bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordinated patterns of cytochrome bd and lactate dehydrogenase expression in Bacillus subtilis
Authors: Larsson Jonas T. , Rogstam Annika , von Wachenfeldt Claes
Published: October 2005

A variety of pathways for electron and carbon flow in the soil bacterium Bacillus subtilis are differentially expressed depending on whether oxygen is present in the cell environment. This study characterizes the regulation of the respiratory oxidase cytochrome bd and the NADH-linked fermentative lactate dehydrogenase (LDH). Transcription of the cydABCD operon, encoding cytochrome bd, is highly regulated and only becomes activated at low oxygen availability. This induction is not dependent on the gene encoding the redox regulator Fnr or the genes encoding the ResDE two-component regulatory system. The DNA-binding protein YdiH was found to be a principal regulator that controls cydABCD expression. Transcription from the cyd promoter is stimulated 15-fold by a region located upstream of the core promoter. The upstream region may constitute a binding site for an unidentified transcription activator that is likely to influence the level of transcription but not its timing, which is negatively controlled by YdiH. This report provides evidence that YdiH also functions as a repressor of the ldh gene encoding LDH and of a gene, ywcJ, which encodes a putative formate-nitrite transporter. Based on the similarity between YdiH and the Rex protein of Streptomyces coelicolor, it is proposed that YdiH serves as a redox sensor, the activity of which is regulated by cellular differences in the free levels of NAD+ and NADH. It is suggested that ydiH be renamed as rex.
Intact molecular characterization of cord factor (trehalose 6,6′-dimycolate) from nine species of mycobacteria by MALDI-TOF mass spectrometry
Authors: Fujita Yukiko , Naka Takashi , McNeil Michael R. , Yano Ikuya
Published: October 2005

Cord factor (trehalose 6,6′-dimycolate, TDM) is an unique glycolipid with a trehalose and two molecules of mycolic acids in the mycobacterial cell envelope. Since TDM consists of two molecules of very long branched-chain 3-hydroxy fatty acids, the molecular mass ranges widely and in a complex manner. To characterize the molecular structure of TDM precisely and simply, an attempt was made to determine the mycolic acid subclasses of TDM and the molecular species composition of intact TDM by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for the first time. The results showed that less than 1 μg mycolic acid methyl ester of TDM from nine representative species of mycobacteria and TDM from the same species was sufficient to obtain well-resolved mass spectra composed of pseudomolecular ions [M+Na]+. Although the mass ion distribution was extremely diverse, the molecular species of each TDM was identified clearly by constructing a molecular ion matrix consisting of the combination of two molecules of mycolic acids. The results showed a marked difference in the molecular structure of TDM among mycobacterial species and subspecies. TDM from Mycobacterium tuberculosis (H37Rv and Aoyama B) showed a distinctive mass pattern and consisted of over 60 molecular ions with α-, methoxy- and ketomycolate. TDM from Mycobacterium bovis BCG Tokyo 172 similarly showed over 35 molecular ions, but that from M. bovis BCG Connaught showed simpler molecular ion clusters consisting of less than 35 molecular species due to a complete lack of methoxymycolate. Mass ions due to TDM from M. bovis BCG Connaught and Mycobacterium kansasii showed a biphasic distribution, but the two major peaks of TDM from M. kansasii were shifted up two or three carbon units higher compared with M. bovis BCG Connaught. Within the rapid grower group, in TDM consisting of α-, keto- and wax ester mycolate from Mycobacterium phlei and Mycobacterium flavescens, the mass ion distribution due to polar mycolates was shifted lower than that from the Mycobacterium avium–intracellulare group. Since the physico-chemical properties and antigenic structure of mycolic acid of TDM affect the host immune responses profoundly, the molecular characterization of TDM by MALDI-TOF mass analysis may give very useful information on the relationship of glycolipid structure to its biological activity.
Combining microarray and genomic data to predict DNA binding motifs
Authors: Mao Linyong , Mackenzie Chris , Roh Jung H. , Eraso Jesus M. , Kaplan Samuel , Resat Haluk
Published: October 2005

