Effects of vatinoxan on cardiorespiratory function, fecal output and plasma drug concentrations in horses anesthetized with isoflurane and infusion of medetomidine.

A constant rate infusion (CRI) of medetomidine is used to balance equine inhalation anesthesia, but its cardiovascular side effects are a concern. This experimental crossover study aimed to evaluate the effects of vatinoxan (a peripheral α2-adrenoceptor antagonist) on cardiorespiratory and gastrointestinal function in anesthetized healthy horses. Six horses received medetomidine hydrochloride 7µg/kg IV alone (MED) or with vatinoxan hydrochloride 140µg/kg IV (MED+V). Anesthesia was induced with midazolam and ketamine and maintained with isoflurane and medetomidine CRI for 60min. Heart rate, carotid and pulmonary arterial pressures, central venous pressure, cardiac output and arterial and mixed venous blood gases were measured. Selected cardiopulmonary parameters were calculated. Plasma drug concentrations were determined. Fecal output was measured over 24h. For statistical comparisons, repeated measures analysis of covariance and paired t-tests were applied. Heart rate decreased slightly from baseline in the MED group. Arterial blood pressures decreased with both treatments, but significantly more dobutamine was needed to maintain normotension with MED+V (P=0.018). Cardiac index (CI) and oxygen delivery index (DO2I) decreased significantly more with MED, with the largest difference observed at 20min: CI was 39±2 and 73±18 (P=0.009) and DO2I 7.4±1.2 and 15.3±4.8 (P=0.014)mL/min/kg with MED and MED+V, respectively. Fecal output or plasma concentrations of dexmedetomidine did not differ between the treatments. In conclusion, premedication with vatinoxan induced hypotension, thus its use in anesthetized horses warrants further studies. Even though heart rate and arterial blood pressures remained clinically acceptable with MED, cardiac performance and oxygen delivery were lower than with MED+V.

Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses.

BACKGROUND: Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral α2 -adrenoceptors. Vatinoxan, a peripheral α2 -antagonist, has been shown experimentally to alleviate the adverse effects of some α2 -agonists in horses. However, vatinoxan has not been investigated during constant-rate infusion (CRI) of medetomidine in standing horses. OBJECTIVES: To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine. STUDY DESIGN: Experimental, randomised, blinded, cross-over study. METHODS: Six healthy horses were given medetomidine hydrochloride, 7 µg/kg i.v., without (MED) and with (MED+V) vatinoxan hydrochloride, 140 µg/kg i.v., followed by CRI of medetomidine at 3.5 µg/kg/h for 60 min. Cardiorespiratory variables were recorded and borborygmi and sedation levels were scored for 120 min. Plasma drug concentrations were measured. The data were analysed using repeated measures ANCOVA and paired t-tests as appropriate. RESULTS: Initially heart rate (HR) was significantly lower and mean arterial blood pressure (MAP) significantly higher with MED compared with MED+V. For example at 10 min HR (mean ± s.d.) was 26 ± 2 and 31 ± 5 beats/minute (P = 0.04) and MAP 129 ± 15 and 103 ± 13 mmHg (P<0.001) respectively. At 10 min, cardiac index was lower (P = 0.02) and systemic vascular resistance higher (P = 0.001) with MED than with MED+V. Borborygmi were reduced after MED; this effect was attenuated by vatinoxan (P<0.001). All horses were sedated with medetomidine, but the mean sedation scores were reduced with MED+V until 20 min (6.8 ± 0.8 and 4.5 ± 1.5 with MED and MED+V, respectively, at 10 min, P = 0.001). Plasma concentration of dexmedetomidine was significantly lower in the presence of vatinoxan (P = 0.01). MAIN LIMITATIONS: Experimental study with healthy, unstimulated animals. CONCLUSIONS: Vatinoxan administered i.v. with a loading dose of medetomidine improved cardiovascular function and gastrointestinal motility during medetomidine CRI in healthy horses. Sedation was slightly yet significantly reduced during the first 20 min.. The Summary is available in Portuguese - see Supporting Information.

Acceptability of flavoured pharmaceutically non-active mini-tablets in pet cats tested with a rapid 3-portal acceptance test with and without food.

