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Biomedical subjects

M M Puig

Publications and source records attributed to M M Puig.

At least 73 records · Page 4Linked to original sources
PubMed1989

The hyperalgesic effect of naloxone is attenuated in streptozotocin-diabetic mice.

In mice with streptozotocin-induced hyperglycemia, nociception was tested after naloxone administration in hot plate and tail immersion tests. The choice of these two tests was to include a supra-spinal nociceptive reflex indicative of higher cognitive process (hot-plate test) as well as a reflex which predominantly represents lower spinal motor mechanisms (tail immersion test). Naloxone-induced hyperalgesia was attenuated in both tests in mice with streptozotocin-induced diabetes. In mice with hyperglycemia induced by intraperitoneal dextrose administration, naloxone hyperalgesia was significantly enhanced in the hot plate test. The basal nociceptive threshold in streptozotocin-treated animals was decreased in the immersion but not in the hot plate test. These results indicate that hyperglycemia per se does not adequately explain the changes in naloxone hyperalgesia in experimental models of diabetes. They also suggest that acute hyperglycemia may modify the interaction of endogenous opioid peptides with their receptors only at supra-spinal sites. However, chronic hyperglycemia appears to affect endogenous opioid peptides both at spinal and supra-spinal levels and their interaction with the opiate receptors.

Animals↗
PubMed1989

Prevention of hyperthermia-induced seizures in immature rats by a hydantoin derivative of naloxone.

The non-specific opiate antagonist naloxone protects immature rats from hyperthermic seizures which occur when the animals are exposed to an environment of 40 degrees C and 55% humidity. Most of the currently used antiepileptic therapeutic agents can be said to contain either a hydantoin or a moiety stereochemically closely related to one. We have added a hydantoin group to naloxone and created a new combined chemical, naloxyl-6-alpha spirohydantoin. The new compound was ten times as effective as naloxone against hyperthermic seizures in 15-day old rat pups. Unlike naloxone, the new naloxone-hydantoin derivative retained a protective effect 24 hrs after injection.

Animals↗
PubMed1989

Effect of yohimbine on nociceptive threshold in normoglycemic and streptozotocin-treated hyperglycemic mice.

The effects of yohimbine (0.1, 1, 3 and 10 mg/kg SC) on nociceptive threshold were tested in mice using the tail-immersion and hot-plate tests. The tail-flick (withdrawal) latency, a monosynaptic spinal nociceptive response, was significantly lowered by yohimbine. This hyperalgesic response was at its peak 0.5 hr after yohimbine injection. The tail-flick latencies expressed as % of basal latencies were, 95 +/- 8, 100 +/- 10, 62 +/- 10, 33 +/- 7 and 28 +/- 4 in vehicle and 0.1, 1, 3 and 10 mg/kg in yohimbine-treated groups respectively. Yohimbine-induced hyperalgesia was observed when stimulus temperature was either 50 degrees C or 45 degrees C; however, the opiate antagonist naloxone (3 mg/kg SC) induced a hyperalgesic response at 50 degrees C and an analgesic response at 45 degrees C stimulus temperature. Streptozotocin-induced hyperglycemia did not influence the hyperalgesic response of yohimbine. In the hot-plate (60 degrees C) test, which involves higher centers and a polysynaptic nociceptive reflex, yohimbine did not modify the jump latency. The data provide evidence for the presence of a tonic spinal noradrenergic inhibitory control of nociceptive mechanism(s) which does not appear to be readily altered by hyperglycemia.

Animals↗
PubMed1989

Tail immersion test for the evaluation of a nociceptive reaction in mice. Methodological considerations.

The effect of two commonly used methods to immobilize the animals, viz. tube restrainer and wrapping in a diaper (chux) on the tail flick latency in immersion test, was evaluated in mice using a stimulus temperature of 50 degrees C. The animals were immobilized either in the tube or chux briefly (25-30 sec) during the tail flick measurements. The basal tail flick latency was 2.8 +/- 0.2 in the tube restrained and 5.5 +/- 0.3 sec in chux restrained groups (p less than 0.001). The analgesic effect of morphine (1, 3, 4, 7, and 10 mg/kg) was significantly higher in the chux-restrained animals as indicated by the dose ratio of 2.16 for the 50% analgesic response in the chux versus tube restrained mice. The tail flick latency, 15 min after naloxone injection (1 and 3 mg/kg), expressed as % of predrug latency was significantly reduced in the chux- but not the tube-restrained group. The hyperalgesic effect of naloxone could not be detected in chux-restrained animals, when the water temperature was increased to 55 degrees C. The results demonstrate that the restraining procedure will influence the analgesic effects of test drugs in tail immersion test. Furthermore, the stimulus temperature appears to be an important variant that could influence the results in this test. The present results demonstrate the hyperalgesic effect of naloxone after systemic administration in the tail immersion test and supports the concept that tail flick response is tonically inhibited by endogenous opioid systems.