The ability to detect regulatory elements within genome sequences is important in understanding how gene expression is controlled in biological systems. In this work, microarray data analysis is combined with genome sequence analysis to predict DNA sequences in the photosynthetic bacteriumRhodobacter sphaeroidesthat bind the regulators PrrA, PpsR and FnrL. These predictions were made by using hierarchical clustering to detect genes that share similar expression patterns. The DNA sequences upstream of these genes were then searched for possible transcription factor recognition motifs that may be involved in their co-regulation. The approach used promises to be widely applicable for the prediction ofcis-acting DNA binding elements. Using this method the authors were independently able to detect and extend the previously described consensus sequences that have been suggested to bind FnrL and PpsR. In addition, sequences that may be recognized by the global regulator PrrA were predicted. The results support the earlier suggestions that the DNA binding sequence of PrrA may have a variable-sized gap between its conserved block elements. Using the predicted DNA binding sequences, a whole-genome-scale analysis was performed to determine the relative importance of the interplay between the three regulators PpsR, FnrL and PrrA. Results of this analysis showed that, compared to the regulation by PpsR and FnrL, a much larger number of genes are candidates to be regulated by PrrA. The study demonstrates by example that integration of multiple data types can be a powerful approach for inferring transcriptional regulatory patterns in microbial systems, and it allowed the detection of photosynthesis-related regulatory patterns inR. sphaeroides.
Intragenomic recombination in the highly leukotoxic JP2 clone of Actinobacillus actinomycetemcomitans
Authors: Eriksen Kirsten T. , Haubek Dorte , Poulsen Knud
Published: October 2005

The highly leukotoxic JP2 clone of Actinobacillus actinomycetemcomitans is strongly associated with aggressive periodontitis in adolescents of African descent. DNA fingerprinting using the frequently cutting restriction enzyme MspI and multilocus sequence typing (MLST) showed that five strains of this clone were genetically virtually identical, although ribotyping of the six rrn genes and EcoRI RFLP analysis of the seven IS150-like elements revealed differences. PCR analyses demonstrated that these multi-copy sequences are subject to intragenomic homologous recombination, resulting in translocations or large inversions. The genome rearrangements were reflected in differences among 25 strains representing the JP2 clone in DNA fingerprinting using the rare-cutting restriction enzyme XhoI and resolved by PFGE. XhoI DNA fingerprinting provides a tool for studying local epidemiology, including transmission of this particularly pathogenic clone of A. actinomycetemcomitans.
Phosphate flow in the chemotactic response system of Helicobacter pylori
Authors: Jiménez-Pearson María-Antonieta , Delany Isabel , Scarlato Vincenzo , Beier Dagmar
Published: October 2005

It is well established that motility is an essential virulence trait of the human gastric pathogenHelicobacter pylori. Accordingly, chemotaxis contributes to the ability ofH. pylorito colonize animal infection models. Chemotactic signal transduction inH. pyloridiffers from the enterobacterial paradigm in several respects. In addition to a separate CheY response regulator protein (CheY1),H. pyloricontains a CheY-like receiver domain (CheY2) which is C-terminally fused to the histidine kinase CheA. Furthermore, the genome ofH. pyloriencodes three CheV proteins consisting of an N-terminal CheW-like domain and a C-terminal receiver domain, while there are no orthologues of the chemotaxis genescheB,cheRandcheZ. To obtain insight into the mechanisms controlling the chemotactic response ofH. pylori, we investigated the phosphotransfer reactions between the purified two-component signalling modulesin vitro. We demonstrate that both CheY1 and CheY2 are phosphorylated by CheA∼P and that the three CheV proteins mediate the dephosphorylation of CheA∼P, but with a clearly reduced efficiency as compared to CheY1 and CheY2. Furthermore, our data indicate retrophosphorylation of CheAY2 by CheY1∼P, suggesting a role of CheY2 as a phosphate sink to modulate the half-life of CheY1∼P.
Tol-Pal proteins are critical cell envelope components of Erwinia chrysanthemi affecting cell morphology and virulence
Authors: Dubuisson Jean-François , Vianney Anne , Hugouvieux-Cotte-Pattat Nicole , Lazzaroni Jean Claude
Published: October 2005

