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H Turndorf

Publications and source records attributed to H Turndorf.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intrathecal administration of liposomal morphine in a mouse model.

The authors determined the duration of analgesia, toxicity, and neuraxial distribution of liposomal morphine after intrathecal administration in the mouse. Analgesic duration was determined using the tail-flick test after intrathecal injection of 12.5, 25, or 50 micrograms of plain or liposomal morphine (n = 6 mice/dose/formulation). Toxicity of the formulations was compared by estimating LD50. Neuraxial morphine distribution was determined after 20 micrograms of plain or liposomal morphine. The excised spinal cord and brain were divided into five segments at 1 min, and at 1, 4, and 8 h after injection for both formulations. In addition, for the liposomal morphine, similar sections were obtained at 24 h (n = 6 mice/formulation/time point). Segmental morphine concentration was quantified using radioimmunoassay. Liposomal encapsulation significantly prolonged duration of analgesia for the 25-micrograms (13.4 +/- 1.64 [SE] vs 4.1 +/- 0.5 h) and 50-micrograms doses (16.8 +/- 4.0 vs 4.6 +/- 1.0 h). The estimated LD50 was 200 (confidence interval 151-257 micrograms) for plain morphine, but was not determinable for the liposomal formulation, since no deaths occurred at the largest dose level which could be tested (371 micrograms). For plain morphine, the drug was not confined to a specific neuraxial segment, and segmental levels declined rapidly. After liposomal morphine, the most morphine was concentrated and persisted in the low spinal cord segment at each time interval. These results show that a single dose of liposomal morphine produces prolonged analgesia with decreased toxicity compared to the plain formulation.

Animals↗
PubMed1995

Propofol modulates the effects of chemoconvulsants acting at GABAergic, glycinergic, and glutamate receptor subtypes.

BACKGROUND: Propofol has been used to treat status epilepticus, but its use in patients with seizure disorders remains controversial, because of concerns that it produces paroxysmal motor phenomenon. Chemoconvulsants act by known discrete mechanisms and neurotransmitters, and therefore, they are useful tools for screening anticonvulsant activity. The main objective of this study was to characterize the effect of propofol pretreatment on convulsions induced by picrotoxin, bicuculline, and strychnine, all which decrease inhibitory neurotransmission, and by N-methyl-D-aspartic acid, kainic acid, and quisqualic acid, which enhance excitatory neurotransmission. METHODS: Groups of male Swiss Webster mice (n > or = 10/group) were given either vehicle (intralipid, 10 ml.kg-1, control groups) or propofol (50 mg.kg-1, test groups) injected intraperitoneally. Five min after injection, convulsions were induced with either bicuculline (1.36-5.44 nmoles), picrotoxin (0.21-1 nmol), N-methyl-D-aspartic acid (0.51-2 nmol), quisqualic acid (1-10 nmol), kainic acid (0.252-2 mole), or strychnine (1.35-10.78 nmol) injected intracerebroventricularly. The number of animals with convulsions after each dose was recorded. Analysis of statistical significance was based on the log-probit lines of the quantal dose-response for the respective control and test groups, calculated 50% effective doses (ED50), the potency ratios (ED50higher/ED50lower) and their 95% confidence limits. RESULTS: Propofol pretreatment decreased the potency ratio of both bicuculline (0.47, 95% confidence interval = 0.23-0.94) and picrotoxin (0.61, 0.47-0.79), signifying an anticonvulsant effect. Conversely, propofol pretreatment significantly enhanced the convulsive potency of kainic acid (potency ratio and 95% confidence interval = 1.66, 1.21-2.29), quisqualic acid (3.17, 1.98-5.09), and strychnine (1.76, 0.79-3.89). CONCLUSIONS: Current results suggest that propofol augments the paroxysmal motor phenomenon induced by kainic acid, quisqualic acid, and strychnine. This action may be, at least partly, responsible for the motor manifestations reported after propofol administration. These in vivo results on modulation of gamma-aminobutyric acid, glycine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptor-mediated transmission may be of significance in understanding the mechanism of propofol action at the excitatory and inhibitory amino acid receptors.

Anesthetics, Intravenous↗
PubMed1994

Antinociception without motor blockade after subarachnoid administration of S-(+)-ibuprofen in rats.

