bluuebunny/crossref_metadata_2025 huggingface dataset:
Properties of athletic mouth protectors and materials
Authors: Craig R. G. , Godwin W. C.
Published: March 2003

The properties of a variety of mouth protectors and sheet materials used to fabricate custom mouth protectors were determined in order to recommend limits for a specification. Hardness, water sorption, water solubility, impact absorption, and tear strength were measured, and limits for these properties were suggested.
Occlusal conditions just after the relief of temporomandibular joint and masticatory muscle pain
Authors: Fujii T.
Published: March 2003

When the signs and symptoms of temporomandibular joint disorders (TMD) are present, it is possible that occlusal conditions and mandibular movements are changed. Accordingly, the presence of occlusal interferences may be misjudged. It is therefore reasonable to consider that occlusal conditions should be examined just after the relief of symptoms. The comparison of occlusal conditions in 52 temparomandibular joint (TMJ) pain patients and 27 muscle pain patients with that in 60 asymptomatic controls was made. Occlusal examination in the patients was administered just after the relief of pain by bite plane therapy alone. The only occlusal factor which was associated with pain symptoms was no canine contact on the working side on laterotrusion. It is suggested therefore that further studies as regards this type of interference should be performed.
Effect of photo‐irradiation on hardness of soft lining materials for denture base
Authors: Fujii K. , Arikawa H. , Kanie T. , Shinohara N. , Inoue K.
Published: March 2003

Nine photo‐activated acrylic‐type (EPL) soft lining materials were produced experimentally to examine their durability. The purpose of this study was to investigate the effect of photo‐irradiation on the hardness of experimental soft lining materials. The hardness (Hex) of the nine EPLs was increased 4·3–170·1% by exposing them to light. The effect of irradiation on the Hex of the EPLs was remarkable when the material contained much ethylmethacrylate, together with smaller amounts of di‐n‐butyl phthalate. Moreover, the Hex tended to increase for EPLs in which the liquid portion contained less di‐n‐butyl phthalate or more ethanol (Et). The weight change ratio (Wc) was greater for EPL specimens containing less Et. The Wcs ranged from 0·118 to 0·661% after 8 weeks. These results showed that the Hexs of six of the EPLs were approximately equal to those of four commercially available soft lining materials, and these six EPLs may have properties favouring their use in clinical dentistry.
The expression of tenascin mRNA in human temporomandibular joint specimens
Authors: Yoshida H. , Fujita S. , Nishida M. , Iizuka T. , Yoshida T. , Sakakura T.
Published: March 2003

Summary The expression of mRNA of tenascin in the temporomandibular joint (TMJ) disc and synovial membrane was examined in 20 human TMJ samples from patients with internal derangement of the TMJ and 10 control specimens by in situ hybridization technique using paraffine‐embedded tissue, and antisense and sense cRNA probes. In control specimens, tenascin mRNA was not expressed. However, we were able to find tenascin mRNA expression in the surgical specimens. In 15 of 20 samples, ranging numbers of synovial cells expressed tenascin mRNA in the hypertrophic synovial membranes. Also, in 6 of 20 samples, tenascin mRNA was identified in fibroblasts. In four specimens, vascular endothelial cells were positive for the mRNA. In internal derangement cases, histopathological findings are often found such as synovitis, new capillary growth and fibrosis. The present study demonstrates that tenascin is produced specifically in synovial cells, vascular endothelial cells and fibroblasts affected in the portion of TMJ with internal derangement.
Analysis of brain activity during clenching by fMRI
Authors: Tamura T. , Kanayama T. , Yoshida S. , Kawasaki T.
Published: March 2003

It has been considered difficult to obtain satisfactory functional magnetic resonance images (fMRI) during jaw movements because the head motion during jaw movements makes artefacts on the images. To avoid these artefacts, we chose clenching task and larger pixels to allow some head motion of the subjects. Further the study discarded all data from subjects whom the head was evaluated to move more than 0·3 mm. The study examined 10 healthy right‐handed volunteers with echo‐planar magnetic resonance (MR) imaging and functional MR signal intensity changes could be obtained in all subjects. However, in the analysis of each pixel of individuals, three different types of pixels were established. It was determined that the pixels that synchronized positively with the task on/off and where signal intensity increase was below 10% expressed the real brain activity. Pixels showing the real brain activity were found in the sensory, motor and pre‐motor cortexes in both hemispheres in all subjects, and also in the insula region of two subjects. No pixels were found in the striatum and supplementary motor areas. From the above careful consideration and individual analysis of each pixel, it was concluded that brain activity during the clenching task could be obtained by fMRI.
The effect of thermocycling on five adhesive luting cements
Authors: Barclay C. W. , Boyle E. L. , Williams R. , Marquis P. M.
Published: March 2003

