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F Ma

Publications and source records attributed to F Ma.

68 records · Page 4Linked to original sources

Acute effects of cocaine on spontaneous and discriminative motor functions: relation to route of administration and pharmacokinetics.

Rats administered cocaine i.p. and p.o. (7.5-30 mg/kg) showed dose-related increases in locomotor (LM) and small-movement activities, with LM rates decreasing over the 2-hr session, except at the largest i.p. dose, for which rates were greater in the 2nd hr. Lidocaine p.o. (15-30 mg/kg) did not increase activity. Relating the area under the curve measures for serum cocaine (concentration-time) and LM activity (LM activity-time) for 2 hr postadministration indicated that cocaine was about twice as potent i.p., compared to p.o., in increasing LM activity. Cocaine (i.p. and p.o.) produced dose-related decrements in both discriminative motor control performance and in task work rate, whereas lidocaine p.o. did not. The motor control decrements produced by cocaine were approximately comparable by i.p. and p.o. routes, whereas effects on LM rates were much greater by i.p. than by p.o. administration. The effects of cocaine by both routes on LM rates were proportionally much greater than its effect on motor control performance. Changes in LM rates and motor control performance over the postadministration period were related to the pharmacokinetic features (maximum serum concentration, time to maximum serum concentration and elimination half-life) of cocaine observed for the routes explored (i.p., p.o. and s.c.). Tail-tip serum samples, although yielding conservative estimates of cocaine concentration, correlated well with trunk serum and brain cocaine levels.

Administration, Oral↗

Chronic oral cocaine self-administration: pharmacokinetics and effects on spontaneous and discriminative motor functions.

Rats receiving repeated doses of oral cocaine (15 mg/kg) showed replicable increases in large-movement and small-movement activity rates, but sensitization to the repeated doses did not develop. With a schedule-induction procedure, as the daily, 3-hr, oral dose of self-administered cocaine increased, marked dose-related increases occurred in both large-movement locomotor activity rate and the time for which these elevations were sustained during the following daily 2-hr activity session. Sensitization developed. At the highest levels of self-administered oral cocaine (about 80 mg/kg), post-administration serum cocaine levels remained undiminished for the activity-session period, as did the large-movement activities of most animals, indicating no development of acute tolerance. Rats receiving repeated doses of oral cocaine (15 mg/kg) showed discriminative motor control deficits as well as increases in work rate. These changes were dose-related in animals self-administering oral cocaine under the schedule-induction procedure. Upon withdrawal of cocaine from the schedule-induction animals, motor behavior returned to precocaine base-line performance for most animals. The behavior of the animal with the largest cocaine intake did not return. After a schedule-induced oral cocaine intake session, the tail-tip and trunk serum measures for cocaine and its metabolites were approximately equivalent, while brain cocaine and norcocaine levels remained markedly elevated over serum values.

Animals↗

Simultaneous determination of cocaine and its metabolites with caffeine in rat serum microsamples by high-performance liquid chromatography.

A single, isocratic high-performance liquid chromatographic method is described for the determination of cocaine and three of its metabolites along with caffeine in serum microsamples (50 microliters). The small sample size permits the tracking of pharmacokinetic data over time in individual, small animals. The method also was used to demonstrate that cocaine, benzoylecgonine and norcocaine in rat serum samples were stable for at least a month without the presence of sodium fluoride.

Animals↗

Effect of low fat-high carbohydrate diets in hypertensive patients with non-insulin-dependent diabetes mellitus.

Effects of variations in dietary fat and carbohydrate content on various aspects of glucose, insulin, and lipoprotein metabolism were evaluated in 11 patients with hypertension, who also had non-insulin-dependent diabetes mellitus (NIDDM). All of these patients were being treated with sulfonylureas, thiazides, and beta-adrenergic receptor antagonists. The comparison diets contained either 40 or 60% of total calories as carbohydrate, with reciprocal changes in fat content from 40 to 20%. The diets were consumed in a random order for 15 days in a crossover experimental design. The ratio of polyunsaturated to saturated fat and total cholesterol intake were held constant in the two diets. Plasma glucose and insulin concentrations were significantly (P less than .001) elevated throughout the day when patients consumed the 60% carbohydrate diet. Fasting plasma total and very-low-density lipoprotein (VLDL) and triglyceride (TG) concentrations increased by 30% (P less than .001) after 15 days on the 60% carbohydrate diet. Total plasma cholesterol concentrations were similar on both diets, as were low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations.

Analysis of Variance↗

Natural inhalation exposure to coal smoke and wood smoke induces lung cancer in mice and rats.

In an rural area with a high mortality rate of lung cancer in humans, mice and rats were placed in an environment in which they inhaled coal smoke and wood smoke in indoor air for 15 to 19 months. The incidences of lung cancer in mice in the control group, wood group, and coal group were 17.0% (29/171), 45.8% (81/177), and 89.5% (188/210), respectively: in rats the incidences were 0.9% (1/110), 0 (0/110), and 67.2% (84/125), respectively. In addition, the pollutants in the air were analyzed. The results indicate that coal smoke is a highly significant risk factor for lung cancer in humans in Xuan Wei County of Yun Nan Province in China.

Adenocarcinoma↗

Regional hyperthermia combined with blockade of the hepatic arterial blood flow by degradable starch microspheres in pigs.

