PubMed Health⌕ Search

Biomedical subjects

C Post

Publications and source records attributed to C Post.

At least 109 records · Page 6Linked to original sources
PubMed1985

Distribution of morphine and meperidine after intrathecal administration in rat and mouse.

Morphine and meperidine distribution in the neuroaxis were studied in rats after intrathecal injection through catheters ending at the lumbar level. 14C-Morphine and 3H-meperidine were injected with pharmacologic doses of each drug. Radioactivity was measured in spinal cord segments at different times. At 14 min the segment with maximum morphine concentration (T11-12) contained 8.6 +/- 2.4 (mean +/- SD) pmol/mg, a value 215 times higher than would be observed if distribution in the body were homogeneous. The ratio between concentration in the most rostral segment (C3-4) and in the segment with maximal concentration was 0.21 +/- 0.10. At 14 min the segment with maximum meperidine concentration (T9-10) contained 161.4 +/- 33.9 pmol/mg wet tissue, a value 75 times higher than would be seen with even distribution in the body. The ratio (C3-4 vs. T9-10) was 0.10 +/- 0.04 at this time. The distribution of 14C-morphine in the whole central nervous system (CNS) was studied in mice by whole body autoradiography after intrathecal injections of 5 microliters at the L5-6 level. High levels of radioactivity were detected in the whole spinal cord and in brain regions close to the basal cisterns until 2 h after injection. At 4 h only the caudal part of the spinal cord had detectable levels of radioactivity. The per cent of the injected dose of morphine that was recovered from the spinal cord was 26.5 +/- 4.5 at 14 min, 19.9 +/- 8.8 at 44 min, and 4.5 +/- 1.7 at 179 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Complete blockade and attenuation of 5-hydroxytryptamine induced analgesia following NA depletion in rats and mice.

The effect of pretreatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), upon the analgesia induced by various doses of 5-hydroxytryptamine (5-HT) was examined in rats and mice. DSP4 treatment (2 X 50 mg/kg, intraperitoneally) of rats caused a complete blockade of 5-HT induced analgesia in the tail-flick, hot-plate and shock titration tests. DSP4 treatment (1 X 50 mg/kg, intraperitoneally) of mice caused a partial blockade of 5-HT induced analgesia in the hot-plate test, but no significant blockade in the tail-flick test. These results are discussed with regard to serotonergic-noradrenergic interactions and the species discrepancy in nociceptive testing.

Analgesics↗
PubMed1985

Effect of a homologous series of halogenated methanes on pulmonary uptake of 5-hydroxytryptamine in isolated perfused rat lung.

The potency of halogenated methanes to inhibit uptake of 5-hydroxytryptamine (5-HT) from the pulmonary circulation was studied using an isolated, perfused and ventilated rat lung preparation. The agents were vaporized and mixed with the inlet air. The results indicate that the degree of chlorination is the most important factor for potency of the methanes to inhibit lung uptake of 5-HT. When hydrogen was substituted with fluorine the potency was decreased dramatically. Bromine seemed to have the opposite effect. The data also suggested that the degree of chlorination was more important rather than hydrophobic/hydrophilic balance of the solvent molecule. These effects seem to be correlated with the narcotic effects of the substances studied.

Animals↗
PubMed1984

Substance P antagonists and the role of tachykinins in non-cholinergic bronchoconstriction.

Electrical field stimulation of guinea-pig isolated hilus bronchi induced tetrodotoxin-sensitive contractions of which only a minor part could be inhibited by atropine. The remaining non-cholinergic bronchoconstriction was antagonized by a heptapeptide and an undecapeptide substance P (SP) analogue (Arg5, D-Trp7,9) SP5-11, IC50 = 24.0 microM and (D-Pro2, D-Trp 7,9) SP, IC50 = 10.0 microM. Of the exogenously added tachykinins, both eledoisin (8 times) and physalaemin (3 times) were more potent bronchoconstrictors than SP. Pretreatment with the SP-analogues shifted concentration-response curves to the tachykinins to the right, eledoisin being most readily antagonized. (Arg5, D-Trp 7,9) SP 5-11 also antagonized the neural response more readily than that of SP. In addition, in the frog isolated sciatic nerve preparation the two SP-analogues were found to possess potent lidocaine-like neurodepressant actions which further complicated the interpretation of the neural inhibitory effects of these compounds. It is concluded that if a tachykinin contributes to non-cholinergic bronchoconstriction, an eledoisin-like peptide is a more likely candidate than SP itself. Since SP-antagonists may have local anaesthetic properties their value as tools in neurophysiology seems limited. Inferentially, the non-cholinergic bronchoconstrictive neurotransmitter remains to be identified.