The importance of bond strengths between dental luting cements and dental restorative materials has become increasingly important as a result of the adhesive technologies that have been developed over recent years. This study investigated the effect on tensile bond strength at the metal to cement interface for a semiprecious alloy for different prepared surfaces, cements and ageing regimes. At 24 h following preparation, silicoating and C & B Metabond appear to have distinct advantages in terms of interfacial bond strength, which was also noted after storage for 7 days in buffered saline. After thermocycling only silicoating conferred greater interfacial tensile strength, and any advantage that the 4‐Methacryloxyethyltrimellitic anhydride (4‐META) chemistry may have had at 24 h was no longer apparent. The poorest performing cement regardless of the ageing regime was Aquacem, although in relative terms its performance improved after 24 h. This preliminary investigation indicated that in vitro environmental ageing including thermocycling erodes the claimed advantages of some more novel dental adhesives. This may have important clinical consequences in their usage, although it must be appreciated that current thermocycling methodology may not be an accurate predictor of in vivo performance.
Effect of ageing on the bond strength of a permanent denture soft lining material
Authors: Al‐Athel M. , Jagger R. , Jagger D.
Published: March 2003

summary  Molloplast‐B is a widely used, long‐term, heat‐cured silicone denture soft lining material. Adhesion failure of this material to poly (methyl methacrylate) denture base material is a problem that is encountered clinically. The purpose of this study was to investigate the effects of long‐term immersion in water at 37 ± 1 °C and of accelerated ageing in water at 50 ± 1 °C on the tensile and shear bond strength values of this denture resilient lining material bonded to a heat‐cured denture base material. Immersion in water for 1 week at 37 ± 1 °C had no significant effect on the measured bond strength values. Longer immersion of specimens in water at 37 ± 1 °C led to a significant reduction in the measured tensile and shear bond strengths. The present study has demonstrated that the reduction in Molloplast‐B bond strength that occurs as a result of long‐term ageing in water at 37 ± 1 °C can be achieved in a shorter period of time by ageing the specimens in water at a higher temperature.
Temperature and thermal stress analysis of a crowned maxillary second premolar tooth using three‐dimensional finite element method
Authors: Toparli M. , Aykul H. , Sasaki S.
Published: March 2003

summary  The purpose of this study was to calculate the temperature and thermal stress distribution as a result of hot/cold liquid in the mouth. This numerical study was carried out using three‐dimensional finite element models and the tooth model was crowned with Au–Pd alloy, Ni–Cr alloy and porcelain. In the first part of the study, temperature changes as a result of hot/cold liquid in the mouth were calculated. In the second part, the thermal stresses caused by temperature changes were obtained. The tooth was assumed isotropic, homogenous, elastic and unsymmetrical. The authors using fortran 77 prepared all calculation programs. The distribution of temperature and thermal stress were plotted for some critical points.
Influence of abutment substrates on the colour of metal‐free polymer crowns
Authors: Nakamura T. , Saito O. , Mizuno M. , Kinuta S. , Ishigaki S.
Published: March 2003

summary  New‐generation composite materials have excellent strength and wear resistance, and thus can be used to make metal‐free crowns. However, composite materials are translucent, and so when using them to make metal‐free crowns, it is necessary to take the effect of the abutments into consideration. In this study, five types of materials including three types of new‐generation composite materials, a conventional composite material, and a ceramic material were used to examine the translucency (contrast ratio) of the materials and the effects of the colour of the abutments on the final appearance of metal‐free crowns. It was found that the materials varied slightly from one‐another in translucency and that it was possible to reproduce the desired colour when gold alloy was used for the background. However, it was difficult to produce an adequate colour match when silver–palladium alloy was used for the background. When a tooth colour material that was darker than the target colour was used for the abutment teeth, some materials could not reproduce the target colour satisfactorily.
Mandibular movement and frontal craniofacial morphology in orthognathic surgery patients with mandibular deviation and protrusion
Authors: Oguri Y. , Yamada K. , Fukui T. , Hanada K. , Kohno S.
Published: March 2003

summary  The present study was conducted to investigate the relationship between mandibular movement (lateral excursion and masticatory movements) and craniofacial morphology in 16 patients with mandibular deviation, using a six degrees‐of‐freedom measuring device. (i) Mandibular deviation was found to be significantly related to frontal maxillary and occlusal plane angles. (ii) Three‐dimensional non‐working condylar and incisal path lengths were longer during the lateral excursion to the non‐deviated side than to the deviated side, and the incisal path moved antero‐inferior. (iii) The lateral motion range of the incisal path was wider during masticatory movement on the non‐deviated side than on the deviated side, and the molar and non‐working condylar path lengths corresponding to the lateral range of the incisal path were also longer on the non‐deviated side. The group with posterior crossbite showed a significantly smaller horizontal range of incisal path, and also significantly smaller frontal projected incisal and molar path angles during masticatory movement on the deviated side than on the non‐deviated side. These results suggest that lateral excursion and masticatory movements could be related to craniofacial morphology and posterior crossbite.
The pH changes of four different calcium hydroxide mixtures used for intracanal medication
Authors: Solak H. , Öztan M. D.
Published: March 2003

summary  The purpose of this study was to determine the pH values of calcium hydroxide mixtures in combination with either distilled water, two different local anaesthetic solutions or physiological saline solution, which are commonly used as a dressing materials during endodontic treatment. The pH of each vehicle prior to mix with calcium hydroxide and subsequently each prepared combination was determined using a digital pH meter. The pH measurements were determined at 3 min, 10 min, 1 h, 24 h, 48 h and 7 days. The results of this study indicated that four different water‐based vehicles demonstrated similar pH changes range within pH 11–12 when mixed with calcium hydroxide.
Is bruxism severity a predictor of oral splint efficacy in patients with myofascial face pain?
Authors: Raphael K. G. , Marbach J. J. , Klausner J. J. , Teaford M. F. , Fischoff D. K.
Published: March 2003