This study was designed to determine whether the nonsteroidal anti-inflammatory drug (NSAID) sodium S-(+)-ibuprofen (IB), can be used intrathecally as a substitute analgesic for opiates to avoid the side effects of intrathecal narcotics. One week or more after surgical implantation of subarachnoid catheters, four groups of Sprague-Dawley rats were given 0.05 ml subarachnoid injections containing one of the following: Group A, normal saline (NS); Group B, IB 0.25 mg, 0.5 mg and 1.5 mg; Group C, morphine (M) 0.05 mg and 0.025 mg; Group D received NS or IB 1.5 mg. Animals were sacrificed for spinal cord examination one week after injection. Tail flick response latency (TFL) was determined before and 15, 30, 60, 120 and 180 minutes after each injection. TFL differences were compared. IB 1.5 mg vs NS, IB 0.5 mg vs NS, IB 0.25 mg vs M 0.05 mg, IB 0.25 mg vs M 0.025 mg, M 0.05 mg vs NS, and M 0.025 vs NS showed p < 0.05. IB 1.5 mg vs M 0.05 mg and M 0.025 mg, IB 0.5 mg vs M 0.05 mg and M 0.025 mg revealed no significant difference. No motor impairment was observed in any animal. Light microscopy of the spinal cord revealed no evidence of pathological changes in any animal (group D).

Analysis of Variance↗
PubMed1994

Methodological variables during analysis of in vivo cerebellar cyclic GMP, an indirect marker of nitric oxide release.

In light of the recent recognition of the physiological significance of nitric oxide, there is considerable interest in the methodological variables that can confound the results of the cerebellar cGMP analysis from in vivo experiments. In this study, using male Swiss Webster mice, the effect of such methodological variables as 1) weight of the animals; 2) tissue extraction procedures used in radioimmunoassay for cGMP; and 3) the commercial source of the assay kit on, harmaline-, pentylenetetrazole- or SNAP-induced increase in cerebellar cGMP in vivo were evaluated. Results indicate that mice in the 15- to 19-g weight range are most sensitive and best suited for in vivo drug effects on cerebellar cGMP. Furthermore, for the extraction of cerebellar cGMP, use of ice-cold 0.5N hydrochloric acid and subsequent dilution of the sample in assay buffer is the simplest and fastest method. Present data also indicate that the source of the radioimmunoassay kit has a significant effect on the cerebellar cGMP results. Based on the present results, the protocol developed and the guidelines drawn are timely and of high practical significance for research in the area of pharmacology of nitric oxide.

Animals↗
PubMed1994

Prolonged analgesia and decreased toxicity with liposomal morphine in a mouse model.

Inadequate control of postoperative pain remains a major clinical problem. A reliable method of providing long-lasting postoperative analgesia with a single dose would be very useful. We synthesized a liposomal morphine formulation and compared it to free morphine with regard to duration of analgesia in the mouse. Analgesia was assessed after intraperitoneal injection using the tail-flick test. The systemic toxicity after administration of liposomal and free morphine was compared. The release rate of morphine from liposomes in vitro was also evaluated. The lethal intraperitoneal dose of free morphine in 50% of mice (LD50) was 400 mg/kg. The maximum safe (non-lethal) dose of free morphine was 130 mg/kg. The highest dose of liposomal morphine administered (1650 mg/kg) did not cause death in any animal. Duration of analgesia was significantly prolonged with the highest dose of liposomal morphine (21.5 +/- 5.3 h) compared to the maximum safe dose of free morphine (3.7 +/- 0.75 h), P < 0.01. In vitro experiments showed a slow release rate of morphine from the liposome depot. Prolonged analgesia and decreased systemic toxicity for liposomal morphine are explained by sustained release of morphine from the liposomal depot. These results suggest that liposomal narcotic formulations may provide prolonged analgesia with single-dose administration.

Analgesia↗
PubMed1993

Chronic administration of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine, and drug-induced increase in cerebellar cyclic GMP in vivo.