Palatable oral pharmaceuticals are crucial for feline medication. The pharmaceutical industry prefers synthetic flavours over organic ones because of hygiene and regulatory issues. The aim of this study was to find a palatable synthetic flavour for future taste-masking of feline pharmaceuticals. The hypothesis was that synthetic meat aromas and free amino acids would be palatable to cats. The palatability of 18 synthetically flavoured mini-tablets was screened with 10-19 pet cats using a rapid 3-portal acceptance test with and without food. The tested flavours were synthetic amino acids (L-carnitine, l-glutamic acid monosodium salt hydrate, l-leucine, l-methionine, l-phenylalanine, l-proline, and taurine), d-(+)-Maltose monohydrate and thiamine hydrochloride. Furthermore, thiamine hydrochloride was combined with amino acids (l-cysteine, l-leucine, l-methionine and l-proline) and synthetic meat flavours (2-acetylpyridine, 2-acetylthiazole, 2-pentylpyridine and 4-hydroxy-5-methyl-3(2H)-furanone). The negative control was a non-flavoured placebo mini-tablet, while positive controls were an organic yeast-flavoured mini-tablet and a yeast- and fish-based commercial vitamin tablet in mini-tablet form. No significant differences were detected between palatable synthetic flavours and the placebo, nor between the synthetic flavours and the yeast flavour. In general, the mini-tablet seemed to be small enough to be accepted inside a food item. These results differ from the earlier literature about the taste preferences of cats for amino acids, and hence free amino acids should not be considered palatable to cats based purely on previous findings.

Effects of dexmedetomidine and MK-467 on plasma glucose, insulin and glucagon in a glibenclamide-induced canine hypoglycaemia model.

The commonly used sedative α2-adrenoceptor agonist dexmedetomidine has adverse cardiovascular effects in dogs that can be prevented by concomitant administration of the peripherally acting α2-adrenoceptor antagonist MK-467. An ancillary effect of dexmedetomidine is to decrease insulin release from the pancreas, whereas MK-467 stimulates insulin release. This study assessed the effects of co-administered dexmedetomidine and MK-467 in a canine glibenclamide-induced hypoglycaemia model. In a randomised, cross-over experiment, eight beagle dogs received five intravenous treatments, comprising two administrations of saline, with dexmedetomidine or dexmedetomidine and MK-467, and three administrations of glibenclamide, with saline, dexmedetomidine or dexmedetomidine and MK-467. Plasma concentrations of glucose, lactate, insulin, glucagon and the test drugs were monitored. Administration of glibenclamide significantly increased insulin secretion and decreased blood glucose concentrations. Dexmedetomidine counteracted glibenclamide-evoked hypoglycaemia. This was opposed by the α2-adrenoceptor antagonist MK-467, but the glibenclamide-evoked hypoglycaemia was not potentiated by co-administration of dexmedetomidine and MK-467. None of the dogs developed uncontrolled hypoglycaemia. Thus, the combination of dexmedetomidine and MK-467 appeared to be safe in this canine hypoglycaemia model. Nevertheless, when MK-467 is used to alleviate the undesired cardiovascular effects of α2-adrenoceptor agonists in dogs, it should be used with caution in animals at risk for hypoglycaemia because of its insulin-releasing and hypoglycaemic effects.

Peripherally acting α-adrenoceptor antagonist MK-467 with intramuscular medetomidine and butorphanol in dogs: A prospective, randomised, clinical trial.

The aim of this study was to investigate the clinical usefulness of MK-467 (vatinoxan; L-659'066) in dogs sedated for diagnostic imaging with medetomidine-butorphanol. It was hypothesised that MK-467 would alleviate bradycardia, hasten drug absorption and thus intensify the early-stage sedation. In a prospective, randomised, blinded clinical trial, 56 client-owned dogs received one of two IM treatments: (1) 0.5mg/m2 medetomidine+0.1mg/kg butorphanol (MB, n=29); or (2) 0.5mg/m2 medetomidine+0.1mg/kg butorphanol+10mg/m2 MK-467 (MB-MK, n=27). Heart rates and visual sedation scores were recorded at intervals. Plasma drug concentrations were determined in venous samples obtained approximately 14min after injection. Additional sedation (50% of original dose of medetomidine IM) and/or IM atipamezole for reversal were given when needed. The area under the sedation score-time curve for visual analogue scale (AUCVAS30) was calculated for the first 30min after treatment using the trapezoidal method. Repeated ANOVA, Mann-Whitney U test and Fisher's exact test were used for parametric, non-parametric and dichotomous data. Heart rate was significantly higher from 10 to 40min with MB-MK than with MB. AUCVAS30 was significantly higher after MB-MK. More dogs treated with MB-MK required additional sedation after 30min, but fewer needed atipamezole for reversal compared with MB. Plasma concentrations of both medetomidine and butorphanol were higher after MB-MK. All procedures were successfully completed. MK-467 alleviated the bradycardia, intensified the early stage sedation and shortened its duration in healthy dogs that received IM medetomidine-butorphanol.

