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Failure of flumazenil to precipitate a withdrawal syndrome in cats chronically treated with the new anxioselective beta-carboline derivative abecarnil.

The effect of chronic administration of the novel anxiolytic beta-carboline derivative, abecarnil (isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate), was examined and compared with the capability of diazepam to induce physical dependence in cats. The acute administration of the benzodiazepine receptor antagonist, flumazenil (20mg/kg i.p.), to cats treated for 2 weeks with diazepam (7mg/kg i.p., three times daily), induced a severe withdrawal syndrome characterized by the appearance of severe physical signs. Within minutes all cats displayed tremors, increased muscle tone, fear response, repeated vocalization and salivation. On the contrary, in all cats treated chronically (2 weeks) with abecarnil (7mg/kg i.p. three times daily) the challenge dose of flumazenil failed to precipitate a clear abstinence syndrome. In fact, a pupillary dilatation and a mild fear response were the only signs present 15-30min after flumazenil administration. This finding indicates that abecarnil, a new potential therapeutic agent for anxiety disorders and seizures, might have advantages over classical benzodiazepines with regard to development of physical dependence.

Journal Article↗

Feeding behaviour of the aphid Rhopalosiphum padi (Hemiptera: Aphididae) on nitrogen and water-stressed barley (Hordeum vulgare) seedlings.

Electrical penetration graphs (EPGs) were used to examine the probing behaviour of adult apterous Rhopalosiphum padi (Linnaeus) on barley seedlings grown under conditions of nitrogen or water stress. Aphids took significantly longer to reach and ingest from sieve elements of nitrogen-deficient seedlings than from nitrogen-sufficient seedlings but there were no such differences between water-stressed or well-watered seedlings. On both nitrogen and water-stressed seedlings the average length of each individual period of salivation into the sieve element was significantly greater compared with their respective unstressed controls.

Animals↗

Lead poisoning in cattle and buffalo near primary lead-zinc smelter in India.

Varying degrees of lead (Pb) poisoning was recorded in cows and buffaloes near a primary lead-zinc smelter in India. Affected animals had history of clinical signs characterized by head pressing, violent movement, blindness and salivation. These animals revealed considerably high lead levels in blood (1.43 +/- 0.07 ppm) and milk (0.75 +/- 0.19 ppm). Animals from the same place without the history of clinical signs suggestive of Pb poisoning recorded lower blood Pb levels than the affected animals; however, their blood Pb was higher than that reported for cattle in rural and urban areas of India. Affected animals also carried high levels of cadmium (Cd) in blood (0.11 +/- 0.01 ppm) and milk (0.05 +/- 0.01 ppm). These values were considerably higher than those for rural cattle in India. The findings indicated varying degrees of exposure of animals to Pb and Cd in the vicinity of the smelter.

Animal Feed↗

[Study of functional rating scale for amyotrophic lateral sclerosis: revised ALSFRS(ALSFRS-R) Japanese version].

Amyotrophic lateral sclerosis(ALS) is progressive, degenerative, fatal disease of the motor neuron. No efficacious therapy is available to slow the progressive loss of function, but several new approaches including neurotrophic factors, antioxidants and glutamate antagonists, are currently being evaluated as potential therapies. Mortality, and/or time to tracheostomy, muscle strength and pulmonary function are used as primary endpoints in clinical trials for treatment of ALS. The effect of new therapies on the quality of patients' lives are also important, so we sought to develop a rating scale to measure it. The revised ALS Functional Rating Scale(ALSFRS-R), which has addition of items to ALSFRS to enhance the ability to assess respiratory symptoms, is an assessment determining the degree of impairment in ALS patients' abilities to function independently in activities of daily living. It consists of 12 items to evaluate bulbar function, motor function and respiratory function and each item is scored from 0(unable) to 4(normal). We translated the English score into Japanese one with minor modification considering the inter cultural difference. And we examined reliability of the translated scale. As a measure of reliability, the intraclass correlation coefficient(ICC) was evaluated for total score and the Kappa coefficient proposed by Cohen and Kraemer was calculated for each item. Moreover, we examined sensitivity to clinical change over time and carried out the factor analysis to analyze the factorial structure. The subjects were 27 ALS patients and each was scored twice for reliability or three times for sensitivity by 2 to 5 neurologists and if possible, nurses. The ICC for total score was 0.97(95% C. I.; 0.94-0.98). Extension of the Kappa coefficients were 0.48 to 1.00 for inter-rater reliability and the averaged Kappa coefficients were 0.63 to 1.00 for intra rater reliability, respectively. Concerning the factorial structure, the contribution of the first factor(the first principal component) were 53.5% principal factor solution. The factor loadings of items were 0.52-0.91 except "salivation" and this factor almost equal to the simple sum of all items was interpreted as the general degree of deterioration. The promax votation revealed the riginally supposed factor structure with 3 factors(groups of items): neuromuscuclar function, respiratory function and bulbar function. The rating scale correlated with Global clinical impression of change(GCIC) scored by neurologists and declined with time, indicating its sensitivity to change. On the bases of these results, ALSFRS-R(Japanese version) is considered to be highly reliable enough for clinical use.

