bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of c‐Fos protein in the trigeminal nuclear complex resulting from quantified force application to the rat molar
Authors: Watanabe M. , Tanaka E. , Suemune S. , Satoda T. , Maeda N. , Uchida T. , Tanne K.
Published: October 2003

summary  This study was conducted to investigate the expression and distribution of c‐Fos‐like immunoreactive neurones (Fos‐neurones), in the rat trigeminal sensory nuclear complex, produced by mechanical forces with various magnitudes and durations applied to the left upper first molar. The magnitudes of forces applied to the tooth were 25, 50 and 100 g and the duration was 2 h. A quantified force of 100 g was also applied to the upper molar for varying durations [short‐time (1–2 min)], 2, 4, 8 and 12 h. Fos‐neurones distributed in the bilateral superficial laminae of the subnucleus caudalis, and the ipsilateral dorsomedial part of subnucleus oralis (Sp5Odm). The number of Fos‐neurones increased in the subnucleus caudalis (Sp5C) according to the force magnitude. In the Sp5C, the number of Fos‐neurones exhibited maximum level, 2 or 4 h after the application. In the Sp5Odm, however, the number of Fos‐neurones reached the maximum level at 8 h. These data suggest that the change in the number of nociceptive neurones in Sp5C reflect changes in encoding the magnitude of force to tooth, and that the nature of pain response to orthodontic forces might have some relation to the delayed expression of c‐Fos protein in the Sp5Odm.
Relationship between occlusal curvatures and mandibular deviation in orthodontic patients with temporomandibular disorders
Authors: Ali I. M. , Yamada K. , Alkhamrah B. , Vergara R. , Hanada K.
Published: October 2003

summary  The aim of this study was to investigate the relationships between occlusal curvature (OC) and frontal craniofacial morphology in patients with and without temporomandibular disorders (TMD), using frontal cephalograms and a sophisticated measuring device (XYZAX S400A). Thirty‐seven female orthodontic patients (mean age 24·0 years) were divided into a TMD group (n = 25) and no‐TMD group (n = 12). In the TMD group, the lateral OCs of the mandibular second premolar, and first and second molars were significantly deeper on the deviated side than on the non‐deviated side, and the anteroposterior OCs of the mandibular second premolar and first molar were also significantly shallower on the deviated side. In the no‐TMD group, however, there were no significant differences in OCs between deviated and non‐deviated sides. The differences between right and left lateral OCs in the mandibular second premolar and first and second molars, as well as the anteroposterior OCs in the mandibular first and second molars, showed significant correlations with mandibular deviation in the TMD group. On the other hand, in the no‐TMD group, there was no significant correlation between OCs and mandibular deviation. The above results suggest that OCs might try to compensate for mandibular deviation in patients with TMD.
Effect of non‐vital tooth bleaching on microleakage of coronal access restorations
Authors: Teixeira E. C. N. , Hara A. T. , Turssi C. P. , Serra M. C.
Published: October 2003

summary  This study evaluated the effect of non‐vital tooth bleaching on microleakage of composite resin/bovine tooth interface at different post‐bleaching times. A total of 320 teeth were cleaned. A pulp chamber access cavity was made at the lingual surface of each tooth. The teeth were randomly divided into four groups: SPH – sodium perborate + 30% hydrogen peroxide; SPW – sodium perborate + distilled water; CP–37% carbamide peroxide; and CON‐distilled water (control). The bleaching agents were replaced every 7 days, over 4 weeks. Following bleaching procedures, the groups were divided into four subgroups (n = 20), according to the post‐bleaching times: 0 (baseline), 7, 14 and 21 days. After that, the cavities were restored with an adhesive system (Single Bond; 3M Co., St Paul, MN, USA) and a composite resin (Z100/3M). The specimens were thermocycled, stained with 2% methylene blue solution (pH 7), and sectioned longitudinally. The teeth were evaluated blind and independently by three previously calibrated examiners, to provide representative scores. The data were submitted to Kruskal–Wallis and multiple comparison tests (α=0·05). At baseline and 7 days, the SPH group showed a higher degree of dye penetration than the CON (P=0·04). At 14 and 21 days, there were no differences among groups. The association of sodium perborate with 30% hydrogen peroxide or with water may affect the sealing ability of composite resin restorations performed up to 7 days after bleaching procedures.
Length of the occlusal glide during chewing in children with primary dentition
Authors: Hayasaki H. , Sawami T. , Saitoh I. , Iwase Y. , Nakata S. , Nakata M.
Published: October 2003

summary  Chewing is one of the most important functions of the mandible, but, to date, there are very few studies of this function in children. The purpose of this study was to quantify the length of the occlusal glide at the lower incisal point during gum chewing in children with primary dentition. Eleven girls with primary dentition were selected for this study. Mandibular excursions with occlusal contacts and gum chewing movement were measured using an optoelectronic system that can measure mandibular movement with six degrees‐of‐freedom at a sampling frequency of 100 Hz. A curved mesh diagram of incisor coordinates during mandibular excursions was established to calculate the length of the occlusal glide for each subject. The occlusal glide lengths of children were compared with previously reported results for adults. The estimated length of the occlusal glide during closing was significantly shorter in children than in adults, contrary to that during opening. This result suggests that children have a characteristic chewing pattern that differs from adults.
Correlation between maximum bite force and craniofacial morphology of young adults in Indonesia
Authors: Sondang P. , Kumagai H. , Tanaka E. , Ozaki H. , Nikawa H. , Tanne K. , Hamada T.
Published: October 2003