Cardiopulmonary effects of vatinoxan in sevoflurane-anaesthetised sheep receiving dexmedetomidine.

The effects of pre-treatment with vatinoxan (MK-467) on dexmedetomidine-induced cardiopulmonary alterations were investigated in sheep. In a crossover study design with a 20-day washout, seven sheep were anaesthetised with sevoflurane in oxygen and air. The sheep were ventilated with the pressure-limited volume-controlled mode and a positive end-expiratory pressure of 5cmH2O. Peak inspiratory pressure (PIP) was set at 25cmH2O. The sheep received either 150µg/kg vatinoxan HCl (VAT+DEX) or saline intravenously (IV) 10min before IV dexmedetomidine HCl (3µg/kg, DEX). Cardiopulmonary variables were measured before treatments (baseline), 3min after vatinoxan or saline, and 5, 15 and 25min after dexmedetomidine. Computed tomography (CT) of lung parenchyma was performed at baseline, 2min before dexmedetomidine, and 10, 20 and 30min after DEX. Bronchoalveolar lavage (BAL) was performed after the last CT scan and shortly before sheep recovered from anaesthesia. After VAT, cardiac output significantly increased from baseline. DEX alone significantly decreased partial arterial oxygen tension, total dynamic compliance and tidal volume, whereas PIP was significantly increased. With VAT+DEX, these changes were minimal. No significant changes were detected in haemodynamics from baseline after DEX. With VAT+DEX, mean arterial pressure and systemic vascular resistance were significantly decreased from baseline, although hypotension was not detected. On CT, lung density was significantly increased with DEX as compared to baseline. No visual abnormalities were detected in bronchoscopy and no differences were detected in the BAL fluid after either treatment. The pre-administration of vatinoxan alleviates dexmedetomidine-induced bronchoconstriction, oedema and hypoxaemia in sevoflurane-anaesthetised sheep.

The impact of MK-467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal.

The effect of MK-467, a peripheral α2 -adrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2-week washout periods. Medetomidine (MED) 30 µg/kg alone or combined in the same syringe with MK-467 300 µg/kg (MMK) was injected intramuscular, followed by ATI 150 µg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30 min later. Plasma was analysed for drug concentrations, and sedation was subjectively assessed with a visual analogue scale. Systemic haemodynamics and blood gases were measured before treatments and at intervals thereafter. With MK-467, medetomidine plasma concentrations were threefold higher prior to ATI, which was associated with more profound sedation and shorter onset. No significant differences were observed in early cardiopulmonary changes between treatments. Atipamezole reversed the medetomidine-related cardiopulmonary changes after both treatments. Sedation scores decreased more rapidly when MK-467 was included. In this study, MK-467 appeared to have a pronounced effect on the plasma concentration and central effects of medetomidine, with minor cardiopulmonary improvement.

ESR study of atomic hydrogen and tritium in solid T2 and T2:H2 matrices below 1 K.

We report on the first ESR study of atomic hydrogen and tritium stabilized in solid T2 and T2:H2 matrices down to 70 mK. The concentrations of T atoms in pure T2 approached 2 × 1020 cm-3 (0.60%) and record-high concentrations of H atoms ∼1 × 1020 cm-3 (0.33%) were reached in T2:H2 solid mixtures where a fraction of T atoms became converted into H due to the isotopic exchange reaction T + H2 → TH + H. The maximum concentrations of unpaired T and H atoms were limited by their recombination which becomes enhanced by efficient atomic diffusion due to the presence of a large number of vacancies and phonons generated in the matrices by ß-particles. Recombination also appeared in an explosive manner, both being stimulated and spontaneously in thick films where sample cooling was insufficient. We suggest that the main mechanism for H and T migration is physical diffusion related to tunneling or hopping to vacant sites in contrast to tunneling chemical exchange reactions which govern diffusion of H and D atoms created in H2 and D2 matrices by other methods.