Thetol-palgenes are necessary for maintaining the outer-membrane integrity of Gram-negative bacteria. These genes were first described inEscherichia coli, and more recently in several other species. They are involved in the pathogenesis ofE. coli,Haemophilus ducreyi,Vibrio choleraeandSalmonella enterica. The role of thetol-palgenes in bacterial pathogenesis was investigated in the phytopathogenic enterobacteriumErwinia chrysanthemi, assuming that this organism might be a good model for such a study. The wholeEr. chrysanthemi tol-palregion was characterized. Tol-Pal proteins, except TolA, showed high identity scores with theirE. colihomologues.Er. chrysanthemimutants were constructed by introducing auidA–kan cassette in theybgC,tolQ,tolA,tolB,palandybgFgenes. All the mutants were hypersensitive to bile salts. Mutations intolQ,tolA,tolBandpalwere deleterious for the bacteria, which required high concentrations of sugars or osmoprotectants for their viability. Consistent with this observation, they were greatly impaired in their cell morphology and division, which was evidenced by observations of cell filaments, spherical forms, membrane blebbing and mislocalized bacterial septa. Moreover,tol-palmutants showed a reduced virulence in a potato tuber model and on chicory leaves. This could be explained by a combination of impaired phenotypes in thetol-palmutants, such as reduced growth and motility and a decreased production of pectate lyases, the major virulence factor ofEr. chrysanthemi.
A family of promoter probe vectors incorporating autofluorescent and chromogenic reporter proteins for studying gene expression in Gram-negative bacteria
Authors: Karunakaran R. , Mauchline T. H. , Hosie A. H. F. , Poole P. S.
Published: October 2005

A series of promoter probe vectors for use in Gram-negative bacteria has been made in two broad-host-range vectors, pOT (pBBR replicon) and pJP2 (incP replicon). Reporter fusions can be made togfpUV,gfpmut3.1, unstablegfpmut3.1variants (LAA, LVA, AAV and ASV),gfp+,dsRed2,dsRedT.3,dsRedT.4,mRFP1,gusAorlacZ. The two vector families, pOT and pJP2, are compatible with one another and share the same polylinker for facile interchange of promoter regions. Vectors based on pJP2 have the advantage of being ultra-stable in the environment due to the presence of theparABCDEgenes. As a confirmation of their usefulness, the dicarboxylic acid transport system promoter (dctAp) was cloned into a pOT (pRU1097)- and a pJP2 (pRU1156)-based vector and shown to be expressed byRhizobium leguminosarumin infection threads of vetch. This indicates the presence of dicarboxylates at the earliest stages of nodule formation.
Functional analysis of the phospholipase C gene CaPLC1 and two unusual phospholipase C genes, CaPLC2 and CaPLC3, of Candida albicans
Authors: Kunze Donika , Melzer Inga , Bennett Désirée , Sanglard Dominique , MacCallum Donna , Nörskau Jan , Coleman David C. , Odds Frank C. , Schäfer Wilhelm , Hube Bernhard
Published: October 2005