Animals↗
PubMed1984

Antinociceptive effects in mice after intrathecal injection of 5'-N-ethylcarboxamide adenosine.

When injected intrathecally in mice in a volume of 5 microliter, adenosine had no effect on tail-flick or hot-plate reaction latencies at dosages up to 1 mM concentration. There were no other behavioral effects observed either. Injecting 1 mM of the adenosine receptor agonist, 5'-N-ethylcarboxamide adenosine (NECA) caused both motor paralysis of the hind-legs with a duration of approximately 4 h and simultaneous antinociception. A slight weakness of the hindlegs, but a profound antinociceptive effect, was observed after the 100 microM dose only. After 10 microM, there was no effect on motor behavior but still a prolongation of the tail-flick and hot-plate reaction latencies. Pretreatment with the adenosine receptor antagonist theophylline attenuated the antinociceptive effect of NECA. Activation of spinal adenosine receptors thus appears to selectively elicit analgesia.

Adenosine↗
PubMed1984

Organ distribution and protein binding of cadmium in autopsy material from heavy smokers.

Male heavy smokers were autopsied within 3 days postmortem. Samples from kidney, liver, and lung were taken for analysis of cadmium levels and degree of protein binding within the cytosolic fraction. The levels in lung, liver, and kidney were 0.50 +/- 0.35 (means +/- SEM), 2.21 +/- 0.63, and 17.4 +/- 8.8 micrograms cadmium/g wet weight tissue, respectively. In liver and kidney, approximately 75% was bound to a low-molecular-weight protein whereas the corresponding figure for the lung cytosolic fraction was 56%, a difference being statistically significant (P less than 0.05). After concentration of the low-molecular-weight cadmium-binding protein(s) ( CdBP ) by ultrafiltration and preparative isoelectric focusing in a granulated gel, the cadmium appeared in one single band with pI values of 5.8 (lung and liver) and 6.0 (kidney), respectively. It is therefore concluded that human lung exposed to cadmium, in this case via cigarette smoke, contains a CdBP , which binds cadmium. The relative degree of binding is less in lung than in liver or kidney, implicating that the metal could be more toxic to the lung than to liver or kidney, as the protein probably serves a role in detoxifying cadmium.

Animals↗
PubMed1984

A new method for studying the distribution of drugs in spinal cord after intrathecal injection.

The pharmacological effect of local anaesthetic solutions in mice including their distribution within the spinal cord, were assessed following intrathecal injection at the L5-L6 interspace. A solution of 5 microliters radioactively labelled lidocaine at a concentration of 50 mg/ml or bupivacaine at 7.5 mg/ml, was used. Both drugs blocked the motor function of the hindlegs in less than 1 min. This persisted for 15.1 +/- 0.8 min. (mean +/- S.E.M.) after lidocaine and 15.2 +/- 2.7 min. after bupivacaine. The highest spinal cord concentration was adjacent to the site of injection, even if traces were present up to the lower cervical cord. The tissue concentration of bupivacaine was considerably less than that of lidocaine, despite a similar motor blockade. When the injected volume was doubled from 5 to 10 microliters, there was a tendency to a more cephalic distribution of lidocaine. When the speed of injection was increased from 2.5 sec., to 30 sec., no difference in results was seen. The drug concentration at the injection site tended to fall in animals alive until 5 min. after the injection, whereas it persisted in animals sacrificed before the intrathecal injection, suggesting that the circulatory transport is the major route of redistribution from the cord.

Anesthesia, Spinal↗
PubMed1983

Behavioural responses induced by intrathecal injection of 5-hydroxytryptamine in mice are inhibited by a substance P antagonist, D-Pro2, D-Trp7,9-substance P.

Intrathecal injection of 5-hydroxytryptamine (5-HT) in mice produced a behavioural syndrome consisting of reciprocal hindlimb scratching and biting or licking of the hindquarters. Pretreatment with either metergoline or morphine given intrathecally inhibited the 5-HT-induced behaviour. The response to 5-HT was similar to the effect of substance P (SP), and it was found that the blocker of the substance P receptor, D-Pro2, D-Trp7,9-SP, not only reduced the effect of substance P, but also that of 5-HT. The behaviour induced by substance P was also significantly reduced by intrathecal injection of either morphine or metergoline. These findings indicate a functional interaction between substance P and 5-HT in the modulation of sensory input at the spinal level.

