Cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in healthy Beagle dogs.

OBJECTIVE: To determine the cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in dogs. STUDY DESIGN: Prospective, randomized, experimental crossover study. ANIMALS: Five adult healthy Beagle dogs (one male and four females, weighing 12.8-16.4 kg). METHODS: Dogs were instrumented for haemodynamic measurements whilst anaesthetized with isoflurane. Three hours after recovery dogs received 0.025 mg kg(-1) acepromazine (AP) or saline (SP) IM followed by 0.5 mg kg(-1) L-methadone/ 0.025 mg kg(-1) fenpipramide IV after 30 minutes. Cardiac output using thermodilution, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary artery occlusion pressure (PAOP), haemoglobin concentration, arterial and mixed-venous blood gas analysis were measured and sedation evaluated at baseline (BL), 30 minutes after acepromazine or saline IM (A/S), 5 minutes after L-methadone/fenpipramide IV application (35), every 15 minutes for 1 hour (50, 65, 80, 95 minutes) and every hour until baseline cardiac output was regained. Standard cardiovascular parameters were calculated. Data were analyzed by repeated measures anova and paired t-tests with p < 0.05 considered significant. RESULTS: Baseline measurements did not differ. Cardiac index decreased after acepromazine administration in treatment AP (p = 0.027), but was not significantly influenced after l-methadone/fenpipramide injection in either treatment. In both treatments heart rate did not change significantly over time. Stroke volume index increased after A/S in both treatments (p = 0.049). Systemic vascular resistance index, MAP, CVP, MPAP, and pulmonary vascular resistance index did not change significantly after either treatment and did not differ between treatments. Dogs were deeply sedated in both treatments with a longer duration in treatment AP. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs the dose of l-methadone/fenpipramide used in this study alone and in combination with acepromazine induced deep sedation without significant cardiovascular changes.

Repeated anaesthesia with isoflurane and xylazine/levomethadone/fenpipramide premedication in female Beagle dogs: influence on general health and wellbeing.

Beagle dogs continue to be used in experimental studies and preclinical and clinical trials, many of which address the usage of anaesthesia. In order to reduce the number of animals, researchers tend to conduct several experiments on a single animal. The question arises, however, as to whether or not this frequent usage involves more than simply additional stress and discomfort for the individual animal. Within the framework of an existing study involving six female Beagle dogs, we investigated the effects of repeated (5) isoflurane anaesthesia with xylazine/levomethadone/fenpipramide premedication carried out at short intervals (2 weeks) and compared these with the effects of two treatments intermitted by a longer resting period (8 weeks). To verify our hypothesis that frequent anaesthesia affects the dog's wellbeing more than the occasional anaesthesia, the following parameters were measured at regular intervals: body weight, body temperature, respiratory rate, blood pressure, reflexes and heart rate, both at rest and during a treadmill exercise. In addition, recovery behaviour subsequent to anaesthesia was monitored for one hour. Our observations indicate that the anaesthetic effects are most prominent 24 h after the anaesthetic treatment. However, crossover analysis of our data cannot show that there is no statistical difference of whether dogs were anaesthetized occasionally or frequently. In our study, it appears that frequent anaesthesia within a two-week period did not affect the wellbeing and general health of Beagle dogs in a super-additive manner and that a minimum of two-week testing-free period is sufficient to ensure complete recovery from the unwanted effects induced by anaesthesia.

[Neurochemical mechanisms of the effect of ACTH on aggressive-defensive behavior in rats]. / Neirokhimicheskie mekhanizmy vliianiia AKTG na agressivno-oboronitel'noe povedenie krys.

It was found that ACTH increased fear and aggressive-defensive behavior in pairs of male rats in response to electrical stimulation. The parameters were the threshold values of squeak reactions, risings and fights, the frequency of fights and the duration of standing in a posture of threat. The ACTH influence was similar to the M-cholinomimetic effect. It increased against the background of M-cholinoreceptors' excitation but did not change in essential under the action of H-cholinoreceptors. An assumption has been made of the extraadrenal action of ACTH on affective aggression. The mechanism of the effect involves facilitation of excitation of the central M-cholinoreceptors.

