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Non-immunoglobulin defense factors in canine saliva and effects of a tooth gel containing antibacterial enzymes.

Selected innate: non-immunoglobulin defense factors in canine saliva were characterized and quantitated. The samples from dogs showed increased pH, higher lysozyme and salivary peroxidase activities, but lower hypothiocyanite concentration and myeloperoxidase activity when compared with human saliva. Secondly, a 1-month clinical pilot study was performed using a commercial tooth gel to determine acute and long-term changes in salivary host defense proteins. Daily application of the tooth gel did not substantially affect the concentrations of these factors in dogs with normal salivation. Our results suggest that canine saliva may be similar to human saliva, comprised of both immune and non-immune antimicrobial factors. However, as in humans, oral administration of antimicrobial proteins as reported here does not seem to benefit dogs with normal saliva secretion. Products such as the tooth gel evaluated in this study may benefit dogs with xerostomia or other clinical conditions causing decreased saliva production.

Animals↗

Diagnosis and treatment of acute poisoning with volatile substances.

1. The acute toxicity of many volatile compounds is similar, being more related to physical properties than to chemical structure. 2. Volatile substance abusers experiences euphoria and disinhibition but this may be followed by nausea and vomiting, dizziness, coughing and increased salivation; cardiac arrhythmias, convulsions, coma and death occur in severe cases. 3. Laboratory analysis of blood and urine samples collected up to 24 h post-exposure may be helpful if the diagnosis of volatile substance abuse is in doubt. 4. There is only a weak correlation between blood toluene and 1,1,1-trichloroethane concentrations and the clinical features of toxicity, possibly because of rapid initial tissue distribution and elimination. 5. Recovery normally occurs quickly once exposure has ceased but support for respiratory, renal or hepatic failure may be needed as well as treatment for cardiac arrhythmias. Therapy with intravenous acetylcysteine should be considered in cases of acute carbon tetrachloride poisoning.

Carbon Tetrachloride Poisoning↗

Toxicosis in dairy cattle exposed to poison hemlock (Conium maculatum) in hay: isolation of Conium alkaloids in plants, hay, and urine.

Cattle in two herds developed signs of bloating, increased salivation and lacrimation, depression, respiratory distress, ataxia, and death after ingestion of hay that contained large amounts of poison hemlock (Conium maculatum). Twenty of 30 Angus cows and calves were affected in the first herd (2 died). In the second herd, 5 of 30 Holstein heifers were affected (1 died). The Conium alkaloids, coniine and gamma-coniceine, were quantified in the hay, the plants from the responsible hayfield, and the urine of affected animals.

Alkaloids↗

Water hemlock (Cicuta douglasii) toxicoses in sheep: pathologic description and prevention of lesions and death.

Water hemlock causes numerous livestock losses in North America every year. Description of pathologic and serum biochemical changes has been lacking in the literature. Tubers of western water hemlock (Cicuta douglasii) induced excessive salivation, tremors, grand mal seizures, skeletal and cardiac myodegeneration, and death in sheep given 1.2-2.7 g fresh tuber/kg body weight by gavage. Seizures were intermittent with periods of relaxation until death occurred from anoxia during seizure activity. In sheep given 1.5-2.5 times the lethal dose of water hemlock by gavage, intravenous administration of sodium pentobarbital at the onset of the first seizure prevented further seizure activity and skeletal and cardiac myodegeneration and resulted in rapid and complete recovery.

Animals↗

Malignant catarrhal fever in bison, acute and chronic cases.