summary  Both the efficacy and mechanism of any effect of oral splint therapy for patients with temporomandibular disorders (TMDs) are a matter of controversy. To address these issues, this study tested the hypothesis that oral splints produce the most marked pain relief for those TMD patients with myofascial face pain (MFP) who also brux (i.e. grind or clench) more than other MFP patients. In a 6‐week randomized controlled clinical trial, 52 women with MFP were randomly assigned to receive either a full‐coverage hard acrylic splint or a palatal‐only splint. Bruxism was assessed both by self‐report and by an objective assessment of molar microwear changes over a 2‐week period prior to the start of the trial. Tested across multiple outcome measures, results indicated that those receiving the full‐coverage splint had marginally better improvement on some pain‐related measures than those receiving the palatal splint, but severity of bruxism did not moderate the therapeutic effect of the full‐coverage splint. These findings strongly argue against the belief that oral splints reduce MFP by reducing bruxism and raise questions about the importance of bruxism in the maintenance of MFP.
Reliability of clinician judgements of bruxism
Authors: Marbach J. J. , Raphael K. G. , Janal M. N. , Hirschkorn‐Roth R.
Published: March 2003

summary  Bruxism is considered to be a parafunctional disorder requiring treatment and is viewed as a risk factor for the development of temporomandibular disorders (TMDs). The purpose of this investigation is to examine the reliability of clinician judgements of bruxism severity. Twenty dentists who are faculty members in a dental school examined 29 stone casts and gold‐plated models of individual teeth for evidence of bruxism. Ordinal ratings of bruxism severity for the 29 augmented models were made on two occasions, approximately 3 months apart. Inter‐rater reliability among all clinicians, evaluated using intraclass correlation coefficients (ICCs), was poor at both time one and time two (i.e. ICC=0·33 and 0·32, respectively), with somewhat better reliability found among those clinicians with above‐average time elapsed since completion of dental training (i.e. ICC=0·48 and 0·50 for time 1 and time 2, respectively). Three‐month test–retest reliabilities were fair (ICC=0·46) for the full group of raters and were unrelated to clinicians' degree of confidence in their ratings. These results indicate a need to standardize methods for clinical assessment of bruxism. Additionally, they have implications for studies using clinical assessments of bruxism to test the association between bruxism and other conditions such as TMDs.
Lessons from history: the politics of psychiatry in the USSR
Authors: Spencer I.
Published: March 2003

The political‐economic base of society affects every aspect of it, including nursing and psychiatry. This can be demonstrated by making a historical analysis of societies with different political‐economic systems. Psychiatry in the USSR took a different form to psychiatry in the West. Differences included the diagnostic categories used and treatments employed. This can be investigated by examining accounts of clinical practice. Soviet psychiatry was also used for the systematic incarceration of political dissidents. Some commentators have drawn on the Soviet experience and used it to support an argument that psychiatry operates as a form of social control in the West as well as the USSR. This article shows how psychiatric abuse in the USSR was a historically specific response to a particular situation. Therefore some of the conclusions about Western psychiatry extrapolated from the Soviet experience are unsupportable. Whatever the role of psychiatry in the West, its mechanism is qualitatively different to that which existed in the USSR. In order to understand why Soviet medical workers were co‐opted into the conscious abuse of psychiatry, it is essential to understand the specific nature of the USSR. This does not necessarily allow generalizations about Western psychiatry to be made from the Soviet experience. As psychiatric nurses, we can also learn from a particularly tragic period of psychiatry's history.
Cardiac autonomic nervous system activity during presleep wakefulness and Stage 2 NREM sleep
Authors: Burgess Helen J. , Trinder John , Kim Young
Published: March 2003

Previous research has found that cardiac parasympathetic nervous system (PNS) activity increases and cardiac sympathetic nervous system (SNS) activity decreases during night‐time sleep. This study aimed to examine in greater detail the time course of these changes in cardiac autonomic nervous system (ANS) activity. In the week prior to the experimental night, nine subjects maintained a constant sleep–wake schedule and experienced an adaptation night. Each subject's experimental night consisted of 2 h of presleep wakefulness, followed by a night of sleep, commencing at each subject's normal sleep onset time. One hundred and twenty beat blocks of presleep wakefulness and stable Stage 2 non‐rapid eye movement (NREM) sleep across the night were selected. SNS activity was assessed using pre‐ejection period, the amplitude of the T‐wave in the ECG and the 0.1 Hz peak from the spectral analysis of the ECG. PNS activity was assessed using respiratory sinus arrhythmia (spectral analysis). Heart rate and respiratory rate were also measured. The results indicated a progressive decrease in SNS activity throughout sleep and a rise in PNS activity during the first half of the normal sleep period. The changes in PNS activity were similar, while the changes in SNS activity were altered, compared with a previous study in which stage of sleep was not controlled. This indicates a likely sleep stage influence on SNS activity, but not on cardiac PNS activity. These results are consistent with the concept of a primarily circadian, but not sleep, influence on PNS activity, and primarily a sleep, but not circadian, influence on SNS activity.
The effects of digital filtering on mismatch negativity in wakefulness and slow‐wave sleep
Authors: Sabri Merav , Campbell Kenneth B.
Published: March 2003

