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At least 955 records · Page 53Linked to original sources
PubMed2003

A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition.

Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption "Zydis Selegiline". The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25 mg or 10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg) in patients with Parkinson's disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10 mg (n=68), or to treatment with Zydis Selegiline 1.25 mg (n=64) or Zydis Selegiline 10 mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5 mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg for 14-16 days in an open-label, randomised parallel group study. Both Zydis Selegiline (1.25 mg and 10 mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10 mg based on comparison of mean total Unified Parkinson's Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range +/-5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg was -2.50 (-4.84, -0.17), and for Zydis Selegiline 10 mg and conventional selegiline tablets 10 mg, 0.04 (-2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25 mg, -2.14 (-3.94, -0.33) and Zydis Selegiline 10 mg, -0.90 (-2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25 mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01). In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5 mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients who preferred Zydis Selegiline (65%) to their usual medication was significantly greater than the null hypothesis of 50% (p<0.001). Similar findings were demonstrated in the 12-week study where a higher proportion of patients who received up to 3 months of treatment indicated a preference for either Zydis Selegiline 1.25 mg (90%) or Zydis Selegiline 10 mg (86%) over conventional selegiline tablets 10 mg. More than 90% of patients found Zydis Selegiline easy to take, with 61% rating it as extremely easy. Most (81%) patients taking Zydis Selegiline 1.25 mg liked the taste compared with 45% taking Zydis Selegiline 5 mg (in the previous study). Zydis Selegiline did not potentiate the tyramine effect: a pressor effect was elicited after 400 mg tyramine both before and after 14 days of treatment with Zydis Selegiline 1.25 mg. In contrast, after 14 days treatment with conventional selegiline tablets 10 mg, the threshold dose required to elicit the tyramine pressor response was significantly (p<0.0001) reduced from 400 mg to 200 mg. In summary, Zydis Selegiline at doses of 1.25 mg and 10 mg was therapeutically equivalent to conventional selegiline tablets 10 mg. The Zydis Selegiline formulation was well-liked by all patients, with most preferring Zydis Selegiline 1.25 mg to their usual selegiline tablet. Furthermore, Zydis Selegiline was well tolerated and, unlike conventional selegiline tablets, appeared to retain specificity for inhibition of monoamine oxidase type B (MAO-B), since it did not potentiate the pressor response to tyramine.

Administration, Oral↗
PubMed2000

Cue exposure in alcohol dependent patients: preliminary evidence for different types of cue reactivity.

Craving is considered to be an important phenomenon in addictive behaviours. However, there is still an unresolved debate on what craving for alcohol means, how it is best measured and which clinical and therapeutical consequences its presence or absence may imply. Cue reactivity paradigms have been developed to elicit craving under standardized experimental conditions. Here we present preliminary results characterizing alcohol-dependent patients with regard to subjective and psychophysiological aspects of exposure to alcohol-associated cues in a cue reactivity paradigm. Thirty-six patients fulfilling at least 5 criteria of alcohol dependence according to DSM-IV criteria were studied after detoxification. Cue reactivity was assessed as subjective (by visual analogue scales) and neurophysiological response (by ECG, EMG, electrodermal activity, respiratory frequency, salivation) to the presentation of the favourite alcoholic beverage or water. While 22% of the patients were both subjective and physiological responders, 42% of the subjects showed only a physiological reaction without subjective response, and 31% of the patients were neither a subjective nor a physiological reaction. Subjective responders to alcohol cues had significantly higher state anxiety levels than subjective non-responders. These results suggest that alcohol dependent patients may be divided into typological subgroups with respect to cue reactivity. Different types of cue reactivity might be important for treatment strategies involving repeated cue exposure or so-called anti-craving drugs.

Adult↗
PubMed2002

Pandysautonomia associated with impaired ganglionic neurotransmission and circulating antibody to the neuronal nicotinic receptor.