Acute malignant catarrhal fever (MCF) was diagnosed in 10 bison from 6 herds and ranging from 1 to 6 years of age. The pattern of clinical signs and morphologic lesions differed among bison. Combinations of corneal opacity, lacrimation, nasal discharge, depression, excess salivation, anorexia, diarrhea, melena, and hematuria were observed. Vasculitis characterized by lymphoid infiltrates in the adventia with variable extension into media and intima was found in multiple tissues in each animal. Fibrinoid vascular necrosis was rare. Ulceration in the alimentary tract was found in 9/10 bison, and ulceration or hemorrhage in the urinary bladder was found in 8/10 bison. Lymphoid infiltrates were present in 7 of 9 livers and 9 of 9 kidneys examined histologically. Hyperplasia of lymph nodes was observed in 5 bison. Chronic MCF was diagnosed in 1 bison with an 80-day course of illness that began with lacrimation, corneal opacity, mucoid nasal discharge, depression, and anorexia. These signs ceased after 15 days but circling and blindness developed on day 76. Chronic vascular lesions characterized by endothelial cell hypertrophy, intimal thickening, fragmentation of the internal elastic membrane, smooth muscle hypertrophy, and adventitial infiltrates of lymphocytes and plasma cells were found in many organs. The retinal arteries had chronic inflammation and acute transmural fibrinoid necrosis. The retinas were infarcted. Polymerase chain reaction technique for amplification of ovine herpesvirus 2 sequences was performed on formalin-fixed tissues, and viral sequences were detected in 1-7 tissues from each animal. These viral sequences were not found in tissues of 4 bison not affected by MCF.

Acute Disease↗

Salivary gland function and aging: a model for studying the interaction of aging and systemic disease.

This review describes an approach to examining the interaction of aging and systemic disease on a key aspect of oral physiology, salivation. The approach requires several steps: defining general health, and a specific physiological function, at different ages; defining a disease of interest and the influence of the disease on the specific physiological function; and determining if the disease can affect performance of the physiological function with increased age.

Aging↗

Intravenous self-administration of elemental mercury: efficacy of dimercaprol therapy.

Deliberate parenteral self-injection of mercury is extremely rare, and is associated with a high degree of mortality and morbidity. Because mercury depresses cellular enzymatic mechanisms by combining with sulfhydryl groups, soluble mercuric salts are toxic to all cells. Embolization of mercury in the lungs has been reported with varying degrees of changes in pulmonary function. Mercury causes urticaria progressing to weeping dermatitis, leukopenia, anemia, diarrhea, salivation, liver damage, and renal damage progressing to acute renal failure with anuria. Dimercaprol is an effective antidote in acute heavy metal intoxication because its two sulfhydryl groups successfully compete with tissue enzyme sulfhydryl groups for the offending metal. Experience with dimercaprol therapy months after the original exposure to mercury is not available. We describe the hospital course of a patient after intravenous elemental injection and the results of dimercaprol therapy months after the original exposure.

Adult↗

Clozapine: a novel antipsychotic agent.

Clozapine is an antipsychotic without the extra-pyramidal adverse effects associated with currently marketed antipsychotics. In animals, this drug has not been shown to induce catalepsy and only weakly antagonizes the stereotypic movements induced by apomorphine and the amphetamines. Clozapine is rapidly absorbed after both single and repeated oral doses, with steady-state concentrations attained within eight to ten days after beginning therapy. It is metabolized to N-oxideclozapine and N-desmethylclozapine, which have less pharmacological activity than the parent compound and are excreted in the urine and, to a lesser extent, in the feces. Clozapine has overall therapeutic efficacy and/or superiority to currently marketed antipsychotics in the treatment of refractory schizophrenia. Usual doses (25-900 mg/d) of clozapine cause fewer extrapyramidal adverse reactions than available antipsychotics. Hypotension, dizziness, salivation, and sedation are the most frequently reported adverse effects and tend to subside over time. Agranulocytosis is the most serious adverse reaction, and those receiving clozapine should undergo weekly white blood cell count determinations. Clozapine is useful for those treatment-resistant patients who have not responded to adequate trials of other antipsychotics.

Clozapine↗

Blood flow and interstitial fluid pressure in the rat submandibular gland during changes in perfusion.

