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At least 1,063 records · Page 59Linked to original sources
PubMed1985

Effects of massive doses of alpha-MSH on thermoregulation in the rabbit.

alpha-MSH-related compounds may prove to be clinically useful antipyretics since the parent peptide is extremely potent in reducing fever, it is effective when given orally, and it neither stimulates corticosteroid activity nor has marked melanotropic effects in man. To determine whether or in what doses alpha-MSH might cause harmful side-effects, we injected doses greatly exceeding those required to reduce fever into a lateral cerebral ventricle of afebrile rabbits. One hundred to seven hundred and fifty micrograms alpha-MSH caused large and prolonged reductions in body temperature and the dose-response relation was bell-shaped for both magnitude and duration. These doses caused no apparent injury to the animals. One mg alpha-MSH elicited hyperthermic responses that were variable in magnitude and duration. Animals that had previously received large doses of alpha-MSH (greater than or equal to 100 micrograms) did not develop hyperthermia, even when given 2 mg, indicating an acquired tolerance to this hyperthermic action of alpha-MSH. All animals, tolerant or previously uninjected, showed symptoms with doses greater than or equal to 1 mg alpha-MSH that included: increased salivation, agitation, ataxia, respiratory distress, and death (in 30% of the animals); those that recovered from these large doses resumed outwardly healthy appearance and behavior. Although alpha-MSH is toxic when given centrally in large doses, the 5000-fold difference between antipyretic and toxic doses indicates a wide safety margin should this peptide be used clinically as an antipyretic drug.

Animals↗
PubMed1991

Natriuresis, not seizures, induced by cholinergic stimulation of the locus coeruleus is affected by forebrain lesions and water deprivation.

Two groups of rats with electrolytic lesions of the medial and upper septal area (MUL) or, alternatively, of the anteroventral portion of the third ventricle (AV3V) and a third group of sham-operated rats were water loaded and received three carbachol injections into the locus coeruleus according to the following schedule: 1) prelesion, 2) on the second postlesion day and 3) on the seventh postlesion day. Both MUL and AV3V lesions inhibited the carbachol-induced natriuresis on the second postlesion day. Recovery was almost complete after MUL but not after AV3V lesion on the seventh day. Water deprivation also reduced the carbachol-induced natriuresis but passive hydration of AV3V animals did not avoid the impairment induced by the lesion. Transient seizure phenomena such as clonic convulsions, salivation and analgesia subsequent to carbachol injection were not altered by the lesions.

Animals↗
PubMed1986

Pharmacologic and reinforcing properties of phencyclidine and the enantiomers of N-allylnormetazocine in the dog.

Experiments were conducted to evaluate the degree of phencyclidine (PCP)-like activity associated with the dextro and levo enantiomers of the sigma agonist N-allylnormetazocine (NANM). In chronic spinal dogs, d- and l-NANM generally produced similar physiologic and gross animal behavior effects which included miosis, tachycardia, hyperthermia, increased secretory activity (lacrimation, rhinorrhea and salivation), nystagmus and stereotyped head movements. For these effects, d- and l-NANM were generally equal in potency and both were about 1/10th as potent as PCP. However, the NANM enantiomers could be differentiated on the basis of their effects on nociceptive reflexes. Comparisons of dose-response curves and efficacies demonstrated that d-NANM was more similar to PCP in its effectiveness in depressing the flexor and skin twitch reflexes than was l-NANM. In addition, naltrexone selectively antagonized or reduced only the effects of l-NANM on reflex activity. In intact dogs, d-NANM and PCP, but not l-NANM maintained self-administration behavior under FR15 or FI900 (FR10:S) schedules of reinforcement. This represented the most stereospecific action of the NANM enantiomers. Additionally, l-NANM failed to maintain self-administration behavior, even following pretreatment with naltrexone, thus suggesting that the opiate activity of l-NANM was not responsible for its lack of reinforcing efficacy. Taken together, the data demonstrate that both d- and l-NANM have PCP-like properties, but d-NANM is pharmacologically more equivalent than l-NANM to PCP and l-NANM has additional activity which is not PCP-like.

Animals↗
PubMed1984

Acute toxicity studies with quinuronium sulfate in laboratory animals and sheep.