We report the case of a patient with chronic autonomic failure who had evidence of decreased postganglionic traffic to intact sympathetic nerve terminals. The patient complained mainly of decreased salivation, constipation, dry skin, and orthostatic intolerance. There was no evidence of central neurodegeneration. Autonomic function testing showed orthostatic hypotension without tachycardia and abnormal blood pressure and pulse rate responses to the Valsalva maneuver, indicating combined sympathetic and parasympathetic neurocirculatory failure. In contrast to patients with pure autonomic failure, the patient had normal left ventricular myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity, establishing intact postganglionic sympathetic innervation; and in contrast to patients with multiple system atrophy or baroreflex failure, the patient had a low plasma norepinephrine concentration and brisk norepinephrine response to orthostasis. These findings indicated an impediment to ganglionic neurotransmission. Serologic testing demonstrated a circulating antibody to the ganglionic nicotinic acetylcholine receptor. The findings in this case support the concept that circulating antibodies to this receptor can interfere with ganglionic neurotransmission and produce autoimmune autonomic neuropathy.

Adrenergic alpha-Agonists↗
PubMed2005

Effect of blood transfusion in combination with Dextran-40 and hypertonic saline solution on cardiopulmonary haemodynamics of endotoxin (lipopolysaccharide) shock in buffalo calves.

The intravenous (i.v.) infusion of lipopolysaccharide (LPS) of E. coli endotoxin in buffalo calves (n = 15) at 5 microg/kg bw per h for 3 h caused a significant (p<0.05) fall in plasma volume, blood volume, haematocrit haemoglobin, and systolic, diastolic and pulse pressure, mean arterial pressure and central venous pressure (CVP), with a marked rise in respiration. Treatment with a combination of i.v. infusion of 7.2% hypertonic saline solution, Plasmex-D-40 (Dextran-40) and blood successfully alleviated hypovolaemia, and raised systolic, diastolic and pulse pressure, mean arterial pressure and central venous pressure. The whole blood was collected from apparently healthy male buffalo calves 24 h prior to infusion and was transfused without cross-matching. No significant fall in haemoglobin, haematocrit and body temperature was observed after transfusion. All these values tended to remain near normal levels. However, this combination of treatment had no effect on high respiratory rate. A one-time blood transfusion did not evoke any cross-reaction and was helpful in raising haematocrit and haemoglobin close to pre-infusion values. The general symptoms of restlessness, respiratory distress, profuse salivation, violent movement of the ears, snoring, intermittent struggle, etc. were markedly reduced. All the treated animals became quiet and lay with eyes open and survived the 7 h of observation.

Animals↗
PubMed2007

Review of oral appliances for treatment of sleep-disordered breathing.

Between 1982 and 2006, there were 89 distinct publications dealing with oral appliance therapy involving a total of 3,027 patients, which reported results of sleep studies performed with and without the appliance. These studies, which constitute a very heterogeneous group in terms of methodology and patient population, are reviewed and the results summarized. This review focused on the following outcomes: sleep apnea (i.e. reduction in the apnea/hypopnea index or respiratory disturbance index), ability of oral appliances to reduce snoring, effect of oral appliances on daytime function, comparison of oral appliances with other treatments (continuous positive airway pressure and surgery), side effects, dental changes (overbite and overjet), and long-term compliance. We found that the success rate, defined as the ability of the oral appliances to reduce apnea/hypopnea index to less than 10, is 54%. The response rate, defined as at least 50% reduction in the initial apnea/hypopnea index (although it still remained above 10), is 21%. When only the results of randomized, crossover, placebo-controlled studies are considered, the success and response rates are 50% and 14%, respectively. Snoring was reduced by 45%. In the studies comparing oral appliances to continuous positive airway pressure (CPAP) or to uvulopalatopharyngoplasty (UPPP), an appliance reduced initial AHI by 42%, CPAP reduced it by 75%, and UPPP by 30%. The majority of patients prefer using oral appliance than CPAP. Use of oral appliances improves daytime function somewhat; the Epworth sleepiness score (ESS) dropped from 11.2 to 7.8 in 854 patients. A summary of the follow-up compliance data shows that at 30 months, 56-68% of patients continue to use oral appliance. Side effects are relatively minor but frequent. The most common ones are excessive salivation and teeth discomfort. Efficacy and side effects depend on the type of appliance, degree of protrusion, vertical opening, and other settings. We conclude that oral appliances, although not as effective as CPAP in reducing sleep apnea, snoring, and improving daytime function, have a definite role in the treatment of snoring and sleep apnea.

Continuous Positive Airway Pressure↗
PubMed1982

Identification of transcalciferin as a major component of human parotid saliva by crossed immunoelectrophoretic mapping.

