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PubMed1991

Dopaminergic hypothesis for retarded depression: a symptom profile for predicting therapeutical responses.

We assessed the therapeutical efficacy of various antidepressants (amineptine, minaprine and clomipramine) in patients affected by retarded depression. All patients exhibited symptoms of retardation, including hypokinesia, anergia, reduction of speech, increased salivation, hypersomnia, Parinaud's syndrome, reduced sexual activity, slowness, hypomimia, orthostatic hypotension, dysphagia and drowsiness. Antidepressant drugs were administered for a 6-week period in a randomized double-blind vs placebo design. The rank order of clinical effectiveness (amineptine much greater than minaprine greater than clomipramine greater than placebo) paralleled the specificity of antidepressants as dopaminomimetic agents. These results support the view that a reduced dopaminergic transmission contributes to the pathophysiology of retarded depression.

Adult↗
PubMed1994

A 12-week double-blind multi-centre study of paroxetine and imipramine in hospitalized depressed patients.

Fifty-seven inpatients with major depression (DSM-III-R) entered a 12-week study comparing paroxetine and imipramine. Trends (not reaching statistical significance) in favour of paroxetine were seen on the Hamilton Depression Rating Scale (HDRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). The UKU Side Effect Rating Scale showed a significant difference in favour of paroxetine on reduced salivation. Global evaluation of side effect symptoms showed that significantly more paroxetine patients had no side effects, both in the investigators' and the patients' opinion. These results are in line with previous findings of paroxetine being an effective and well tolerated antidepressant.

Adult↗
PubMed2006

Personality analysis of patients complaining of sialorrhoea.

BACKGROUND: Sialorrhoea, the symptom of apparent excessive secretion of saliva is a relatively uncommon complaint. Some authors consider that in the absence of clinical findings, then these patients have a psychiatric disorder masquerading as a physical illness. However, there is little evidence in the literature to support this conclusion and a detailed psychological assessment of this population has not previously been reported. METHODS: In total, 18 patients and 18 age- and sex-matched controls were studied. All had a history of a complaint of excess salivation in the absence of any oral mucosal or systemic abnormality. All patients completed an Eysenck Personality Questionnaire. RESULTS: There were no differences in the extroversion of psychoticism scores between the study and control group. However, the result showed significant increases in the neuroticism and Lie Scale score in the patient group. CONCLUSIONS: The overall results of this study indicate that the complaint of sialorrhoea in otherwise healthy individuals does not have an organic basis and suggest that sialorrhoea is associated with high levels of neuroticism and a tendency to dissimulate.

Case-Control Studies↗
PubMed1984

Stimulated salivary flow rate, pH and lactobacillus and yeast concentrations in medicated persons.

Flow rate, pH and lactobacillus and yeast counts of paraffin-stimulated whole saliva were analyzed in an adult population of 463 medicated persons. Of the very large number of drugs only a few groups were found to decrease salivation to such an extent that they can be considered to cause dental harm. Persons using neuroleptics, tricyclic antidepressants or antihypertensives were nevertheless found to produce stimulated saliva at rates significantly lower than unmedicated persons. Age had no influence on the flow rate, but postmenopausal age seems to predispose medicated women to a decrease in salivary flow. Higher microbial counts were found in the medicated men.

Adult↗
PubMed1987

Substance K and salivary secretion in the rat.

Intravenous injections of substance K (SK), a novel member of the family of tachykinins, evoked secretion from the three major salivary glands of the rat in the presence of muscarinic, alpha-adrenergic and beta-adrenergic receptor blockade; the submaxillary glands contributed most and the sublingual glands least to the total volume secreted. SK was less potent than substance P (SP) in evoking fluid and amylase secretion. However, the amylase concentration in parotid saliva evoked by SK was twice that evoked by SP, a finding which indicates that in the glands there are more than just one type of tachykinin receptors. Vasoactive intestinal peptide enhanced the SK evoked fluid response and increased the amylase concentration in parotid saliva. SK is a possible transmitter involved in the atropine-resistant parasympathetic nerve evoked salivation in the rat.

Amylases↗
PubMed1992

Acute and long term effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in tests of nociception in mice.