summary  The present study was conducted to evaluate the relationship between maximum bite force and craniofacial morphology. Sixty‐four Indonesian female dental students aged 19–27 years with normal occlusion served as the subjects. The Dental Prescale System® was used to measure the maximum bite force using a pressure sensitive sheets while craniofacial morphology measurements were determined from conventional lateral radiograms. The antero‐posterior and right–left position of the occlusal load centre (the OLC) were measured also. Stepwise multiple regression analysis was performed to evaluate the relationship between bite force and craniofacial morphology while correlation analysis was used to evaluate the antero‐posterior position of the OLC related to craniofacial morphology. Fifty‐five per cent of the bite force could be explained by variations in the posterior facial height, gonial angle, antero‐posterior size of the maxilla, and posterior length of the cranial base. The result showed a larger bite force implies a greater posterior facial height, smaller gonial angle, larger maxilla and straighter posterior length of the cranial base. This study suggests that among Indonesians, maximum bite force could be explained by craniofacial morphology as found in Caucasians. In addition, we proposed a clinical standard of the OLC for the comprehensive evaluation of occlusion.
Effect of fluorosis on dentine shear bond strength of a self‐etching bonding system
Authors: Banu Ermiş R. , Gokay N.
Published: October 2003

summary  The purpose of this study was to investigate the effect of dental fluorosis on shear bond strength of a composite material to dentine. Forty human premolar teeth were classified according to the severity of fluorosis using the Thylstrup and Fejerskov index and were divided into four groups (TFI scores of 0, 3, 4 and 5) of 10 teeth. Non‐fluorosed teeth (TFI score of 0) served as the control group. A self‐etching light‐cured bonding system, Clearfil SE Bond, and a micro‐hybrid light‐cured composite, Clearfil AP‐X were selected for the study. Buccal surfaces of mounted teeth were ground flat to expose the dentine. Composite cylinders, 4 mm diameter and 4 mm length, were bonded to the treated dentine surfaces. Shear bond strength was measured with an universal testing machine at a cross‐head speed of 0·5 mm min−1. After failure, the fracture surfaces were examined under a stereo microscope. The mean bond strength was 24·37 ± 3·54 MPa for non‐fluorosed teeth and varied between 22·72 ± 3·52 and 27·02 ± 5·91 MPa for fluorosed teeth. The difference between the mean values for bond strength was not statistically significant (P > 0·05). Adhesive mode of failure was most prevalent in non‐fluorosed teeth. It can be concluded that fluorosis does not affect the shear bond strength of composite material to human dentine.
Crown retention with use of different sealing systems on prepared dentine
Authors: Wolfart S. , Linnemann J. , Kern M.
Published: October 2003

summary  The purpose of this in vitro study was to evaluate crown retention after using different sealing systems on prepared dentine. Ca(OH)2 suspension was used in comparison with three adhesive bonding systems (Gluma Desensitizer, Optibond FL, Prompt L‐Pop). Extracted human premolars were uniformly prepared with the use of a special parallelometer (11° taper, 4 mm axial length). Groups of 20 teeth each were treated with each sealing system. Then crowns were fabricated and temporarily cemented twice. Finally the abutments were cleaned and the crowns were cemented with a glass–ionomer cement Ketac‐Cem. Subgroups of 10 crowns were removed with a universal testing machine following storage in distilled water either for 3 days or for 150 days. Prior to dislodging, the crowns of both groups were subjected to chewing simulation. The mean dislodgement stresses in MPa were between 4ḃ9 and 6ḃ9. A range test of Student–Newmann–Keuls revealed significant differences between Ca(OH)2 and Optibond FL (P < 0ḃ05), while the storage time had no significant effect. The level of microleakage increased significantly with storage time (P < 0ḃ05). It is concluded, that the use of Gluma Desensitizer and Prompt L‐Pop did not affect crown retention as compared with Ca(OH)2, thus may be used in combination with glass–ionomer cement to desensitize prepared teeth.
Pressure–pain threshold of oral mucosa and its region‐specific modulation by pre‐loading
Authors: Ogawa T. , Ogimoto T. , Sumiyoshi K. , Koyano K.
Published: October 2003

summary Once subjected to denture wearing, oral mucosa has to withstand mechanical loads of various levels and durations. However, how this load affects oral mucosal sensitivity is unknown. This study investigated the pressure–pain threshold (PPT) of oral mucosa with or without pre‐loading. An electric pressure algometer was developed specifically for measuring the PPT of oral mucosa. Measurements of 10 dentulous maxillae showed that the baseline PPT (BPPT) of the palatal site was 4·9‐ and 3·7‐fold greater than that of the labial or buccal sites, respectively. The PPT of the labial site decreased significantly compared with its BPPT after 2 s–100% BPPT and 5 s–100% BPPT pre‐loading. The PPT of the palatal site increased after 5 s–50% BPPT and 5 s–80% BPPT and 0·2 s–100% BPPT and 2 s–100% BPPT pre‐loading. The PPT of the buccal site did not change after all levels and durations of pre‐loadings tested. These results indicated the disproportionate modulation of oral mucosal PPT following various loads, suggesting that oral mucosa possesses region‐specific psychophysical tolerance to mechanical stimuli.
Influence of liquid temperature and flow rate on enamel erosion and surface softening
Authors: Eisenburger M. , Addy M.
Published: October 2003