The submandibular gland is a cell-rich encapsulated organ with high transport of fluid through the interstitial space during salivation. We hypothesized that the gland is a low-compliant tissue, i.e., that a modest increase in fluid volume will produce a rise in interstitial fluid pressure (IFP) counteracting fluid filtration into the interstitium. To test this hypothesis, we measured IFP with micropipettes and glandular blood flow (GBF) with a laser-Doppler flowmeter during changes in perfusion. Clamping of the carotid artery or the jugular vein, or electrical stimulation of the sympathetic or parasympathetic nerve to the gland, induced changes in perfusion. Baseline IFP averaged 3.5 +/- 0.5 mm Hg. Clamping of the artery reduced IFP and GBF (-56.5 +/- 8.4% and -53.1 +/- 6.4%, respectively), whereas clamping of the vein decreased GBF (-21.6 +/- 14.3%) and increased IFP (141.2 +/- 27.4%). Sympathetic nerve stimulation reduced both parameters (-86.9 +/- 16.5% and -74.4 +/- 7.0%, respectively). In contrast, stimulation of the parasympathetic nerve elicited an increase in GBF (133.2 +/- 5.9%) and in IFP (173.3 +/- 41.4%). Thus, changes in vascular volume led to concomitant changes in IFP consistent with low tissue compliance, a phenomenon of importance for fluid volume regulation.

Animals↗

Influence of bitter taste on mastication pattern.

Mastication is a rhythmic activity that can be modified by peripheral information generated in the mouth. To study whether taste cognition could influence the way in which a food is broken down in the mouth, subjects masticated firm, sugar-based gelatine gels with differing concentrations of quinine, up to 1500 micromol/kg, while electromyography (EMG) of masticatory muscles was recorded. Taste intensity and composition of saliva were measured. With increasing quinine concentration, the average number of chews for nine subjects decreased from 30 to 22, and their average clearance time increased from 7 to 14 sec. Quinine concentration had no effect on chewing frequency (1.3 Hz) or on the rate of salivation (5.5 g/min). Bitterness increased, while acceptability and sweetness decreased, with increasing concentration of quinine in the gel and in saliva. Taste cognition could therefore modify food breakdown in the mouth.

Adult↗

Use of pesticides and its impact on health of farmers in South India.

The relationship between extent of pesticide use and signs and symptoms of illnesses due to exposure was assessed in a cross-sectional survey of 631 farmers (537 men and 94 women) in South India. Responses to questionnaires showed that 433 farmers (68.6%) sprayed pesticides themselves and were thus directly exposed. More than 75% used moderately or highly hazardous pesticides; 88% used no protection while handling pesticides. About 50% of sprayers mixed different brands. Retailers were the source of information about pesticides for 56%. The farmers reported excessive sweating (36.5%), burning/stinging/itching of eyes (35.7%), dry/sore throat (25.5%), and excessive salivation (14.1%), all more prevalent among sprayers. Among men, excessive sweating and eye and throat problems were significantly associated with exposure. There is a need to raise farmers' and authorities' awareness of the need to use protective gear when handling pesticides.

Adult↗

Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana.

BACKGROUND: The cockroach salivary gland consists of secretory acini with peripheral ion-transporting cells and central protein-producing cells, an extensive duct system, and a pair of reservoirs. Salivation is controlled by serotonergic and dopaminergic innervation. Serotonin stimulates the secretion of a protein-rich saliva, dopamine causes the production of a saliva without proteins. These findings suggest a model in which serotonin acts on the central cells and possibly other cell types, and dopamine acts selectively on the ion-transporting cells. To examine this model, we have analyzed the spatial relationship of dopaminergic and serotonergic nerve fibers to the various cell types. RESULTS: The acinar tissue is entangled in a meshwork of serotonergic and dopaminergic varicose fibers. Dopaminergic fibers reside only at the surface of the acini next to the peripheral cells. Serotonergic fibers invade the acini and form a dense network between central cells. Salivary duct segments close to the acini are locally associated with dopaminergic and serotonergic fibers, whereas duct segments further downstream have only dopaminergic fibers on their surface and within the epithelium. In addition, the reservoirs have both a dopaminergic and a serotonergic innervation. CONCLUSION: Our results suggest that dopamine is released on the acinar surface, close to peripheral cells, and along the entire duct system. Serotonin is probably released close to peripheral and central cells, and at initial segments of the duct system. Moreover, the presence of serotonergic and dopaminergic fiber terminals on the reservoir indicates that the functions of this structure are also regulated by dopamine and serotonin.