Difficulties in administration of oral medication formulations to pet cats: an e-survey of cat owners.

The purpose here was to determine the problems cat owners encounter in medicating their cats with orally administered drugs at home. The study was carried out as an open e-questionnaire survey addressed to cat owners in which the authors focused on the oral administration route. A total of 46 completed questionnaires were included in the survey. In the study, 46 cats received 67 orally administered drugs. Approximately half of the drugs were registered for use in cats by the European Medicines Agency (54 per cent), and there were also off-label drugs registered for human (36 per cent) and canine medication (7.4 per cent) and an ex tempore drug (3.0 per cent). The owners were unable to give the doses as prescribed for their cats for one-fourth of the medications (16/67). Drugs that were registered for feline medication were significantly more palatable than drugs registered for other species (odds ratio (OR) 4.9), and liquid formulations were significantly more palatable than solid formulations (OR 4.8). However, most of the owners (22/38) preferred a solid dosage form, while few (4/38) chose a liquid formulation. The results indicate that there is still a need for more palatable and easily administered oral drugs for cats.

Tunneling chemical exchange reaction D + HD → D2 + H in solid HD and D2 at temperatures below 1 K.

We report on a study of the exchange tunneling reaction D + HD → D2 + H in a pure solid HD matrix and in a D2 matrix with a 0.23% HD admixture at temperatures between 130 mK and 1.5 K. We found that the exchange reaction rates, kexHD ∼ 3 × 10-27 cm3 s-1 in the pure HD matrix, and kexD2 = 9(4) × 10-28 cm3 s-1 in the D2 matrix, are nearly independent of temperature within this range. This confirms the quantum tunnelling nature of these reactions, and their ability to proceed at temperatures down to absolute zero. Based on these observations we concluded that exchange tunneling reaction H + H2 → H2 + H should also proceed in a H2 matrix at the lowest temperatures. On the other hand, the recombination of H atoms in solid H2 and D atoms in solid D2 is substantially suppressed at the lowest temperatures as a result of a decreased probability of resonant tunneling of atoms when they approach each other.

The impact of medetomidine on the protein-binding characteristics of MK-467 in canine plasma.

This study determined the unbound fraction of the peripheral α2 -adrenoceptor antagonist MK-467 alone and combined with medetomidine. MK-467 (0.1, 1 and 10 µm) was incubated in canine plasma with and without medetomidine (molar ratio 20:1), with human serum albumin (HSA) and with α1-acid glycoprotein (AGP). Rapid equilibrium dialysis was used for the measurement of protein binding. All samples were analysed by liquid chromatography and tandem mass spectrometry to obtain the unbound fraction (fu ) of MK-467. Unbound fractions (fu ) of MK-467 in canine plasma (mean ± standard deviation) were 27.6 ± 3.5%, 26.6 ± 0.9% and 42.4 ± 1.2% at 0.1, 1.0 and 10 µm concentrations, respectively. In the presence of medetomidine, fu were 27.5 ± 0.4%, 26.6 ± 0.9% and 41.0 ± 2.4%. The fu of MK-467 in HSA were 50.1 ± 2.5% at 0.1 µm, 49.4 ± 1.2% at 1.0 µm and 56.7 ± 0.5% at 10 µm. fu of MK-467 in AGP was 56.3 ± 3.7% at 0.1 µm, 54.6 ± 5.6% at 1.0 µm and 65.3 ± 0.4% at 10 µm. Protein binding of MK-467 was approximately 70% between 0.1 and 1.0 µm. Medetomidine had no apparent effect on the protein binding of MK-467.

Effects of MK-467 on the antinociceptive and sedative actions and pharmacokinetics of medetomidine in dogs.

