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Actions of some transmitters and their antagonists on salivary secretion in a tick.

Cholinomimetics (pilocarpine, carbachol, physostigmine, acetylcholine, acetyl-beta-methylcholine) and sympathomimetics (dopamine, epinephrine), when injected into the hemolymph, provoked salivary fluid secretion in the female ixodid tick Amblyomma hebraeum Koch. Atropine, but not tubocurarine or toxiferine, abolished pilocarpine-induced secretion without reducing the response to dopamine. Reserpine and guanethidine likewise selectively attenuated pilocarpine-induced secretion. Following extirpation of the synganglion, pilocarpine no longer provoked a secretory response whereas dopamine did. Thus, the salivary gland appears to be innervated directly by catecholaminergic rather than cholinergic secretory nerves. It is suggested that pilocarpine elicits salivation by interacting with muscarinic-type cholinergic receptors situated either on the cell bodies of the secretory nerves, or alternatively in the integrative or sensory pathway.

Acetylcholine↗

Disordered drinking in developing spontaneously hypertensive rats.

Eating and drinking in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were measured at 5-17 wk of life. The SHR drank significantly more water in 24 h than WKY as early as wk 9, spilled more dry food than did WKY, and exhibited an inverse relation between 24-h water intake and dry food spilled. When eating a meal of dry food after 12 h food deprivation, SHR drank earlier and drank more in a 1-h test than WKY rats. Moreover, SHR exhibited (as early as wk 7) a striking pattern of interrupting eating to drink. This pattern was not present when SHR ate liquid food, and it was attenuated by infusion of water through a cheek fistula. Adult SHR (22 wk) salivated less than WKY in response to intraperitoneal 3.25 mg/kg pilocarpine nitrate. When developing SHR and WKY were maintained on liquid and solid food, SHR gained disproportionately more weight than WKY during development. When young SHR were permitted to drink no more water than WKY rats, the development of hypertension was retarded, and body weight gain was slowed. Because restricted access to food, which produced an equivalent slowing of body weight gain as did restricted access to water, also retarded development of hypertension, it appears that restricted access to water retards development of hypertension due to delayed growth. These results demonstrate that hyperdipsia, apparently caused by deficient salivary function, is not necessary for the development of hypertension in SHR.

Animals↗

Respiratory muscle function during emesis in awake canines.

Emesis requires a coordinated differential recruitment of gastrointestinal smooth muscle, upper airway muscles, and several muscles involved in respiration. In seven awake intact canines we measured the electrical activity (electromyogram) and shortening of costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis during emesis that was induced by instillation of apomorphine into the lower conjunctival fornix. The process of emesis was tightly coordinated with ventilation and showed four respiratory phases: baseline ventilation (Base), initial preemetic hyperventilation (Hyperv), prodromal ventilation associated with salivation and probable nausea (Prodrome), and finally retching and expulsion (Expel) of gastric contents. Ventilation was suppressed during expulsive events, but a small inspiratory airflow was interjected between expulsions. Resting electromyogram of all four muscles increased during the process of emesis, with costal and crural segments showing a marked decrease in resting length through Prodrome and Expel. To produce an expulsive maneuver, both inspiratory and expiratory muscles were activated synchronously, unlike their usual sequential activation during ventilation, with costal and crural segments and transversus abdominis showing the most shortening. The crural segment showed a biphasic length change with initial shortening and then lengthening to assist esophageal sphincter function during Expel. These results indicate a strong coordinated interaction between brain stem centers responsible for control of respiration and of emesis.

Algorithms↗

Autonomic nervous system disorders in Parkinson's disease.

This paper gives a review on the clinical features of autonomic failure which occur in idiopathic Parkinson's disease (PD), mainly based on the recent publications, especially from Japan. In 1817, James Parkinson already mentioned bowel and bladder dysfunctions in his original article. Since then, a number of clinical studies have disclosed the occurrence of autonomic failure in this disease. It is known that relatively minor degrees of orthostatic hypotension are not rare, but other features of autonomic failure are rather uncommon, generally mild in severity and nonprogressive. Orthostatic hypotension is suggested as a possible side effect of L-dopa. Postprandial hypotension is occasionally found, and vasopressin is proven to prevent it remarkably. There is low electrocardiographic R-R interval variability which indicates impaired parasympathetic activity. Thermoregulatory sweating is nearly normal, but its center is functionally impaired. Resting skin temperature is slightly lower. Both salivation and lacrymation are quantitatively within normal limits. Little is known on sexual function in PD.