Animals↗
PubMed1983

Lung uptake of lidocaine in man as influenced by anaesthesia, mepivacaine infusion or lung insufficiency.

Pulmonary uptake of lidocaine was investigated in patients before surgery, and aimed at elucidating the influence of general anaesthesia, the presence of another local anaesthetic agent in the blood, or the possible impact of lung insufficiency. When the lung uptake of lidocaine, injected as a bolus together with indocyanine green dye, was calculated as uptake at 95% pass of the dye, there were no statistically significant differences between the four groups. When the extraction in each of the arterial blood samples was calculated on the basis of the relation between relative concentrations, there were statistically significant differences, with a general tendency towards higher extraction of lidocaine in the awake, healthy volunteers, not given mepivacaine, compared to the other groups. In the group in whom mepivacaine was infused, the arterial concentration of mepivacaine increased transiently after the injection of lidocaine. This probably reflects a displacement of mepivacaine from binding sites for both agents. From this study, it is postulated that the ability of the pulmonary circulation to clear the blood of lidocaine is high, and that it is not affected markedly by those situations studied in the present investigation.

Adult↗
PubMed1982

Uptake of zimelidine and inhibition of uptake of 5-hydroxytryptamine in the isolated, ventilated and perfused rat lung.

Uptake of zimelidine from the perfusate in isolated perfused rat lung was concentration-dependent. Accumulated zimelidine was released from the lung according to a two-compartment model and lidocaine injected as a bolus did partially displace zimelidine. The properties of the displacement curves indicated, however, that the affinity to the lung tissue was greater for zimelidine than lidocaine. Uptake of 5-hydroxytryptamine added to the perfusion buffer was inhibited by zimelidine. The displacement of zimelidine by lidocaine did not, statistically, significantly alter the extraction of 5-hydroxytryptamine.

Animals↗
PubMed1982

Trichlorethylene and halothane inhibit uptake of 5-hydroxytryptamine in the isolated perfused rat lung.

Lung uptake of 5-hydroxytryptamine (5-HT) was determined in isolated perfused and ventilated rat lung, and was found to decrease with time according to a two-compartmental model. When the lungs were exposed to either trichlorethylene (TRI) or halothane, the uptake of 5-HT was drastically reduced. Both TRI and halothane gave log dose inhibition curves, which were superimposed, i.e. they were equally potent to inhibit lung uptake of 5-HT. At a concentration TRI of 18,000 ppm, the extraction of 5-HT was inhibited by 80 +/- 2 (X +/- S.E.M.) per cent, at 8500 ppm the inhibition was 65 +/- 6 per cent and 25 +/- 1 per cent at 3000 ppm. When the lungs were exposed to halothane, the inhibition was 85 +/- 6 per cent at 40,000 ppm, 48 +/- 1 per cent at 6000 ppm, and 15 +/- 0.3 per cent at 2000 ppm. When exposure to the solvent was discontinued, extraction of 5-HT was rapidly normalized. There was no detectable displacement of [3H]-5-HT from lungs saturated with the amine when they subsequently were exposed to solvent-containing atmosphere. This inhibition of lung uptake of 5-HT from the circulation is therefore postulated as to be an effect dependent on concentration solvent in the tissue, and is probably due to a reversible membrane stabilization of the endothelium.

Animals↗
PubMed1982

Dependence of lung uptake of lidocaine in vivo on blood pH.

Lung uptake of lidocaine was studied in anaesthetized Swedish landrace pigs using the double indicator dilution method with indocyanine green dye as intravascular marker. The pigs were given infusions of sodium bicarbonate or hydrochloric acid to arterial blood pH in the range 7 to 8. Lung uptake of lidocaine was found to correlate statistically significant (P less than 0.05) with pH. Lung uptake in the first injection before the infusion of acid or base, was 42 +/- 4 (mean +/- S.E.M.)%. The uptake was not found to correlate to cardiac output. The conclusion from this work is therefore that lung uptake of xenobiotic amines in part is dependent on blood pH.

Animals↗
PubMed1979

[Clinically unrecognised tuberculosis in autopsy material (author's transl)].

Among 18,724 unselected postmortems performed between 1955 and 1975 811 (4.33%) cases of post-primary tuberculosis were found among which 370 (45.6%) were active and 441 (54.4%) inactive. Occurrence of death involved tuberculosis in 32% of all cases discovered at autopsy. The age group over 50 years was mainly affected and males were clearly more frequently involved, particularly in pulmonary tuberculosis. 333 cases of tuberculosis (41.1%) had been recognised clinically and had mainly consisted of chronic pulmonary forms. In the older age group the proportion of cases diagnosed prior to death decreased steadily. Tuberculosis was associated with other diseases in most patients, particularly with cardiovascular disease and malignant tumours. During the investigation period the number of patients with active tuberculosis decreased. The number of cases of miliary tuberculosis among the active forms remained approximately the same.