N omega-nitro-L-arginine (NG-nitro-L-arginine) is a potent nitric oxide synthase inhibitor which crosses the blood brain barrier and does not undergo extensive metabolism in vivo. In this study, effect of chronic pretreatment of N omega-nitro-L-arginine (75 mg/kg, i.p., twice daily for 7 days) on the harmaline- (100 mg/kg, s.c.), picrotoxin- (4 mg/kg, s.c.), pentylenetetrazole- (50 mg/kg, i.p.), and L-glutamic acid- (400 micrograms/10 microliters/mouse, i.c.v.) induced increase in cerebellar cGMP was assessed. All the four drugs produced significant increase in cerebellar cGMP in vehicle pretreated control animals. Cerebellar cGMP increased induced by harmaline, picrotoxin, and L-glutamic acid was attenuated in N omega-nitro-L-arginine pretreated animals. These results indicate that in vivo cerebellar cGMP levels are increased by the prototype excitatory amino acid receptor agonist, L-glutamic acid and also by the drugs which augment the excitatory amino acid transmission. Furthermore, parenteral chronic administration of N omega-nitro-L-arginine blocks NO synthase in the brain and hence cerebellar cGMP response in chronic N omega-nitro-L-arginine treated animals could be used as a tool to assess the physiological functions of nitric oxide in vivo.

Amino Acid Oxidoreductases↗
PubMed1993

Effect of propofol on memory in mice.

The amnestic effects of the intravenous hypnotic anesthetic agent 2,6-diisopropylphenol (propofol; Diprivan) were studied in a single-trial passive avoidance task. Mice were injected with propofol 10 min before or immediately after training. Memory was impaired in a dose-dependent fashion when the anesthetic was administered before learning, but no amnesia was apparent with posttraining injections. Examination of the acquisition of passive avoidance using a multitrial task showed that propofol-treated mice learned the response normally but forgot the learning significantly faster than vehicle-treated controls. The anterograde amnesia was not the result of state-dependent learning. Propofol also disrupted extinction of fear conditioning when the anesthetic was given during the extinction session. Propofol-induced amnesia could be attenuated by amphetamine (1 mg/kg) injected 30 min before the retention test.

Amnesia, Retrograde↗
PubMed1993

Effect of cocaine on macromolecular syntheses and cell proliferation in cultured glial cells.

In the present study the effect of cocaine on thymidine, uridine and leucine incorporation was assessed in primary cortical glial and C6 glioma cells. Cocaine exposure for 24 h inhibited thymidine and uridine incorporation in cortical glial and C6 glioma cells. However, the effect of cocaine on uridine incorporation was less prominent compared to thymidine incorporation. High concentrations of cocaine inhibited leucine incorporation in C6 glioma cells but not in cortical glia. Cocaine exposure for four days decreased cell proliferation of cortical glial and C6 glioma cells. Cocaine-induced attenuation of macromolecular syntheses was not due to cell death since cocaine-treated cells were not stained with Trypan Blue and did not release lactate dehydrogenase into culture supernatants. Furthermore, cocaine had no effect on glutamate uptake either in cortical glia or in C6 glioma cells. These results indicate that cocaine inhibits macromolecular syntheses in glial cells. The inhibition of macromolecular syntheses in glial cells may be the mechanism involved in cocaine-induced fetal brain growth retardation.

Animals↗
PubMed1993

Assessing local anesthetic effect using the mouse tail flick test.

We used the tail flick test to quantify duration of local anesthetic-induced conduction block in the mouse. Using a baseline tail flick latency (TFL) between 1.0 and 2.5 sec, sensory block was considered present if TFL was > or = 4 sec. Two 20-microL local anesthetic injections were made on opposite sides of the tail base. TFL was tested every 10 min, and local block duration was interpreted as the time to return of TFL to < 4 sec. We tested three different concentrations of procaine (1%, 2%, and 4%), tetracaine (0.125%, 0.5%, and 1%), and lidocaine (0.5%, 1%, and 2%) with and without epinephrine. The testing method could discriminate between the duration of the various local anesthetic concentrations used. For the 1% concentrations, the duration of sensory block was 2 +/- 4 min (S.D.) for procaine, 20 +/- 10 min for lidocaine, 40 +/- 10 min for tetracaine, and 66 +/- 15 min for lidocaine with epinephrine. We found this to be a simple and reliable means of assessing local anesthetic conduction block in the mouse.

Anesthesia, Local↗
PubMed1993

A two-dose epidural morphine regimen in cesarean section patients: pharmacokinetic profile.