Acute and long term changes in nociception after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 80 mg/kg (four injections of 20 mg/kg given at two hr intervals) were investigated in mice. MPTP caused shivering, lacrimation, salivation, teeth chattering and fur erection a few minutes after drug injection, but all these behavioural changes were normalized within 30 min., when the first behavioural testing was performed. No significant alteration in general behaviour, sensorimotor performance or body temperature could be detected at the time of nociceptive testing. The acute effects of MPTP on nociception were a reduced response latency in the tail flick test and a prolonged response latency compared to controls in the constant temperature hot plate test. No significant effects of MPTP were found in the increasing temperature hot plate test. The long term effects were a reduced response latency both in the tail flick test and the constant temperature hot plate test, indicating that the MPTP induced lesions of dopaminergic pathways result in hyperalgesia. In the increasing temperature hot plate test and the formalin test, no significant long term changes were demonstrated. Seven days after injection, the dopamine content was reduced to 62% of control values in striatum, to 51% in the rest of the forebrain, and to 41% in the spinal cord. Noradrenaline levels were only slightly and transiently reduced. Serotonin levels were not affected 7 days after injection, but 14 days after injection, a great increase was found in the forebrain and in the spinal cord. The results suggest that dopaminergic systems tonically inhibit nociception.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Domoic acid toxicity in rats and mice after intracerebroventricular administration: comparison with excitatory amino acid agonists.

A behavioural study of the domoic acid (DOM)-induced convulsive behaviour after intracerebroventricular administration was carried out in rats and mice. DOM-induced behaviours were compared to those elicited by other excitatory amino acid (EAA) agonists N-methyl-D-aspartate (NMDA), alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid (KA), in such a way as to assess the possible similarities between DOM-induced effects and EAA subtype receptor activation in vivo. In rat, DOM (0.03-3 nmol/rat) caused a complex pattern of convulsive behaviour, quantified by means of a 15-point rating scale. DOM-induced behavioural profile was characterized at the lower doses by "preconvulsive" behaviours as wet dog shakes, hypermotility, mild facial clonus. At higher doses, DOM caused clonic convulsions followed by the "status epilepticus" syndrome (wet dog shakes, forelimb clonus, rearing, salivation). Rats treated with KA (0.3-10 nmol/rat) showed an almost identical behavioural profile. AMPA (1-10 nmol/rat)-induced convulsive behaviour was similar to DOM and KA only at the higher doses. NMDA (0.25-10 nmol/rat) caused clonic convulsions but not "status epilepticus". In mice, similar results were obtained: all the tested drugs induced generalized seizures, but only animals treated with DOM, KA and AMPA showed a prolonged sequence of seizures with forelimb clonus. Our results confirm the findings reported in the literature and support the hypothesis that DOM and KA act at the same EAA receptor.

Animals↗
PubMed1992

Intoxications with anticholinesterases: effect of different combinations of antidotes on the dynamics of acetylcholine in mouse brain.

Intoxications with organophosphorus compounds are normally treated with a mixture of atropine and an enzyme regenerating oxime. The addition of diazepam to the conventional drug therapy is reported to greatly improve the antidotal effect. The implication of the cholinergic system in such intoxications prompted us to study the effect of different combinations of antidotes on the acetylcholine (ACh) synthesizing system in mouse brain in vivo. The antidotes studied in this paper are diazepam, HI-6 and 1-hyoscyamine, the active enantiomer of atropine. Diazepam decreases the synthesis rate of ACh both when administered separately and in combination with 1-hyoscyamine and HI-6. This is in contrast to 1-hyoscyamine which, in addition to blocking muscarinic receptors, also increases the release and rate of synthesis of ACh, which probably is an unfavourable effect of the antidote. This might at least partly explain the advantage of combining 1-hyoscyamine and an oxime with diazepam in intoxications with anticholinesterases. Mice administered soman (0.75 x LD50), after pretreatment with the three-drug combination of antidotes, show no cholinergic symptoms despite a 50% increase in endogenous ACh. The rate of synthesis of ACh in these mice is in the same range as in animals administered diazepam alone. Mice administered the same dose of soman with no antidotal pretreatment suffer from severe tremor and salivation, and have a strongly reduced synthesis rate of ACh.

Acetylcholine↗
PubMed1992

Metrifonate and tacrine: a comparative study on their effect on acetylcholine dynamics in mouse brain.

