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At least 865 records · Page 48Linked to original sources
PubMed1997

Further pharmacological study on Sho-seiryu-to as an antiallergic.

Examination was made of the pharmacological characteristics of Sho-seiryu-to, an antiallergic kampo medicine. Sho-seiryu-to suppressed histamine release from rat peritoneal mast cells, but failed to inhibit the binding of [3H]-mepyramine to histamine H1 receptors in guinea pig cerebral cortex and lung. Sho-seiryu-to had no effect on cutaneous reactions induced by serotonin, platelet-activating factor (PAF), leukotriene (LT) C4 or LTD4. Ketotifen prolonged electrically induced convulsions, while Sho-seiryu-to did not. Sho-seiryu-to did not affect salivation induced by pilocarpine. Sho-seiryu-to thus does not appear to inhibit histamine H1 receptors or inflammation induced by serotonin, PAF, LTC4 and LTD4, but suppresses mast cell activity. Sho-seiryu-to would thus have only a few side effects such as dry mouth and convulsions due mainly to the blockage of the action of muscarinic in salivary glands and histamine in the brain.

Animals↗
PubMed1992

Diagnosis and management of parotitis.

Of all the salivary glands, the parotid gland is most commonly affected by an inflammatory process. Infections of the parotid gland range from acute to severe. Assessment of the disease process should differentiate local primary parotid infection from systemic infection when this gland is also involved as part of a generalized inflammatory condition. Viral parotitis can be caused by paramyxovirus (mumps), Epstein-Barr virus, coxsackievirus, and influenza A and parainfluenza viruses. Acute suppurative parotitis is generally caused by Staphylococcus aureus, Streptococcus species, and rarely, gram-negative bacteria. Anaerobic bacteria, mostly Peptostreptococcus species and Bacteroides species, and pigmented Porphyromonas species and Prevotella species have been recently recognized as an important cause of this infection. beta-Lactamase-producing organisms can be isolated in almost three fourths of the patients. Predisposing factors to suppurative infections are dehydration, malnutrition, oral neoplasms, immunosuppuration, sialolithiasis, and medications that diminish salivation. Pus, aspirated from a suppurative parotic abscess, should be plated on media that are supportive for the growth of aerobic and anaerobic bacteria, mycobacteria, and fungi. Early and proper antimicrobial therapy may prevent suppuration. Initial empiric therapy that is directed against both aerobic and anaerobic bacteria may be required until a specific causal diagnosis is available. Surgical drainage may be indicated when pus has formed. This may prevent complications and facilitate recovery.

Diagnosis, Differential↗
PubMed2001

Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison.

BACKGROUND: Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison with a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. METHODS: Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. RESULTS: Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine-treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. CONCLUSIONS: Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.

Adult↗
PubMed1999

Nerve growth factor preserves a critical motor period in rat striatum.

We previously found the occurrence of a critical motor period during rat postnatal development where circling training starting the 7-day schedule at 30 days-but not before or after-induces a lifetime drop in the binding to cholinergic muscarinic receptors (mAChRs) in striatum. Here, we studied whether nerve growth factor (NGF) participates in this restricted period of muscarinic sensitivity. For this purpose, we administered mouse salival gland 2.5S NGF (1.4 or 0.4 microg/day, infused by means of ALZA minipumps) by intrastriatal unilateral route between days 25 and 39, and then trained rats starting at 40 days. Under these conditions, NGF induced a long-term reduction in the striatal [3H] quinuclidilbenzylate (QNB) binding sites despite the fact that motor training was carried out beyond the natural critical period. Thus, at day 70, measurement of specific QNB binding in infused striata of trained rats showed decreases of 42% (p < .0004) and 33% (p < .02) after administration of the higher and lower NGF doses, respectively, with respect to trained rats treated with cytochrome C, for control. Noncannulated striata of the NGF-treated rats also showed a decrease in QNB binding sites (44%; p < .0001) only at the higher infusion rate. This effect was not found in the respective control groups. Our observations show that NGF modulates the critical period in which activity-dependent mAChR setting takes place during rat striatal maturation.

