bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated activity of the oxidative and non‐oxidative pentose phosphate pathway in (pre)neoplastic lesions in rat liver
Authors: Frederiks Wilma M. , Vizan Pedro , Bosch Klazina S. , Vreeling‐Sindelárová Heleen , Boren Joan , Cascante Marta 
Published: April 2008

Summary(Pre)neoplastic lesions in livers of rats induced by diethylnitrosamine are characterized by elevated activity of the first irreversible enzyme of the oxidative branch of the pentose phosphate pathway (PPP), glucose‐6‐phosphate dehydrogenase (G6PD), for production of NADPH. In the present study, the activity of G6PD, and the other NADPH‐producing enzymes, phosphogluconate dehydrogenase (PGD), isocitrate dehydrogenase (ICD) and malate dehydrogenase (MD) was investigated in (pre)neoplastic lesions by metabolic mapping. Transketolase (TKT), the reversible rate‐limiting enzyme of the non‐oxidative branch of the PPP, mainly responsible for ribose production, was studied as well. Activity of G6PD in (pre)neoplastic lesions was highest, whereas activity of PGD and ICD was only 10% and of MD 5% of G6PD activity, respectively. Glucose‐6‐phosphate dehydrogenase activity in (pre)neoplastic lesions was increased 25 times compared with extralesional parenchyma, which was also the highest activity increase of the four NADPH‐producing dehydrogenases. Transketolase activity was 0.1% of G6PD activity in lesions and was increased 2.5‐fold as compared with normal parenchyma. Transketolase activity was localized by electron microscopy exclusively at membranes of granular endoplasmic reticulum in rat hepatoma cells where G6PD activity is localized as well. It is concluded that NADPH in (pre)neoplastic lesions is mainly produced by G6PD, whereas elevated TKT activity in (pre)neoplastic lesions is responsible for ribose formation with concomitant energy supply by glycolysis. The similar localization of G6PD and TKT activity suggests the channelling of substrates at this site to optimize the efficiency of NADPH and ribose synthesis.
Endocannabinoids, Blood Pressure and the Human Heart
Authors: Sarzani R. 
Published: April 2008

The effects of exogenous and endogenous cannabinoids on the cardiovascular system have been the focus of extensive research. The direct and indirect effects of cannabinoids on heart and blood vessels depend upon experimental conditions, animal species, and, in humans, clinical background. Cannabinoids decrease blood pressure in hypertensive rodents primarily because of decrease cardiac contractility, leading researchers to postulate a role in the treatment of hypertension and cardiac hypertrophy. Rimonabant, the CB1 receptor blocker in clinical use in many countries, induced a marked and sustained increase in cardiac contractility and blood pressure in hypertensive rats but, on the contrary, contributed to decrease blood pressure in weight‐loss clinical trials especially in obese patients with hypertension.In the midst of the obesity pandemic and from the cardiometabolic point of view, the overactivation of the endocannabinoid system present in intra‐abdominal obesity appears to be very harmful. Moreover, novel human findings suggest a relationship between CB1‐mediated overactive endocannabinoid system and nephrovascular damage. Overall, it appears that CB1 blockade in obese patients behaves as a ‘multiplier’ of the many beneficial effects of body weight loss induced by a hypocaloric diet and increased physical activity (the ‘lifestyle changes’ that are so difficult to start and maintain). Thus, the concept − based mostly on experimental results using in vitro or animal models − that CB1‐mediated endocannabinoid effects are beneficial for the cardiovascular system should be revised at least in obese patients.The results of long‐term clinical trials such as the STRADIVARIUS and the CRESCENDO trials will tell whether the improvement in the cardiometabolic risk profile induced by Rimonabant translates into vascular changes, reducing the risk of myocardial infarction, stroke and cardiovascular death in patients with abdominal obesity. Time (and much more work) will tell us much more about cannabinoids and the human heart.
Cerebral dopamine, apomorphine and oral activity in the neonatal pig
Authors: FRY J. P. , SHARMAN D. F. , STEPHENS D. B. 
Published: April 2008