Animals↗

5-HT loss in rat brain by type II pyrethroid insecticides.

STUDY OBJECTIVE: Type II pyrethroids are a group of insecticides largely used in agriculture and public health. The nervous system is the main target for pyrethroids in insects and mammals. One notable form of toxicity associated with over exposure has been a facial cutaneous paraesthesia and irritation-related respiration symptoms including behavioural excitation mainly observed in workers spraying pyrethroids or in occupational settings. In acutely exposed rats, type II pyrethroids produce a severe syndrome characterized by salivation and choreoathetosis. Because many of the acute functional effects of type II pyrethoids can be associated with the neurotoxic effect on 5-hydroxytryptamine (5-HT) neurones, the objective of the present study was to examine whether deltamethrin, cyfluthrin and lambda-cyhalothrin administration results in changes of 5-HT content in rat brain. Characterizing this target will help us to better understand the toxicological effects of type II pyrethroids. DESIGN: Rats were injected with either corn oil or pyrethroids (deltamethrin, 20 mg/kg per day, i.p., for 6 days; cyfluthrin, 14 mg/kg per day, i.p., for 6 days; lambda-cyhalothrin, 8 mg/kg per day, i.p., for 6 days). The frontal cortex, hippocampus, midbrain and striatum were removed at 24 hours post treatment and were analysed for content of 5-HT and 5-HIAA using a HPLC method with electrochemical detection. RESULTS: A serotonin depleting effect was produced by these type II pyrethroids. The concentration of 5-HT and its metabolite 5-HIAA decreased in the brain regions from pyrethroid treated animals. Pyrethroids accelerated the turnover of 5-HT in midbrain and striatum areas. It is concluded that pyrethroids affect serotonin neurotransmission.

Analysis of Variance↗

Clinical manifestations of VX poisoning following percutaneous exposure in the domestic white pig.

Nerve agents are a class of organophosphorus chemicals that inhibit certain cholinesterase enzymes (ChE). If untreated, percutaneous exposure to nerve agents, such as VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) can cause paralysis, apnoea and death. Much of the information concerning the percutaneous absorption and subsequent toxicity of nerve agents has been obtained using various rodent models. However, the most relevant 'skin model' is arguably the pig. Therefore, the purpose of this study was to examine the clinical manifestations of VX intoxication in the domestic white pig following a 2 LD50 (120 microg/kg) percutaneous challenge. There was a consistent onset of signs (where present) in each animal: mastication was followed by miosis, salivation, fasciculations and apnoea. Whilst ChE activity did not correlate with the onset of signs, there was a qualitative relationship in that mastication preceded substantial ChE inhibition, miosis lagged behind the linear decrease in acetylcholinesterase (AChE) activity and fasciculations and apnoea occurred after maximum ChE inhibition had been attained (5-10% of normal). These observations may be of use for the triage of patients exposed to VX. In comparison with similar studies with GD, VX did not affect glucose utilization. However, VX was similar to GD in that it caused a mild hyperkalaemia and hyperphosphataemia, although the significance of this observation was not clear. There was substantial lateral diffusion of the initial droplet of VX over the application site, indicating that, when decontaminating exposed skin, attention should also be directed to areas peripheral to the original site of exposure.

Acetylcholinesterase↗

Lack of effect of the alpha-adrenergic agonist clonidine on pulsatile luteinizing hormone secretion in a double blind study in men.