The mismatch negativity (MMN) is a response to a deviant auditory stimulus that occurs infrequently in a sequence of otherwise repetitive, homogeneous standard auditory stimuli. The MMN is presumed automatic and independent of conscious awareness. Recording of the MMN during unconscious states may be problematic. The frequency content of the long‐lasting MMN may overlap and summate with other event‐related slow potentials and low‐frequency background electroencephalogram (EEG) activity. The purpose of this study is to determine the optimal filter settings for recording the MMN during unconscious states. Auditory event‐related potentials (ERPs) were recorded from eight subjects in an oddball paradigm during wakefulness and Stages 3 and 4 of sleep [slow‐wave sleep (SWS)] using a 0.16–35 Hz analogue bandpass. Deviant probability was 0.033. Stimulus‐onset asynchrony was 150 ms. The EEG data were subsequently digitally filtered in the frequency domain. The low‐pass filter was set at either 24, 12 or 6 Hz, and the high‐pass filter at either 1, 2, 3 or 4 Hz. Applying a low‐pass filter down to 12 Hz had a minimal impact on the waking or sleeping MMN amplitude. On the other hand, increasing the high‐pass setting from 2 to 3 Hz permitted the visualization of the MMN recorded during sleep. The 4 Hz filter showed a similar trend but also markedly attenuated the amplitude of the waking MMN. A high‐pass setting of 3 Hz provides a reasonable compromise. It has only a slight effect on the MMN when the subject is conscious, but still attenuates most of the unwanted slow potential activity when the subject enters SWS.
Spectral analysis of all‐night human sleep EEG in narcoleptic patients and normal subjects
Authors: Mukai Junko , Uchida Sunao , Miyazaki Shinichi , Nishihara Kyoko , Honda Yutaka
Published: March 2003

To investigate the pathophysiology of narcoleptic patients' sleep in detail, we analysed and compared the whole‐night polysomnograms of narcoleptic patients and normal human subjects. Eight drug‐naive narcoleptic patients and eight age‐matched normal volunteers underwent polysomnography (PSG) on two consecutive nights. In addition to conventional visual scoring of the polysomnograms, rapid eye movement (REM)‐density and electroencephalograph (EEG) power spectra analyses were also performed. Sleep onset REM periods and fragmented nocturnal sleep were observed as expected in our narcoleptic patients. In the narcoleptic patients, REM period duration across the night did not show the significant increasing trend that is usually observed in normal subjects. In all narcoleptic patient REM periods, eye movement densities were significantly increased. The power spectra of narcoleptic REM sleep significantly increased between 0.3 and 0.9 Hz and decreased between 1.0 and 5.4 Hz. Further analysis revealed that non‐rapid eye movement (NREM) period duration and the declining trend of delta power density in the narcoleptic patients were not significantly different from the normal subjects. Compared with normal subjects, the power spectra of narcoleptic NREM sleep increased in the 1.0–1.4 Hz and 11.0–11.9 Hz frequency bands, and decreased in a 24.0–26.9 Hz frequency band. Thus, increased EEG delta and decreased beta power densities were commonly observed in both the NREM and REM sleep of the narcoleptic patients, although the decrease in beta power during REM sleep was not statistically significant. Our visual analysis revealed fragmented nocturnal sleep and increased phasic REM components in the narcoleptic patients, which suggest the disturbance of sleep maintenance mechanism(s) and excessive effects of the mechanism(s) underlying eye movement activities during REM sleep in narcolepsy. Spectral analysis revealed significant increases in delta components and decreases in beta components, which suggest decreased activity in central arousal mechanisms. These characteristics lead us to hypothesize that two countervailing mechanisms underlie narcoleptic sleep pathology.
Lidocaine in the horse: its pharmacological effects and their relationship to analytical findings
Authors: Harkins  , Mundy  , Woods  , Lehner  , Karpiesiuk  , Rees  , Dirikolu  , Bass  , Carter  , Boyles  , Tobin
Published: March 2003

Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no‐effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme‐linked immunosorbent assay (ELISA) screening, administration of the HNED of lidocaine to eight horses yielded peak serum and urine concentrations of apparent lidocaine of 0.84 ng/mL at 30 min and 72.8 ng/mL at 60 min after injection, respectively. These concentrations of apparent lidocaine are readily detectable by routine ELISA screening tests (LIDOCAINE ELISA, Neogen, Lexington, KY).

 ELISA screening does not specifically identify lidocaine or its metabolites, which include 3‐hydroxylidocaine, dimethylaniline, 4‐hydroxydimethylaniline, monoethylglycinexylidine, 3‐hydroxymonoethylglycinexylidine, and glycinexylidine. As 3‐hydroxylidocaine is the major metabolite recovered from equine urine, it was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for 3‐hydroxylidocaine as recovered from horse urine. Following subcutaneous (s.c.) injection of the HNED of lidocaine, the concentration of 3‐hydroxylidocaine recovered from urine reached a peak of about 315 ng/mL at 1 h after administration.