summary  Enamel erosion and softening are based on chemical processes which could be influenced by many factors including temperature and acid flow rate. Knowledge of the influence of these variables could have relevance to research experiments and clinical outcomes. Both parameters were investigated using an ultrasonication and profilometry method to assess erosion depth and surface softening of enamel. The influence of temperature was studied by eroding polished human enamel samples at 4, 20, 35 or 50 °C for 2 h. Secondly, different liquid flow conditions were established by varying acid agitation. Additionally, a slow laminar flow and a jet of citric acid, to simulate drinking through a straw, were applied to specimens. Erosion depth increased significantly with acid temperature from 11·0 μm at 4 °C to 35·8 μm at 50 °C. Surface softening increased much more slowly and plateaued at 2·9 μm to 3·5 μm after 35 °C. A strong dependence of erosion on liquid flow was revealed. In unstirred conditions only 8·6 μm erosion occurred, which increased to 22·2 μm with slow stirring and 40·9 μm with fast stirring. Surface softening did not increase correspondingly with its largest extent at slow stirring at 3·4 μm.The implication of these data are: first, the conditions for erosion experiments in vitro or in situ need to be specified for reliable comparisons between studies. Secondly, erosion of teeth by soft drinks are likely to be influenced both by the temperature of the drink and individual drinking habits.
Association between condylar position, joint morphology and craniofacial morphology in orthodontic patients without temporomandibular joint disorders
Authors: Kikuchi K. , Takeuchi S. , Tanaka E. , Shibaguchi T. , Tanne K.
Published: October 2003

summary  The present study investigated condylar position and joint morphology in adolescent patients and elucidated the possible association between the joint structure and condylar position, and craniofacial morphology. Sixty‐five adolescent patients were selected as subjects and their tomograms and lateral cephalograms were analysed. No significant differences in joint spaces were found between the right and left temporomandibular joints. Both the condyles in this population were located slight anteriorly in the glenoid fossa. With respect to the association between condylar position, joint morphology and craniofacial morphology, the ramus plane angle also exhibited significant negative correlations with posterior, lateral and medial joint spaces. Furthermore, there was a significant negative correlation between the gonial angle and the anterior joint space. These findings imply that the condyle was likely to show more posterior position in the glenoid fossa when the mandible exhibited clockwise rotation. In conclusion, the condyle in the adolescent subjects showed a symmetrical anterior position relative to the glenoid fossa. In addition, the joint spaces and it ratios were significantly related to the craniofacial morphology associated with vertical dimension. It is suggested that the condylar position may be affected by craniofacial growth pattern.
Influence of number and position of flasks in the monomer release, Knoop hardness and porosity of a microwave‐cured acrylic resin
Authors: de Oliveira V. M. B. , Léon B. L. T. , Del Bel Cury A. A. , Consani S.
Published: October 2003

summary  Simultaneous irradiation of multiple flasks may have deleterious effects on the polymerization of microwave cured‐acrylic resins. This study evaluated the effect of the number and position of flasks in the monomer release, Knoop hardness and porosity of a microwave‐cured acrylic resin. Samples were made of Acron MC® (AMC, GC Dent. Ind. Corp.) processed at 500 W. The following associations of the number and position of the flasks were tested: one simple flask centrally placed on the turning plate (I, control); two flasks, one in the centre (IIa) and the other peripherally placed in the plate (IIb); two flasks centrally, one above (IIIa) and the other below (IIIb). The processing time varied according to the number of flasks: 3 or 4·5 min for one or two flasks, respectively. For monomer release, each specimen (n = 12) was put in an assay glass tube containing 6 mL of deionized water that was changed daily. Monomer levels were obtained by spectrophotometry at 206 nm. For hardness test (n = 10), 12 indentations were made in the surface of each specimen. Immersing the polished specimens in permanent ink and counting the porous in a stereo light microscope verified the porosity. Monomer release was significant before 24 h: GI = 263·1(153·3)a, GIIa = 236·9(180·2)a, GIIb = 441·5(446·2)a, GIIIa = 1216·6(857·9)b. Tukey test showed no statistically significant differences among the groups for porosity and hardness. Monomer release was affected by the position of the flask (P < 0·05).
Plasma treatment increased shear bond strength between heat cured acrylic resin and self‐curing acrylic resin
Authors: Nishigawa G. , Maruo Y. , Oka M. , Oki K. , Minagi S. , Okamoto M.
Published: October 2003

summary  Self‐curing acrylic resin is generally used for the repair of a fractured denture base. However, re‐fracture of the repaired denture base resin often occurs because of poor bonding strength between the base resin and self‐curing repair resin. The effect of plasma treatment on the shear bond strength between heat cured acrylic resin and the self‐cured acrylic was examined. It was revealed that plasma irradiation is effective in increasing the shear bond strength. Plasma irradiation does not cause environmental pollution, as it does not require chemicals. It is a useful method to increase adhesive strength between heat cured acrylic resin and self‐curing acrylic resin.
Report on the determination of occlusal vertical dimension and centric relation using swallowing in edentulous patients
Authors: Millet C. , Jeannin C. , Vincent B. , Malquarti G.
Published: October 2003