This study was designed to evaluate the effects of alpha-adrenergic stimulation on the hypothalamic LHRH pulse generator in men. In 10 normal men, venous blood was sampled on 2 occasions at 10-min intervals for 8 h, beginning 30 min after oral administration of either placebo or 0.3 mg clonidine according to a randomized double blind protocol. Compared to placebo, clonidine induced a marked release of GH (P less than 0.0001 for response areas under the curve after placebo and clonidine), a fall in systolic and diastolic blood pressure and in heart rate (P less than 0.002 for areas under the curve after placebo and clonidine), and feelings of sedation and dry mouth (P less than 0.002 and P less than 0.05 for areas under the cumulative scores for changes in alertness and salivation, respectively). There was no difference between the results obtained after placebo and clonidine for the mean number of LH pulses [3.3 +/- 0.4 (+/- SE) and 3.3 +/- 0.3 pulses/8 h], for the mean amplitude of all LH pulses (3.8 +/- 0.4 and 4.1 +/- 0.5 IU/L), or for the areas under the LH concentration-time curve (2741 +/- 251 and 2728 +/- 215 IU/L.min). The lack of effect of clonidine on LH secretion at a dose that effectively induced GH secretion and other centrally mediated effects indicates that the actions of testosterone and opiates to decelerate the frequency of the LHRH pulse generator in men are not mediated by diminished alpha-adrenergic stimulation. From these results, taken together with previous data, we conclude that alpha-adrenergic systems do not play a major role in the regulation of episodic LH release in men.

Adult↗

The quicksilver prize: Mercury vapor poisoning aboard HMS Triumph and HMS Phipps.

In 1810, two British ships, HMS Triumph and HMS Phipps, salvaged a large load of elemental mercury from a wrecked Spanish vessel near Cadiz, Spain. The bladders containing the mercury soon ruptured. The element spread about the ships in liquid and vapor forms. The sailors presented with neurologic compromises: tremor, paralysis, and excessive salivation as well as tooth loss, skin problems, and pulmonary complaints. The events are reviewed in the context of what was known about mercury vapor inhalation.

History, 19th Century↗

Dystonic posturing in seizures of mesial temporal origin: electroclinical and metabolic patterns.

OBJECTIVE: To test the hypothesis that extratemporal neuronal networks are involved in dystonic posturing (DP) observed in mesial temporal epilepsy (MTLE). METHODS: The authors analyzed electroclinical findings in 36 patients with MTLE with or without DP. Three DP types were defined (types I, II, III) corresponding to a gradual increase in duration and complexity. Interictal [18F]fluorodeoxyglucose-PET in different groups and subgroups was compared with control subjects using statistical parametric mapping software (SPM99). RESULTS: DP was found in 20 patients (55%), contralateral to the epileptogenic focus in 95%. Patients with DP had longer seizure duration, higher frequency of head deviation, salivation, motor manifestations, secondary generalization, severe clouding of consciousness, and prolonged postictal confusion when compared with patients without DP. Ictal discharge patterns during DP consisted of fast rhythmic activity spreading to frontal or suprasylvian areas, whereas slow rhythmic activity restricted to the temporal areas occurred in the absence of DP. In patients with DP, widespread temporal and extratemporal hypometabolism including the putamen was found. Hypometabolism was restricted to the anteromesial part of the temporal lobe and anterior insula in patients without DP. Putaminal hypometabolism was found in all DP types, but different extratemporal cortical involvements were found in DP subgroups: insula and inferior frontal gyrus in type I, inferior and superior frontal gyri and anterior cingulate gyrus in type II, and parietal areas in type III. CONCLUSION: Dystonic posturing may result from involvement of both putaminal and extratemporal cortical areas. Moreover, different frontal or parietal networks may be involved according to the duration or complexity of dystonic posturing.

Adolescent↗

Cholinergic dysautonomia and Eaton-Lambert syndrome.

Cholinergic autonomic function was abnormal in a 47-year-old woman with Eaton-Lambert syndrome (ELS), not associated with carcinoma. Pupillary constriction to light and accommodation, sweating, lacrimation, and salivation were all affected. There was no evidence of Sjogren syndrome or botulinum intoxication. The defect of acetylcholine release from presynaptic terminals in the Eaton-Lambert syndrome may not be restricted to the neuromuscular junction of skeletal muscle.

Cholinergic Fibers↗