Activities of Daily Living↗

Intoxication of goats by Plumbago scandens in Northeastern Brazil.

In the State of Paraiba, Northeastern Brazil, goat mortality occurred with the ingestion of Plumbago scandens. The fresh plant was then given experimentally to 4 goats at 5, 10, 17.5 or 25 g/kg bw. Depression, anorexia, salivation with foamy saliva, bellowing, bruxism, humpbacked posture, bloat, ruminal atony, continuous lateral head movements, tachycardia, dyspnea and dark brown to black urine were observed in the goats given 17.5 or 25 g/kg bw. The goats receiving 5 or 10 g/kg bw had less severe signs. The goat dosed with 25 g/kg bw died after 18-20 h. All others recovered in 3-9 d. At necropsy of the high dose goat, the main lesions were dark violet to black discoloration of the mucosa of the tongue, esophagus, reticulum and ventral sac of the rumen, and gelatinous edema in the visceral ruminal peritoneum. Histologically the reticulum and ventral rumen sac had diffuse epithelial necrosis and severe edema and neutrophilic infiltration of the submucosa. Separation of the ruminal epithelium from the submucosa was observed. Epithelial degeneration and necrosis was also seen in the omasum, esophagus and tongue. Reproduction of the disease with clinical signs similar to those observed by the farmer in the spontaneously affected goats suggests that the clinical mortality was caused by ingestion of Plumbago scandens.

Animals↗

Bovine atypical interstitial pneumonia associated with the ingestion of damaged sweet potatoes (Ipomoea batatas) in Northeastern Brazil.

Atypical interstitial pneumonia in cattle associated with the ingestion of damaged sweet potatoes is reported in the State of Paraíba, Northeastern Brazil. The sweet potatoes were severely damaged by Myzus tersicae, and had an obvious fungal infection. Eighteen milking cows, 1 bull and 1 steer were fed approximately 400 kg of the sweet potatoes. Six days after consumption 13 cows were affected with labored abdominal breathing, extended and lowered head, coughing, expiratory grunt, salivation and protruded tongue. Six animals died and the others recovered in 4-7 d. At necropsy lungs were distended and did not collapse when the thorax was opened. Bullous emphysema and gelatinous exudates were observed in the interlobular, peribronchial and subpleural tissues. Microscopically, the lungs had severe edema and emphysema, congestion, and alveolar epithelial cell hyperplasia. The sweet potatoes were cultured but Fusarium spp was not isolated, probably because a zigomycete fungus covered the plates in 48 h of incubation.

Animal Feed↗

[Teratogenicity study of 2,2,3,3,3-pentafluoro-1-propanol (5FP) in rats by oral administration].

Teratogenicity of 2,2,3,3,3-pentafluoro-1-propanol (5FP), an alternative cleaning agent for chlorofluorocarbon, was examined in rats. 5FP was diluted with sesame oil and given to pregnant rats (Crj: Wistar) by gavage once a day from day 7 to 17 of pregnancy at doses of 0, 250, 500 and 1000 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. In the pregnant rats, 5FP caused wheezing, salivation, ptosis, reduced body weight gain and reduced food consumption at 500 and 1000 mg/kg/day. In the fetuses, 5FP reduced body weight, increased the incidences of skeletal variations and retarded the ossification at 1000 mg/kg/day, but did not increase the incidences of malformations. It was concluded from these results that 5FP has no teratogenicity in rats when given by gavage. The no-observed-adverse-effect level was 500 mg/kg/day for rat fetuses, and 250 mg/kg/day for pregnant rats.

Abnormalities, Drug-Induced↗

[Teratogenicity study of morpholine salts of fatty acids (oleic acid, 50% water solution) in rats by oral administration].