Age Factors↗
PubMed1999

Psychological and physiological characteristics of sweet food "addiction".

OBJECTIVE: Drug addicts in general can be distinguished from nonaddicts by their affective and physiological and craving responses to drug-related cues. The purpose of this study was to examine similar affective, physiological, and behavioral variables in chocolate "addicts" and control subjects. METHODS: Sixteen addicts and 15 control subjects took part in two laboratory experiments in which their heart rate, salivation, and self-reported responses were measured. RESULTS: In the presence of external chocolate cues, chocolate addicts were more aroused, reported greater cravings, experienced more negative affect, and also ate more chocolate than control subjects. Self-report measures on eating attitudes and behavior, body image, and depression confirmed that a relationship exists between "chocolate addiction" and problem eating. Chocolate addicts showed more aberrant eating behaviors and attitudes than controls, and were also significantly more depressed. DISCUSSION: Chocolate addicts may be considered to be a parallel with addicts generally, because they differ from controls in craving for chocolate, eating behavior, and psychopathology (in respect of eating and affect).

Adult↗
PubMedDate not supplied

Cardiorespiratory effects of O-isobutyl S-[2-(diethylamino)-ethyl] methylphosphonothioate -- a structural isomer of VX.

O-Isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate (VR) is a structural isomer of a more well-known chemical warefare agent, O-ethyl S-[2(diisopropylamino)ethyl]methylphosphonothioate (code designation VX). In this study, cardiorespiratory and central nervous system (CNS) effects of VR (2LD50 or 22.6 microg kg(-1); s.c.) were evaluated in urethane-anesthetized (Group 1) and unanesthetized (Group 2) guinea pigs instrumented for concurrent recordings of electrocorticogram (ECoG) and a variety of cardiorespiratory activities. The first sign of intoxication was a state of progressive bradycardia, vascular hypotension and arrhythmia (Group 1, approximately 13 min post-VR; Group 2, approximately 6 min post-VR). Bradypnea, excessive salivation and compensatory changes in blood pressure typically did not emerge until 3-5 min prior to apnea (Group 1, approximately 28 min post-VR; Group 2, approximately 15 min post-VR). An idioventricular rhythm, which signalled a failing myocardium, appeared at the same time or shortly after the development of a bradypneic profile. Another notable toxicity component of VR, based on arterial pH, pO2/pCO2 and bicarbonate (HCO3-) level data, was a state of combined hypercapnia, acidemia and hypoxemia during the development of bradypnea. Taken together, findings from this study indicated that changes in medullary respiratory unit activity and ECoG data displayed little, if any, notable signs of CNS perturbation prior to the terminal stage (approximately 1 min prior to respiratory failure). Thus, in addition to displaying a greater sensitivity to perturbation by VR, the peripheral cardiorespiratory system components also appeared to play a more important role in precipitating a progressively dysfunctional cardiorespiratory status that ultimately led to collapse of central respiratory mechanisms and death.

Acidosis↗
PubMedDate not supplied

Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs.

Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.

