS). This results in rapid depletion of intracellular nicotinamide adenine dinucleotide and adenosine 5'-triphosphate (ATP) and eventually induces irreversible cytotoxicity. In this study, we demonstrated that niacinamide, a PARS inhibitor, attenuated ischemia/reperfusion (I/R)-induced liver injury. Ischemia was induced by clamping the common hepatic artery and portal vein of rats for 40 min. Thereafter, flow was restored and the liver was reperfused for 90 min. Blood samples collected prior to I and after R were analyzed for methyl guanidine (MG), NO, tumor necrosis factor (TNF-alpha) and ATP. Blood levels of aspartate transferase (AST), alanine transferase (ALT) and lactate dehydrogenase (LDH) which served as indexes of liver injury were measured. This protocol resulted in elevation of the blood NO level (p < 0.01). Inflammation was apparent, as TNF-alpha and MG levels were significantly increased (p < 0.05 and p < 0.001). AST, ALT and LDH were elevated 4- to 5-fold (p < 0.001), while ATP was significantly diminished (p < 0.01). After administration of niacinamide (10 mM), liver injury was significantly attenuated, while blood ATP content was reversed. In addition, MG, TNF-alpha and NO release was attenuated. These results indicate that niacinamide, presumably by acting with multiple functions, exerts potent anti-inflammatory effects in I/R-induced liver injury.

Adenosine Triphosphate↗

PubMedDate not supplied

The effect of althesin, ketamine or pentothal on renal function in saline loaded rats.

Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery. A steady-state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excretion rates, GFR, ERPF, ERBF and blood pressure were measured. Five groups of rats were studied: (1) control animals given saline in place of any anaesthetic agent, all parameters measured remained constant; (2) althesin (1.2 mg/kg), all parameters remained constant except for the blood pressure which decreased slightly for 5 min; (3) althesin (12 mg/kg); (4) ketamine (50 mg/kg); (5) pentothal (50 mg/kg). The above anaesthetics altered all of the measured parameters except urine output. Various mechanisms for these anaesthetic agents are discussed. In althesin anaesthetized rats, all the retarded renal parameters recovered within 30 min. It is concluded that for the study of renal function, if a brief anaesthesia is needed, althesin is a more suitable anaesthetic agent.

Alfaxalone Alfadolone Mixture↗

PubMedDate not supplied

Effects of acute and chronic phenytoin on the electrolyte content and the activities of Na+, K+-, Ca2+, Mg2+-, and HCO3- -ATPases and carbonic anhydrase of neonatal and adult rat cerebral cortex.

Various parameters of anion and cation transport were measured in the cerebral cortex of neonatal (3-day-old) and adult rats following acute and chronic treatment with phenytoin (PHT). Acutely, PHT significantly inhibited the enzyme Na+, K+-ATPase in both neonatal and adult rats. This effect was accompanied by a significant increase in cerebral cortical Na+ content and a decrease in K+ content only in neonatal animals. Chronic treatment (two and four times a day for 7 days) of adult rats with PHT significantly reduced Na+ content without affecting whole homogenate Na+, K+-ATPase activity. The activity of this enzyme was markedly increased in the myelin- (glial product) and slightly decreased in the synaptosomal- (neuronal) fractions following chronic (four times a day for 7 days) PHT treatment. These results suggest that PHT differentially affects the two forms (neuronal and glial) of the enzyme Na+, K+-ATPase. The possible relevance of this hypothesis in relationship to the anticonvulsant and excitatory properties of PHT is discussed. Chronic (two and four times a day for 7 days) PHT treatment increased both DNA content and activity of the glial marker enzyme carbonic anhydrase. Activity of the mitochondrial enzyme HCO3- -ATPase was also increased following chronic PHT treatment. These two enzymes are intimately involved in the regulation of HCO3- -Cl- transport across glial cell and mitochondrial membranes, and these results suggest that PHT is able to affect beneficially glial regulatory processes. The ability to enhance glial regulation of anions and cations in extracellular fluid provides new and important insights into the mechanism of the anticonvulsant action of PHT.

Adenosine Triphosphatases↗

PubMedDate not supplied

Effects of rat bile infusion on renal function in rats.