Phospholipases C are known to be important regulators of cellular processes but may also act as virulence factors of pathogenic microbes. At least three genes in the genome of the human-pathogenic fungusCandida albicansencode phospholipases with conserved phospholipase C (Plc) motifs. None of the deduced protein sequences contain N-terminal signal peptides, suggesting that these phospholipases are not secreted. In contrast to its orthologue inSacharomyces cerevisiae,CaPLC1seems to be an essential gene. However, a conditional mutant with reduced transcript levels ofCaPLC1had phenotypes similar to Plc1p-deficient mutants inS. cerevisiae, including reduced growth on media causing increased osmotic stress, on media with a non-glucose carbon source, or at elevated or lower temperatures, suggesting that CaPlc1p, like the Plc1p counterpart inS. cerevisiae, may be involved in multiple cellular processes. Furthermore, phenotypic screening of the heterozygous ΔCaplc1/CaPLC1mutant showed additional defects in hyphal formation. The loss ofCaPLC1cannot be compensated by two additionalPLCgenes ofC. albicans(CaPLC2andCaPLC3) encoding two almost identical phospholipases C with no counterpart inS. cerevisiaebut containing structural elements found in bacterial phospholipases C. Although the promoter sequences ofCaPLC2andCaPLC3differed dramatically, the transcriptional pattern of both genes was similar. In contrast toCaPLC1,CaPLC2andCaPLC3are not essential. AlthoughCaplc2/3mutants had reduced abilities to produce hyphae on solid media, these mutants were as virulent as the wild-type in a model of systemic infection. These data suggest thatC. albicanscontains two different classes of phospholipases C which are involved in cellular processes but which have no specific functions in pathogenicity.
Phylogenetic relationships in Dichroplus Stål (Orthoptera: Acrididae: Melanoplinae) inferred from molecular and morphological data: testing karyotype diversification
Authors: Colombo Pablo , Cigliano María M. , Sequeira Andrea S. , Lange Carlos E. , Vilardi Juan C. , Confalonieri Viviana A.
Published: October 2005

The neotropical genus Dichroplus and related genera are characterized by a relatively uniform external morphology and a remarkably divergent male genitalia and hence its taxonomy is controversial. It also shows an extreme karyotypic diversification. In this study we used molecular and morphological characters to test the monophyly of the genus and to evaluate chromosome evolution. Twenty‐seven species from Dichroplus and related genera were included in the analysis. Morphological characters refer to the general morphology, male genitalia and female structures. Molecular studies were performed, sequencing part of two mitochondrial genes, cytochrome oxidase I and II. Independent and combined phylogenetic analyses of the data were performed under maximum parsimony. The karyotypic characters (rearrangements) were either mapped onto the combined topology or combined with the other data sets. While the molecular analysis confirms some results attained with morphology, some others do not. All point towards the paraphyly of the genus. Our results show the relevance of morphological data in phylogenetic studies because morphology and molecules supply complementary evidence. The mapping of chromosome characters on the combined tree shows that the most extreme karyotype, in D. silveiraguidoi, is a derived condition, probably reached through several centric fusions, and that X‐autosome centric fusions were recurrently fixed during the evolution of the group.

© The Willi Hennig Society 2005.
Nocturnal enuresis: a survey of parental coping strategies at 7½ years
Authors: Butler R. J. , Golding J. , Heron J. ,   the ALSPAC Study Team
Published: October 2005

Background  Childhood nocturnal enuresis is a potentially distressing experience. Parents have been found to adopt many approaches designed to help their child become dry at night. This study sought to understand, through a large cohort of children at 7½ years of age, the strategies parents adopt, both during the child's development and currently, to help their child overcome bed‐wetting.

Methods  A longitudinal cohort of 13 971 children with expected date of delivery between April 1991 – December 1992, in the County of Avon (Bristol) formed the population study group. At 7½ years parents were asked, as part of a regular self‐report questionnaire, what methods they had tried or were currently using to help their child stop bed‐wetting. Eleven options were supplied.