 The mean pH of the 1 h post dosing urine samples was 7.7, and there was no apparent effect of pH on the amount of 3‐hydroxylidocaine recovered. Within the context of these experiments, the data suggests that recovery of less than 315 ng/mL of 3‐hydroxylidocaine from a post race urine sample is unlikely to be associated with a recent local anaesthetic effect of lidocaine. Therefore these data may be of assistance to industry professionals in evaluating the significance of small concentrations of lidocaine or its metabolites in postrace urine samples. It should be noted that the quantitative data are based on analytical methods developed specifically for this study, and that methods used by other laboratories may yield different recoveries of urine 3‐hydroxylidocaine.
Repeated administration of trimethoprim/sulfadiazine in the horse –pharmacokinetics, plasma protein binding and influence on the intestinal microflora
Authors: Gustafsson  , Båverud  , Franklin  , Gunnarsson  , Ögren  , Ingvast‐Larsson
Published: March 2003

Six healthy adult horses were given repeated administrations of trimethoprim/sulfadiazine (TMP/SDZ) intravenously (i.v.) (2.5 mg/kg TMP and 12.5 mg/kg SDZ) and orally (p.o.) as a paste (5 mg/kg TMP and 25 mg/kg SDZ). Both formulations were given twice daily for 5 days, with a 3‐week interval between i.v. and oral administration. The influence of the drug combination on the intestinal microflora was examined and the plasma concentrations, pharmacokinetic parameters and plasma protein binding were determined. There were no major changes in the bacterial intestinal flora and no clinical evidence of gastrointestinal disturbances following the i.v. and oral TMP/SDZ administration. An initial reduction in the number of coliform bacteria during the treatment was notable, though with no evident difference between i.v. and oral treatment. The minimum concentration during a dose interval at steady state (Cminss), the elimination half‐life (t1/2β) and the mean residence time (MRT) were significantly greater after oral administration compared to i.v. for both TMP and SDZ. The plasma protein binding was measured to be 20% for SDZ and 35% for TMP. Oral administration of TMP/SDZ in a dose of 30 mg/kg given twice daily in the form of paste appeared as a satisfactory method for obtaining plasma levels above MIC (minimum inhibitory concentration in vitro) values during the interdosing interval.
Single‐dose pharmacokinetics of flumequine in halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus)
Authors: Hansen  , Horsberg
Published: March 2003

Flumequine was administered to halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus) intravenously (i.v.) and orally (p.o.) at a dose of 10 mg/kg bodyweight, and as a bath‐treatment at a dose of 10 mg/L water for 2 h, using identical experimental designs. The study was performed in seawater with a salinity of 3% and a temperature of 10.3 ± 0.4°C (halibut) and 18.0 ± 0.3 °C (turbot). Pharmacokinetic modelling of the data showed that flumequine had quite similar pharmacokinetic properties in halibut and turbot. Following intravenous administration, the volumes of distribution at steady state (Vss) were 2.99 L/kg (halibut) and 3.75 L/kg (turbot). Plasma clearances (Cl) were 0.12 L/kg (halibut) and 0.17 L/h.kg (turbot) and the elimination half‐lives (t½λz) were calculated to be 32 h (halibut) and 34 h (turbot). Mean residence times (MRT) were 25.1 h (halibut) and 22.2 h (turbot). Following oral administration, the t½λz were 43 h (halibut) and 42 h (turbot). Maximal plasma concentrations (tmax) were 1.4 mg/L (halibut) and 1.9 mg/L (turbot), and were observed 7 h post administration in both species. The oral bioavailabilities (F) were calculated to 56% (halibut) and 59% (turbot). Following bath administration maximal plasma concentrations were 0.08 mg/L (halibut) and 0.14 mg/L (turbot), and were observed 0 h (halibut) and 3 h (turbot) after the end of the bath. The bioavailability in halibut following a 2‐h bath treatment was 5%.
Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in chickens
Authors: García Ovando H. , Gorla N. , Luders C. , Poloni G. , Errecalde C. , Prieto G. , Puelles I.
Published: March 2003

The pharmacokinetics of enrofloxacin (EFX) and ciprofloxacin (CFX) was investigated in broiler chickens. Each antimicrobial was administered intravenously at a dose of 5 mg/kg body weight. Blood was taken in different preset times: prior and at 0.03, 0.06, 0.13, 0.25, 0.5, 1, 2, 4, 8, 12 and 24 h following drug administration. The concentrations of EFX and CFX in plasma were determined by high pressure liquid chromatography (HPLC). Plasma concentrations vs. time were analysed by a compartmental independent pharmacokinetic model that provided the most important kinetic parameters.

 Statistically significant differences between the two antimicrobials were found for most of the pharmacokinetic parameters: Area under the curve (AUC), area under first moment curve (AUMC), mean residence time (MRT), total body cleareance (ClB), volume of distribution beta (Vd beta) and volume of distribution at the steady state (Vdss). Both antimicrobials were widely distributed in chickens throughout the body with a mean Vdss of 1.98 ± 0.18 L/kg for EFX, and 4.04 ± 0.69 L/kg for CFX. The ClB for CFX was five times higher than that obtained for EFX. AUC, MRT and the diminished half time for EFX were two–four times higher than those obtained for CFX. These results indicate that CFX remains in the body for less time than the other quinolone. This characteristic of CFX suggests the advantage of a shorter withdrawal time for food producing animals treated with this antimicrobial.
Influence of platelet activating factor on gastrointestinal electrical activity and some haematological and clinical parameters in the conscious miniature pig
Authors: Wechsung  , Houvenaghel
Published: March 2003