We investigated the influence of the peripherally acting α2 -adrenoceptor antagonist MK-467 on the sedative and antinociceptive actions and plasma drug concentrations of medetomidine, an α2 -adrenoceptor agonist that is used in veterinary medicine as a sedative and analgesic agent. Eight healthy beagle dogs received intravenous medetomidine (10 µg/kg) or medetomidine with MK-467 (250 µg/kg) in a randomized crossover design. A standardized nociceptive pressure stimulus was applied to a nail bed of a hindlimb. Times for withdrawal of the limb and for head lift were measured, and sedation was scored. EEG data were collected prior to and after stimulation. Plasma drug concentrations were measured. Co-administration of MK-467 significantly attenuated medetomidine analgesia, as assessed with limb withdrawal, and also shortened the duration of sedation. The apparent plasma clearance of both enantiomers of medetomidine, dexmedetomidine and levomedetomidine, was more than doubled in the presence of MK-467. Antagonism by MK-467 of medetomidine-evoked vasoconstriction is seen as the mechanism behind this pharmacokinetic drug interaction. Thus, MK-467 attenuated the antinociceptive and sedative effects of medetomidine. This can probably be explained by increased clearance and decreased concentrations of dexmedetomidine in plasma after co-administration of MK-467 with racemic medetomidine.

Bose-Einstein condensation of magnons in atomic hydrogen gas.

We report on experimental observation of Bose-Einstein condensation (BEC)-like behavior of quantized electron spin waves (magnons) in a dense gas of spin-polarized atomic hydrogen. The magnons are trapped and controlled with inhomogeneous magnetic fields and described by a Schrödinger-like wave equation, in analogy to the BEC experiments with neutral atoms. We have observed the appearance of a sharp feature in the ESR spectrum displaced from the normal spin wave spectrum. We believe that this observation corresponds to a sudden growth of the ground-state population of the magnons and emergence of their spontaneous coherence for hydrogen gas densities exceeding a critical value, dependent on the trapping potential. We interpret the results as a BEC of nonequilibrium magnons which were formed by applying the rf power.

Low serum level of 1,25(OH)2 D is associated with chronic periodontitis.

BACKGROUND AND OBJECTIVES: Vitamin D has been studied primarily for its involvement in calcium and phosphate absorption and bone metabolism. The active form of vitamin D-1,25(OH)2 D-has also been investigated for its immune modulatory properties. We explored associations between serum levels of 25(OH)D and 1,25(OH)2 D and periodontal health. SUBJECTS AND METHODS: This case-control study included 55 subjects with chronic periodontitis (cases) and 30 periodontally healthy subjects (controls). Their serum levels of 25(OH)D, 1,25(OH)2 D, ultrasensitive C-reactive protein and high-density lipoprotein cholesterol were determined. Associations between vitamin D and periodontal health status were studied using logistic regression analysis. RESULTS: A statistically significant association was found between serum 1,25(OH)2 D level and periodontal health status; in that subjects with a low 1,25(OH)2 D were more likely to belong to the periodontitis group (OR = 0.97, 95% CI = 0.95-1.00). There was practically no association between 25(OH)D level and periodontal health status. CONCLUSION: In this case-control study low serum 1,25(OH)2 D level appeared to be associated with periodontitis, which was in line with the previously reported associations between serum 1,25(OH)2 D levels and other inflammatory diseases. Whether this association is causal in nature, remains to be confirmed in future studies.

Perceptions and practices of Finnish dairy producers on disbudding pain in calves.

Disbudding causes pain-related distress and behavioral changes in calves. Local anesthesia and non-steroidal anti-inflammatory drugs are effective for treating disbudding-related pain. Dairy producers play a key role in whether or not calves to be disbudded are properly medicated. Pain and distress related to disbudding of calves often remains untreated. Thus, we conducted this study to characterize perceptions and practices of dairy producers on disbudding and disbudding-related pain management. A questionnaire was sent to 1,000 randomly selected Finnish dairy producers (response rate: 45%). Our aim was to investigate producer perceptions about disbudding-related pain, the perceived need for pain alleviation before disbudding, and how these perceptions affect the valuing and use of pain alleviation before disbudding. More than 70% of Finnish dairy farms disbud their calves. Producers who ranked disbudding-related pain and need for pain alleviation higher called a veterinarian to medicate calves before disbudding more often than producers who ranked disbudding pain and need for pain alleviation lower. Among respondents who disbudded calves on their farms, 69% stated that disbudding caused severe pain, 63% stated that pain alleviation during disbudding is important, and 45% always had a veterinarian medicate their calves before disbudding. Producers with a herd healthcare agreement with their veterinarian estimated disbudding-related pain to be higher and had a veterinarian medicate calves more often than producers without such an agreement. Producers with tiestall systems and producers who did not use disbudding valued pain alleviation prior to disbudding higher than producers with freestalls and producers who used disbudding.