The acute toxicity of quinuronium was investigated by measurements of lethal doses (LD50) in mice and rats, cholinesterase activity in vivo in whole blood, and protection from anticholinesterase activity by atropinisation in sheep and rabbits. The LD50s in mice injected i.p. and s.c. were 4.80 and 5.40 mg/kg and in rats 6.3 and 6.5 mg/kg for i.p. and s.c. routes, respectively. Signs of salivation, defecation, anorexia and muscular spasms were observed in sheep. In rabbits anorexia and depression only were observed. There was species variation in normal cholinesterase activity, rabbits being low in activity. Quinuronium inhibited cholinesterase activity from 10 min to 24 h after treatment in sheep by 24% of the normal baseline values. The enzyme activity returned to normal at 48 h. Atropinisation partially protected against anticholinesterase activity in sheep; cholinesterase activity was inhibited by only 14% of the normal baseline values 10 min to 2 h after treatment. This study indicates that quinuronium is highly toxic and that rabbits are moderately resistant.

Animals↗
PubMed1991

Teratogenicity study of tri-n-butyltin acetate in rats by oral administration.

A teratological test was carried out on tri-n-butyltin acetate (TBTA) used as a biocide and anti-fouling agent. Pregnant Wistar rats were treated orally with TBTA at dose levels of 0, 1, 2, 4, 8, and 16 mg/kg from days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. In pregnant rats, salivation and depression of body weight gain and food intake were observed at a late stage of pregnancy at the highest dose level of TBTA. Atrophy of the thymus was also observed in a dose-dependent manner on day 20 of gestation. In the fetuses, treatment with the highest dose level increased embryonic and fetal deaths, increased the incidence of fetuses with cleft palate, cervical rib and/or rudimentary lumbar rib, and decreased the body weights of fetuses.

Abnormalities, Drug-Induced↗
PubMed1995

Pyrethroids, nerve poisons: how their risks to human health should be assessed.

The extensive worldwide efforts of structural modification of natural pyrethrins for better performances have resulted in successful development of a wide variety of synthetic pyrethroids with tremendously high efficacy, knock-down activity or vapor action, and/or with acceptable environmental stability and safety. Currently these pyrethroids including their preferentially manufactured stereoisomers are widely used in agriculture, and for public health as well as household insect control. The detailed toxicology and metabolism studies intended to attain human risk assessment have revealed that with voltage-dependent sodium channel as target site pyrethroids induce pronounced repetitive activity characterized grossly by tremor, hypersensitivity, choleoathetosis, and salivation. In addition, so-called cyano-pyrethroids cause transient skin paresthesia in workers. With regard to tumorigenicity, mutagenicity, teratogenicity and developmental toxicity, no significant findings have been reported. Pyrethroids are eliminated from the animals quite rapidly and completely, undergoing oxidation and ester hydrolysis followed by various conjugations, with low tissue residues. Thus, overall, sound scientific bases exist for human risk assessment under the present usage conditions.

Animals↗
PubMed1979

Jaborandi: an interdisciplinary appraisal.

In spite of many references to Pilocarpus Jaborandi Holmes in ethnological and botanical sources and suggestions of its employment for a variety of diseases, it has not been possible to pin down the use of its leaves to any particular purpose amongst South American Indians. While the medically important jaborandis are species of Pilocarpus, it is true that this vernacular name is commonly applied to other rutaceous and numerous piperaceous plants as well. The introduction of jaborandi leaves to western medicine goes back to 1873, when Symphronio Coutinho went to Europe, taking with him samples of the leaves. The copious sweating and salivation brought about by the leaves attracted the attention of French physicians. Soon jaborandi leaves were being employed in the treatment of many diseases. In 1875, Hardy and Gerrard independently discovered the alkaloid pilocarpine. Most therapeutic applications of jaborandi leaves and pilocarpine fell into disuse and were discontinued. What remained was the use of the latter in ophthalmology, where it had been introduced as a miotic by Weber in 1876. The mixture of pilocarpine and another natural product, physostigmine, remains to this day one of the mainstays in ophthalmology.

Alkaloids↗
PubMed1986

Psychopharmacologic analysis of an alleged oneirogenic plant: Calea zacatechichi.

Calea zacatechichi is a plant used by the Chontal Indians of Mexico to obtain divinatory messages during dreaming. At human doses, organic extracts of the plant produce the EEG and behavioral signs of somnolence and induce light sleep in cats. Large doses elicit salivation, ataxia, retching and occasional vomiting. The effects of the plant upon cingulum discharge frequency were significantly different from hallucinogenic-dissociative drugs (ketamine, quipazine, phencyclidine and SKF-10047). In human healthy volunteers, low doses of the extracts administered in a double-blind design against placebo increased reaction time and time-lapse estimation. A controlled nap sleep study in the same volunteers showed that Calea extracts increased the superficial stages of sleep and the number of spontaneous awakenings. The subjective reports of dreams were significantly higher than both placebo and diazepam, indicating an increase in hypnagogic imagery occurring during superficial sleep stages.