Tetrahydroaminoacridine (THA) and metrifonate are cholinesterase inhibitors used in the treatment of Alzheimer's disease. In experimental animals they inhibit acetylcholinesterase activity and have been reported to increase levels of brain acetylcholine. This paper presents results from studies of their effect at two dose levels on the dynamics of acetylcholine in mouse brain. Metrifonate at two doses (10 and 30 mg/kg intraperitoneally), known to cause cholinesterase inhibition, had no effect on levels of acetylcholine or choline or on the rate of synthesis of acetylcholine. THA (3 mg/kg intraperitoneally) had no effect on levels of acetylcholine and choline but had a shortlasting decreasing effect on the synthesis rate of acetylcholine. THA (10 mg/kg intraperitoneally) increased levels of acetylcholine and choline and markedly decreased the synthesis rate of acetylcholine. At this dose, the animals showed severe cholinergic effects, e.g. tremor and salivation. It is suggested that a moderate cholinesterase inhibition in brain facilitates cholinergic nerve transmission which is obtained at a broader dose range for metrifonate than for THA.

Acetylcholine↗
PubMed1996

The toxicity of repeated exposures to rolipram, a type IV phosphodiesterase inhibitor, in rats.

Rolipram is a selective inhibitor of Type IV phosphodiesterase isozymes (PDE IV) which is often used as a baseline comparator for compounds in this class. To document the toxicological effects of rolipram, it was administered to female rats at 0, 10, 30 or 100 mg/kg/day orally for up to 2 weeks. One treatment-related death in the 100 mg/kg/day dose group was observed on day 3, and all rats at this dose level were considered moribund and euthanatized on day 5. Several clinical signs were observed in treated rats, including increased salivation, slight distention of the abdomen, emaciated appearance, and ataxia. After 14 days of treatment, the rats were necropsied and tissues examined microscopically. A number of compound-related histopathological changes were observed in rats receiving 30 or 100 mg/kg/day. Myocardial degeneration and necrosis, endocardial fibrosis, epicarditis, and arteritis/periarteritis of intramural and extramural coronary arteries were observed in the heart. A necrotizing vasculitis and inflammation were observed in the mesentery and interstitial areas of the liver, affecting medium-sized portal arteries and veins. Focal necrosis was also observed in the glandular mucosa of the stomach at these 2 dose levels. Other treatment-related effects included squamous hyperplasia and hyperkeratosis with or without ulceration in the nonglandular stomach of at least one animal from all treatment groups. Enlarged salivary glands were noted at necropsy in animals treated with 100 mg/kg/day, and this finding correlated microscopically with dilatation and degeneration of ducts and acini in the sublingual gland with secondary inflammation and edema. The results of this study demonstrate that rolipram, a selective inhibitor of the type IV class of PDE, can cause effects on the heart and vasculature of rats which heretofore have been ascribed only to selective inhibitors of the PDE III class of isozymes. Therefore, these organs should be closely examined in studies with other PDE IV inhibitors. In addition, the gastrointestinal tract and salivary glands were sites for rolipram-induced toxicity and may be targets of other PDE IV inhibitors.

Animals↗
PubMed1997

Toxicity of bupivacaine and ropivacaine in relation to free plasma concentrations in pregnant rats: a comparative study.

The relationship between free drug concentration and toxicity of bupivacaine and ropivacaine, a new local anaesthetic agent, was studied in a pregnant rat model. The compounds were given subcutaneously to rats in late pregnancy. Dose levels (bupivacaine 5.5 to 24 mg/kg and ropivacaine 5.3 to 26 mg/kg) were selected based upon the proposed human dosage and the known pharmacological activity of the compounds. Chewing, spasm, dyspnoea, drowsiness, salivation and convulsions were observed in a dose-dependent manner in the animals given 14 to 24 mg/kg of bupivacaine, while only a few animals receiving 26 mg/kg of ropivacaine showed less severe symptoms. Deaths from clonic convulsions were occasionally seen in animals receiving 14 mg/kg or more of bupivacaine. No animals receiving ropivacaine died. No effects on litter size offspring loss or weight of the offspring at birth were observed with one exception. After 24 mg/kg of bupivacaine an increased postnatal loss of the offsprings were noticed, most likely due to impaired maternal care. Protein binding, at expected Cmax, were significantly lower for ropivacaine (around 49%) compared with bupivacaine (around 69%) at dose levels. The results suggest an increased safety margin before onset of toxic side effects after treatment with ropivacaine, compared to bupivacaine, in pregnant rase.

Amides↗
PubMed2005

Preliminary results of moisture checker for Mucus in diagnosing dry mouth.