Animals↗

Vestibular-induced vomiting after vestibulocerebellar lesions.

Vestibular stimulation, by means of sinusoidal electrical polarization of the labyrinths of decerebrate cats, can produce vomiting and related activity resembling that seen in motion sickness. The symptoms include panting, salivation, swallowing, and retching as well as vomiting. These symptoms can be produced in cats with lesions of the posterior cerebellar vermis. In contrast to a previous proposal by Wang and Chinn in 1956, we suggest that a transcerebellar pathway from the vestibular apparatus through the nodulus and uvula to the 'vomiting center' is not essential for vestibular-induced vomiting and, by analogy, for the occurrence of many symptoms of motion sickness.

Animals↗

Vasopressin released by nicotine in the monkey.

The objective of this study was to determine the effects of i.v. nicotine on plasma arginine vasopressin (AVP), plasma osmolality, and behavior in the conscious monkey. Adult, female, chronically prepared monkeys (Macaca mulatta) were studied with i.v. infusion of 5% dextrose and water in control experiments without change in parameters. Nicotine infusion (100 mug/kg/min) in 14 experiments produced a significant increase in plasma AVP from control levels of 0.6 +/- 0.5 muU/ml to end-of-infusion levels of 35 +/- 17 muU/ml (p less than 0.001). During the 15-20 min of nicotine infusion, a behavioral sequence of restlessness, yawning, retching, salivation and chewing accompanied AVP release. Plasma osmolality remained unchanged. Pretreatment of the monkeys with promethazine (Phenergan) and diphenhydramine (Benadryl) at 1-5 mg/kg reduced both the plasma AVP increase and the behavioral effects. These results provide conclusive evidence that nicotine can release large amounts of AVP in the monkey.

Animals↗

Alteration of D1 and D2 dopaminergic receptor kinetics in specific rat brain regions following repeated administration of opiates.

The present study was conducted to investigate the effects of repeated administration of opiates on the binding characteristics of D1 and D2 dopamine receptors in specific rat brain regions. Male Sprague-Dawley rats (150-175 g) were adapted for 1 week under controlled conditions (22 +/- 1 degree C, 40% relative humidity, 12 h light:12 h dark illumination cycle). After the adaptation period, rats were randomly assigned into six groups (n = 15/group) for two sets of experiments; one for D1 and the other for D2 receptor binding evaluation. In each set, group 1 served as saline control, group 2 was treated with morphine (1 mg/kg/day for 7 days) and group 3 was treated with naloxone (2 mg/kg/day for 7 days). Following the third day of morphine injection, rats showed restlessness, hyperactivity, increased urination, diarrhea, lacrimation, irritability and squealing on touch, head and body shakes and salivation just prior to morphine dosage. These observed signs are typical for morphine withdrawal. One hour after the last injection, rats were sacrificed by decapitation, brains were removed and kept at -70 degrees C. The frozen brains were further dissected into cortex (CTX), hypothalamus (HYPO), hippocampus (HIPP) and midbrain (MID), pooled (5/pool), homogenized and used for radioreceptor assays. For D1 binding study, 3H-SCH-23390 was used as ligand and for D2 receptor binding 3H-YM-09151-2 was employed. Following repeated morphine or naloxone treatment, Bmax values for 3H-SCH-23390 binding to membranes of HYPO and MID were increased and decreased, respectively, whereas Kd values were significantly decreased in both HYPO and MID of morphine and naloxone-treated animals. In rat brain CTX, both morphine and naloxone decreased Kd and Bmax values of 3H-SCH-23390 binding, however the decrease in Bmax values noted after morphine administration was not statistically significant. Decrease in both Bmax and Kd values of dopamine D1 receptors were observed after naloxone but not morphine treatment in HIPP. Morphine administration increased the density of D2 receptors in HIPP and MID and decreased the affinity of 3H-YM-09151-2 binding in CTX, HIPP and MID. Naloxone treatment resulted in increased number of 3H-YM-09151-2 binding sites in CTX, HYPO and HIPP. While naloxone treatment increased Kd values of 3H-YM-09151-2 in HYPO and HIPP, it decreased these values in CTX and MID. It is concluded that repeated intermittent treatment with opiates induces alterations in D1 and D2 dopamine receptors binding properties and that these changes are regionally specific.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Specific xerostomia during Urbach-Wiethe disease.