The maternal pharmacokinetics, metabolism of, and possible neonatal transmission of epidural morphine in cesarean section patients were investigated. Maternal plasma, breast milk, and maternal and neonatal urine concentrations of unconjugated and conjugated (UM and CM) morphine were measured in patients given two 5-mg doses of epidural morphine for post-cesarean section analgesia. The first dose was administered after delivery and the second dose 24 h later. Maternal venous blood samples (n = 10) were collected at times 0, 0.25, 0.5, 1, 2, 3, 4, 6, 12, and 24 h after each dose, and maternal urine was collected for three consecutive 24-h periods (n = 30). Maternal breast milk (n = 30), and neonatal urine samples (n = 20) were also collected. Serum, urine, and breast milk UM and CM levels were measured using radioimmunoassay. Pharmacokinetic values were calculated using noncompartmental analysis. The results were expressed as mean +/- 1 s.e. mean and analyzed using repeated measures analysis of variance and the paired t-test. Maternal serum UM remained 40-50% higher, and CM 50-100% higher in the first hour following dose 2 than the respective values after dose 1 (P < 0.05). Values for AUC, AUMC, T1/2, and MRT increased 28%, 83%, 35% and 36%, respectively, with the second dose (P < 0.05), while CI decreased 19% (P < 0.05) with no significant difference in Vss. Total urinary excretion of morphine decreased significantly from 1.98 +/- 0.15 mg on day 1 to 1.6 +/- 0.2 mg and 0.19 +/- 0.002 mg on days 2 and 3, respectively (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Electrocardiographic changes during cesarean section: a cause for concern?

A Holter monitor was used to record ST segment changes during cesarean section in 170 consecutive healthy parturients starting 2 h before and ending 3 h after surgery. Lumbar epidural anesthesia (LEA, n = 120) or subarachnoid anesthesia (SA, n = 50) was used. Transthoracic 2-D echocardiograms were obtained in 30 patients from the LEA group. ST depression or elevation occurred 160 times in 44 patients from both groups. Ninety-eight percent of these changes occurred between induction of anesthesia and the end of surgery, with 78% of the episodes registering -1 mV. In the LEA group, the number of episodes tended to increase after delivery, but in the SA group, the frequency remained constant. ST segment depression was recorded in 38% and 14% of patients in the LEA and SA groups, respectively (P < 0.05, x2 analysis). No wall motion abnormality was noted in the echocardiogram during ST segment depression. Neither the 12-lead electrocardiogram nor plasma myocardial specific creatine kinase suggested myocardial damage. The operative events, alone or in combination, including hypertension, tachycardia, hypotension, bradycardia, air embolism (precordial Doppler) were neither specific nor sensitive as predictors of ST segment change (stepwise logistic regression). Tachycardia was associated with ST segment changes in 10% of time epochs (5 min) (P = 0.05, x2 analysis). Thus, ST segment changes during cesarean section are not caused by myocardial ischemia and are not of any clinical consequence.

Adult↗
PubMed1992

Effect of nitric oxide on mitogenesis and proliferation of cerebellar glial cells.

In the brain, nitric oxide (NO) has been identified as a messenger molecule and a mediator of excitatory amino acid-induced neurotoxicity. In this study, the effects of NO on serum-induced mitogenesis and cell proliferation of the cerebellar glial cells were assessed. NO-generating agent, S-nitroso-N-acetylpenicillamine (SNAP) increased intracellular cyclic guanosine monophosphate (cGMP) levels. Furthermore, 2 chemically dissimilar NO-generating agents, SNAP and sodium nitroprusside (SNP) inhibited serum-induced thymidine incorporation and cell proliferation. The antimitogenic effect of NO was mimicked by 8-bromo-cGMP and blocked by hemoglobin, a known inhibitor of NO. The effect of NO was not cytotoxic, since the cells were not stained with Trypan blue and did not show increased release of lactate dehydrogenase in the culture supernatants. However, NO-treated cells showed decreased conversion of tetrazolium to blue formazan suggesting that NO inhibited mitochondrial activity in the glial cells. These results demonstrate that NO inhibits serum-induced mitogenesis and cell proliferation of cultured rat cerebellar glial cells.

Animals↗
PubMed1992

Halothane anesthesia causes state-dependent retrieval failure in mice.