Neonatal piglets in which oral stimulation associated with feeding was reduced by intragastric tube feeding displayed an increase in stereotyped snout rubbing, licking and chewing behaviour. An investigation of a possible neurochemical basis for this behaviour was made by using sensitive radioenzymatic and micro‐fluorimetric assays to estimate the concentrations of the catecholamines and of the dopamine metabolites homovanillic acid (HVA) and 3,4‐dihydroxyphenyl‐acetic acid (DOPAC) in different brain regions. These observations revealed that the increased non‐nutritive oral activity of such piglets did not appear to be caused by an increased release of dopamine in the brain, since it was not associated with increases in the concentrations of the acidic metabolites of dopamine in either the caudate nucleus, the putamen, the nucleus accumbens, the olfactory tubercle, the hypothalamus, or the substantia nigra. The only neurochemical changes observed were small decreases in the concentration of HVA in the putamen and the nucleus accumbens. A lack of effect on catecholamine concentrations in any of the six brain regions examined suggested that the environmental manipulation caused no changes in the development of catecholamine‐containing nerve endings.Subcutaneous injection of apomorphine was found to increase the non‐nutritive oral activity of piglets. Apparent conditioning effects of the environment on apomorphine‐induced stereotyped behaviour however, prevented any satisfactory testing of possible changes in cerebral dopamine receptor sensitivity following reduced oral stimulation.
Disposition of ampicillin administered intravenously and intratracheally to young calves
Authors: LONG PATRICIA E. , GUARNIERI JOSEPH A. , HERBST DORIS V. , TESKE RICHARD H. 
Published: April 2008

Long, P.E., Guarnieri, J.A., Herbst, D.V. & Teske, R.H. Disposition of ampicillin administered intravenously and intratracheally to young calves. J. vet. Pharmacol. Therap. 6, 273 279.The profile of the blood concentration of ampicillin vs time was compared in 24 calves after ampicillin administration (10 mg/kg body weight) by the intratracheal (i.t.) and the intravenous (i.v.) routes in a crossover study. In a subsequent study, 12 of the calves were given ampicillin i.v. and 12 were given ampicillin i.t.; at 15 min and 2 h after drug administration, the calves were killed and lungs, kidneys, liver, urine and plasma were collected for ampicillin assay. The mean ampicillin concentration in blood after i.v. treatment was significantly (P<0.01) higher than after i.t. treatment. The mean ampicillin level in lungs after i.t. treatment was significantly higher than the level after i.v. treatment, but concentrations in kidneys, liver, urine and plasma after i.v. treatment were higher (but not significantly) than those after i.t. treatment.
The absorption of anabolic agents from pellets implanted at the base of the ear in sheep
Authors: HARRISON LYNNE P. , HEITZMAN R.J. , SANSOM B. F. 
Published: April 2008

Twenty wether sheep were allocated to seven groups and received implants near the base of one ear with pellets containing: for group 1, (OE) 20 mg oestradiol‐17β alone; for group 2, (TBA/OE) 20 mg oestradiol‐17β intimately mixed with 140 mg trenbolone acetate; for group 3, (T/OE) 20 mg oestradiol‐17β mixed with 200 mg testosterone; for group 4, (P/OE) 20 mg oestradiol‐17β mixed with 200 mg progesterone; for group 5, (TBA/OE2) 20 mg oestradiol‐17β in one ear and 140 mg trenbolone in the other ear; for group 6, (TBA/OE1) 20 mg oestra‐diol‐17β and 140 mg trenbolone as separate pellets in one ear; group 7 sheep received implants of carrier material and served as controls. The concentrations of steroids were measured in plasma samples collected from both jugular veins during the 16‐week period after implantation. The absorption of oestradiol‐1 7β was slower and more sustained from the pellets in which it was mixed with other steroids (groups 2, 3 and 4) than from the pellets containing oestradiol‐17β alone (groups 1, 5 and 6).The concentration of each steroid in plasma was higher in the jugular vein ipsilateral to the implant than in the vein on the opposite side. The difference between the concentrations in the two veins was used to calculate the biological half‐lives of the steroids; for oestradiol‐17β and trenbolone the mean values ranged from 1.8 to 6.8 min and from 3 to 4 min, respectively, and for testosterone and progesterone the mean values were 4.7 and 3.5 min, respectively.
Effects of erythromycin‐inactivating Lactobacillus crop flora on blood levels of erythromycin given orally to chicks
Authors: DEVRIESE L. A. , DUTTA G. N. 
Published: April 2008