The effects of intravenous (i.v.) infusion of platelet‐activating factor (PAF), 100 ng/kg/min for 10 min, with and without pretreatment with a selective PAF‐antagonist on gastrointestinal electrical activity, arterial pressure and clinical and haematological parameters were studied. Conscious miniature pigs with electrodes implanted in the wall of the antrum pylori and small and large intestine were used. Platelet‐activating factor induced restlessness or depression, shivering, tachypnoea and coughing, retching and vomiting, hypotension and a delayed and sustained increase in leucocyte count with an increase in percentage of segmented neutrophils. The PAF‐antagonist, SAH 63–675, administered at 10 mg/kg intravenously, inhibited these effects. Platelet‐activating factor resulted in a decrease in electrical activity in the antrum and large intestine, whereas small intestinal activity was not significantly influenced. Pretreatment with the antagonist suppressed these inhibitory effects.
Disposition of oxytetracycline in pigs after i.m. administration of two long‐acting formulations
Authors: El Korchi G. , Prats C. , Arboix M. , Pérez B.
Published: March 2003

El Korchi, G., Prats, C., Arboix, M., Pérez, B. Disposition of oxytetracycline in pigs after i.m. administration of two long‐acting formulations J. vet. Pharmacol. Therap.24, 247–250.

Two commercially available long‐acting oxytetracycline (OTC) formulations were administered by the intramuscular (i.m.) route to six healthy pigs at the recommended dose of 30 mg/kg. After 2 h the mean maximum concentration (Cmax) reached values of 8.1 ± 2.2 and 15.4 ± 11.1 μg/mL, respectively. These concentrations remained higher than 0.5 μg/mL for more than 5 days after drug administration. The area under the concentration time curve (AUC09 days) of each formulation was 255 ± 76.5 and 399.2 ± 123 μg · h/mL, respectively, and the mean residence time (MRT) was around 3 days for both formulations. No significant differences were observed between the pharmacokinetic parameters of the two formulations, showing the bioequivalence of the two formulations studied according to the criteria established by the Food and Drug Administration (FDA) and the Committee for Veterinary Medicinal Products (CVMP).
Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations
Authors: Wiuff C. , Lykkesfeldt J. , Aarestrup F. M. , Svendsen O.
Published: March 2003

The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum and colon from pigs killed at 2, 3 and 6 h after dosing. Intramuscular administration resulted in significantly higher concentrations in plasma, intestinal tissue and lymph nodes at 2 h but not at 3 or 6 h compared with p.o. administration. The absorption and distribution phase was longer after oral administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5‐day dosing regimen with i.m. and p.o. administration were determined by both HPLC and bio‐assay. Higher concentrations were found after i.m. administration during the first day, but the difference was not significant after 2 days. The biologically active concentrations determined by bio‐assay constituted 48–75% of the total concentrations determined by HPLC. On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route.
A physiologically based pharmacokinetic model for oxytetracycline residues in sheep
Authors: Craigmill A. L.
Published: March 2003

A physiologically based pharmacokinetic model (PBPK) for oxytetracycline (OTC) residues in sheep was developed using previously published data from a combined serum pharmacokinetic and tissue residue study [Craigmill et al. (2000)J. Vet. Pharmacol. Ther.23, 345]. Physiological parameters for organ weights and tissue blood flows were obtained from the literature. The tissue/serum partition coefficients for OTC were estimated from the serum and tissue residue data obtained at slaughter. The model was developed to include all of the tissues for which residue data were available (serum, kidney, liver, fat, muscle and injection site), and all of the remaining tissues were combined into a slowly perfused compartment with low permeability. Total body clearance of OTC calculated in the previous study was used as the starting value for clearance in the PBPK model, with the kidney being the only eliminating organ. The model was built using ACSL (Advanced Continuous Simulation Language) Graphic Modeler®, and the model was fit to the serum and tissue data using the ACSL Math/Optimizer® software (AEgis Technologies Group, Inc., Huntsville, AL, USA). A sensitivity analysis was also performed to determine which parameters had the greatest effect on the goodness of fit. Numerous strategies were tested to model the injection site, and a model providing a biexponential absorption of the drug from the injection bolus gave the best fit to the experimental data. The model was validated using the clearance parameters calculated from the traditional pharmacokinetic model for each individual animal in the PBPK model. This simple PBPK model well predicted OTC residues in sheep tissues after intramuscular dosing with a long‐acting preparation and may find use for other species and other veterinary drugs.
Antifungal agents of use in animal health – chemical, biochemical and pharmacological aspects
Authors: Bossche H. Vanden , Engelen M. , Rochette F.
Published: March 2003

A limited number of antifungal agents is licensed for use in animals, however, many of those available for the treatment of mycoses in humans are used by veterinary practitioners. This review includes chemical aspects, spectra of activity, mechanisms of action and resistance, adverse reactions and drug interactions of the antifungals in current use.
Hepatitis G virus infection in hepatitis C virus‐positive patients co‐infected or not with hepatitis B virus and/or human immunodeficiency virus
Authors: Thiers V. , Pol S. , Persico T. , Carnot F. , Zylberberg H. , Berthelot P. , Bréchot C. , Nalpas B.
Published: March 2003