Effects of exposure to halothane on memory processing was studied using single-trial inhibitory avoidance learning to measure retention. Mice were anesthetized with halothane either before training, immediately after training, or both before training and before testing. Results showed that memory was not impaired by posttraining halothane exposure, indicating that the anesthetic does not cause retrograde amnesia. Mice trained after recovery from halothane showed a robust memory loss 24 h later. This deficit could be alleviated by reexposure to the anesthetic before the retention test. Mice given multiple training trials following recovery from the anesthetic showed a normal rate of learning when compared with controls, but deficient retention. This indicates that the performance deficit was the result of impaired retention (anterograde amnesia) rather than disrupted acquisition. Anterograde amnesia occurred when training was delayed up to 2 h after recovery from anesthesia. These findings indicate that the memory impairment following halothane anesthesia is the result of a state-dependent retrieval failure.

Amnesia, Retrograde↗
PubMed1992

On the mechanism of the interaction of ketamine and halothane in vitro.

1. Electrically induced contraction of guinea pig ileum myenteric plexus-longitudinal muscle was inhibited by ketamine and halothane with IC50s of 2.1 x 10(-4) M and 1.8 v/v% respectively. 2. The inhibitory action of ketamine was partially antagonized by naloxone and the selective kappa antagonist nor-binaltorphimine. 3. The actions of ketamine and halothane were synergistic at high levels of response (above 30% inhibition). 4. The actions of ketamine and halothane became antagonistic after treatment with pertussis toxin. 5. The interaction of ketamine and halothane was similar to the interaction of morphine and halothane.

Animals↗
PubMed1992

Bretylium tosylate and electrically induced cardiac arrhythmias during hypothermia in dogs.

The effect of bretylium tosylate on plasma catecholamines and on electrically induced arrhythmias was evaluated in anesthetized hypothermic dogs. Bretylium at a dose of 7.5 mg/kg was administered prior to cooling from 37 degrees C to 27 degrees C. During cooling, the ventricular arrhythmia threshold (VAT) in control animals decreased from 10.1 +/- 1.9 to 4.4 +/- 1.3 impulses, while the VAT in bretylium-treated animals increased from 9.8 +/- 2.9 to 23.2 +/- 2.7 impulses. Catecholamine levels increased during cooling in all animals. In control animals, the epinephrine/norepinephrine ratio was unchanged, but in animals treated with bretylium tosylate, the ratio increased more than 10-fold (from 0.48 +/- 0.1 to 5.49 +/- 0.32 at 29.9 degrees C). The demonstrated increase in catecholamine levels during hypothermia suggests that the protection offered by bretylium tosylate against cardiac arrhythmias is not explained by modification of catecholamine levels, and is more likely due to an alteration of the electrophysiologic properties of cardiac tissues.

Animals↗
PubMed1992

Prolongation of spinal anesthesia. Differential action of a lipid drug carrier on tetracaine, lidocaine, and procaine.

This study evaluates prolongation of spinal anesthesia by incorporating local anesthetics in lipid formulation. The duration and intensity of local anesthetic effect produced by different concentrations of procaine (1%, 2%, 4%), lidocaine (1%, 2%, 4%), or tetracaine (0.5%, 1%, 2%) dissolved in normal saline were compared to those produced by the same concentration of drugs in lipid (iophendylate) solution. Fifty rabbits with chronic indwelling subarachnoid catheters were divided into ten equal groups. Three days after the operation the catheters were injected with aqueous solutions of the anesthetics, and 24 h later each animal received an equivalent dose of the corresponding drug in free-base form dissolved in iophendylate. The duration and intensity of motor blockade were assessed using a modified Bromage scale. A separate group of animals received plain normal saline and, 24 h later, iophendylate alone. The Kruskal-Wallis test followed by the Tukey-type test for nonparametric multiple comparisons and the Mann-Whitney and Friedman tests were used for statistical analysis at P less than 0.05. Normal saline or iophendylate alone did not produce any motor blockade. Our data show that iophendylate preparations of local anesthetics produce prolonged but less intense motor blockade than the aqueous solutions, except for tetracaine 0.5% in iophendylate, which produced shorter duration of motor blockade. The reduced intensity of motor blockade may be explained by decreased availability of local anesthetic at the nerve tissue due to storage of drug in the lipid depot. The increased duration of blockade signifies a sustained release of drug from the depot.

Anesthesia, Spinal↗