The benefit of hepatic arterial microembolization by degradable starch microspheres (DSM) was investigated in regional hyperthermia of the liver. Hyperthermia with and without blood flow blockade of the hepatic artery using degradable starch microspheres was performed on six pigs. Heat was given for 30 min in each treatment by 8 MHz radiofrequency capacitive heating equipment. To maintain blood flow blockade during hyperthermia, 10 mg/kg of degradable starch microspheres was administered into the hepatic artery as an initial dose and 5 mg/kg of the drug was added periodically under the measurement of hepatic arterial blood flow by an electromagnetic flowmeter. To evaluate the effect of degradable starch microspheres, the temperature increase in the liver and rectum was compared between the treatment with and without DSM. All pigs showed a larger increase in intrahepatic temperature when heated in combination with degradable starch microspheres than without. On the other hand, temperature increase in the rectum as a result of hyperthermia to the liver was suppressed by DSM as compared with hyperthermia alone. These results indicate that hepatic arterial embolization by degradable starch microspheres potentiates radiofrequency capacitive heating of the liver. Although this study was not made with liver tumors, regional hyperthermia may be effective in the control of liver tumors when heat is given after the blockade of the hepatic artery by DSM.

Animals↗

Microencapsulated hepatocytes: an in vitro and in vivo study.

Using a modified alginate-polylysine membrane, we have successfully encapsulated rat hepatocytes with little loss of viability. Urea and albumin release from encapsulated liver cells was comparable to that from non-encapsulated cells during the first 4 days in culture. Histological studies also showed that more than 50% of the encapsulated hepatocytes remained viable 35 days after implantation in the peritoneal cavity of both normal rats and rats with galactosamine induced fulminant hepatic failure. Transplantation of microencapsulated hepatocytes provides a potential clinical treatment for liver failure.

Albumins↗

Induction of polyphosphoinositide breakdown in rat corpus luteum by prostaglandin F2 alpha.

The present study examines the possibility that, in the rat corpus luteum, an initial action of prostaglandin F2 alpha (PGF2 alpha) is to induce a ligand-stimulated breakdown of membrane inositol phospholipids. Luteal cells in primary culture were prepared from immature rats after PMSG and human CG priming. In 32P-prelabeled cells, PGF2 alpha caused a rapid decrease in the level of radiolabel found in phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, as early as 20 sec after addition of the hormones. At 1 and 2.5 min, the effect of 10(-6) M PGF2 alpha on phosphatidylinositol 4,5-bisphosphate was significantly greater than that caused by 10(-6) M LHRH in identical cell cultures. By contrast, the levels of the 32P-prelabeled phosphatidylinositol and phosphatidic acid were increased at 5 min by PGF2 alpha or LHRH. Concomitant with the alterations in cellular levels of 32P-prelabeled phospholipids, PGF2 alpha markedly enhanced the accumulation of 3H-labeled inositol phosphates, i.e. inositol 1-phosphate, inositol diphosphate, and inositol triphosphate, during a 5-min incubation. A significant increase of radiolabeled inositol diphosphate was seen as early as 1 min after the addition of either PGF2 alpha or LHRH; PGF2 alpha was more effective than LHRH in this regard. The stimulatory effect of LHRH on inositol phosphate accumulation could be blocked completely by the concomitant presence of a potent LHRH antagonist, and at the concentration used (10(-6) M) the effects of PGF2 alpha and LHRH were not additive. Interestingly, the addition of an exogenous phospholipase C also caused a similar enhancement of inositol phosphate accumulation in identical cell cultures. For the first time, these data suggest that, at the level of the corpus luteum, hydrolysis of phosphoinositides may immediately follow PGF2 alpha (and to a lesser extent LHRH) receptor binding, and this in turn may lead to the generation of 1,2-diacylglycerol and inositol phosphates, resynthesis of phosphatidic acid and phosphatidylinositol, and mobilization of Ca2+.

Animals↗

Luteinizing hormone-releasing hormone enhances polyphosphoinositide breakdown in rat granulosa cells.

A 2-min addition of LHRH to [3H]inositol-prelabeled rat granulosa cells in primary culture evoked significant increases in the accumulation of [3H]inositol phosphates, i.e. radiolabeled inositol monophosphate (IP), inositol diphosphate (IP2), and inositol triphosphate (IP3) levels increased to 210, 590 and 520%, respectively, when compared to control cultures. By contrast, addition of FSH failed to elicit such a response. The effect of LHRH was completely blocked by the concomitant presence of a specific LHRH antagonist. LHRH evoked increase in [3H]IP3 and [3H]IP2 accumulation as early as 30 sec, while the increase in [3H]IP became significant at 2 min. These data support the hypothesis that polyphosphoinositide breakdown may be an early step in the intracellular signal mechanism which mediates the action of LHRH.

Animals↗

Response of mammary tumors of C3H/He mice to hyperthermia and bleomycin in vivo.

The cytotoxicity of bleomycin in vitro has previously been shown to be enhanced by hyperthermia. This study demonstrates in vivo a synergistic interaction between local hyperthermia (43 degrees C, 45 min) and bleomycin (15 mg/kg) against implanted mammary tumors of C3H/He mice. Hyperthermia was given by water bath heating. When combined treatments of heat and bleomycin were administered within 30 min of each other, a synergistic effect was observed. In contrast, when the interval between heat and bleomycin injection was longer than 30 min, only an additive effect was obtained. Timing is therefore considered to be a critical factor for the optimal combination of hyperthermia and bleomycin.

Animals↗