Experimental cell for molecular beam deposition and magnetic resonance studies of matrix isolated radicals at temperatures below 1 K.

We present the design and performance of an experimental cell constructed for matrix isolation studies of H and D atoms in solid H2/D2 films, which are created by molecular beam deposition at temperatures below 1 K. The sample cell allows sensitive weighing of the films by a quartz microbalance (QM) and their studies by magnetic resonance techniques in a strong magnetic field of 4.6 T. We are able to regulate the deposition rate in the range from 0.01 to 10 molecular layers/s, and measure the thickness with ≈0.2 monolayer resolution. The upper QM electrode serves as a mirror for a 128 GHz Fabry-Perot resonator connected to an electron spin resonance (ESR) spectrometer. H and D atoms were created by RF discharge in situ in the sample cell, and characterized by ESR and electron-nuclear double resonance. From the magnetic resonance measurements we conclude that the films are smooth and provide homogeneous trapping conditions for embedded atoms. The current sample cell design also makes it possible to calibrate the ESR signal and estimate the average and local concentrations of H and D radicals in the film.

Exploration of known stereotypic behaviour-related candidate genes in equine crib-biting.

Crib-biting in horses is a stereotypic oral behaviour. Genetic susceptibility has been suggested on a causal basis, together with environmental factors such as stress, gastric discomfort and frustration caused by stall restrictions. This study aimed to test the associations of known or suspected stereotypic genes with equine crib-biting, including Ghrelin, Ghrelin receptor, Leptin, Dopamine receptor, µ-opioid receptor, N-cadherin, Serotonin receptor and Semaphorin. We conducted a candidate gene study with a case-control design, including 98 crib-biting and 135 control horses of two breeds, Finnhorses and half-breds. Detailed phenotypic information on crib-biting behaviour was surveyed through an owner-completed questionnaire. Control horses were more than 10 years old and without a history of crib-biting. Single nucleotide polymorphisms flanking the candidate genes were genotyped using either Sanger sequencing or Taqman assays. According to the survey, the affected horses started crib-biting at a young age, had exhibited crib-biting for more than a year, and expressed the behaviour after feeding or when stressed. Comparison of allele frequencies between the cases and controls for each breed separately did not provide evidence of an association at any of the tested loci. These results suggest that the previously known stereotypic genes are not major risk factors for crib-biting in horses, and further genome-wide studies are warranted on larger sample cohorts.

Dynamic nuclear polarization of high-density atomic hydrogen in solid mixtures of molecular hydrogen isotopes.

We report on magnetic resonance studies of high-density atomic hydrogen and deuterium in solid hydrogen matrices at temperatures below 1 K. Average concentrations of H atoms ≈3×10(19) cm(-3) are obtained in chemical tunneling reactions of isotope exchange with D atoms. The products of these reactions are closely located pairs of H atoms near D2 molecules with strong exchange interactions. We discovered a dynamic nuclear polarization effect on H atoms created by pumping the center of the H electron spin resonance spectrum, similar to the Overhauser effect in metals. Our results indicate that H atoms may be arranged inside molecular matrices at separations equivalent to local concentrations of 2.6×10(21) cm(-3). This opens up a way to build a metallic state of atomic hydrogen at zero pressure.

Dose-response investigation of oral ketoprofen in pigs challenged with Escherichia coli endotoxin.

In order to determine the effective dose, the effects of orally administered ketoprofen were evaluated in pigs following intravenous challenge with Escherichia coli endotoxin. One hour after the challenge, five groups of pigs were treated with either tap water or ketoprofen (0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg). The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B(2) and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered blood thromboxane B(2) concentrations when compared with the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. The appropriate dose of orally administered ketoprofen in pigs in this model is 2 mg/kg, as the higher dose of 4 mg/kg failed to provide an additional benefit.

Guiding and trapping of electron spin waves in atomic hydrogen gas.

We present a high magnetic field study of electron spin waves in atomic hydrogen gas compressed to high densities of ∼10(18) cm(-3) at temperatures ranging from 0.26 to 0.6 K. We observed a variety of spin wave modes caused by the identical spin rotation effect with strong dependence on the spatial profile of the polarizing magnetic field. We demonstrate confinement of these modes in regions of strong magnetic field and manipulate their spatial distribution by changing the position of the field maximum.