summary  When constructing a complete denture, the correct vertical dimension of occlusion (VDO) and centric relation (CR) can be difficult to determine. The aim of this study was to compare the swallowing technique used to determine the maxillomandibular relationship with a conventional technique. Fifteen edentulous patients were selected, each having a complete denture. The VDO and CR were assessed using acrylic base plates and a Boley gauge. First, the VDO was established by means of the vertical dimension of rest (VDR) and interocclusal rest space, and the CR was obtained by mandibular manipulation. Secondly, the VDO and the antero‐posterior mandibular position were determined using swallowing. All measurements were repeated three times and the average was calculated. The results showed that (i) the VDO determined by means of the swallowing method was reproducible and significantly higher than the one established from the VDR (P < 0·01), and (ii) the swallowing position was located 2 mm anterior to CR (P < 0·01) and was moderately reproducible. This study suggests that swallowing can be used to determine the vertical position but no as a reference position in the sagittal plane.
Characterisation of the response of equine digital arteries and veins to substance P
Authors: Katz L. M. , Marr C. M. , Elliott J.
Published: October 2003

Substance P (SP), a potent vasodilator, has been detected in equine digital sensory‐motor nerves. The aim of the study was to characterise the functional responses of equine digital blood vessels to exogenous SP. Pre‐constricted equine digital arteries (EDA) and veins (EDV) vasodilated in a biphasic, endothelium‐ and concentration‐dependent manner to SP. A nitric oxide (NO) synthase inhibitor Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME; 300 μm) inhibited both phases of the relaxation response curve of EDAs to SP by >70%. In EDVs, the first relaxant phase to SP was largely L‐NAME‐resistant, whereas the second phase was inhibited by 60%. Both L‐NAME and a cyclo‐oxygenase inhibitor (ibuprofen; 10 μm) were required to inhibit EDV relaxation to SP by ≥80%. Experiments determining the receptor mediated responses to physiological concentrations of SP (1 nm) revealed that the relaxant responses of both EDA and EDV were inhibited by a neurokinin‐1 (NK1) receptor antagonist (CP‐96 345; 10 nm). In conclusion, SP is an endothelium‐dependent vasodilator of both EDA and EDV. NO is the predominant pathway activated in EDA, whereas both prostacyclin and NO pathways are involved in EDVs. NK1receptors appear to mediate responses to low concentrations of SP.
Bioavailability and pharmacokinetics of florfenicol in broiler chickens
Authors: Shen J. , Hu D. , Wu X. , Coats J. R.
Published: October 2003

The bioavailability and pharmacokinetic disposition of florfenicol in broiler chickens were investigated after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 15 and 30 mg/kg body weight (b.w.). Plasma concentrations of florfenicol were determined by a high performance liquid chromatographic method in which plasma samples were spiked with chloramphenicol as internal standard. Plasma concentration–time data after i.v. administration were best described by a two‐compartment open model. The elimination half‐lives were 168 ± 43 and 181 ± 71 min, total body clearance 1.02 ± 0.17 and 1.02 ± 0.16 L·kg/h, the volume of distribution at steady‐state 4.99 ± 1.11 and 3.50 ± 1.01 L/kg after i.v. injections of 15 and 30 mg/kg b.w., respectively. Plasma concentration–time data after i.m. and oral administrations were adequately described by a one‐compartment model. The i.m. bioavailability and the oral bioavailability of florfenicol were 95, 98 and 96, 94%, respectively, indicating that florfenicol was almost absorbed completely after i.m. and oral administrations of 15 and 30 mg/kg b.w.
Disposition of cyclosporine after intravenous and multi‐dose oral administration in cats
Authors: Mehl M. L. , Kyles A. E. , Craigmill A. L. , Epstein S. , Gregory C. R.
Published: October 2003

The aim of this study was to evaluate the disposition of cyclosporine after intravenous (i.v.) and oral administration and to evaluate single sampling times for therapeutic monitoring of cyclosporine drug concentrations in cats. Six adult male cats (clinically intact) were used. Two treatments consisting of a single i.v. cyclosporine (1 mg/kg) and multiple oral cyclosporine (3 mg/kg b.i.d p.o. for 2 weeks) doses. Whole blood cyclosporine concentrations were measured at fixed times by high performance liquid chromatography and pharmacokinetic values were calculated. Mean values for the i.v. data includedAUC(7413 ng/mL·h),t1/2distribution and elimination (0.705 and 9.7 h, respectively),Cmax(1513 ng/mL), andVd(ss)(1.71 L/kg). Mean values for the oral data includedAUC(6243 ng/mL·h),t1/2of absorption and elimination (0.227 and 8.19 h, respectively), andCmax(480.0 ng/mL). Bioavailability of orally administered cyclosporine was 29 and 25% on days 7 and 14 respectively. Whole blood comment cyclosporine concentration 2 h after administration (C2) better correlated withAUCon days 7 and 14 than trough plasma concentration (C12). The rate of oral cyclosporine absorption was less than expected and there was substantial individual variation. Therapeutic drug monitoring strategies for cyclosporine in cats should be re‐evaluated.
Effects of different propofol infusion rates on EEG activity and AEP responses in rats
Authors: Antunes L. M. , Roughan J. V. , Flecknell P. A.
Published: October 2003