We describe the case of a 59-year-old woman who had suffered from a typical Urbach-Wiethe disease since childhood and who complains of progressive mouth and ocular dryness since the age of 54 years. Xerostomia was severe with very poor salivation and was associated with a slight keratoconjunctivitis sicca. A specific lipoid proteinosis was evidenced in salivary glands (lower lip biopsy) with a PAS-positive hyalin-like deposit around vessels, capillaries and salivary gland canaliculi. An ultrastructural study showed the typical aspect of multilamination of the basal lamina of capillary vessels. Dysphonia and hoarseness are commonly found in Urbach-Wiethe disease, but, to our knowledge, a specific xerostomia has never been reported.

Biopsy↗

Submandibular gland excision: short- and long-term complications.

During a 10-year period, 159 benign submandibular gland excisions were performed in 157 patients. 86 of the patients were available for follow-up evaluation. Both short- and long-term complications were listed. Neurapraxia to the mandibular branch of the facial nerve was frequent after the operation, but restoration of function was seen in 92.3%. Scar problems, sensation changes, reduced salivation and taste perception were noticed by the patients in several cases, but rarely caused dissatisfaction. 18.2% of the patients in the salivary stone group had residual stones in Wharton's duct after the operation. The indication for removal of both glands should be carefully considered because of development of xerostomia.

Adolescent↗

Prolongation of gastric emptying by aerosolized atropine.

Aerosolized atropine causes anticholinergic side effects. We evaluated gastroparesis, a previously unreported side effect of inhaled atropine, in a double-blind, placebo-controlled, crossover study. Six young asthmatics received atropine (0.05 mg/kg) or placebo at 4-h intervals for 3 dosages, on 2 separate days at least 1 wk apart. Subjective complaints, pulse, visual accommodation, and citric-acid-stimulated salivary flow were recorded 30 min after each dose on each study day. A radionuclide (99mTc) study of gastric emptying time was done 30 min after the final dose on each study day. Atropine prolonged mean gastric half emptying time (112 +/- 59 min) compared with placebo (65 +/- 34 min) (p less than 0.05). However, gastric emptying after atropine was in the abnormal range in only 2 patients. Stimulated salivary flow decreased after atropine (1.97 +/- 1.7 g saliva) compared with flow after placebo (4.1 +/- 1.2 g) (p less than 0.05). No changes in visual accommodation or pulse rate were seen. Dry mouth and decreased salivation correlated with delayed gastric emptying (r = 0.76, p less than 0.05). Anticholinergic side effects of aerosolized atropine include prolonged gastric emptying in some patients. Gastroparesis after inhaled atropine is suggested by the symptom of dry mouth.

Adult↗

Subjective experiences of clozapine treatment by patients with chronic schizophrenia.

A 37-item survey covering a variety of somatopsychic domains was constructed to explore patients' subjective response to treatment with clozapine. The survey was administered to 130 patients with diagnoses of chronic schizophrenic or schizoaffective disorders who were on a stable clozapine regimen. The majority reported improvement in their level of satisfaction, quality of life, compliance with treatment, thinking, mood, and alertness. Most patients reported worsening in nocturnal salivation, and smaller numbers reported worsening in various gastrointestinal and urinary symptoms and weight gain. This general health survey highlights the patients' positive regard for clozapine, despite adverse bodily experiences. Subjective reports are a useful component of outcome measures of drug treatment.

Adult↗

Recognition and management of teething diarrhea among Florida pediatricians.