Distribution of selenium in sheep treated with dipheny diselenide / Distribuição do selênio em ovinos tratados com disseleneto de difenila

The aim of the present study was to report the in vivo distribution of selenium in sheep. For this, animals were allocated into two groups (control group and treated group) and kept in metabolic cages for a period of 37 days. The treated group received a single dose (6µmol/kg) of Diphenyl Diselenide, intravenously. Plasma and erythrocytes samples were collected at different times. Adipose tissue, muscles (latissimusdorsi, semitendinosus, and supra-scapular) heart, liver, lung, kidney, intestine and brain were sampled at 30 days post-treatment, in order to determine the selenium concentration. The results demonstrated that the selenium, from the Diphenyl Diselenide group, was higher in erythrocytes (4.8mg/L, six hours post-treatment) when compared with the control sheep. The deposition of selenium occurred in the liver (7.01µg/g), brain (3.53µg/g) and kidney (2.02µg/g). After 30 days of a single intravenous injection of Diphenyl Diselenide, liver was the main organ of selenium deposition.(AU)

O objetivo do presente estudo foi investigar a distribuição in vivo do selênio em ovinos. Para isso, os animais foram distribuídos em dois grupos (grupo controle e grupo tratado) e mantidos em gaiolas metabólicas por um período de 37 dias. O grupo tratado recebeu uma dose única (6µmol/kg) de disseleneto de difenila, por via intravenosa. As amostras de plasma e de eritrócitos foram recolhidas em momentos diferentes. Tecido adiposo, músculos (latissimus dorsi, semitendinoso e supraescapular) coração, fígado, pulmão, rim, intestino e cérebro foram amostrados aos 30 dias pós-tratamento, a fim de se determinar a concentração de selênio. Os resultados demonstraram que o selênio, do grupo disseleneto de difenila, foi maior em eritrócitos (4,8mg/L, seis horas após o tratamento) quando comparado com o grupo controle. A deposição de selênio ocorreu no fígado (7,01µg/g), cérebro (3,53µg/g) e rim (2,02µg/g). Após 30 dias de uma única injeção intravenosa de disseleneto de difenila, o fígado foi o principal órgão de deposição de selênio.(AU)

Metabolism of arylacetic acids. 3. The metabolic fate of diphenylacetic acid and its variation with species and dose.

1. [carboxy-14C]Diphenylacetic acid has been administered to seven primate species including man, and four other mammals and the qualitative and quantitative aspects of its elimination determined. 2. In most species, 50-100 percent of the administered 14C was excreted in the urine in 48 h; 2-30 percent of the dose was recovered unchanged in the 24 h urine. 3. In all species the only urinary metabolite detected by radiochromatogram scanning was diphenylacetylglucuronide (10-70 percent of dose). Reverse isotope dilution additionally revealed the formation of trace amounts (less than 1 percent of dose) of the glycine conjugate by four species and of the taurine conjugate by the cat. No evidence was found for the formation of a glutamine conjugate. 4. The influence of dose on the pattern of metabolism and excretion of diphenylacetic acid has been studied in the rat. In this species diphenylacetic acid undergoes extensive elimination and enterohepatic circulation.

Pharmacologic effect of thiphenamil HCl on lower urinary tract function of healthy asymptomatic volunteers.

The effect of thiphenamil HCl on the urodynamic parameters of bladder filling, voiding and isometric contraction was examined in controls. Data were obtained from 25 control female subjects with a mean age of 27.6 +/- 6.6 years. Three urodynamic studies were done on each subject on 3 different days. These studies were: (1) control study, (2) drug study with a single oral dose of 400 mg thiphenamil HCl and (3) another with 800 mg. Each urodynamic study involved filling and voiding cystometrograms to characterize stability, sensations of fullness and urgency, bladder capacity, urethral opening pressure, maximum flow rate, maximum detrusor pressure and residual urine. In addition, isometric detrusor pressure measurements were made at bladder volume increments of 100 ml. Each urodynamic study was done in the sitting position using medium fill water cystometry at 20 ml/min. Isometric pressures were made by catheterizing the subject with an 18-french three-way Foley catheter with a 30-ml balloon. One lumen was used to fill the bladder and the second to measure pressure. The results show that bladder capacity and the volume at which sensations of fullness and urgency are expressed are not significantly changed under the influence of thiphenamil HCl. Significant differences were seen in the maximum pressure generated by the detrusor during voiding and in the maximum urine flow rate. These differences were most pronounced at the 800-mg thiphenamil HCl dose. The isometric data show a highly significant increase in the maximum isometric pressure developed at the low bladder volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