Human parotid saliva collected from Stenson's duct during sour candy-stimulated salivation was studied by crossed immunoelectrophoresis (X-IEP). Eleven antigens were identified in a pool of salivas from 10 adult, caucasoid males and females. Four were related to serum antigens, three being previously known: IgG, IgA and albumin. The fourth was identified as Gc globulin, also known by function as transcalciferin. Salivary Gc is electrophoretically different from serum Gc, migrating as an alpha 2-beta component rather than as an alpha 1 globulin. The quantities of 8 of the 11 antigens detected by X-IEP were compared for salivas from 10 subjects. These quantities and their ratios to each other were highly variable, indicating idiosyncratic secretory patterns. Only quantities of amylase were moderately consistent from donor to donor. Quantitatively, Gc is a major antigen in parotid saliva. Large proportions of a salivary antigen, alpha 1c, were found in two of the 10 subjects--adult males who never had developed caries. Among the other 8 subjects, all with caries, proportions of alpha 1c were much lower, and 2 subjects lacked it. None of the other antigens measured showed any correlation with caries resistance. The nature and function of alpha 1c are unknown.

Adult↗
PubMed1988

Contrasting effects of autonomic agents and prostaglandins on 22Na uptake in rat submandibular salivary acini.

Uptake of this isotopic tracer by the acini occurred in a time-dependent manner and was increased by 1 microM concentrations of acetylcholine and of isoproterenol, but not of prostaglandins E1, E2 and F2 alpha. The lack of effect of prostaglandins on Na transport in salivary acini contrasts with their inhibitory effect on salivation in vivo, suggesting that in vivo the effects are independent of the ion-transport mechanisms underlying saliva formation.

Acetylcholine↗
PubMed1989

Secretion of amylase from the rat parotid salivary gland after degeneration of the auriculotemporal nerve.

The output of amylase into saliva secreted after injection of methacholine or substance P was increased after parasympathetic denervation, but the salivary concentration of amylase was unchanged. The increased output corresponded to the increased flow. Isoprenaline injected during the methacholine-induced secretion raised the output, more being secreted from the denervated than from the contralateral gland. Vasoactive intestinal peptide, given while substance P caused salivation, also increased the amylase output, but equally from the two glands.

Amylases↗
PubMed1990

Leucine-enkephalin-, neurokinin A- and cholecystokinin-like immunoreactivities in the guinea pig tongue.

The occurrence of these neuropeptides was examined by immunofluorescence. Leu-Enk-like immunoreactivity was seen in nerve fibres associated with the epithelium, blood vessels and lingual salivary glands as well as in ganglionic cells within the tongue. Neuropeptide A-like immunoreactivity was found in nerve fibres associated with the epithelium, taste buds, blood vessels and lingual salivary glands. Cholecystokinin-like immunoreactivity was found in some nerve fibres around blood vessels as well as in ganglionic cells. The coexistence of these neuropeptides and substance P was also demonstrated in some nerve fibres and ganglionic cells within the tongue. Like substance P, these neuropeptides could be involved in blood flow regulation, salivation and as trophic factors for taste buds.

Animals↗
PubMed1994

Effects of cholinergic stimulation and aldosterone administration on salivary parotid secretion in the brushtail possum, Trichosurus vulpecula.

Parotid salivation was stimulated by infusion of bethanechol chloride into anaesthetized brushtail possums to ascertain maximal flow rates, salivary composition and dietary adaptations of salivary function. Secretion rates for one gland ranged from 5.3 +/- 0.16 to 84.3 +/- 3.20 microliters/min (2.4 +/- 0.07 to 37.8 +/- 1.43 microliters/min per kg body weight). Salivary osmolality (160.8 +/- 15.39 to 248.2 +/- 8.70 mosmol/kg) and the concentrations of Na (63.1 +/- 10.93 to 124.1 +/- 5.52 mmol/l) and HCO3 (19.5 +/- 3.41 to 89.0 +/- 3.19 mmol/l) were positively correlated with flow rate. The concentrations of urea (7.8 +/- 0.64 to 4.6 +/- 0.33 mmol/l), PO4 (2.6 +/- 0.25 to 0.96 +/- 0.10 mmol/l), H+ (46.2 +/- 16.30 to 9.0 +/- 1.51 nequiv/l), K (21.4 +/- 3.73 to 13.7 +/- 2.33 mmol/l), Ca (3.7 +/- 0.53 to 2.2 +/- 0.27 mmol/l) and Mg (0.3 +/- 0.07 to 0.04 +/- 0.007 mmol/l) fell with increasing flow rate. The relations between flow rate and amylase activity (22.6 +/- 10.47 to 10.5 +/- 3.68 mu kat/l), protein concentration (2.7 +/- 0.61 to 1.3 +/- 0.28 g/l), and Cl concentration (62.1 +/- 6.88 to 50.6 +/- 6.37 mmol/l) were inconsistent between experiments. Salivary Na/K ratios were not decreased by infusion of aldosterone (2.2-22.2 nmol/h for 5 h), showing that the gland of Na-replete possums is unresponsive to short-term increases in mineralocorticoids. The low salivary amylase activity, less than that of kangaroos, presumably reflects the interaction of evolutionary history of the possum with its natural low-starch diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1996