Animals↗
PubMed1989

Antinociceptive effects of azepexole (BHT 933) in mice.

Subcutaneous (s.c.) administration of azepexole (BHT 933) at doses between 4 and 40 mg/kg produced dose-dependent antinociceptive effects in mice as assessed by tail-immersion, tail-pinch and acetic acid writhing tests. The ED16s were 5.6 +/- 0.4, 6.7 +/- 1.2 and 2.96 +/- 0.2 mg/kg respectively. Similarly, morphine produced analgesia in the same tests with ED16s of 0.87 +/- 0.03, 0.47 +/- 0.1 and 0.45 +/- 0.01 mg/kg respectively. In all instances naloxone (0.1 mg/kg s.c.) shifted the dose-response curves to morphine to the right in a parallel manner. Naloxone (0.1 and 1 mg/kg s.c.) partially antagonized the effect of azepexole in the tail-immersion and tail-pinch tests but significantly decreased the slope of the dose-response curve suggesting that a competitive interaction at the level of the opioid receptors did not occur. Naloxone had no effect on the antinociceptive action of azepexole in the acetic acid writhing test.

Analgesics↗
PubMed1989

Beta-endorphin and ACTH levels in the perioperative period.

1. The purpose of this study was to determine the plasma levels of beta-endorphin (beta-END) and ACTH in the perioperative period, define correlations of hormonal plasma levels with clinical parameters and establish the effect of droperidol premedication on hormonal levels and clinical parameters. 2. Twenty two were assigned to one of two groups: (1) Control (no premedication) and (2) droperidol (7.5 mg im) premedication. 3. Venous blood samples and clinical evaluations were done the day prior to surgery, just prior to induction of anesthesia and 1-1.5 hr postoperatively. 4. The results indicate that (1) expectancy of surgery on arrival to the operating room increases beta-END but not ACTH plasma levels, (2) this increase in beta-END is not affected by droperidol administration and (3) postsurgical stress increases beta-END and ACTH above operating room levels. 5. These results indicate that although beta-END and ACTH are both produced by the pituitary and derived from a common precursor, the type of stimuli (pre- versus postsurgical stress) seems to differentially affect their plasma levels.

Adrenocorticotropic Hormone↗
PubMed1989

Hyperglycemia does not modify the pupillary effects of mu and kappa opiate agonists in mice.

The effects of mu and kappa opiate agonists were assessed on the pupillary size in normoglycemic and hyperglycemic conditions in mice. The mu agonists used were, morphine (10, 30 and 100 mg/kg), fentanyl (50, 100 and 150 micrograms/kg) and sufentanil (5, 10 and 20 micrograms/kg). The highly selective kappa opiate agonists used were, U-50488H and U-69593 (30 mg/kg). Chronic hyperglycemia was induced by streptozotocin injection (200 mg/kg i.p) 7-8 days before the experiment. Acute hyperglycemia was induced by intraperitoneal glucose (5 g/kg i.p) injection at the time of subcutaneous injection of opiates. In the normoglycemic mice, the mu agonists produced significant mydriasis (P less than 0.05), while kappa agonists had no effect on the pupil. However, both acute and chronic hyperglycemic condition did not affect the mydriatic ratio of the mu opiate agonists. These results indicate that mu opiate receptors induce mydriasis in mice and suggest that the hyperglycemia is not the mechanism involved in the opiate induced mydriasis in mice. With the dose of kappa agonists used, the involvement of kappa receptors in the pupillary effects in mice were not clear. These results support the hypothesis that hyperglycemia is not the primary mechanism for the altered sensitivity of opiates in the animal models of diabetes.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Hypothermia enhances the effects of morphine on hormonal and histamine release.