Germ‐free, day‐old chickens were colonized with a Lactobacillus fermentum strain isolated from poultry which was able to inactivate in vitro erythromycin and other macrolide and lincosamide antibiotics. Similar control chickens were colonized with a non‐degrading L. fermentum strain. Only in chickens colonized with the non‐degrading strain were blood levels considered to be therapeutically active achieved with erythromycin in the drinking water.Five groups of broiler chickens of different age originating from three farms all possessed an erythromycin‐degrading crop flora. In none of these were therapeutic blood levels attained when erythromycin was given in the drinking water.
Gastro‐intestinal motor disturbances induced by lysine‐acetylsalicylate treatment in sheep
Authors: HONDE C. , BUÉNO L. 
Published: April 2008

The effects of intravenous (i.v.), intramuscular (i.m.) and oral administration of lysine‐acetylsalicylate (Lys‐ASA) on gastro‐intestinal motility were investigated in sheep using electromyography. A dose of 20 mg/kg Lys‐ASA intravenously reduced the frequency of reticular contractions for 86 ± 18 min, produced abomasal hypomotility and caused a disruption of the cyclical pattern of intestinal motility for at least 120 min. The frequency of reticular contractions measured from 20 to 30 min after Lys‐ASA administration was negatively correlated (ß= 0.97; PΔ0.01) to the log of the dose used for doses varying from 10 to 40 mg/kg. Similar effects were observed with intramuscular and oral dose rates of 40 and 80 mg/kg, respectively. Previous i.v. administration of phentolamine (0.1 mg/kg) or tolazoline (2 mg/kg) abolished the effects of Lys‐ASA (20 mg/kg) administered intravenously on both reticular contractions and abomaso‐intestinal motility.It was concluded that Lys‐ASA administered at therapeutic doses in sheep produced gastro‐intestinal motor disturbances and that α‐and α2‐adrenergic antagonists are able to block them.
A health index to evaluate clinically a ß‐hemolytic streptococcal infectious disease model in the horse
Authors: POWERS J. D. , POWERS T. E. , VARMA K. J. , GABEL A. A. , SPURLOCK S. L. 
Published: April 2008

Quantification of the clinical manifestations of a disease has been a serious problem particularly as related to clinical trials or drug efficacy studies. Historically, this quantification has been limited to categorizing each patient into one of three or four groups, e.g. worse, no improvement, improved. This problem becomes serious when an investigation utilizes an experimentally induced animal disease model.A health index, which quantifies the clinical state of horses which have an experimentally induced ß‐hemolytic streptococcal infection, is described. Aspects of experimental design and statistical analysis are also discussed in relationship to the use of the index for drug efficacy studies.
Milk fever and calcium metabolism
Authors: ALLEN W.M. , SANSOM B.F. 
Published: April 2008

Allen, W.M. & Sansoni, B.F. Milk lever and calcium metabolism. J. vet. Pharmacol. Therap. 8, 19–29. W.M. Allen, Department of Functional Pathology, AFRC Institute for Research on Animal Diseases, Campion, Newbury, Berkshire RC16 ONN, England.
Pharmacological evidence for the involvement of alpha‐2 adrenoceptors in the sedative effect of detomidine, a novel sedative‐analgesic
Authors: VIRTANEN R. , RUSKOAHO H. , NYMAN L. 
Published: April 2008