Salivary flow-rate and composition in schizophrenic patients on clozapine: subjective reports and laboratory data.

The extent of hypersalivation was evaluated in a group of 25 schizophrenic patients on clozapine. A high prevalence of the complaint was detected by a questionnaire; up to 80% of the patients complained of hypersalivation at night. Salivary flow-rate and composition was examined in 17 patients who agreed to participate and in a matched group of healthy controls. No significant differences were detected in composition or flow-rates of resting and stimulated saliva. The salivary flow-rates in the schizophrenic patients on clozapine did not correlate with the subjective complaint of hypersalivation. Because the severity and prevalence of the complaint was higher at night, a possibility of an altered circadian rhythm of salivation might be suggested in these patients.

Adult↗
PubMed1978

Behavioral and prolactin responses to 5-hydroxytryptophan in rats treated during development with 5,7-dihydroxytryptamine.

The serotonin precursor, 5-hydroxytryptophan (5-HTP), can induce a behavioral syndrome characterized by rigidity, splayed feet, tremor, head weaving, salivation and forepaw treading. This response to 5-HTP was markedly potentiated in adult rats treated intracisternally with 5,7-dihydroxytryptamine (5,7-DHT) during development. Prevention of the 5,7-DHT-induced reduction of brain norepinephrine with pargyline or desipramine did not diminish the potentiation of 5-HTP, suggesting that noradrenergic fibers are not contributing to the altered 5-HTP response. It was also found that treatments with 5,7-DHT potentiated the release of prolactin and the disruption of responding in a fixed-ratio operant task induced by 5-HTP. Other experiments indicated that 5,7-DHT treatments potentiated 5-HTP without affecting the action of L-dihydroxyphenylalanine. In addition, administration of the decarboxylase inhibitor, R0-4-4602, at a dose that inhibits enzyme activity in brain, blocked the 5-HTP-induced behavioral syndrome in 5,7-DHT-treated rats, indicating that 5-HTP must be converted to serotonin for 5-HTP to alter behavior. Thus, the present studies indicate that destruction of serotonergic fibers during development can produce permanent changes in central serotonergic mechanisms.

5,7-Dihydroxytryptamine↗
PubMed1979

Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly.

Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates.

Aggression↗
PubMed1990

Analgesic, anesthetic, and respiratory effects of the competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 in rhesus monkeys.

The competitive excitatory amino acid antagonist cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) increased the latency for monkeys to remove their tails from warm water (analgesia); larger doses produced ataxia, loss of righting, salivation, and eliminated reactivity to stimulation (anesthesia). CGS 19755 decreased tidal volume and had little effect on frequency of respiration. Although longer lasting, the effects of CGS 19755 were similar to the effects of ketamine, suggesting these effects result from actions at the NMDA receptor complex.

Analgesics↗
PubMed1990

Differences in physical dependence induced by selective mu or delta opioid agonists and by endogenous enkephalins protected by peptidase inhibitors.