1. The effects of intravenous (i.v.) morphine on adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-END), total catecholamines (CA) and histamine (HIS) plasma concentrations, were determined in anaesthetized dogs at 30 degrees C and 37 degrees C. 2. Hypothermia initially increased CA levels by 29%, but the values returned to baseline after 2 h. Morphine (1 mg/kg, i.v.) produced a significant decrease in CA both at 37 degrees C and 30 degrees C (34% and 54%, respectively). Subsequent administration of naloxone (1 mg/kg, i.v.) significantly increased CA levels in both groups. 3. Hypothermia per se had no effect on ACTH, beta-END, and HIS concentrations. Morphine produced a significant increase in pituitary hormones and HIS, in hypothermic but not in normothermic animals. Morphine concentrations were significantly higher at 30 degrees C during the first 45 min. 4. The results suggest that the effects of morphine on hormonal and histamine release observed at 30 degrees C are concentration-dependent and related to changes in morphine pharmacokinetics.

Adrenocorticotropic Hormone↗
PubMed1989

Hyperglycaemia as a factor affecting kappa-opiate agonist-induced inhibition of the gastrointestinal transit in mice.

The effects of highly selective kappa-opiate agonists were assessed on the gastrointestinal motility in normoglycaemic and hyperglycaemic conditions in mice. Chronic hyperglycaemia was induced by streptozocin injection (200 mg kg-1 i.p.), 7-8 days before the experiment. Acute hyperglycaemia was induced by glucose injection (5 g kg-1 i.p.) at the time of opiate administration. The kappa-opiate agonists, U-50488H and U-69593 (1, 3 and 10 mg kg-1) were injected (i.p.) just before the charcoal meal. The animals were killed 45 min later and the distance travelled by the test meal was measured. In the normoglycaemic mice, both kappa-agonists significantly (P less than 0.05) inhibited the meal transit and this effect was significantly (P less than 0.05) augmented in acute hyperglycaemic animals. However, in chronic hyperglycaemic animals U-50488H failed to inhibit the charcoal meal transit, while U-69593 produced anti-transit effect comparable to that observed in normoglycaemic mice. These results demonstrate that kappa-opiate agonists produce anti-transit effects in mice that these effects are enhanced during acute hyperglycaemia. The disparity of anti-transit effects of kappa-opiate agonists in acute vs chronic hyperglycaemia supports the hypothesis that elevated glucose levels are not the primary mechanism for the altered response to opiates observed in the experimental models of diabetes.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Plasma beta-endorphin levels in the umbilical cord blood of preterm human neonates.

Maternal venous (MV) and neonatal umbilical venous (UV) and umbilical arterial (UA) plasma beta-endorphin concentrations were measured at birth in two groups of patients undergoing cesarean section (CS). Patients in group 1 carried a term gestation (n = 12, birth weight 3,640 +/- 150 g, 1 SEM). Patients in group 2 (n = 12) carried a preterm gestation (birth weight 1,956 +/- 150 g). In the term neonate the UV and UA plasma beta-endorphin were 11.5 +/- 4 and 13.5 +/- 4 picomoles/liter, respectively. In the preterm neonate the UV and UA values were 23.6 +/- 4 and 23.5 +/- 5 picomoles/liter, respectively. Both values in the preterm neonate were significantly greater than the corresponding value in the term neonate (p less than 0.05). The MV plasma beta-endorphin did not significantly differ among the two groups. Data suggest that in preterm neonates increased plasma beta-endorphin levels occur at the time of birth.

Cesarean Section↗
PubMed1989

Sufentanil pharmacokinetics in neurosurgical patients.

The effects of respiratory alkalosis and dehydration on the pharmacokinetics of sufentanil have been determined. Forty neurosurgical patients entered the study: group I (n = 20) had spinal surgery while group II (n = 20) had elective craniotomies. All patients received a single intravenous bolus of sufentanil (2 micrograms/kg) during induction of anesthesia. Patients in group II received furosemide (40 mg) and mannitol (1 g/kg) prior to surgery and were hyperventilated to a PaCO2 below 30 mmHg. The anesthetic management was identical in both groups. Arterial blood samples were collected to determine sufentanil concentrations (RIA), blood gases, pH, hematocrit and electrolytes. Patients in group II had significantly higher blood pH and urinary output when compared to group I (p less than 0.05). Plasma sufentanil concentrations were best fitted to a bi-exponential curve and the pharmacokinetic variables calculated using a curve stripping program (STRIPE). No significant differences were observed between groups regarding plasma sufentanil concentrations or pharmacokinetic parameters. Our results demonstrate that respiratory alkalosis and dehydration do not alter the pharmacokinetics of sufentanil after intravenous bolus administration.