Teratogenicity of morpholine salts of fatty acids was examined in Wistar rats (Crj: Wistar). Morpholine salts of fatty acids (oleic acid, 50% water solution) was given to pregnant rats by gavage once a day from day 6 through day 15 of pregnancy at doses of 0, 234, 468 and 936 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Morpholine salts of fatty acids caused nasal discharge, dirty nose and salivation in pregnant rats at doses from 234 mg/kg/day. However, fetal effects, such as malformation and growth retardation, were not observed even at 936 mg/kg. It was concluded that morpholine salts of fatty acids has no teratogenicity in rats when given by oral administration. The no-observed-adverse-effect level was 936 mg/kg/day for rat fetuses and less than 234 mg/kg/day for pregnant rats.

Abnormalities, Drug-Induced↗

[Histopathological changes in the skin of small mammals in the area of feeding of Ixodes trianguliceps, I. Persulcatus i I. Ricinus (Ixodidae) ticks].

Histopathological changes in the places of attachment and feeding of the Ixodes trianguliceps, I. persulcatus, and I. ricinus on natural hosts are similar. They pass through the stages of skin inflammation: perforation, exudation and proliferation. The mouthparts of tick contact with the host tissues. The fibrin deposit and callogen capsule surround the mouthparts. These species of ticks do not form the cement. Formation of the feeding cavity is caused by the salivation of ticks and neutrophil infiltration into surrounding tissues. Unnatural hosts (mice, rabbits) do not form the callogen capsule in the places of feeding, the callogen fibres are disposed irregular. Mast cells accumulate in the tick attachment site in the skin of natural host and degranulate in response to the tick salivary antigens releasing the histamine. Mediators involve cutaneous hypersensitivity reactions.

Animals↗

[The salivary glands within the history of physiology].

In the rapid development of physiology during the second half of the 19th century the salivary glands played a remarkable part. Numerous of the famous physiologists of that age used these glands in experiments, which yielded new knowledge of far-reaching importance, particularly to neurophysiology. Nerves with hitherto unknown functions were found when Carl Ludwig discovered the secretory nerves and Claude Bernard the vasodilator nerves in experiments on the submaxillary gland. Motor nerves to myoepithelial cells were first observed in parotid glands. The conception of an "autonomic nervous system", composed of a parasympathetic and a sympathetic part, was created by Langley after observations, inspired by decades of work on salivary glands. Pavlov based the idea of the "conditioned reflexes", through which he studied the function of the cerebral cortex, mainly on experiments on salivary glands. Present research on nonadrenergic non-cholinergic transmission of nerve impulses has its origin in Heidenhain's observations on the action of atropine on salivary glands. The understanding of the secretory process in general was also promoted in these early experiments on salivation. Results from simultaneous measurements of the pressure in the sallivary duct and the arterial system, carried out by Ludwig, excluded the then current hypothesis that saliva is formed by filtration of the blood. Barcroft demonstrated that activity in salivary glands is accompanied by increased consumption of oxygen and formation of carbon dioxide. The salivary glands have also attracted physiologists in more recent years. For instance, the first observations on the electrical events on the cellular level in glands were made in submaxillaries; and the first normal tissue in which the presence of the nerve growth factor was found, was the submaxillary gland of the mouse.

Gastroenterology↗

[Orthodontic appliance made from silicone elastomer, evaluated clinically and from patient opinions after treatment for malocclusion].

Elastodontics is a new branch of orthodontics dealing with orthodontic appliances made with silicone elastomer. The appliances are simple in construction and function, easy to use, and safe. One of the simplest is the elasto-aligner used in some forms of malocclusion. The purpose of this work was: 1) to evaluate the results of treatment of malocclusion with this type of appliance in relation to age of patient and duration of treatment; 2) to gather the opinions of patients; 3) to assess the costs and duration of treatment. 70 patients were examined clinically and asked to fill in a questionnaire (Tab. 1, 3). The elasto-aligner was especially useful when applied in malocclusion after treatment with a fixed appliance. The silicone appliance is recommended for the youngest of patients and should be worn for at least 12 hours per day (Tab. 2). Adaptation to the silicone appliance was long and the most uncomfortable symptoms were toothache, excessive salivation, and dry lips in elderly patients (Fig. 1). The time needed to make the elasto-aligner was up to 20 hours and the cost of materials varied between an acrylic activator and a fixed appliance.

Activator Appliances↗

[Dysautonomic features in patients with Cuban type 2 spinocerebellar ataxia].