This was a retrospective study to evaluate the prevalence and impact of hepatitis G virus (HGV) infection in hepatitis C virus (HCV)‐positive drug addicts, according to the serological status of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co‐infection. Two hundred and thirty‐five randomly selected intravenous drug addicted patients (147 French, 88 Italian) were studied. All patients were positive for antibodies to HCV (anti‐HCV). HGV RNA positivity was measured by reverse transcriptase–polymerase chain reaction (RT–PCR). Comparisons of HCV RNA positivity rate, and biological and histopathological variables, were made between HGV RNA‐positive and negative patients, according to their HBV and HIV status. HGV prevalence was around 30% in both French and Italian groups. No clear association between HGV infection and a particular HCV genotype was observed. The rate of HCV RNA positivity did not differ between HGV‐positive and HGV‐negative patients after stratification for hepatitis B surface antigen (HBsAg) and HIV positivity. Histological severity of the underlying chronic hepatitis did not differ according to the HGV status; however, in HIV‐positive HBsAg‐negative patients, the hepatitis activity was moderately increased in HGV‐positive patients. A striking negative influence of HBsAg positivity on HCV replication was observed in HIV‐negative patients: an HCV RNA‐positive rate of 25% was found in HBsAg‐positive patients vs 86% in HBsAg‐negative patients; similar significant results were observed in HIV‐positive patients, although to a lesser extent. The underlying chronic hepatitis was significantly more severe in HBsAg‐positive than in HBsAg‐negative HIV‐negative patients. Hence, HGV infection is highly prevalent in anti‐HCV positive drug addicts but the co‐infection with HCV does not seem to influence HCV replication nor to worsen the underlying chronic hepatitis, in HIV‐negative patients at least. Reciprocal influence between HBV, HCV and HIV appears rather complex, HBsAg carriage seeming to exert per se a negative effect on HCV replication, particularly in HIV‐negative patients, suggesting that interactions between hepatitis viruses should always be analysed in the light of HIV status.
Report from the International Symposium on viral hepatitis, 24–25 October 1997, Warsaw, Poland
Authors: Madali´nski K. , Mazur W.
Published: March 2003

The authors present the results of an International Symposium on ‘Viral Hepatitis’, held in Warsaw on 24–25 October 1997 and dedicated to the scientific activity of Professor Adam Nowoslawski, the founder of the Polish school of Immunopathology, with many contributions to the viral hepatitis research. The symposium was divided into main sessions and poster reports which covered most of the topics in this field. This successful meeting has gathered many distinguished speakers from different countries and was attended by ca. 350 participants, mainly from Poland, but also from the neighbouring countries.
Hepatitis B third‐generation vaccines: improved response and conventional vaccine non‐response – third generation pre‐S/S vaccines overcome non‐response
Authors: Zuckerman J. N.
Published: March 2003

A new triple‐S containing recombinant hepatitis B vaccine was evaluated in terms of immunogenicity and reactogenicity in a cohort of healthy healthcare professionals who were persistent non‐responders to the currently licensed hepatitis B vaccines. One hundred subjects were allocated randomly to receive two doses of 5, 10, 20 or 40 μg of a new hepatitis B vaccine 2 months apart. The overall seroconversion rate was 70% with a single dose of 20 μg of the vaccine being as effective as two doses of either 20 μg or 40 μg of the vaccine formulation in terms of seroconversion, seroprotection and geometric mean titres.
Cellular immune response to the hepatitis C virus
Authors: Rehermann B.
Published: March 2003

Hepatitis C virus (HCV) infection is most often clinically inapparent and rarely associated with symptoms of acute hepatitis. Most patients, however, fail to resolve the acute infection and proceed to develop chronic hepatitis with the risk of liver cirrhosis and hepatocellular carcinoma later in life. Since the kinetics of the earliest events of virus–host interaction are likely to determine the outcome of infection, research has focused on the characterization of the strength and kinetics of the antiviral immune response in different stages of disease. The identification of the immunological correlates of viral clearance is pivotal for the development of vaccines and efficient therapies.
A comparison of reverse transcription–polymerase chain reaction and branched‐chain DNA assays for hepatitis C virus RNA in patients receiving interferon treatment
Authors: Pockros P. J. , Bain V. G. , Hunter E. B. , Conrad A. , Balart A. , Hollinger F. B. , Albert D. , Group The Consensus Interferon Study
Published: March 2003

Measurement of hepatitis C virus (HCV) RNA may be beneficial in managing the treatment of patients with chronic HCV infection. In a phase 3 study comparing consensus interferon (IFN) and IFN‐α2b treatment in patients with chronic HCV infection, serum samples were assayed for HCV RNA using two different assays: a quantitative multicycle reverse transcription–polymerase chain reaction (RT–PCR) method and the Quantiplex branched‐chain DNA (bDNA) method. Lower and upper detection limits were 100 copiesml–1 and 5×106 copiesml–1, respectively, for the RT–PCR method, and 3.5×105 and 4×107 genome equivalentsml–1, respectively, for the bDNA method. The two assays were generally concordant over the common range of detectability. The major discrepancy was where PCR still indicated detectable virus in the sample but the bDNA result was negative. Assessment of serum samples during IFN treatment demonstrated that 37% of samples were negative for HCV RNA by bDNA but positive by RT–PCR. Differences were also noted in the quantification of baseline HCV RNA by genotype. These data suggest that HCV patients could be categorized as treatment responders by the bDNA assay when the more sensitive RT–PCR assay indicates lack of complete viral response.
Granulocyte–macrophage colony‐stimulating factor enhances the efficacy of hepatitis B virus vaccine in previously unvaccinated haemodialysis patients
Authors: Kapoor D. , Aggarwal S. R. , Singh N. P. , Thakur V. , Sarin S. K.
Published: March 2003