Alkalosis↗
PubMed1988

Stereospecific inhibition of gastrointestinal transit by kappa opioid agonists in mice.

Systemic administration of highly selective kappa opiate agonists, U-50488H and U-69593 (3, 10 and 30 mg/kg i.p.) produced significant inhibition of the gastrointestinal transit in mice as assessed by charcoal meal test. In contrast, the (+) stereoisomer of U-50488H, U-53455E did not inhibit the gastrointestinal motility. Furthermore, the kappa-selective antagonist, Mr 2266 (3 mg/kg) when administered along with the agonists, reversed the effects of the agonists. These results suggest that stereospecific kappa opiate receptors are involved in inhibition of gut motility in mice.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Influence of hypo and hyperthermia on disposition of morphine.

Using morphine as a prototype opiate anesthetic, the dispositional changes and cardiovascular effects during hypothermia (30 degrees C) and hyperthermia (40 degrees C) in dogs under isoflurane anesthesia was assessed. Single intravenous bolus injection of 1 mg/kg morphine resulted in a significant and sustained decrease in mean arterial pressure in hypothermic, but not in hyperthermic or normothermic (37 degrees C) conditions. Hypothermic dogs showed significantly higher levels of morphine both in plasma and in cerebrospinal fluid. In contrast, hyperthermia did not affect these levels. Body temperature did not affect the t1/2 alpha, however t1/2 beta and mean residence time were significantly increased while volume of distribution at steady state and total body clearance were decreased during hypothermia. The results provide evidence that hypothermia is likely to be associated with a sustained increase in opiate levels and might be associated with a enhanced side effects. The results suggests the need for a controlled clinical trial to assess the dose of opiate anesthetics during hypothermia.

Animals↗
PubMed1988

Effects of mu receptor agonists and droperidol on motor coordination in mice.

The effects of morphine, fentanyl, sufentanil and droperidol on motor coordination in mice were studied. Animals were trained to complete successfully the rotarod test before assessing the effects of drugs. Administration of analgesic doses of the mu agonists morphine, fentanyl and sufentanil did not inhibit motor coordination. Droperidol produced a dose related inhibition of motor coordination. When a subthreshold dose of droperidol was administered followed by an opiate, a significant inhibition of motor coordination was observed. The results indicate that although analgesic doses of mu opioid agonists do not affect motor coordination, their combination with droperidol results in motor incoordination. The mechanisms and/or opioid receptor sub-types involved in this in vivo interaction remain to be established.

Animals↗
PubMed1988

Droperidol enhances fentanyl and sufentanil, but not morphine, analgesia.

1. The effect of droperidol pre-treatment on the analgesic potency of morphine, fentanyl and sufentanil was assessed in mice. 2. Acetic acid writhing test and tail immersion test were used to measure the analgesic response. 3. The neuroleptic augments the effects of sufentanil and fentanyl. 4. Thus, the dose-response curves for fentanyl and sufentanil were shifted to the left and the ED50 of the analgesics lowered in droperidol pre-treated animals. 5. However, morphine analgesia was not influenced by droperidol. 6. The results suggest that combination of sufentanil or fentanyl with droperidol may be better than morphine to produce neuroleptanalgesia and anesthesia.

Analgesics, Opioid↗
PubMed1988

Synergistic interaction of morphine and halothane in the guinea pig ileum.

The present study describes the effects of halothane on morphine activity in the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum. Morphine and halothane produced a dose-related inhibition of the electrically induced muscle contractions with IC50 of 1.9 X 10(-7) and 1.7 V/V%, respectively. The effects of morphine, but not halothane, were antagonized by naloxone. The IC50 of morphine was decreased in the presence of halothane (0.8-3.0 V/V%). Hill coefficients derived from dose-response curves were less than one for morphine or halothane alone, while it was 1.4 for the combination. The pA2 values (a measure of affinity of the antagonist for the opioid receptor) for naloxone in the absence and presence of halothane (1.6%) were 9.4 and 9.1, respectively. These results indicate that 1) halothane increases the potency of morphine in the guinea pig ileum at clinically relevant concentrations, 2) the interaction between the agents is synergistic, and 3) halothane does not modify the binding of naloxone to opioid receptors, but may affect membrane or intracellular processing of the receptor signal.

Animals↗
PubMed1988

High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

Animals↗