According to current medical opinion, teething diarrhea (TD) is a myth; yet cross-cultural data document a worldwide distribution of popular belief in the association of frequent, loose stools with tooth eruption. A mail survey in 1990 of 215 pediatricians practicing in Florida investigated beliefs and practices related to TD. Thirty-five percent of respondents believed there is a real association between diarrhea and tooth eruption. When compared with pediatricians who do not believe in TD, these respondents were more likely to be more recent graduates of medical school, to be in general pediatric practice, to be female, to see more patients per week, and to practice in metropolitan areas. The most common explanations for the link between dentition and diarrhea were changes in eating habits, increased salivation, and stress. Respondents reported that both they and the parents of their patients tended to view TD as less serious than other types of diarrhea, and both managed it accordingly. When compared with earlier studies, our findings indicate that belief in TD among pediatricians may have increased since the 1970s. The results suggest a need for more empirical research on the effects of tooth eruption on bowel function.

Diagnosis, Differential↗

Secretion of monovalent ions and water in ferret salivary glands: a micropuncture study.

The acinar mechanisms of secretion of the monovalent ions, Na+, K+, Cl-, and HCO3-, and water in the parotid and submandibular glands of the ferret, Mustela putorius furo, were investigated using micropuncture and microanalytical techniques during salivation induced by pilocarpine. The osmolarity and monovalent ionic composition of the primary secretory fluid obtained from the intercalated ducts of these glands were determined.

Animals↗

Remineralization of artificial caries-like lesions in human enamel in situ by chewing sorbitol gum.

The objective of the study was to determine quantitatively the effect on the potential for in situ remineralization of artificial caries-like lesions in human enamel when sugar-free gum containing mainly sorbitol as sweetener was chewed after meals and snacks. Artificial white-spot lesions were created in extracted human premolars and divided into three parts. One part was used as reference and the other two worn consecutively for two 21-day periods by 10 volunteers in a cast silver band cemented on lower molar teeth and covered with gauze to promote plaque formation. During the experimental periods, the subjects used fluoridated toothpaste twice daily, and consumed three meals (breakfast, lunch, and dinner) and two snacks (selected from chocolate bar, raisins, chocolate wafer, and iced cupcake). Sorbitol gum was chewed for 20 min immediately after each meal or snack during one of the experimental periods. The three parts of the enamel lesions were then sectioned (congruent to 80 microns) and examined together by means of quantitative microradiography and by polarized light microscopy. All estimates of mineral content indicated that significant remineralization occurred and was approximately doubled with gum-chewing. It is suggested that sorbitol gum stimulates salivation, which is responsible for the significantly enhanced remineralization, thus contributing to a therapeutic, caries-preventive effect. Because the gum was chewed immediately after meals and snacks, inhibition of demineralization may also have occurred.

Adult↗

Management of seizures in children with falciparum malaria.

Falciparum malaria is the most common cause of convulsions in children admitted to hospital in malaria endemic areas. Detection of convulsions requires close monitoring and one should be on the look out for signs of subtle convulsions. About a third of acute seizures in children with cerebral malaria, do not manifest as convulsions, but as changes in eye deviation, salivation and/or eye deviation. It is important to terminate convulsions lasting more than 5 min, since prolonged convulsions are associated with neurological deficits in survivors of children with severe malaria. Initial management should include putting the child into the left lateral position, checking the blood glucose and administering oxygen if hypoxic. The benzodiazepines, particularly diazepam, are used as the initial anticonvulsants. Phenobarbital and phenytoin are used as second-line treatments. Prompt and effective management of falciparum malaria associated convulsions may contribute to a better outcome in children with severe malaria.

Anticonvulsants↗

Nasal toxicity of CI-959, a novel anti-inflammatory drug, in Wistar rats and Beagle dogs.