Administration, Inhalation↗
PubMed2004

Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neuromuscular disease characterized by progressive muscle weakness resulting in paralysis, which might be treated with ciliary neurotrophic factor. OBJECTIVES: The objective of this review was to examine the efficacy of ciliary neutrophic factor in amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (searched June 2003) for randomized trials, MEDLINE (from January 1966 to October 2003) and EMBASE (from January 1980 to October 2003), checked the reference lists of papers identified and contacted the authors of studies identified to get additional unpublished results. SELECTION CRITERIA: We considered the following selection criteria: Types of studies: randomized controlled clinical trials; TYPES OF PARTICIPANTS: adults with a diagnosis of either probable or definite amyotrophic lateral sclerosis according to the El Escorial criteria; Types of interventions: treatment with ciliary neurotrophic factor for at least six months, in a placebo-controlled randomized format; Types of outcome measures Primary: survival; Secondary: muscle strength, respiratory function, changes in bulbar functions, changes in quality of life, proportion of patients with adverse side effects (such as cough, asthenia, nausea, anorexia, weight loss and increased salivation). DATA COLLECTION AND ANALYSIS: We identified two randomized trials. The data were extracted and examined independently by the reviewers. Some missing data were obtained from investigators. MAIN RESULTS: Two trials, with a total population of 1,300 amyotrophic lateral sclerosis patients treated with subcutaneous injections of recombinant human ciliary neurotrophic factor, were examined in this review. The methodological quality of these trials was considered adequate. No significant difference was observed between ciliary neurotrophic factor and placebo groups for survival, the primary outcome measure. The relative risk was 1.07 (95% CI 0.81 to 1.41). No significant differences between the groups were observed for most of the secondary outcomes. However, a significant increase of the incidence of several adverse events was noted in groups treated with higher doses of CNTF. REVIEWERS' CONCLUSIONS: Ciliary neurotrophic factor treatment has no effect on amyotrophic lateral sclerosis progression. At high concentration, several side effects were observed. A combination of ciliary neurotrophic factor with other neurotrophic factors (as suggested by results on animal models), and more efficient delivery methods should be tested.

Amyotrophic Lateral Sclerosis↗
PubMed1991

Investigation of a fatality among parathion applicators in California.

Staff of the California Department of Health Services investigated the death of a parathion applicator in California that was thought to be pesticide-related. A crew of eleven workers (including six sprayers, three mixer/loaders, one mixer/sprayer and one foreman) had been applying 0.125% parathion spray to almond orchards for approximately three weeks. On the day of the fatality, a sprayer rapidly developed symptoms of salivation, sweating, and convulsions after a half-day of work. Despite aggressive medical treatment, the worker died within one hour of his initial symptoms. Significant laboratory results for the decreased case included: parathion residue on the inner and outer garments worn by the worker, parathion in the post-mortem gastric contents, and elevated urinary metabolites consistent with acute parathion intoxication. Interviews with the work crew revealed that three of the 10 workers had complaints of headaches, vomiting, and/or sore throat; yet, subsequent plasma and red cell cholinesterase tests of the co-workers did not show any significant depressions in comparison with pre-season baseline values. This worker death is consistent with prior reports of parathion-related sprayer/applicator intoxications and is the first worker-related parathion death in California since 1972. Substitution of pesticides with less toxic active ingredients or the elimination of parathion is recommended.

Adult↗
PubMed1987

Postherpetic gustatory flushing and sweating.

An 11-year-old girl who had suffered right facial herpes zoster at the age of 6 years was left with anesthetic scars in the distribution of the third division of the trigeminal nerve. Since then, certain tastes provoked flushing and sweating localized to the scarred areas, lasting for 10 to 15 minutes after a latency of a few seconds. The response was evoked most readily from the ipsilateral posterior section of the tongue and was virtually abolished by local administration of anesthesia to the tongue. It remained unaltered after blockade of the sphenopalatine and stellate ganglia but was diminished by blockade of the mandibular nerve. Thermoregulatory sweating and flushing were diminished in the scarred areas. Patchy destruction of sympathetic fibers, which are known to accompany peripheral trigeminal nerve branches, and reinnervation of the affected areas by parasympathetic fibers that normally mediate salivation may explain the phenomenon. It is thus analogous to the gustatory flushing and sweating that may follow damage to the auriculotemporal nerve in the region of the parotid gland (Frey's syndrome).

Child↗
PubMed1996

A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group.

Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.

Adult↗
PubMed2005

Stereology and ultrastructure of the salivary glands of diabetic Nod mice submitted to long-term insulin treatment.