INTRODUCTION: Dysautonomic features are the clinical signs and symptoms derived from anomalous functioning of the sympathetic or parasympathetic nervous systems in either the peripheral or central parts. OBJECTIVE: To identify the clinical features related to dysautonomia in a patient with spinocerebellar ataxia with severe functional disability. PATIENTS AND METHODS: We studied a series of cases, including 21 patients with severe disability (confirmed to their bed or wheelchair, unable to walk and totally or partly dependent on other people for essential everyday activities). The patients and their families were closely questioned, and full clinical examination included a test for orthostasia. RESULTS: All patients had some signs of peripheral dysautonomia: all had vasomotor disorders (orthostasia, distal pallor and coldness, Raynaud s phenomenon, etc.), 95.2% (constipation, urinary and rectal incontinence, polachuria, palpitations, tachycardia at rest, etc.), exocrine gland disorders in 71.4% (increased lachrymation, reduced sweating, increased or reduced salivation), 87.5% peripheral tissue nutrition disorders. Similarly, in all patients studied there was evidence of central dysautonomic disorder, with a syndrome of cachexia with bulimia, sleep disorders together with dysregulation of thirst and body temperature. CONCLUSIONS: In patients with type 2 hereditary spinocerebellar ataxia with severe disability there was involvement of the peripheral and central nervous system regulating autonomic function.

Adult↗

[Idiopathic autonomic neuropathy (pandysautonomia)].

On the basis of current literature, clinical and neuropathologic features of idiopathic autonomic neuropathy is presented. Idiopathic autonomic neuropathy is a disease characterized by acute or subacute onset, monophasic course over a period of several years, it is often preceded by an infection. The spectrum of autonomic changes ranges from cholinergic or adrenergic dysfunction to pandysautonomia, leading to heterogeneity of its clinical features. Possible sympathetic system abnormalities found in autonomic neuropathy are: poor pupillary response to light in darkness, orthostatic hypotension leading to syncope, hypotension without compensatory tachycardia, ejaculation disturbances and vasomotor instability. Possible parasympathetic dysfunctions are: salivation and lacrimation disturbances, absent pupillary constriction to light and near gaze, gastrointestinal tract immobility and impairment of gastrointestinal function, atonic bladder with large residual volume, erectile impotence. Pandysautonomia is thought to result from an immune mediated mechanism and responds well to plasmaferesis and intravenous immunoglobin therapy leading to gradual, sometimes not full, recovery. Moreover in this article we pay attention to the clinical value of many tests like cardiovascular or pharmacological studies in the diagnosis of pandysautonomia and in differentiation of pre- and postganglionic changes. In order to diagnose idiopathic autonomic neuropathy one has to rule out a large number of diseases with autonomic dysfunction e.g.: diabetes, malignant neoplasms, acute intermittent porphyria, Shy-Drager syndrome, Riley-Day's dysautonomia, Parkinson's disease, amyloidosis and others.

Adolescent↗

[A case with frontal lobe epilepsy presenting with absence seizures as cardinal manifestation: ictal EEG findings].

We report here a 9-year-old boy presenting with absence and complex partial seizures. Absence seizures occurred several times a day, with sudden arrest of speech and gesture, alteration of consciousness, myoclonus of unilateral or bilateral angles of the mouth, occasional simple automatism and brisk recovery of consciousness. Complex partial seizures occurred once to three times a month with loss of consciousness, salivation, deviation of the head and eyes toward the left, elevation of upper limbs and tonic convulsion of the left upper and lower limbs. Interictal EEG showed right frontal pole-dominant high-voltage slow waves or spike-and-waves. Ictal simultaneous video-EEG recordings of absence seizures revealed a frontal dominant 3-3.5 Hz spike-wave burst lasting several seconds. A partial seizure never preceded the absence seizure. Transverse topographical analysis revealed that the first spike component of the spike-wave burst of absence seizure always showed phase reversal on the right anterior temporal electrode. The following ones, however, showed phase reversal on the left anterior temporal electrode. Ictal EEG of the complex partial seizure could not be detected because it rarely occurred. There was no abnormal finding on brain MRI. Interictal single photon emission tomography (SPECT) indicated hypoperfusion of the dorsal and medial cortex of the right middle frontal lobe. Interictal positron emission tomography (PET) also indicated hypometabolic areas in the dorsal and medial cortex of the right frontal lobe, together with those in the right temporal and parietal cortex. EEG evolution and neuroimaging studies suggested that the epileptic focus of the absence seizure might have originated at the dorsal cortex of the right middle frontal lobe and immediately spread to the medial cortex. Both the seizures were well controlled by the combination of phenytoin and high dose sodium valproate.

Brain↗

[Intoxication in cattle caused by a batch of sugar beet pulp (author's transl)].