OBJECTIVE: To evaluate the ability of Moisture Checker for Mucus (MCM), a device which measures the weight percent of water content in the oral mucosal epithelium, for the diagnosis of dry mouth. METHOD: Forty-three consecutive patients seen at the Dry Mouth Clinic of Tsurumi University were divided into two groups by the diagnostic criteria of hyposalivation defined by the stimulated salivary flow rate < or =10 ml per 10 min. The MCM values in the buccal, tongue and labial mucosa in each group were compared. RESULTS: The value of the normal salivation group was significantly higher when compared with that of the hyposalivation group both in the buccal and tongue mucosa, P = 0.01 and P = 0.046, respectively. CONCLUSION: Moisture Checker for Mucus has the potential to be a useful device in the screening of hyposalivation.

Adult↗
PubMed2001

A case of trisomy 28 in cattle revealed by both banding and FISH-mapping techniques.

A case of presumed trisomy 22 in cattle, as earlier reported, was investigated by using both chromosome banding and FISH-mapping techniques. A one year old Hereford female calf showed slow growth, brachygnathia superior, hyper-salivation. strabisbusmus convergence, macroclitoris and supernumerary nipples. At necropsy, a duplication of the uterine cervix and an extra aortic cusp were also observed. The R-banding technique revealed that BTA28 (not BTA22, as erroneously earlier reported) was involved in the trisomy. This was confirmed by FISH-mapping with chromosome-specific markers. Phenotypic characteristics achieved in cattle carrier and those earlier reported in humans carrying partial trisomy 10 were discussed.

Animals↗
PubMed2001

Effects of mouthrinses with linseed extract Salinum without/with chlorhexidine on oral conditions in patients with Sjögren's syndrome. A double-blind crossover investigation.

OBJECTIVES: To study the effect of mouthrinses with salivary replacement substances on oral conditions in patients with primary Sjögren's syndrome. DESIGN: Cross-over, double-blind study. SETTING: Facilities at the Centre for Oral Health Sciences, Malmö University and at Malmö University Hospital, Malmö, Sweden. SUBJECTS: Twenty-two patients with Sjogren's syndrome. INTERVENTION: Linseed extract Salinum alone (Sal) or with addition of chlorhexidine (Sal/Chx) was used for mouthrinsing during 3-week periods of rinsings separated by a 3-week "wash-out" period. MEASUREMENTS: Recordings of percentages of sites with dental plaque and bleeding on probing, mirror friction test and microbiological analyses. Questionnaire on oral symptoms due to reduced salivation. RESULTS: Dental plaque and bleeding on probing were reduced after Sal and after Sal/Chx. Friction was reduced after both treatments. No significant differences for counts of studied microbial groups were seen after Sal but the total anaerobically cultured microorganisms and of mutans streptococci fell after Sal/Chx (p<0.05 and p<0.001). Symptoms of oral dryness improved following Sal and Sal/Chx (p<0.05 and p<0.001 respectively). Speaking problems and burning mouth symptoms improved after use of Sal (p<0.05). CONCLUSIONS: Positive effects on symptoms in patients with Sjögren's syndrome were seen after use of Salinum without or with chlorhexidine.

Adult↗
PubMed2006

Susceptibility of newborn rats to 3-ethylphenol and 4-ethylphenol compared with that of young rats.

Newborn rat studies were conducted with oral administration of 3-ethylphenol (3EP) and 4-ethylphenol (4EP) on postnatal days (PND) 4-21 to allow comparison of no observed adverse effect level (NOAEL) and unequivocally toxic level (UETL) with those from 28-day studies of young rats starting at 5-6 weeks of age. In the newborn rat studies, slightly lowered body weight was observed after 3EP treatment, and deaths, hypoactivity, Straub tail, deep respiration and delayed righting reflex were clearly observed after 4EP treatment. In the young rat studies, salivation, staggering gait, changes in the liver including high values of liver weight and alanine aminotransferase or total cholesterol and the lesions in the forestomach were clearly observed after 3EP and 4EP treatments. NOAELs of 3EP and 4EP in the newborn rat studies appeared to be almost 3 times lower than those in the young rat studies. As a clear toxicity of 3EP was not observed in newborn rats, UETLs were not established for 3EP. Regarding 4EP, UETL of young rats was 4-5 times higher than that of newborn rats. In conclusion, newborn rats were 3-5 times more susceptible to 3EP and 4EP than young rats.

Administration, Oral↗
PubMed2006

Veratridine-induced wet dog shake behaviour and apoptosis in rat hippocampus.