Parameters calculated from the auditory‐evoked potential (AEP) recorded over the auditory cortex and from the electroencephalogram (EEG) recorded over the near vertex were compared in rats at three different infusion rates of propofol (62.5, 35 and 25 mg/kg/h). Depth of anaesthesia was assessed clinically using the strength of the pedal withdrawal reflex. Well‐defined AEP responses were consistently obtained. As the propofol concentration was reduced, peak latencies decreased and peak to peak amplitudes increased. Amplitude and latency values were closely associated with the strength of the pedal withdrawal responses. Parameters calculated from the EEG showed no significant change as the propofol concentration was reduced. Periods of burst suppression became more frequent as the propofol infusion rate was increased. The study showed some of the difficulties that may be encountered when using EEG as a tool to assess depth of anaesthesia during propofol infusion. The AEP showed dose dependent changes in rats at different infusion rates of propofol. However, large variability between animals limits the use of this technique for monitoring depth of anaesthesia.
Modification of spontaneous contractility of smooth muscle preparations from the bovine abomasal antrum by serotonin receptor agonists
Authors: Spring C. , Mevissen M. , Reist M. , Zulauf M. , Steiner A.
Published: October 2003

The effects of serotonin (5‐hydroxytryptamine, 5‐HT), a 5‐HT2‐receptor agonist,α‐methyl‐5‐hydroxytryptamine (α‐M‐5‐HT) and RS‐67506, a 5‐HT4receptor partial agonist, on spontaneous contractility of bovine abomasal smooth muscle preparations were investigatedin vitro. Preparations from the abomasal antrum of freshly slaughtered healthy dairy cows were cut parallel to the longitudinal fibres, suspended in isolated organ baths, and concentration–response curves were performed by cumulative application of the 5‐HT receptor agonists. Blockade of 5‐HT2‐induced response was tested with atropine and hexamethonium. Serotonin evoked a significant increase in the area under curve (AUC), whilst the 5‐HT2receptor agonistα‐M‐5‐HT significantly increased theAUCand resting tone (RT). RS‐67506 induced a significant increase inAUCand RT and a significant decrease in the maximum force. The effect ofα‐M‐5‐HT was mediated by a muscarinic cholinergic pathway, as the effect ofα‐M‐5‐HT was inhibited in the presence of atropine but not hexamethonium. It is concluded that 5‐HT2and 5‐HT4receptors are present in the bovine abomasal antrum. Muscarinic receptors are involved in the increase in RT seen after 5‐HT2receptor stimulation.
Investigation on the efficacy of meloxicam in sows with mastitis–metritis–agalactia syndrome
Authors: Hirsch A. C. , Philipp H. , Kleemann R.
Published: October 2003

The efficacy of meloxicam in the treatment of sows with mastitis–metritis–agalactia syndrome was investigated in comparison with flunixin. Basic therapy comprised administration of an antibiotic and oxytocin. A total of 200 sows and litters were examined in a double‐blind clinical study with observations up to 8 days after the first treatment. The primary parameter, the clinical index score on day 2, consisting of rectal temperature, feed intake, general demeanour, respiratory rate, vaginal discharge, degree of inflammation of mammary glands, milk flow and nursing behaviour, revealed a significant (P ≤ 0.05) non‐inferiority of meloxicam in comparison with flunixin implying equal efficacy of both drugs. No significant differences were noted in the distribution of clinical efficacy scores within both groups at each day of examination. The differences in litter weight and daily weight gain per piglet were not significant between the two test groups. The mortality rates until day 8 of the study were without significant difference between groups. In piglets of diseased litters, however, the mortality rate was 50% lower in the meloxicam group in comparison with the reference group, this difference reaching statistical significance (P ≤ 0.05).
Emerging therapeutic agents for transmissible spongiform encephalopathies: a review
Authors: Koster T. , Singh K. , Zimmermann M. , Gruys E.
Published: October 2003

Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders associated with misfolding of prion protein, from PrPC to PrPSc. Different types of experimental studies have resulted in a better understanding of the pathogenesis of the prion diseases. Genetic and molecular properties of PrP isoforms have been explained but the conformational conversion of the PrPC isoform to the PrPSc isoform has not yet been entirely elucidated. However, a number of possible therapeutic agents have been tried and some have proven to be effective against TSEs but most have limitations in terms of toxicity and pharmacokinetics. Congo red (CR), anthracyclines, and polyanionic dextran sulfate have limited ability to cross the blood–brain barrier and may be toxic. The efficacy of polyene antibiotics seems to be restricted to certain scrapie strains. Tetrapyrroles and tetracyclines with low toxicities and favorable pharmacokinetics could be useful in preventing PrPSc accumulation. Compounds like branched polyamines, Cp‐60, analogs of CR, quinacrine and chlorpromazine, β‐sheet breaker peptides and inhibitory peptides, active immunization using recombinant PrP and passive immunization with anti‐PrP antibodies, have potential use as therapeutic agents but would need further research and clinical trials.
The comparative serum disposition kinetics of subcutaneous administration of doramectin, ivermectin and moxidectin in the Australian Merino sheep
Authors: Barber S. , Bowles V. , Lespine A. , Alvinerie M.
Published: October 2003