Virtanen, R., Ruskoaho, H. & Nyman, L. Pharmacological evidence for the involvement of alpha‐2 adrenoceptors in the sedative effect of detomidine, a novel sedative‐analgesic. J. vet. Pharmacol. Therap. 8, 30–37.The sedative effect and mechanism of action of a novel imidazole derivative, detomidine, were studied in laboratory animals. Three methods were used to quantify drug‐induced sedation: (i) decrease in spontaneous activity of mice; (ii) increase in barbiturate induced anaesthesia lime in mice; (iii) loss of righting reflex in chicks. Clonidine and xylazine were included in the studies for comparison. The sedative potency of detomidine was shown to be approximately equal to that of clonidine and much higher than that of xylazine. In all tests, the sedative effect of detomidine was inhibited by antagonists of alpha‐2 adrenoceptors (yohimbine, rauwolscine and idazoxan) but not by alpha‐1 antagonists (prazosin, corynanthine). Furthermore, an ex vivo receptor binding study in the rat showed that detomidine‐induced decrease in spontaneous activity was significantly correlated to [3Hc]onidine but not to [3H]prazosin displacement in brain membranes. These results show that detomidine has potent sedative effects in mice, rats and chicks, and suggest that this action is mediated through stimulation of alpha‐2 adrenoceptors.Raima Virtanen, Fartnos Group Ltd, Research Centre, P.O. Box 425, SF‐20101 Turku 10, Finland.
An increase in metabolic acidosis induced by chloralose anaesthesia in dogs after sino‐vagal denervation
Authors: SHUKLA R. , SHUKLA S. B. 
Published: April 2008

Shukla, R. & Shukla, S.B. An increase in metabolic acidosis induced by chloralose anaesthesia in dogs after sino‐vagal denervation. J. vet. Pharmacol, Therap. 8, 71–75.Chloralose anaesthesia in dogs increased the H+ ion concentration significantly from its reference values. The findings favoured thai it was most probably engendered through anaesthetic depression of neural centre regulating H+ ion concentration of blood. Such increase was largely contributed by a significant increase in its metabolic fraction. A further increase of metabolic fraction after separate and joint section of carotid sinus nerves and vagi indicated their holding effect. The section of carotid sinus nerve induced greater increase in this fraction than that of vagi. It indicated differences between the two nerves in their metabolic fraction controlling influence. Hvperpnoea after vagi section decreased the carbonic acid fraction, whereas marginally reduced ventilation alter carotid sinus nerve section increased the carbonic acid fraction. Moreover, the overall changes in H+ ion concentration followed the changes in carbonic acid fraction. The present study suggested that the depressive effect of chloralose anaesthesia on H+ ion controlling neural mechanism could be largely determined by degree of increase in its metabolic fraction. R. Shukla, Department of Physiology, Institute of Medical Sciences, B.H.U. Varanasi‐221005, India.
Pharmacokinetic studies of theophylline in horses
Authors: INGVAST‐LARSSON C. , PAALZOW G. , PAALZOW L. , OTTOSSON T. , LINDHOLM A. , APPELGREN L. E. 
Published: April 2008

Ingvast‐Larsson, C, Paalzow, G., Paalzow, L., Ottosson, T., Lindholm, A. & Appelgren, L.E. Pharmacokinetic studies of theophylline in horses. J. vet. Pharmacol. Therap. 8, 76–81.The pharmacokinetics of theophylline were determined in Standardised trotters after single intravenous and oral administration. A bi‐exponential equation was fitted to the intravenous data and a tri‐exponential equation to the oral data. The biological half‐life of theophylline was found to be 14.8 h, the volume of distribution 1.02 l/kg and the total plasma clearance 0.86 ml/kg/min. The oral absorption of the drug was complete (bioavailability 108%) and rapid (absorption half‐life 0.4 h). Professor L. E. Appelgren, Department of Pharmacology and Toxicology, Biomedicum. Box 573, S‐75J 23 X'ppsala, Sweden.
The pharmacokinetic behaviour of chloramphenicol in liver‐damaged mini‐pigs
Authors: KROKER R. 
Published: April 2008