During the period from Dec. 7th 1972 to Jan. 8th 1973 76 cattle deaths were reported in 20 herds on the island of Møon and the adjacent south-eastern area of Sealand. The disease was characterized by a sudden onset and a rapid and invariably fatal course. Initially, there was a loss of appetite, depression, excessive salivation and incoordination. These symptoms progressed to paralysis and, in some animals, trmor and convulsions. Death usually ensued less than 2 hours after the first observation of symptoms. Losses in the herds varied from 1 to 12 animals. In herds with multiple incidents the majority of deaths occurred in the 24-hour-period following observation of the first case. Pathology: Gross lesions were few and inconclusive. Histology revealed marked dilatation of cerebral and maningeal blood vessels (arterioles, venoles and capillaries), with perivascular edema and haemorrhage. Adjacent neurons and glia cells showed various degrees of degeneration, apparently secondary to the vascular lesion. In all affected herds sugar beet pulp from one particular sugar mill had been used during the period preceding the outbreak. The syndrome was reproduced by feeding sugar beet pulp from this batch to two heifers. The heifers showed symptoms after 19 and 32 days' feeding, resp. and died after a few hours. Clinical and pathological features were identical with those observed in the spontaneous disease. Thus, it was proved that the particular batch of pulp was responsible for the disease. The investigation did not, however, reveal a toxic factor in this batch. Analyses for lead, arsenic, mercury, nitrite, alkyl phosphates, chlorinated insecticides and Cl. botulinum toxin were negative. Batches of the sugar beet pulp showed pronounced microbial deterioration, the flora being dominated by yeasts and filamentous fungi (moulds). Several species of fungi have been isolated but so fat their possible role in the etiology of the syndrome remains unsettled. The syndrome bears some resemblance to cerebrocortical necrosis (C.C.N.) but differs in several clinical and pathological details. It is tentatively suggested that the beet pulp may have contained one or more toxic substances that interfere with microbial activity in the rumen, resulting in a disturbance of synthesis or absorption of essential metabolites. The clinical, epidemiological and pathological findings are compatible with the hypothesis that the syndrome might be due to fungal toxins. Accordingly, the isolated fungi are now being studied in more detail.

Animal Feed↗

Accidental ingestion of alprazolam in 415 dogs.

Alprazolam is a benzodiazepine anti-anxiety agent that acts at the limbic, thalamic, and hypothalamic level of the CNS and has anxioytic. sedative, hypnotic, skeletal muscle relaxant, and anticonvulsant properties. A retrospective study was conducted of 415 alprazolam ingestions in dogs reported to the ASPCA Animal Poison Control Center between January 1998 and August 2000: 238 suspected alprazolam toxicoses in dogs were evaluated. Clinical signs were ataxia/disorientation, depression, hyperactivity, vomiting, weakness, tremors, vocalization, tachycardia, tachypnea, hypothermia, diarrhea, and increased salivation that developed within 10-30 min post-ingestion. Treatment included standard decontamination procedures, such as emesis and activated charcoal: the specific benzodiazepine antagonist, flumazenil, may be used for severe CNS depression.

Alprazolam↗

Lethality in a ram from the bite of a Palestine viper (Vipera xanthina palestinae).

A lethal bite to a 5-y-o ram from a Palestine viper is described. Severe edematous swelling in the pectoral area developed into skin, subcutaneous and muscle necrosis, accompanied by tachypnea, tachycardia, salivation and depression. Prominent biochemical findings were increased LDH, CK, urea and protein. The ram died because delayed treatment prevented successful antivenin administration.

Animals↗

Acupuncture for xerostomia: clinical update.

BACKGROUND: In the authors' clinic, patients with xerostomia after radiation therapy for malignancy have been offered acupuncture as potential palliation of their symptoms since November 1999. Preliminary data revealed that many patients achieve relief, even for symptoms refractory to pilocarpine therapy. METHODS: Acupuncture technique has been refined since the authors' previous publication. Originally described as a two-step process, a single treatment with eight needles is now used. Three points are treated in each ear, and one in the radial aspect of each index finger. Patients are also provided a sugar-free lozenge in the mouth to further stimulate salivation. Response is measured by the xerostomia inventory (XI). RESULTS: Fifty patients have undergone 318 treatments (median, 5; range, 2-15 treatments). Median follow-up since the first treatment is 224 days (range, 9-455 days). Median palliation as described by the XI was 9 points (range, 0-25 points). Response (defined as improvement of 10% or better over baseline XI values) occurred in 35 patients (70%). Twenty-four patients (48%) have received benefit of 10 points or greater on the XI. Duration of effect for 13 patients (26%) has exceeded 3 months. CONCLUSIONS: Acupuncture palliates xerostomia for many patients. A regimen of three to four weekly treatments followed by monthly sessions is now recommended, although some patients achieve lasting response without further therapy.

Acupuncture Therapy↗