Adolescent↗
PubMed1979

Lung uptake of lidocaine in healthy volunteers.

Eleven patients with no known history of heart or lung disease received an i.v. bolus injection of a mixture of lidocaine and indocyanine green dye (Cardiogreen). The dose of lidocaine, given once (or twice 10 min apart), was 0.5 mg/kg b.w. Time concentration curves from the appearance of indocyanine green were constructed for both substances from blood samples taken from the common femoral artery for approx. 50 s at the rate of one sample every 1.2 s. The extraction of lidocaine in each sample and the uptake of lidocaine, when 95% of the injected dose of indocyanine green had been recovered, were calculated. Nine patients showed an initial plateau of high extraction, which was 0.92 +/- 0.02 (mean +/- s.e mean) and 0.91 +/- 0.02 for the first and second injections, respectively, for the entire material. In two cases, however, a short plateau and a rapid decline in the extraction curve were observed. The 95% first pass uptake was 60 +/- 5% in the first injection and 55 +/- 12% for the second injection. Extraction of lidocaine dominated over back diffusion for the approximately 25 s. It is concluded that: (1) The described technique for studying lung uptake gave consistent and reproducible results in human volunteers; (2) Lung uptake of lidocaine in healthy man exceeds that previously observed in anaesthetized pigs; (3) The initial uptake during the first 5 s after appearance of indocyanine green in the arterial samples was more than 90%. (4) The lungs thus have a dampening effect on the arterial concentration, which might be of importance if lidocaine is accidentally injected intravenously.

Adult↗
PubMed1979

Physico-chemical modification of lidocaine uptake in rat lung tissue.

The uptake of lidocaine, methyllidocaine, bupivacaine, etidocaine was studied in rat lung slices at different pH-values. The accumulation of the quaternary analogue, methyllidocaine, was not changed in the pH interval 7.0--8.0. The uptake of the three other substances was about 3--4 times lower at pH 7.0 than at pH 8.0. The rank order of distribution at a fixed cation/base ratio was bupivacaine greater than etidocaine greater than lidocaine. Interactions between lidocaine and other substances were studied in lung slices and in isolated perfused lungs. Bupivacaine and nortriptyline counteracted the accumulation of 14C-lidocaine in lung slices in a dose-dependent manner. Nortriptyline was more effective than bupivacaine. In isolated perfused lung, bolus injections of nortriptyline and lidocaine rapidly displaced 14C-lidocaine from the tissue. In this study we suggest that the base form of local anaesthetics accumulate in the lung tissue, while the cationic form binds to accessible binding sites in the cell membranes.

Animals↗
PubMed1979

Displacement of nortriptyline and uptake of 14C-lidocaine in the lung after administration of 14C-lidocaine to nortriptyline intoxicated pigs.

Six anaesthetized Swedish land-race pigs were intoxicated by an intravenous infusion of nortriptyline-HCl (NT) up to a concentration of 4.58 +/- 0.58 (mean +/- S.E.M.) microM in arterial whole blood. A rapid injection of 2 mg/kg b.wt. lidocaine-HCl in the right atrium was followed by a rise in arterial whole blood concentration of NT up to a maximum of 7.32 +/- 0.28 microM NT. Amount displaced NT from the cardio-pulmonary circulation after the 14C-lidocaine bolus, was calculated to be 0.66 +/- 0.03 mumol. Lung uptake of 14C-lidocaine during first-pass through the lung was not influenced to any statistically signficant degree compared to a control group. Thus, first pass uptake (FPU) was 30 +/- 8 (mean +/- S.E.M.)% and 39 +/- 5% respectively. The duration of the QRS-complex of the ECG was increased (P less than 0.01) during the infusion of NT from 0.07 +/- 0.01 (mean +/- S.E.M.) sec. to 0.14 +/- 0.02 sec. when 250 mg NT-HCl had been administered. The QRS-duration was decreased (P less than 0.01) after the injection of the 14C-lidocaine bolus to 0.09 +/- 0.01 sec. Mean arterial blood pressure and heartrate decreased slightly during the infusion of NT, but did not change immediately after the 14C-lidocaine bolus.

Animals↗