Adult↗
PubMed1991

Adult respiratory distress syndrome from organophosphate poisoning.

A 46-year-old man after an accidental exposure to organophosphates developed florid adult respiratory distress syndrome (ARDS). A markedly suppressed level of pseudocholinesterase and red blood cell cholinesterase with profuse salivation and sweating confirmed the diagnosis of organophosphate poisoning. Within 48 hours, patient developed respiratory distress needing intubation. Despite maximum ventilatory support and positive end-expiratory pressure, hypoxia persisted, Swan Ganz (Baxter Healthcare Inc, Irvine, CA) pressures showed low pulmonary capillary wedge pressure and patient died on the third hospital day. An autopsy confirmed the picture of ARDS. Other potential causes of ARDS were excluded. Although rare, organophosphate poisoning should be added to the list of toxins causing ARDS.

Humans↗
PubMed1986

A comparative study of salivary secretion by parotid and mandibular glands of anaesthetized Capra hircus: effect of pilocarpine.

A study was made of basal secretion and the effect of the infusion of pilocarpine on the flow and composition of saliva in the parotid and mandibular glands of the anaesthetized lactating goat. In the parotid gland there was a basal flow (1.6 +/- 0.29 microliter/min) which was not present in the mandibular gland. There is a statistically significant dose-effect relationship between pilocarpine and salivary flow in both glands. Salival composition and its variation with respect to the flow of saliva did not conform to either of the two glands to an exclusive monogastric or ruminant model.

Animals↗
PubMed1992

The effects of clonidine and three 2-imidazoline derivatives on the secretion of protein and some electrolytes by rat submandibular and parotid glands.

1. Three imidazoline analogues of clonidine were potent secretagogues for the parotid and submandibular glands at relatively high doses. 2. Salivation in response to clonidine was completely abolished by prazosin, phentolamine, phenoxybenzamine and dihydroergotamine. 3. The gamma-type of proteins was secreted in response to three of the analogues, whereas with p-aminoclonidine the alpha-type of proteins was secreted by the submandibular gland. 4. Albumin was specifically secreted by the submandibular gland in response to clonidine but not to isoproterenol or phenylephrine.

Animals↗
PubMedDate not supplied

Behavioral effects of pydrin and ambush in male mice.

Male Swiss mice, 20-25 g, were utilized to assess the effects of dermal and oral administration of the pyrethroid insecticide formulations Pydrin (30% fenvalerate) and Ambush (25.6% permethrin). Animals were subjected to a conditioned taste aversion procedure using a normally preferred 0.3% saccharin solution. Subjects were allowed 30 min access to a drinking syringe containing the saccharin solution, followed immediately by the administration of the pyrethroid or control solution. Pydrin (0.3, 3.0, or 30 mg/kg orally; 60, 600, or 1800 mg/kg dermally) and Ambush (0.5, 5.0, or 50 mg/kg orally; 30, or 300 mg/kg dermally) produced significant (p less than 0.05) reductions in the percent saccharin consumed. Total fluid intake, however, was not significantly altered by any of the treatments. The effect of the insecticides on both grouped and individual activity was also assessed in 20-25 g male Swiss mice. Activity measurements were taken over the 4-hr time period immediately following the administration of the pyrethroid or control solution. Pydrin (30 mg/kg orally; 600 and 1800 mg/kg dermally) and Ambush (50 mg/kg orally; 300 mg/kg dermally) significantly (p less than 0.05) increased activity in both grouped and individually tested mice. When subjects were individually tested, significant increases were seen in non-ambulatory, but not in ambulatory activity. The results of this work indicate that administration of the commercially available preparations of Pydrin and Ambush in mice at doses that do not induce the tremor and choreoathetosis-salivation syndromes usually associated with pyrethroid insecticides may result in behavioral changes.

Administration, Cutaneous↗
PubMedDate not supplied

Assessment of the acute acrylonitrile-induced neurotoxicity in rats.