This study evaluates the comparative serum disposition kinetics of injectable formulations of doramectin (DRM), ivermectin (IVM) and moxidectin (MXD) in Australian Merino sheep. Thirty‐six, 2‐year‐old sheep were allocated by weight into six groups of six animals. Animals in each group received 200 μg/kg of DRM, MXD, IVM or a combination of two of these drugs by subcutaneous (s.c.) injection. Blood was collected at designated intervals (between 1 h and 40 days after treatment) and the serum analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that MXD administration produced a significantly higher maximum serum concentration and a more rapid absorption as compared with DRM and IVM. MXD and DRM had a significantly larger area under the concentration vs. time curve (AUC) than IVM, suggesting a more persistent effect for the former two products in sheep. The AUC for DRM was significantly higher when administered alone as compared with that observed when given in combination with MXD or IVM, suggesting preferential elimination of DRM compared with IVM and MXD from concurrent s.c. administration.
Possible therapeutic benefits of adenosine‐potentiating drugs in reducing age‐related degenerative disease in dogs and cats
Authors: Scaramuzzi R. J. , Baker D. J.
Published: October 2003

Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co‐factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re‐cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine‐potentiating drugs in the treatment of age‐related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age.
Increased high‐affinity phosphodiesterase PDE2 gene expression in germ tubes counteracts CAP1‐dependent synthesis of cyclic AMP, limits hypha production and promotes virulence of Candida albicans
Authors: Bahn Yong‐Sun , Staab Janet , Sundstrom Paula
Published: October 2003

Frequent interconversion between yeasts, pseudohyphae and true hyphae is a hallmark of Candida albicans growth in mammalian tissues. The requirement for transient CAP1‐dependent pulses of cAMP for generating true hyphae, Hwp1 and virulence raises questions about the role of yeast and pseudohyphal forms in the pathogenesis of candidiasis. In this study, hyperfilamentous mutants, limited in their capacity to produce buds, were generated by disrupting the high‐affinity phosphodiesterase gene PDE2. Degradation of cAMP by the PDE2 gene product was confirmed by higher basal cAMP levels in the pde2/pde2 mutant and by accumulation of cAMP to levels permitting germ tube formation upon disrupting PDE2 in the cap1/cap1 mutant. Similar phenotypes of the C. albicans and Saccharomyces cerevisiae pde2/pde2 mutants were found, including sensitivity to nutritional starvation and exogenous cAMP and defective entry into stationary phase. Importantly, the hyperfilamentous mutants were as avirulent as hypofilamentous mutants in a systemic model of candidiasis. Growth in a multiplicity of forms appears to be a virulence attribute that is controlled by tight coupling of cAMP synthesis and degradation. Delayed increases in PDE2 mRNA in cAMP‐deficient cap1/cap1 mutants during germ tube‐inducing conditions suggested a mechanism of control involving cAMP‐dependent induction of PDE2 mRNA.
Recipient‐induced transfer of the symbiotic plasmid pRL1JI in Rhizobium leguminosarum bv. viciae is regulated by a quorum‐sensing relay
Authors: Danino Vittoria E. , Wilkinson Adam , Edwards Anne , Downie J. Allan
Published: October 2003

Analysis of the regulation of plasmid transfer genes on the symbiotic plasmid pRL1JI in Rhizobium leguminosarum bv. viciae has revealed a novel regulatory relay that is specifically poised to detect an N‐acyl‐homoserine lactone (AHL) made by different cells (potential recipients of pRL1JI). Adjacent to the traI‐trbBCDEJKLFGHI plasmid transfer operon on pRL1JI are two regulatory genes, bisR and traR, which encode LuxR‐type quorum‐sensing regulators required for conjugation. Potential recipients of pRL1JI induce the traI‐trb operon and plasmid transfer via a quorum‐sensing relay involving BisR, TraR and the traI‐trb operon in donor cells. BisR induces expression of traR in response to N‐(3‐hydroxy‐7‐cis‐tetradecenoyl)‐l‐homoserine lactone (3‐OH‐C14:1‐HSL), which is produced by CinI in potential recipient strains. In donor strains (carrying pRL1JI), BisR represses the expression of the chromosomal gene cinI; this repression results in a very low level of formation of 3‐OH‐C14:1‐HSL and hence relatively low levels of expression of traR and the traI‐trb operon in strains carrying pRL1JI. However, if 3‐OH‐C14:1‐HSL from potential recipients is present, then traR and plasmid transfer are induced. The induction of traR occurs at very low concentrations of 3‐OH‐C14:1‐HSL (around 1 nm). TraR then induces the traI‐trb operon in a quorum‐sensing dependent manner in re‐sponse to the TraI‐made AHLs, N‐(3‐oxo‐octanoyl)‐l‐homoserine lactone and N‐(octanoyl)‐l‐homoserine lactone. The resulting autoinduction results in high levels of expression of the traI‐trb operon. Premature expression of the traI‐trb operon is reduced by TraM, which probably titres out TraR preventing expression of traI when there are low levels of traR expression. Expression of traR in stationary phase cells is limited by feedback inhibition mediated by TraI‐made AHLs.
Structural aspects of DNA repair: the role of restricted diffusion
Authors: Minsky Abraham
Published: October 2003