The aim of the present study was to investigate if a physical dependence could be induced by chronic activation of the endogenous enkephalinergic system. We have therefore evaluated naloxone-induced withdrawal syndrome in rats after central infusion during 7 days of comparable antinociceptive doses of RB 38 A ((R,S)HONH-CO-CH2-CH(CH2C6H5)-CONH-CH(CH2C6H5)-COOH), a mixed enkephalin catabolism blocker and of the selective mu, DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) and delta, DSTBULET (Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr), opioid agonists. The responses were compared to those induced by RB 38 B ((S,S)HONH-CO-CH2-CH(CH2C6H5)-CONH-CH(CH2C6H5)-COOH), a selective inhibitor of the 24.11 neutral endopeptidase (NEP) 'enkephalinase'. DAGO induced a severe withdrawal syndrome evidenced by a large weight loss, hypothermia, jumping, mastication, teeth chattering, diarrhoea, lacrimation and salivation. In contrast, DSTBULET and RB 38 A produced only a moderate physical dependence. Only two signs were statistically different in these two groups: wet dog shakes and temperature. Chronic i.c.v. administration of DAGO, DSTBULET and RB 38 A produced a time-dependent reduction in analgesia, but 120 h after continuous infusion only RB 38 A was able to still induce a significative antinociceptive effect. The present data suggest that even in the drastic conditions used here long-term complete inhibition of enkephalin catabolism induces a weak tolerance and a moderate physical dependence, similar to that produced by delta opioid agonists. This effect was not observed after chronic selective inhibition of NEP by RB 38 B.

Animals↗
PubMed1992

CNS cell groups projecting to the submandibular parasympathetic preganglionic neurons in the rat: a retrograde transneuronal viral cell body labeling study.

The retrograde transneuronal viral tracing method was used to study the CNS nuclei that innervate the parasympathetic preganglionic neurons controlling the submandibular gland in the rat. A genetically engineered beta-galactosidase expressing Bartha strain of pseudorabies virus (PRV) was injected into the submandibular gland of rats. After 4 days, PRV infected tissues were reacted with the Bluo-Gal substrate (halogenated indolyl-beta-D-galactoside) and labeled cell bodies were identified throughout the brain. In the medulla oblongata, cell body labeling was seen in the superior salivatory nucleus, and throughout the medullary reticular formation as well as in the nucleus of the solitary tract, spinal trigeminal nucleus, and deep cerebellar nuclei. In the pons, PRV labeled neurons were found bilaterally in the locus ceruleus, subceruleus region, and parabrachial complex. In the mesencephalon, labeled cells were found in the Edinger-Westphal nucleus, deep mesencephalic nucleus, and central grey matter. Several hypothalamic regions were labeled including the lateral, perifornical and paraventricular hypothalamic nuclei. In the telencephalon, PRV-positive cell bodies were observed in the substantia innominata, bed nucleus of the stria terminalis and central nucleus of the amygdala. The results suggest that widespread areas of the CNS are involved in control of salivation.

Animals↗
PubMed1975

Alterations in hepatic drug metabolism and lipid peroxidation during administration of Baygon, a pesticide.

Biochemical studies during low- and high-dose administration of Baygon (a pesticide) to young male rats were performed. It was observed that the activities of drug-metabolizing enzymes were decreased even at a low dose of Baygon and the decrease was much more significant during high-dose injections. Lipid peroxidation was increased with a low dose and the increase was much more pronounced with a high dose. Besides these changes the animals showed physical changes such as salivation, fasciculations, etc. The presence of conjugated diene absorption patterns and malonaldehyde formation indicated the in vivo lipid peroxidation dut to Baygon administration. Toxic effects leading to death were noted when the animals were injected with a high dose of the pesticide, Baygon above 25 mg/kg.

Acetanilides↗
PubMed1978

Caffeine elicited withdrawal signs in morphine-dependent rhesus monkeys.

In the dose range of 4.0--32.0 mg/kg s.c., caffeine produced most of the signs which are commonly seen after the administration of naloxone (0.05 mg/kg s.c.) to morphine-dependent monkeys. The signs designated as lying on side or abdomen, avoiding contact, vocalizing, crawling or rolling, restlessness or pacing, tremors, retching, vomiting, coughing, vocalizing when abdomen palpated, rigid abdomen and salivation were noted. A randomized and blind experimental design, which included vehicle and positive (naloxone) controls was used. The significance of the differences between total scores for the whole syndrome was tested by the Mann-Whitney U-test. In preliminary studies in naive monkeys, caffeine was found to elicit some withdrawal signs but the results were equivocal. Na benzoate also elicited some withdrawal signs in morphine-dependent monkeys at 32.0 mg/kg s.c., but few signs were seen in naive monkeys. Caffeine was found to be approximately 10X more active than Na benzoate in inhibiting cAMP phosphodiesterase activity in a neuroblastoma cell whole homogenate assay. These results are consistent with the observations of Collier and Francis that morphine abstinence in rodents is associated with increased brain levels of cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