We have previously evaluated veratridine as an in vitro model of seizure using conventional electrophysiological recordings in rat hippocampal CA1 pyramidal neurones. The aim of this investigation is to further characterize this convulsant as an in vivo model of seizure. Veratridine was administered intraperitoneally to male Fisher rats in a dose range of 100-400 mug/kg. Within 5 min. after the injections, the animals entered a quiescent period which was followed 10-15 min. later by facial automatism (washing), grooming, masticatory jaw movement and profuse salivation. This phenomenon was followed by the development of wet dog shake and forelimb clonus. The time (mean+/-S.E.M.) for the onset of induction of these shakes for all tested doses was 31.65+/-2.85 min. and the number of shakes (mean+/-S.E.M.) 30 min. after the onset was 17.2+/-2.85. The onset and number of wet dog shakes induced by veratridine was dose-dependent. No rat death was recorded until 2 weeks after the experiments. Histopathological studies of animals 2 weeks after veratridine administration showed evidence of apoptosis in the hippocampus. Our results indicate that veratridine produced a behavioural pattern of a limbic seizure which mimics temporal lobe epilepsy in man. Based on our previous findings in vitro and of this investigation in vivo, veratridine can be used as an experimental tool to evaluate potential antiepileptic drugs effective against this type of limbic behaviour.

Animals↗
PubMed1981

Complementary role of vasoactive intestinal polypeptide (VIP) and acetylcholine for cat submandibular gland blood flow and secretion. I. VIP release.

The effects of parasympathetic and sympathetic nerve stimulation on VIP release in relation to blood flow and secretion were studied in the cat submandibular salivary gland. Parasympathetic nerve stimulation caused a marked VIP overflow (over thousand fold increase in VIP output) into the venous effluent from the gland which was simultaneous with profuse salivation and an about 10-15 fold increase in blood flow. The VIP output was dependent on the stimulation frequency, the duration of the stimulation period as well as the glandular blood flow. At 15 Hz maximal VIP output (about 4 fmol per impulse) was obtained after about 5 min of stimulation simultaneously with the maximum of the maintained phase of vasodilation. About 50 pmol VIP was recovered in the venous effluent from the gland during 1 h of maximal nerve stimulation. The VIP output after 1 h, was only about 20% of maximal, however, suggesting that the storage reserves and/or resupply of VIP might be running out. Under physiological conditions (frequencies less than or equal to 6 Hz) it was estimated that the axonal transport mechanism should be sufficient for replacement of VIP. At lower frequencies (2 and 6 Hz) the VIP output was parallel to vasodilation and secretion, while at a high frequency (15 Hz) a much more pronounced VIP output was seen. The increased overflow at 15 Hz may either be due to an actual increase in release or to a saturation of local VIP inactivating mechanisms. When stimulated simultaneously, the parasympathetic vasodilator mechanism seemed much more potent than sympathetic vasoconstriction. Since VIP may be present in cholinergic neurons, data from the literature concerning acetylcholine release are discussed in relation to the observed VIP output.

Acetylcholine↗
PubMed1985

Physiological responses associated with feigned death in the American opossum.

Heart rate, respiratory rate and body temperature of four free-ranging American opossums, Didelphis marsupialis of both sexes (2.47 +/- 0.27 kg; mean +/- SE), were monitored during mild provocation and during death feigning ('play possum'). Mild provocations, caused by the approach of either man or dog, elicited a freezing response. The behavioural response was accompanied by a 12% decrease in heart rate (218 +/- 11 to 192 +/- 10 beats X min-1; mean +/- SE) and a 31% reduction in respiratory rate (26.7 +/- 1.7 to 18.4 +/- 1.4 breaths X min-1) from pre-stimulation values. Death feigning was induced by vigorous tactile stimulation by either investigator or dog. The response was marked by immobility, prone position and stiffness of the body. Mouth was open and the animal showed no response to touch or pinching. Death feigning was always accompanied by salivation, urination, defaecation and erection of the penis (in males). Heart rate decreased 46% (222 +/- 10.6 to 120 +/- 17 beats X min-1) and respiratory rate was reduced 30% (27.4 +/- 1.5 to 19.2 +/- 2.3 breaths X min-1) from pre-stimulation values. Body temperature dropped from 34.8 +/- 0.2 to 34.2 +/- 0.3 degrees C. During death feigning the animal was fully conscious as was evident by heart rate reduction during the re-approach of the dog. Atropine treatment had no obvious effect on behaviour but abolished the bradycardia when compared to pre-stimulus condition.

Animals↗