Acrylonitrile (VCN) is an aliphatic nitrile which is used extensively in manufacturing of synthetic fibers, plastics, and rubber. Although the neurotoxicity of VCN is recognized, no thorough characterization of this effect has been reported. Current studies were designed to quantitatively characterize the acute phase of VCN-induced cholinomimetic neurotoxicity, and to determine the effects of dose, route of administration, and atropine on such toxicity. Administration of a single gavage or subcutaneous doses of 20, 40, or 80 mg VCN/kg to male Sprague-Dawley rats causes two distinctive phases of acute neurotoxic effects. Signs observed in the early phase had a rapid onset, and were cholinomimetic in nature. They included salivation, lacrimation, chromodacryorrhea, polyuria, miosis, vasodilatation in face, ears and extremities, increased gastric secretion, and diarrhea. A late phase developed hours after VCN dosing, and the toxic signs included depression, convulsions, and respiratory failure followed by death at high doses. These results revealed that the cholinomimetic toxicity induced by VCN was dose related regardless of the route of administration. In another study, rats were pretreated with atropine (1 mg/kg, IP) prior to VCN (40 mg/kg) in order to investigate the role of the cholinergic system. Atropine protected rats against VCN-induced cholinomimetic neurotoxicity, suggesting possible involvement of the cholinergic system. Finally, this work provides essential basic information for studying the biochemical, pharmacological, and neurological basis of VCN-induced neurotoxicity in the rat.

Acrylonitrile↗
PubMedDate not supplied

Utility of a neurobehavioral screening battery for differentiating the effects of two pyrethroids, permethrin and cypermethrin.

The ability of a neurobehavioral screening battery to differentiate the effects of two pyrethroids, permethrin and cypermethrin, was assessed in this experiment. Although the structures of these pesticides differ only in the alpha-cyano group, the behavioral syndromes associated with the Type I and II pyrethroids are quite different. The tests included a functional observational battery which is a series of subjective and quantitative measures of neurological function and behavior, and an automated measure of motor activity. Our results verified previous reports in the literature describing these different syndromes, i.e., aggressive sparring behavior, fine to whole-body tremor, hyperthermia, and decreased motor activity for the Type I pyrethroid permethrin, and pawing, burrowing, salivation, whole body tremor to choreoathetosis, hypothermia, and lowered motor activity for the Type II pyrethroid cypermethrin. In addition, we report that permethrin produced decreased grip strengths, increased resistance to capture, increased reactivity to a click stimulus, and induced head and forelimb shaking and agitated behaviors, whereas cypermethrin produced pronounced neuromuscular weakness and equilibrium changes, retropulsion, lateral head movements, alterations in responses to various stimuli, and increased urination. Although there were similarities in some effects (e.g., decreased motor activity), the pesticides differed sufficiently in their overall behavioral profiles, and severity and time course of effects, to discriminate these two compounds. Thus, this type of screening approach is sensitive enough to differentiate these pyrethroids for hazard identification purposes.

Animals↗
PubMedDate not supplied

Comparisons of the acute effects of cholinesterase inhibitors using a neurobehavioral screening battery in rats.

The clinical signs of intoxication produced by cholinesterase inhibitors, many of which are used as pesticides, are considered important information for regulatory purposes. We conducted acute studies of cholinesterase inhibitors to compare their effects as determined by a functional observational battery (FOB) and motor activity. The acute effects of two carbamates (carbaryl, aldicarb) and five organophosphates (OP) (chlorpyrifos, diazinon, parathion, fenthion, and diisopropyl fluorophosphate, or DFP) were evaluated on the day of dosing at the time of peak effect, at 1 and 3 days, and 1 week after dosing (oral gavage, in corn oil). A high dose was selected that produced clear cholinergic signs, and lower doses were chosen to produce a range of effects. Generally all cholinesterase inhibitors produced autonomic signs of cholinergic overstimulation (salivation, lacrimation, and miosis), hypothermia, mild tremors and mouth-smacking (chewing motions), lowered motor activity, decreased tail-pinch response, and altered neuromuscular function (gait changes and increased foot splay). The measures generally found to be most sensitive on the day of dosing were body temperature, motor activity, gait, and the presence of mouth-smacking and fine tremors. However, no single measure was the most sensitive across all compounds; for example, the lowest dose of fenthion decreased motor activity by 86% but did not alter the tail-pinch response, whereas the lowest dose of parathion did not lower activity but did decrease the tail-pinch response. For some measures, differences in the slopes of the dose-response curves were evident. Many effects were still observed at 24 h, but recovery was apparent for all compounds. Interestingly, residual effects at 72 h were obtained with the carbamates (carbaryl, aldicarb) as well as with the Op fenthion, but not with the other compounds. Thus, the overall clinical picture of toxicity was similar for these cholinesterase inhibitors, but compound-specific differences emerged in terms of the individual measures, dose-response, and time course.

Aldicarb↗
PubMed1996

[Unilateral gustatory flushing syndrome in a child].

BACKGROUND: Auriculo-temporal syndrome is rarely seen in children: it is sometimes considered as secondary to an obstetrical injury. CASE REPORT: A 2.5 year-old boy was examined because he suffered from post-prandial flushing of the right cheek for 2 years. He was born normally and neurologic examination was normal. The rash was not associated with sweating or tearing. CONCLUSION: There is no evidence to support food allergy in this case: rather, this syndrome probably occurs in response to salivation.