Koker, R. The pharmacokinetic behaviour of chloramphenicol in liver‐damaged mini‐pigs. J. vet. Pharmacol. Therap. 8, 82–87.Using mini‐pigs with an indwelling vascular catheter, the pharmacokinetics of chloramphenicol were investigated in healthy and liver‐damaged animals. The liver damage was induced by thioacetamide and its degree was estimated by measuring the level of bile acids in serum. Employing a two‐compartment open model for analysing the time‐dependent course of the chloramphenicol concentration in serum, it was shown that in liver‐damaged animals the elimination half‐time was almost doubled as a result of reduced total body clearance. The consequences of liver damage for withdrawal limes and dosage schedules are discussed. R. Kroker, Federal Health Office. Institute for Veterinary Medicine, 1000 Berlin 33. Germany.
Pharmacokinetics of pentobarbital and thiamylal as combined anesthetics in sheep
Authors: SHORT CHARLES R. , KAPPEL LEONARD C. , RUHR LAWRENCE P. , BAGGOT J. DESMOND 
Published: April 2008

Short, C.R., Kappel, L.C., Ruhr, L.P. & Baggot, J.D. Pharmacokinetics of phenobarbital and thiamylal as combined anesthetics in sheep. J. vet. Pharmacol. Therap. 8, 234–245.This study was performed to investigate the possible mechanisms underlying prolongation of anesthesia times in sheep caused by the sequential administration of thiamylal and pentobarbital. Sodium thiamylal was injected as an intravenous bolus dose (13.2 mg/kg) followed in 7 min by sodium pentobarbital (14.3 mg/kg) by the same route to seven sheep. Separate studies were conducted for each of the two drugs administered separately to the same animals at the same doses. Mean anesthesia times (to the return of the palpebral reflex) were 7.89 min (thiamylal), 5.39 min (pentobarbital) and 34.1 min (the sequential combination). The kinetic parameters Vd(area), Vd(ss), t1/2ß, and ClB for either drug were not affected by the other when given in combination. The t1/2α was shorter, and the Vc was smaller, for pentobarbital when administered with thiamylal, while there were no changes in thiamylal disposition for the combination regimen. Computer‐generated curves, associated with the two‐compartment open model showing the fraction of dose in each compartment as a function of time, illustrated that pentobarbital rapidly achieved higher concentrations in the peripheral compartment after prior thiamylal administration. Protein‐binding studies showed that this could not be attributed to displacement of pentobarbital from plasma albumin by thiamylal. Calculation of total and free drug concentrations at the time of awakening showed that, when the drugs were combined, the concentration of each drug was less than half of that observed at awakening when they were studied separately. It can be concluded that the prolonged sleeping times associated with the sequential combination of the two agents were not due to an alteration in kinetic parameters of either drug caused by the other, but rather to an additive effect of the subanesthetic concentrations of the two drugs when combined. The fact that sleeping times were supra‐additive is attributed to a shift of awakening time from the distribution (α) phase, when given independently, to the elimination (ß) phase when administered in combination. Charles R. Short, Department of Veterinary Physiology, Pharmacology and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, U.S.A.
Immediate and long‐term effects of halothane anesthesia on equine platelet function
Authors: KELLY A. B. , STEFFEY E. P. , McNEAL D. , WILLITS N. 
Published: April 2008