DNA repair and protection processes impose arduous demands upon cellular systems. The high‐fidelity recombinational repair pathway entails a rapid genome‐wide search for sequence homology. The efficiency of this transaction is intriguing in light of the uniquely adverse diffusion traits of the involved species. DNA protection in cells exposed to continuous stress or prolonged starvation is equally enigmatic, because the ability of such cells to deploy energy‐dependent enzymatic repair processes is hampered as a result of progressive perturbation of the intracellular energy balance. DNA repair in radio‐resistant bacteria, which involves accurate chromosome reconstruction from multiple fragments, is similarly associated with apparently insurmountable logistical obstacles. The studies reviewed here imply that the mechanisms deployed to overcome these intrinsic hurdles have a basic common denominator. In all these cases, condensed and ordered chromatin assemblies are formed, within which molecular diffusion is restricted and confined. Restricted diffusion thus appears as a general strategy that is exploited by nature to facilitate homologous search, to promote energy‐independent DNA protection through physical DNA sequestration and attenuated accessibility to damaging agents, and to enable error‐free repair of multiple double‐strand DNA breaks.
Host collagen signal induces antigen I/II adhesin and invasin gene expression in oral Streptococcus gordonii
Authors: Heddle Catherine , Nobbs Angela H. , Jakubovics Nicholas S. , Gal Micaela , Mansell Jason P. , Dymock David , Jenkinson Howard F.
Published: October 2003

Microbial interactions with host molecules, and programmed responses to host environmental stimuli, are critical for colonization and initiation of pathogenesis. Bacteria of the genus Streptococcus are primary colonizers of the human mouth. They express multiple cell‐surface adhesins that bind salivary components and other oral bacteria and enable the development of polymicrobial biofilms associated with tooth decay and periodontal disease. However, the mechanisms by which streptococci invade dentine to infect the tooth pulp and periapical tissues are poorly understood. Here we show that production of the antigen I/II (AgI/II) family polypeptide adhesin and invasin SspA in Streptococcus gordonii is specifically upregulated in response to a collagen type I signal, minimally the tri‐peptide Gly‐Pro‐Xaa (where Xaa is hydroxyproline or alanine). Increased AgI/II polypeptide expression promotes bacterial adhesion and extended growth of streptococcal cell chains along collagen type I fibrils that are characteristically found within dentinal tubules. These observations define a new model of host matrix signal‐induced tissue penetration by bacteria and open the way for novel therapy opportunities for oral invasive diseases.
Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs
Authors: Singh Ramandeep , Rao Vivek , Shakila H. , Gupta Radhika , Khera Aparna , Dhar Neeraj , Singh Amit , Koul Anil , Singh Yogendra , Naseema M. , Narayanan P. R. , Paramasivan C. N. , Ramanathan V. D. , Tyagi Anil K.
Published: October 2003

Protein tyrosine kinases and tyrosine phosphatases from several bacterial pathogens have been shown to act as virulence factors by modulating the phosphorylation and dephosphorylation of host proteins. The identification and characterization of two tyrosine phosphatases namely MptpA and MptpB from Mycobacterium tuberculosis has been reported earlier. MptpB is secreted by M. tuberculosis into extracellular mileu and exhibits a pH optimum of 5.6, similar to the pH of the lysosomal compartment of the cell. To determine the role of MptpB in the pathogenesis of M. tuberculosis, we constructed a mptpB mutant strain by homologous recombination and compared the ability of parent and the mutant strain to survive intracellularly. We show that disruption of the mptpB gene impairs the ability of the mutant strain to survive in activated macrophages and guinea pigs but not in resting macrophages suggesting the importance of its role in the host–pathogen interaction. Infection of guinea pigs with the mutant strain resulted in a 70‐fold reduction in the bacillary load of spleens in infected animals as compared with the bacillary load in animals infected with the parental strain. Upon reintroduction of the mptpB gene into the mutant strain, the complemented strain was able to establish infection and survive in guinea pigs at rates comparable to the parental strain. These observations demonstrate a   role   of MptpB in the pathogenesis   of M. tuberculosis.
ComX is a unique link between multiple quorum sensing outputs and competence in Streptococcus pneumoniae
Authors: Luo Ping , Li Haiying , Morrison Donald A.
Published: October 2003

Natural competence for genetic transformation in Streptococcus pneumoniae is achieved directly by specific proteins that are involved in DNA uptake and chromosomal recombination, and is regulated indirectly by a quorum‐sensing system encoded by two loci, comAB and comCDE. The alternative sigma factor, ComX, is thought to be the unique link between quorum sensing and competence‐specific genes. To test this hypothesis, we replaced the quorum‐sensing inducible promoter (PQ) of the comX gene with either a constitutive promoter (PC) or a raffinose‐inducible promoter (PR), so that comX transcription would be independent of quorum sensing. Surprisingly, both competence and expression of late genes, such as ssbB, cglA or celB, were found to depend on CSP in these mutants. An unknown, CSP‐dependent regulator was needed when comX was expressed from these ectopic promoters, and it appears to act post‐transcriptionally. However, when a multicopy nisin‐inducible ComX‐overexpressing plasmid was introduced, pneumococcal cells developed competence in the presence of nisin even despite deletion of comE. At 1% of the normal protein peak level, ComX protein stimulated competence without the participation of the pheromone response circuit. Thus, ComX is a unique link to competence‐specific genes, but depends on multiple outputs of quorum sensing for maximal expression.
Cell cycle‐ and age‐dependent activation of Sod1p drives the formation of stress resistant cell subpopulations within clonal yeast cultures
Authors: Sumner Edward R. , Avery Angela M. , Houghton John E. , Robins R. Adrian , Avery Simon V.
Published: October 2003