The response to vaccination with recombinant hepatitis B virus (HBV) vaccine is poor in haemodialysis patients. A defect in the antigen‐presenting cells may be responsible for this hyporesponsiveness. To overcome this and to improve the response to HBV vaccine in dialysis patients, we used granulocyte–macrophage colony‐stimulating factor (GM‐CSF) as a vaccine adjuvant. Fifteen consecutive patients with chronic renal failure (CRF), commenced on dialysis, were stratified to receive either 40μg HBV vaccine (Engerix‐B) at 0, 1, 2 and 6 months (group A, n=9) or 3μg kg–1 GM‐CSF (Leucomax) on day 1 followed by the vaccination schedule described above (group B, n=6). All patients were negative for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti‐HCV) and human immunodeficiency virus (HIV) serology. Titres of antibody to HBsAg (HBsAb) were quantitatively assayed, using enzyme‐linked immunosorbent assay (ELISA), at 1, 2, 6 and 7 months from the first dose of vaccination. Only 44% of the patients in group A developed protective antibody levels (mean HBsAb: 22 IU l–1) Fifty per cent of responders developed protective antibody levels (HBsAb >10 IU l–1) only after the fourth dose of vaccination. In contrast, all six patients (100%) in group B developed protective levels of HBsAb (mean HBsAb: 70 IU l–1) (P<0.02). Sixty‐seven per cent of the responders were protected after only the second dose of vaccination (P=0.046). No serious adverse effects of GM‐CSF were observed in group B. Hence, haemodialysis patients respond poorly to HBV vaccine. GM‐CSF is a safe vaccine adjuvant capable of stimulating an earlier and a stronger antibody response to HBV vaccine in haemodialysis patients.
Influence of transfusion‐transmitted virus infection on the clinical features and response to interferon therapy in Japanese patients with chronic hepatitis C
Authors: Hagiwara H. , Hayashi N. , Mita E. , Oshita M. , Kobayashi I. , Iio S. , Hiramatsu N. , Sasaki Y. , Kasahara A. , Kakinuma K. , Yamauchi T. , Fusamoto H.
Published: March 2003

Recently, the genome of a novel DNA virus, transfusion‐transmitted virus (TTV), was cloned from the plasma of a blood donor who had an elevated aminotransferase level but no serological markers of known hepatitis viruses. In this study, we investigated the influence of TTV infection on the clinical features and response to interferon (IFN) therapy in patients with chronic hepatitis C. We studied 247 patients who had received a 16‐ or a 24‐week course of IFN‐α therapy. The serum of these patients was analysed for TTV DNA using a hemi‐nested polymerase chain reaction and TTV was detected in 114 patients (46%). No significant differences were found with respect to clinical features (gender, age, liver‐related biochemical tests, hepatitis C virus (HCV) genotype and serum HCV RNA levels) between the patients who were positive for TTV DNA and those who were negative for TTV DNA. The fibrosis score was higher in TTV‐positive patients (2.1 ± 1.1) than in TTV‐negative patients (1.7 ± 1.1, P = 0.023). The biochemical sustained‐response rate was 25% in TTV‐positive patients and 25% in TTV‐negative patients (not significant). A sustained HCV clearance rate was achieved in 26% of TTV‐positive patients and in 22% of TTV‐negative patients (not significant). TTV DNA clearance after IFN therapy was observed in 36 of 69 patients (52%) for whom stored serum samples were available. The disappearance of TTV DNA had no effect on the biochemical response to IFN therapy. In conclusion, TTV co‐infection is frequently observed in Japanese patients with chronic hepatitis C. In chronic hepatitis C, TTV does not modify the clinical features or the response to IFN.
The core promoter of hepatitis B virus
Authors: Kramvis A. , Kew M. C.
Published: March 2003

The core promoter (CP) of hepatitis B virus (HBV) plays a central role in HBV replication and morphogenesis, directing the transcription of both species of 3.5 kb mRNA: pregenomic (pg) RNA and precore (pre‐C) mRNA. The CP overlaps the 3′ end of the X open‐reading frame (ORF) and the 5′ end of the pre‐C/C ORF. The major functional elements of the CP are the upper regulatory region (URR) and the basic core promoter (BCP). The BCP is sufficient for accurate initiation of both pre‐C mRNA and pgRNA transcription. It contains four AT‐rich regions and the initiators for pre‐C mRNA and pgRNA transcription. The upstream regulatory region consists of the negative regulatory element and the core upstream regulatory sequence. Co‐operative interaction of various liver‐enriched and ubiquitous transcription factors is necessary for liver‐specific expression from the CP. These factors bind to the CP. Sequence conservation within the CP is crucial for maintaining active viral replication, and variation may contribute to the persistence of HBV within the host, leading to chronic infection and, ultimately, hepatocarcinogenesis. The most frequently described mutations within this region are an A to T transversion at position 1762 together with a G to A transition at position 1764. This double mutant is accompanied by a reduced level of hepatitis B e antigen (HBeAg) expression. Deletions, insertions and duplications occur within the CP.