Kelly, A.B., Steffey, E.P., McNeal, D. & Willits, N. Immediate and long‐term effects of halothane anesthesia on equine platelet function. J. vet. Pharmacol. Therap. 8, 284–289.The acute and long‐term quantitative and qualitative effects of halothane anesthesia on equine platelet performance were studied in fourteen horses. Horses were anesthetized with only halothane in O2 for about 8.0 MAC* hours. Platelet numbers declined during the anesthetic period but returned to normal within 24 h. Platelet aggregation was significantly diminished during the anesthetic period and for up to 4 days after anesthesia. A period of hyperaggregability occurred at the 7th day. Dr A. B. Kelly, Department of Surgery, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
Central and peripheral serotonergic control of forestomach motility in sheep
Authors: SORRAING JEAN‐MARC , FIORAMONTI JEAN , BUÉNO LIONEL 
Published: April 2008

Sorraing, J.‐M., Fioramonti, J. & Bueno, L. Central and peripheral serotonergic control of forestomach motility in sheep. J. vet. Pharmacol. Therap. 8, 312–319.Participation of tryptaminergic receptors in the control of forestomach motility was investigated in conscious sheep using strain‐gauges and chronically implanted electrodes. Two hours after feeding the sheep, serotonin (5‐HT) was infused into the jugular vein (i.v.), or the carotid artery (i.e.), or into the lateral cerebral ventricles (i.e.v.), over a 10‐tnin period. An i.v. dose of 16 μg/kg/min abolished the cyclic propagated contractions throughout the forestomach, increased ruminoreticular tone, and induced simultaneous contractions of all the parts of the rumen. A dose of 1.6 μg/kg/min i.c. or i.v. 5‐HT inhibited phasic contractions.The effects of 5‐HT were blocked completely by i.c.v. administration of methysergide (20 μg/kg) and imipramine (200 μg/kg), and blocked partially by naloxone (25 μg/kg), but unaffected by atropine (50 μg/kg).The inhibitory effects of i.v. 5‐HT were antagonized by methysergide (200 μg/kg, i.v.) but unaffected by imipramine (2 mg/kg, i.v.) and atropine (250 μg/kg, i.v.). Only the i.v. administration of methysergide blocked the inhibition induced by i.c. infusion (1.6 μg/kg/min) of 5‐HT.It is suggested that 5‐HT exhibits an inhibitory control on forestomach phasic contractions through hypothalamic and bulbar 5‐HT receptors, and exerts peripheral excitatory effects on the tone of the rumen wall. Dr L. Buéno, Station de Pharmacologie‐Toxicologie, INRA, 180 chemin de Tournefeuille, 31300 Toulouse, France.
The kinetics of triclabendazole disposition in sheep
Authors: HENNESSY D. R. , LACEY E. , STEEL J. W. , PRICHARD R. K. 
Published: April 2008

Hennessy, D.R., Lacey, E., Steel, J.W. & Prichard, R.K. The kinetics of triclabendazole disposition in sheep. J. vet. Pharmacol. Therap. 10, 64–72.To investigate whether the disposition of triclabendazole (TCBZ) and its metabolites in blood or bile influenced its flukicidal potency, TCBZ was administered intraruminally at 10 mg kg‐1 to sheep surgically fitted with a permanent re‐entrant bile duct cannula. The profiles of TCBZ metabolites in peripheral plasma and bile were determined using high performance liquid chromatography.In plasma, only TCBZ sulphoxide (TCBZ‐SO) and TCBZ sulphone were present and reached their maximum concentrations (> 13 μg ml‐1) at 18 and 36 h, respectively, after administration. TCBZ metabolites were specifically bound to plasma albumin, which is believed to exert a major influence on the duration of plasma TCBZ metabolite concentrations and consequent exposure of liver fluke.In bile, the major TCBZ metabolites were hydroxylated in the 4'position and secreted predominantly as sulphate esters with lesser proportions as glucuronide conjugates. The major biliary metabolite was conjugated hydroxy TCBZ‐SO which reached a maximum concentration in excess of 40 μg ml‐′ and contributed almost half the total conjugated metabolites. The major free biliary metabolite was TCBZ‐SO. Of the administered TCBZ dose, 9.7% was secreted as free metabolites in bile whereas 35.8% was secreted as conjugated metabolites. Approximately 6.5% of the dose was excreted in urine.