CI-959, 5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-yl-benzo[b]thio phene-2-carboxamide, an anti-inflammatory agent, was considered for development as a treatment for rhinitis. Two-week topical nasal studies in Wistar rats and Beagle dogs were performed to assess nasal toxicity of CI-959. Rats were given daily doses in the right nostril of 0.05 ml of solutions of varying concentrations (0.5, 2, 10, 20, 30, 60, and 90 mg/ml; doses of 0.08, 0.3, 1.6, 3.2, 4.8, 9.6, and 14.6 mg/kg) of CI-959. Beagle dogs were given daily doses in the right nostril of 0.5 ml of 10, 20, 30, 60, and 90 mg/ml solutions (doses of 0.5, 0.8, 1.2, 2.8, and 3.7 mg/kg) of CI-959. Rats given > or = 60 mg/ml either lost weight or had decreased weight gain. Salivation at dosing was seen in both species. Four sections of nasal cavity were examined from each animal. In rats, 0.5 mg/ml was the "no effect" dose; minimal changes were seen at 2 mg/ ml, and significant changes were dose related in severity at > or = 10 mg/ml in all 4 nasal levels. Degeneration and necrosis of respiratory and olfactory epithelia were minimal to moderate in severity. Adhesions and fibro-osseous proliferation of ethmoturbinates, epithelial hyperplasia, squamous metaplasia, and exudate were also seen. In dogs, 10 mg/ml was the no effect dose; respiratory epithelium was affected at > or =20 mg/ml. Respiratory epithelial degeneration was minimal to mild, with loss of ciliated and goblet cells and thinning of mucosa. Distribution of degeneration increased with increased concentrations. In both species, in accordance with the suggested action of CI-959, infiltration with neutrophils was not significant. CI-959 was locally toxic to nasal cavity respiratory and olfactory epithelia in rats and respiratory epithelium in dogs.

Administration, Topical↗

Acute arsenic toxicosis in five horses.

Five adult horses presented with acute clinical signs of watery diarrhea, excessive salivation, muscle tremors, ataxia, and depression. Four died within 24 hours and the fifth was euthanatized approximately 48 hours after onset of clinical signs. Necropsy finds in two of the horses included hyperemia of gastric mucosa, intestines filled with green to black watery fluid, and multifocal to coalescing, hemorrhagic 1.0-2.0-cm-diameter ulcers of the mucosa of the cecum and large colon. Histopathologic changes in the cecum and large colon consisted of mucosal necrosis and ulceration, vascular thrombosis, necrosis of submucosal blood vessels, and infiltration by mixed mononuclear inflammatory cells and neutrophils. Arsenic toxicosis was suspected. The owner had not been feeding the horses any grain; however, a mixture of grain and pink powder was found in the pasture. Liver arsenic concentrations in the two horses were 14.0 and 11.0 ppm, a sample of renal cortex contained 108 ppm arsenic, and the grain/powder mixture found in the pasture was positive for arsenic at > 3,000 ppm. kidney lead concentrations were 6.5 and 4.2 ppm. Results were consistent with lead arsenate or lead arsenite poisoning.

Animals↗

Oral ketamine or midazolam or low dose combination for premedication in children.

This randomized controlled trial was designed to evaluate whether the combination of low dose oral midazolam (0.25 mg/kg) and low dose oral ketamine (3 mg/kg) provides better premedication than oral midazolam (0.5 mg/kg) or oral ketamine (6 mg/kg). Seventy-eight children of ASA physical status I or II scheduled for elective ophthalmic surgery were randomly divided into three groups and given premedication in the holding area 30 minutes before surgery. Two subjects from each group vomited the medication and were excluded, leaving 72 subjects for further analysis. The onset of sedation was earlier in the combination group than the other two groups. At 10 minutes after premedication 12.5% in the combination group had an acceptable sedation score compared with none in the other two groups. After 20 minutes 54% in the combination group had an acceptable sedation score, 21% in the midazolam group and 16% in the ketamine group (P<0.05). There were no significant differences in the parental separation score, response to induction and emergence score. The mean time for best parental separation score was significantly less in the combination group (19+/-8 min) than either the midazolam (28+/-7) or ketamine (29+/-7 min) groups (P<0.05). Recovery was earlier in the combination group, as the time required to reach a modified Aldrete score of 10 was significantly less in the combination group (22+/-5 min) than in the oral midazolam (36+/-11 min) or ketamine (38+/-8 min) groups. The incidence of excessive salivation was significantly higher in the ketamine alone group (P<0.05). In conclusion, the combination of oral ketamine (3 mg/kg) and midazolam (0.25 mg/kg) has minimal side effects and gives a faster onset and more rapid recovery than ketamine 6 mg/kg or midazolam 0.5 mg/kg for premedication in children.

Adjuvants, Anesthesia↗