The influence of rat bile infusion on renal function in rats and the possible role of bile-induced hemolysis in these effects were examined. The hemolytic action of rat bile and some bile salts were determined in vitro. After the i.v. infusion of rat bile (70 mg freeze-dried powder/2.55 ml) into pentobarbitone-anesthetized rats, the urine, sodium and potassium excretion rates were reduced more than half, which was due to the decrease of glomerular filtration rate and increase of tubular water and sodium reabsorption. A fall in blood pressure, a rise in hematocrit, and hemolysis were also found. Infusion of hemolysed (30 microliters RBC) solution produced by distilled water and then made isotonic caused a short-duration increase in renal excretion and glomerular filtration rate, and the blood pressure was unchanged. Infusion of a rat bile-hemolysed solution after removal of bile acids with cholestyramine increased renal excretions at first with reduction thereafter. Infusion of the rat bile-hemolysed solution treated with barium sulfate produced a renal response very similar to rat bile alone. It is proposed that two factors are involved in the renal response after bile infusion, namely bile acid-induced hemolysis producing diuresis with natriuresis, and bile acid-induced antidiuresis and antinatriuresis, possibly due to a direct renal effect.

Animals↗

PubMedDate not supplied

Role of renal nerves in volume expansion in chronic hypoxic rats.

This work was designed to study the significance of the renal nerves in chronic hypoxic (high-altitude; HA) rats after saline loading. Female Wistar rats (200-290 g) under sodium pentobarbital (40 mg/kg i.p.) anesthesia were used in these experiments. Hypoxia was induced by placing the rats in an altitude chamber (5,500 m) for 4 weeks. Both the renal efferent nervous activity (RENA) and the renal afferent nervous activity (RANA) were recorded simultaneously throughout the experimental period. It was found that the responses of RENA and RANA to an intravenous saline infusion (10 ml, 10 min) were significantly different between the sea level (SL) control and HA rats. In SL rats, a depression of RENA was found; the depressed RENA had not recovered 80 min after cessation of the saline infusion. In HA rats, an initially depressed RENA was also found; however, it returned to the control level within 10 min following the cessation of saline infusion. RANA enhanced twice a few minutes after saline loading in SL rats; however, the changes of RANA in HA rats were not significant. In both groups of rats, whether renally denervated or intact, the amount of excretory urine and sodium after saline loading was unchanged. The renal norepinephrine levels were also measured by a high-pressure liquid chromatography system in both groups of rats, and it was found that the renal norepinephrine content of the HA rats was significantly higher than in the SL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Altitude Sickness↗

PubMedDate not supplied

An experimental study of the antitumour effect of bleomycin hydrochloride microcapsules.

The controlled release behaviour of bleomycin hydrochloride microcapsules was investigated by an in vitro dissolution method and an in vivo antitumour test. Bleomycin hydrochloride microcapsules prepared using the highest cooling rate exhibited sustained release characteristics and its release rate obeyed a nearly zero order release kinetics. Microcapsules containing bleomycin hydrochloride were locally injected into the solid tumour of uterine cervix carcinoma bearing nude mice. Tumour growth was markedly inhibited by treatment using bleomycin hydrochloride microcapsules compared to the control group and the group receiving direct local administration of bleomycin hydrochloride. No significant differences in the changes of body weight after treatment were found between the control group and the treated group. These results suggest that controlled release microcapsules may be applicable as a drug carrier for delivery of antitumour agents in cancer chemotherapy.

Animals↗

PubMedDate not supplied

Purification of phosphatidylinositol-specific phospholipase C from NG108-15 cells.

The phosphatidylinositol-specific phospholipase C from the membrane of NG108-15 cells has been purified to homogeneity by using DEAE Bio-Gel A agarose, hydroxyapatite, and heparin agarose chromatography. The purified phosphatidylinositol-specific phospholipase C has been purified 422-fold and its molecular weight has been estimated to be 28,000. We have obtained a final specific activity of 3.8 mumols of phosphatidylinositol hydrolyzed/min/mg of protein. The purified enzyme is specific to phosphatidylinositol. The purified enzyme has an apparent pH optimum of 7.0. Calcium ions are required for its activity.

Animals↗

PubMedDate not supplied

Antitumor agent, physalin F from Physalis angulata L.

Physalin F and physalin D were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Systematic fractionation of the ethanolic extract of the plant led to characterization of physalin F from the fraction PAIV-2 as an active ingredient which showed cytotoxicity in vitro by DEA and MTT assays on 8 cancer cell lines, five human cancer cell lines: HA22T(hepatoma), HeLa(cervix uteri), KB(nasopharynx), Colo-205(colon) and Calu-1(lung); and three animal cancer cell lines: H1477(melanoma), Hep-2(laryngeal) and 8401(glioma). It was found that the anti-hepatoma action is the strongest, and the anti-HeLa is the next. Physalin F also had an antitumor effect in vivo against P388 lymphocytic leukemia in mice whereas physalin D was inactive both in vitro and in vivo.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Experimental antitumor agents from Solanum indicum L.