Child, Preschool↗
PubMed1987

Recent views on the pathogenesis of gastro-oesophageal reflux disease.

The pathogenesis of GORD depends on a mix of factors which vary amongst individual patients. The central issue in the pathogenesis of gastro-oesophageal reflux is understanding of the mechanisms that lead to reflux, since the effects of all other factors depend on this event. Consequently, new information and views about the mechanisms of gastro-oesophageal reflux have been presented in detail. This information suggests that defective lower oesophageal sphincter motility is the most important abnormality that underlies pathological gastro-oesophageal reflux. Two major forms of LOS dysfunction have been identified as responsible for pathological gastro-oesophageal reflux in the horizontal position: (1) an excessively frequent rate of occurrence of transient LOS relaxations; and (2) defective basal LOS tone. Both of these dysfunctions appear to arise from abnormal neural control of the LOS, probably by the central nervous system. The effect of these LOS dysfunctions on gastro-oesophageal competence is probably significantly influenced by non-sphincteric factors, the most important of these apparently being hiatus hernia. Though there is currently poor understanding about the ways in which hiatus hernia impairs gastro-oesophageal competence, measurement techniques have now advanced sufficiently to allow significant accrual of knowledge in this field. Once reflux has occurred, the efficiency of oesophageal acid clearance plays a major role in determining the impact of reflux on the oesophageal mucosa. Recent studies have shown that oesophageal acid clearance depends on both effective volume clearance and neutralization by saliva of residual acid in the oesophageal lumen. The efficiency of oesophageal volume clearance of both stimulated and real reflux has not been studied formally in GORD patients, but the high incidence of peristaltic dysfunction in reflux disease suggests that volume clearance will be defective in some patients. The limited information available about salivation in GORD patients suggests that salivary secretion is no different from that of age-matched controls, but that there is an age-dependent loss of the salivary response to oesophageal acidification. This impairment of salivary response may produce an age-dependent decline of the efficiency of oesophageal acid clearance. Unusually aggressive refluxate and impaired mucosal resistance to injury have been proposed as significant variables which contribute to pathogenesis of reflux disease. The evidence for these factors is circumstantial and scanty. Their importance has probably been overestimated.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMedDate not supplied

Pharmacokinetics and effects of 9-amino-1,2,3,4-tetrahydroacridine in the immediate postoperative period in neurosurgical patients.

STUDY OBJECTIVE: To determine the effects of intravenous (IV) 9-amino-1,2,3,4-tetrahydroacridine (THA) on postoperative somnolence in comparison to its pharmacokinetics. DESIGN: Open-label study of the pharmacokinetics and effects of THA. SETTING: Postoperative intensive care ward at the Department of Neurosurgery, Uppsala University Hospital, Sweden. PATIENTS: Ten neurosurgical patients immediately after their operations were given 30 mg of THA for reversal of postoperative somnolence. INTERVENTIONS: Plasma concentrations of THA and, in seven cases, the metabolite 1-hydroxy-THA were assayed using high-performance liquid chromatography. The pharmacokinetic data were compared to the degree of sedation and pain relief. After an IV dose of 30 mg THA, plasma concentrations were fit to an open two- or three-compartment model. MEASUREMENTS AND MAIN RESULTS: The antagonistic effect of THA on sedation occurred immediately following IV administration and lasted 60 to 90 minutes. At a mean plasma THA concentration of 44 +/- 18 ng/ml, patients were resedated. There was no obvious relation between analgesia and plasma THA concentrations. Side effects such as nausea, salivation, and lower heart rate (HR) were observed in several patients. Plasma clearance (C1) was high and showed a twofold inter-individual variation, with a mean of 2.64 +/- 1.17 L/h. Volume of distribution (Vd gamma) varied between 300 and 850 liters, with a mean of 477 +/- 185 liters. The plasma half-lives of rapid and slow distribution, and elimination were 2.1 +/- 0.7 minutes, 26 +/- 18 minutes, and 133 +/- 48 minutes, respectively. Maximum plasma concentrations of 1-hydroxy-THA were 27 to 90 ng/ml in five patients; the concentration was below 1 ng/ml in two other patients. CONCLUSIONS: The duration of the effects of THA as an antagonist of postoperative sedation was only about double that seen previously after the IV administration of physostigmine in a similar group of patients, although the elimination half-life of THA was six times longer than that of physostigmine. A larger dose of THA possibly could have been given to prolong the period of antagonism of sedation, but the profile of adverse effects seen even at the doses used precluded that option.

Adult↗