Insulin-dependent diabetes mellitus compromises the salivary glands, altering their morphology and the mechanisms of salivation, which are fundamental for oral health. Thus, the aim of the present study was to determine the effects of prolonged insulin treatment on the morphology of the salivary glands in Nod mice. Forty-five female mice were divided into five groups: nine positive diabetic Nod mice for 10 days (group 1), nine positive diabetic Nod mice for 20 days (group 2), nine diabetic Nod mice for 10 days (group 3), nine diabetic Nod mice for 20 days (group 4), and nine nondiabetic BALB/c mice (group 5). Animals of groups 3 and 4 received 4-5 U of insulin daily, whereas animals of groups 1, 2, and 5 received the same dose of physiological saline simulating the experimental conditions. Samples of the salivary glands were analyzed by light, transmission, and scanning electron microscopies. The results showed intense alterations in diabetic animals characterized by nuclear and cytoplasmic atrophy, biomembrane disorganization, an increase in fibrillar components of the extracellular matrix, and the presence of inflammatory cells. Insulin treatment exerted positive effects on the recovery of the changes resulting from the diabetic state in both parotid and submandibular glands but the pattern continued to be altered. It can be concluded that, in addition to compromising the processes of tissue maintenance and renewal, tissue destructuring leads to alterations in functional mechanisms in both diabetic animals and animals submitted to glycemic control.

Animals↗
PubMed2006

Developmental toxicity of orally administered technical dimethoate in rats.

BACKGROUND: Dimethoate (O,O-dimethyl-S-(N-methylcarbamoyl-methyl) phosphorodithioate), an organophosphate insecticide, was examined for its potential to produce developmental toxicity in rats after oral administration. METHODS: Pregnant Fischer 344 rats were given sublethal doses of 0 (corn oil), 7, 15, and 28 mg/kg/day dimethoate by gavage on gestation days (GD) 6-15. Maternal effects in 15 and 28 mg/kg/day dose groups included cholinergic signs such as tremors, diarrhea, weakness, and salivation, and depression in the maternal and fetal brain acetylcholinesterase (AChE) activities. Other maternal toxicity that included reduction in body weight and feed consumption was observed only in the treated group of 28 mg/kg/day. No maternal toxicity was apparent in the 7 mg/kg/day dose group. RESULTS: Maternal exposure to dimethoate during organogenesis significantly affected the number of live fetuses, early resorption, and mean fetal weight in the 28 mg/kg/day dose group. No external, visceral, and skeletal abnormalities were observed in any of the treated groups compared to the control. CONCLUSIONS: On the basis of the present results dimethoate can produce clinical signs of toxicity and significant inhibition of the maternal and fetal AChE activities in dose groups of 15 and 28 mg/kg/day and showed fetotoxicity without teratogenic effects at 28 mg/kg/day.

Abnormalities, Drug-Induced↗
PubMed1993

Targeting expression of keratinocyte growth factor to keratinocytes elicits striking changes in epithelial differentiation in transgenic mice.

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. Synthesized by cells of the dermal component of skin, KGF's potent mitogenic activity is on the epidermal component, which harbors the receptors for this factor. To explore the possible role of KGF in mesenchymal-epithelial interactions in skin, we used a human keratin 14 promoter to target expression of human KGF cDNA to the stratified squamous epithelia of transgenic mice. Mice expressing KGF in their epidermis typically appeared frail and weak, and often had grossly wrinkled skin. These mice exhibited a gross increase in epidermal thickness accompanied by alterations in epidermal growth and differentiation. Most remarkably, animals displayed several striking and unexpected changes, including a marked suppression of hair follicle morphogenesis and suppression of adipogenesis. With age, some animals developed gross transformations in the tongue epithelium and in epidermis. In addition, they exhibited elevated salivation and their salivary glands showed signs of altered differentiation. Collectively, our findings provide new and important insights into the roles of KGF, implicating this potent growth factor in eliciting global effects not only on growth, but also on development and differentiation, of skin and other tissues. In particular, KGF seems to interfere with signalling of some mesenchymal-epithelial interactions.

Animals↗
PubMedDate not supplied

Clinical relevance of cannabis tolerance and dependence.

Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. Mechanisms appear more functional than metabolic. Acquisition rate depends on dose and dose schedule. Dependence, manifested by withdrawal symptoms after as little as 7 days of THC administration, is characterized by irritability, restlessness, insomnia, anorexia, nausea, sweating, salivation, increased body temperature, altered sleep and waking EEG, tremor, and weight loss. Mild and transient in the 120 subjects studied, the syndrome was similar to sedative drug withdrawal. Tolerance to drug side effects can be useful. Tolerance to therapeutic effects or target symptoms poses problems. Clinical significance of dependence is difficult to assess since drug-seeking behavior has many determinants. Cannabis-induced super sensitivity should be considered wherever chronic drug administration is anticipated in conditions like epilepsy, glaucoma or chronic pain. Cannabis pharmacology suggests ways of minimizing tolerance and dependence problems.

Cannabinoids↗
PubMedDate not supplied

Tolerance of healthy adult males in intravenous infusion of cetiedil, a vasoerythroactive drug.

The intravenous infusion of cetiedil to a group of ten male volunteers elicited atropine-like side effects on salivation, bronchomotor tone and visual accommodation. With repeated infusions of cetiedil, the incidence as well as the duration of the side effects were reduced significantly, indicating the development of tolerance. Since normal subjects can tolerate repeated intravenous infusions of cetiedil, the clinical investigation of this drug in sickle cell disease can proceed, including those patients suffering from vasoocclusive crises.

Adult↗
PubMed1990

Pharmacodynamic action and pharmacokinetics of moxonidine after single oral administration in hypertension patients.

Moxonidine is a new centrally acting alpha 2-adrenoceptor agonist that differs from others by a lower incidence of side effects in hypertensive patients. The effects of moxonidine and placebo on blood pressure, pulse rate, plasma catecholamines, plasma renin activity, sedation, and salivary flow were evaluated in eight hypertensive patients by an intraindividual comparison. Moxonidine induced a significant decrease in blood pressure that corresponded with its plasma concentrations. The maximum antihypertensive effect appears to be delayed when compared with the peak plasma level. Plasma norepinephrine, epinephrine, and plasma renin activity were significantly reduced by moxonidine, and blood pressure reduction corresponded with decrease of plasma norepinephrine. Heart rate, sedation, and salivary flow were not different using moxonidine compared with placebo. Only one patient mentioned dry mouth. No further relevant adverse effects were seen in the patients. This study demonstrates a significant decrease of blood pressure, plasma renin activity, norepinephrine, and epinephrine with a single dose of 0.25 mg moxonidine, but no significant effect on pulse rate, salivation, and sedation.

Adult↗
PubMedDate not supplied

Clinical and pathological effects of short-term cyanide repeated dosing to goats.

The purpose of this work is to determine and describe the effects of subacute cyanide toxicity to goats. Eight female goats were divided into two groups. The first group of five animals was treated with 8.0 mg KCN kg(-1) body weight day(-1) for seven consecutive days. The second group of three animals was treated with water as controls. Complete physical examination, including observation for behavior changes, was conducted before and after dosing. One treated animal was euthanized immediately after dosing. Later, two of the remaining treated animals and a control goat were euthanized after a 30-day recovery period. Euthanized animals were necropsied and tissues were collected and prepared for histologic studies. Clinical signs in treated goats were transient and included depression and lethargy, mild hyperpnea and hyperthermia, arrhythmias, abundant salivation, vocalizations, expiratory dyspnea, jerky movements and head pressing. Two goats developed convulsions after day 3 of treatment. One animal developed more permanent behavioral changes as she became less dominant and aggressive. Histologic changes included mild hepatocellular vacuolation and degeneration, mild vacuolation and swelling of the proximal convoluted tubules of the kidneys and spongiosis of the white matter (status spongiosis) of the cerebral white tracts, internal capsule, cerebellar peduncles, spinal cord and peripheral nerves. In summary, sub-lethal cyanide intoxication in goats resulted in behavioral changes, and during the treatment period animals showed delayed signs of toxicity. Significant histologic lesions in goats were observed and need to be characterized further.

Animals↗