beta-Sitosterol (SI-0), beta-sitosterol glucoside (SI-1), dioscin (SI-2), methyl protoprosapogenin A of dioscin (SI-3), methyl protodioscin (SI-4) and protodioscin (SI-5) were isolated and characterized from the whole plant of Solanum indicum L. (Solanaceae). Except for beta-sitosterol, these compounds have not been previously isolated from Solanum indicum L. Both CHCl3 soluble (SI-IV) and insoluble (SI-V) fractions of the ethanolic extract (SI-I) showed cytotoxicity on seven cancer cell lines: Colo-205 (colon), KB (nasopharynx), HeLa (uterine cervix), HA22T (hepatoma), Hep-2 (laryngeal epidermoid), GBM8401/TSGH (glioma) and H1477 (melanoma). The purified constituents, SI-2 and SI-4 showed more potent effects by DEA and MTT assay. SI-2,3,4 and 5 also demonstrated cytotoxicity on cultured C6 glioma cells by PRE assay, ans SI-3,4 and 5 showed a tumor inhibitory effect in vivo in C6 glioma cells. In addition, SI-2 had an inhibitory effect on the DNA synthesis of C6 glioma cells at 10 micrograms/ml.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

45,XO/46,XY in a newborn with the stigmata of Turner syndrome: report of one case.

A newborn with ambiguous external genitalia and the stigmata of Turner syndrome presented with the following features: short stature, hypertelorism, bilateral epicanthal folds, ptosis, low-set ears with prominent auricles, high-arched palate, low posterior hairline, webbed neck, broad and short chest, widely-spaced and hypoplastic nipples and clitoris-like phallus with hypospasdias. He also had patent ductus arteriosus, the secundum type of atrial septal defect and mitral stenosis. Chromosomes of peripheral blood showed mosaicism of cells with 45,XO/46,XY. An exploratory laparotomy was performed at five months of age. The right side ovotestis-like gonad was removed. The left side gonad in the scrotum was normal. No pathological gonadoblastoma was found.

Abnormalities, Multiple↗

PubMedDate not supplied

Facioscapulohumeral type spinal muscular atrophy: report of a case.

A case of muscular weakness and atrophy with a facioscapulohumeral distribution is described in this report. The neurogenic origin, as judged from the results of laboratory studies, is discussed. The diagnosis and classification of the spinal muscular atrophy syndrome are also discussed. Facioscapulohumeral type spinal muscular atrophy is thought to constitute a distinct form of spinal muscular atrophy.

Adolescent↗

PubMedDate not supplied

[Clinical observation of spinal muscular atrophy].

Explore the source record for details and available documents.

Biopsy↗

PubMedDate not supplied

Age-period-cohort analysis of breast cancer mortality.

The objective of this study is to develop a hypothesis about the carcinogenesis of breast cancer from a descriptive analysis. This study is an application of the age-period-cohort model (APC model) on the mortality rate of breast cancer in Taiwan over the period from 1964 to 1991. Age-specific and age-adjusted mortality rates are described and then age, period, and cohort effects are separately analysed. (Female) breast cancer mortality data in Taiwan from 1964 to 1991 were abstracted from the annual reports of the Taiwan Provincial Department of Health. The population data in Taiwan from 1964 to 1991 were abstracted from the demographic data in Taiwan compiled by the Ministry of Interior, R.O.C. The results show that both age-adjusted and age-specific mortality rates of breast cancer are increasing over the study period and with birth cohorts. The bimodal pattern becomes more apparent in later periods. The Clemmensen's hook is five years later both in the descriptive study and the APC analysis. The findings suggest a possible role of later life overnutrition as the major period effed (promoter) and a change in reproductive behavior as the cohort effect (initiator). The application of the APC model also denotes the possible role of later life overnutrition and a change in reproductive behavior after the birth cohort of 1929. These findings may help us develop hypotheses of carcinogenesis of breast cancer.

Adult↗

PubMedDate not supplied

Disposition of magnolol after intravenous bolus and infusion in rabbits.

A simple and sensitive high-performance liquid chromatographic method was developed for the determination and identification of magnolol to study its pharmacokinetics in rabbits after a 5 mg/kg i.v. bolus and 76 micrograms/kg/min i.v. infusion. Plasma concentration time profiles were suited to a two-compartment open model. The elimination half-lives of magnolol were 14.56 and 15.71 min, and the total body clearances were 75.86 and 72.72 ml/min/kg for i.v. bolus and i.v. infusion, respectively. There were no significant differences in elimination half-life and total body clearance between i.v. bolus and i.v. infusion, which suggests that magnolol pharmacokinetics are linear.

Animals↗