Phenotypic heterogeneity describes non‐genetic variation that exists between individual cells within isogenic populations. The basis for such heterogeneity is not well understood, but it is evident in a wide range of cellular functions and phenotypes and may be fundamental to the fitness of microorganisms. Here we use a suite of novel assays applied to yeast, to provide an explanation for the classic example of heterogeneous resistance to stress (copper). Cell cycle stage and replicative cell age, but not mitochondrial content, were found to be principal parameters underpinning differential Cu resistance: cell cycle‐synchronized cells had relatively uniform Cu resistances, and replicative cell‐age profiles differed markedly in sorted Cu‐resistant and Cu‐sensitive subpopulations. From a range of potential Cu‐sensitive mutants, cup1Δ cells lacking Cu‐metallothionein, and particularly sod1Δ cells lacking Cu, Zn‐superoxide dismutase, exhibited diminished heterogeneity. Furthermore, age‐dependent Cu resistance was largely abolished in cup1Δ and sod1Δ cells, whereas cell cycle‐dependent Cu resistance was suppressed in sod1Δ cells. Sod1p activity oscillated ∼fivefold during the cell cycle, with peak activity coinciding with peak Cu‐resistance. Thus, phenotypic heterogeneity in copper resistance is not stochastic but is driven by the progression of individual cells through the cell cycle and ageing, and is primarily dependent on only Sod1p, out of several gene products that can influence the averaged phenotype. We propose that such heterogeneity provides an important insurance mechanism for organisms; creating subpopulations that are pre‐equipped for varied activities as needs may arise (e.g. when faced with stress), but without the permanent metabolic costs of constitutive expression.
Targeting of two signal transduction pathways to different regions of the bacterial cell
Authors: Wadhams G. H. , Warren A. V. , Martin A. C. , Armitage J. P.
Published: October 2003

Components of bacterial chemosensory pathways which sense via transmembrane receptors have been shown to localize to the cell poles. Many species, however, have operons encoding multiple putative chemosensory pathways, some including putative cytoplasmic receptors. In‐genome fusions to single or multiple genes encoding components of two chemosensory pathways in Rhodobacter sphaeroides, cheOp2 and cheOp3, revealed that while sensory transducing proteins associated with transmembrane receptors and encoded on cheOp2 were targeted to the cell poles, the proteins associated with putative cytoplasmic receptors and encoded on cheOp3 were all targeted to a cytoplasmic cluster. No proteins were localized to both sites. These data show that bacteria target components of related pathways to different sites in the cell, presumably preventing direct cross‐talk between the different pathways, but allowing a balanced response between extracellular and cytoplasmic signals. It also indicates that there is intracellular organization in bacterial cells, with specific proteins targeted and localized to cytoplasmic regions.
Molecular characterization of thymidine kinase from Ureaplasma urealyticum: nucleoside analogues as potent inhibitors of mycoplasma growth
Authors: Carnrot Cecilia , Wehelie Rahma , Eriksson Staffan , Bölske Göran , Wang Liya
Published: October 2003

Ureaplasma urealyticum (U. urealyticum), belonging to the class Mollicutes, is a human pathogen colonizing the urogenital tract and causes among other things respiratory diseases in premature infants. We have studied the salvage of pyrimidine deoxynucleosides in U. urealyticum and cloned a key salvage enzyme, thymidine kinase (TK) from U. urealyticum. Recombinant Uu‐TK was expressed in E. coli, purified and characterized with regards to substrate specificity and feedback inhibition. Uu‐TK efficiently phosphorylated thymidine (dThd) and deoxyuridine (dUrd) as well as a number of pyrimidine nucleoside analogues. All natural ribonucleoside/deoxyribonucleoside triphosphates, except dTTP, served as phosphate donors, while dTTP was a feedback inhibitor. The level of Uu‐TK activity in U. urealyticum extracts increased upon addition of dUrd to the growth medium. Fluoropyrimidine nucleosides inhibited U. urealyticum and M. pneumoniae growth and this inhibitory effect could be reversed by addition of dThd, dUrd or deoxytetrahydrouridine to the growth medium. Thus, the mechanism of inhibition was most likely the depletion of dTTP, either via a blocked thymidine kinase reaction and/or thymidylate synthesis step and these metabolic reactions should be suitable targets for antimycoplasma chemotherapy.
CotB is essential for complete activation of green light‐induced genes during complementary chromatic adaptation in Fremyella diplosiphon
Authors: Balabas Barbara E. , Montgomery Beronda L. , Ong Laura E. , Kehoe David M.
Published: October 2003

The dramatic modifications of photosynthetic light harvesting antennae called phycobilisomes that occur during complementary chromatic adaptation in cyanobacteria are controlled by two separate photosensory systems. The first system involves the signal transduction components RcaE, RcaF and RcaC, which appear to make up a complex multistep phosphorelay. This system controls the light responsive expression of the cpcB2A2H2I2D2, cpeBA and cpeCDE operons, which encode phycobilisome proteins. The second system, which is not yet characterized, acts in concert with the first but only regulates the light responses of cpeBA and cpeCDE. We have generated and characterized a new mutant class, named the Tan mutants. In at least one member of this class, light‐regulated RNA accumulation patterns are altered for cpeBA and cpeCDE, but not for cpcB2A2H2I2D2. Thus this mutant contains a lesion that may impair the operation of the second system. We demonstrate that several Tan mutants are the result of improper expression of the gene cotB. CotB has limited similarity to lyase class proteins, particularly those related to NblB, which is required for degradation of phycobilisomes in other cyanobacteria. Possible roles of CotB in the biogenesis of phycobilisomes are discussed.