[Electric stimulation of the dental pulp in the evaluation of the central effect of analgesics]. / La stimolazione elettrica della polpa dentaria nella valutazione dell'effetto centrale degli analgesici.

We conducted a double-blind cross-over study in ten volunteers aged from 19 to 30 years, to compare the pain control effects of a single oral dose of two analgesic compounds (drug A: propyphenazone mg 250, ethylmorphine mg 5, caffeine mg 5; drug B: dipyrone mg 500, diphenhydramine mg 12.5, adiphenine mg 5, ethyl aminobenzoate mg 2.5) in an experimental pain model using stimulation of dental pulp. Constant voltage stimuli were delivered through silver chloride electrodes placed in contact with the vestibular surface of the upper medial incisor. At the beginning of the session, the pain input was graded by asking the subject to identify the weakest stimulus perceived (threshold level) and the strongest stimulus endurable (tolerance level). The range between threshold and tolerance level was divided in nine steps plus a subliminal step. The ten steps were delivered randomly, and each series of steps was repeated eight times. The subjects were instructed to rate the pain sensation in an arbitrary scale of 5 degrees. The procedure was repeated at 60 min and 180 min after drug administration. Each subject received two tablets of drug A or drug B in two different sessions at weekly intervals. Statistical analysis of the procedures showed that neither drug A nor drug B significantly affected the pain threshold. Drug A significantly reduced the total pain score (P less than 0.01) and its action peaked 60 min after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic treatment of detrusor incontinence with thiphenamil HCl.

A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment of detrusor incontinence using thiphenamil HCl in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks of thiphenamil HCl or placebo administration were followed by 1 week of washout followed by a cross-over to an additional 2 weeks of placebo or thiphenamil HCl administration. Of the 23 patients 7 dropped out at various stages of the study. The mean age of patients studied was 44 +/- 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time of voiding and the incidence of incontinence. Three urodynamics studies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters of bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the frequency of incontinence, which was based on the patients' responses, decreased significantly (0.01 less than p less than 0.025). There was an insignificant decrease in the number of voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing problems caused by urine loss during baseline and thiphenamil treatment, analysis shows a significant decrease of problems due to loss of urine (p = 0.01) when the patient was taking the drug compared to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the acute toxicity, neuropathology, and electrophysiology of N,N-diethyl-m-toluamide and N,N-dimethyl-2,2-diphenylacetamide in rats.

The insect repellent DEET and the structurally related herbicide diphenamid both cause ataxia associated with a spongiform myelinopathy largely confined to the cerebellar roof nuclei. This local myelinopathy was accompanied by the formation of neuronal cytoplasmic clefts and was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide (DEET). These dose levels also produced a severe and often fatal prostration and clear electrophysiological signs of prolonged suppressed seizure activity. Diphenamid produced an identical myelinopathy after doses of 0.8 to 1.5 g/kg but without the severe prostration, suppressed seizures, or neuronal clefts. The effects of diphenamid were shown to be reversible over 3 to 7 days by neuropathological, motor, and auditory evoked response indices. Both compounds caused characteristic changes in auditory evoked response which may be useful in clinical diagnosis. Six other alkyl amides, two of which produce signs of CNS excitation, failed to produce myelinopathy at the maximum tolerated doses. Our findings show close parallels with a number of human cases of DEET poisoning and indicate that other amides, like diphenamid, also pose a potential hazard.