Results  Of 8269 parents responding to the questionnaire, 3376 (40.8%) indicated they had tried at least one of 11 strategies, with restricting night‐time fluids and lifting being the predominant methods employed. Amongst strategies employed in the past, lifting and showing displeasure were used significantly more by parents of children with nocturnal enuresis than by those with children dry at 7½ years. However, a greater proportion of parents of dry children encouraged their offspring to toilet more regularly in the daytime than parents of those with nocturnal enuresis or infrequent wetting. In terms of treatment interventions, the enuresis alarm had been employed with 19.2% and medication with 13.1% of those with nocturnal enuresis, although only 31.9% of those with nocturnal enuresis had seen a health worker. The results are discussed in relation to preventative and clinical implications.
The assessment of functional status in Turkish children with cerebral palsy (a preliminary study)
Authors: Erkin G. , Aybay C. , Kurt M. , Keles I. , Cakci A. , Ozel S.
Published: October 2005

Introduction  Cerebral palsy (CP) is one of the most common causes of disability in childhood leading to functional limitations. Assessment of the functional limitations is important to determine the severity of the disability in CP and to evaluate the benefit of the rehabilitation programme. However, the results of the measurements show variations according to different sociocultural characteristics. The Functional Independence Measure of Children (WeeFIM) had not been studied in Turkish children previously. The aims of this study were to evaluate the functional disability of Turkish children with CP by using WeeFIM and to compare the results with those of healthy counterparts.

Methods  A total of 86 children aged 24 months to 120 months were included in the study. Forty‐five children with CP and 41 healthy children representing the controls were evaluated with WeeFIM. Both children with CP and healthy controls were categorized into four groups according to their chronological age. The variations in the WeeFIM subsets scores (self‐care, sphincter control, transfers and locomotion, communication and social cognition) and total WeeFIM scores in children with CP and healthy controls were analysed.

Results  The children with CP had lower WeeFIM scores than healthy controls. The sphincter control subset scores of children with CP increased as they grew up. There was no statistically significant difference in all WeeFIM subset scores and the total WeeFIM scores among the four age groups of children with CP.

Conclusion  The WeeFIM appears to be a useful instrument for measuring the disability of Turkish children with CP. However, studies with wider series are needed to generalize our results.
Socioeconomic factors and adolescent pregnancy outcomes: distinctions between neonatal and postneonatal deaths?
Authors: Reading Richard
Published: October 2005

?
 
Markovitz B.P.,
Cook R.,
Flick L.H.,
Leet T.L.
(
2005
)

,
5
,
79
. doi:10.1186/1471‐2458‐5‐79. URL http://www.biomedcentral.com/1471‐2458/5/79

Background  Young maternal age has long been associated with higher infant mortality rates, but the role of socio‐economic factors in this association has been controversial. We sought to investigate the relationships between infant mortality (distinguishing neonatal from post‐neonatal deaths), socio‐economic status and maternal age in a large, retrospective cohort study.

Methods  We conducted a population‐based cohort study using linked birth‐death certificate data for Missouri residents during 1997–1999. Infant mortality rates for all singleton births to adolescent women (12–17 years, n = 10 131; 18–19 years, n = 18 954) were compared with those for older women (20–35 years, n = 28 899). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for all potential associations.

Results  The risk of infant (OR 1.95, CI 1.54–2.48), neonatal (1.69, 1.24–2.31) and post‐neonatal mortality (2.47, 1.70–3.59) were significantly higher for younger adolescent (12–17 years) than older (20–34 years) mothers. After adjusting for race, marital status, age‐appropriate education level, parity, smoking status, prenatal care utilization, and poverty status (indicated by participation in WIC, food stamps or Medicaid), the risk of post‐neonatal mortality (1.73, 1.14–2.64) but not neonatal mortality (1.43, 0.98–2.08) remained significant for younger adolescent mothers. There were no differences in neonatal or post‐neonatal mortality risks for older adolescent (18–19 years) mothers.

Conclusions  Socio‐economic factors may largely explain the increased neonatal mortality risk among younger adolescent mothers but not the increase in post‐neonatal mortality risk.
Population pharmacokinetics of pyrazinamide in elephants
Authors: ZHU M. , MASLOW J. N. , MIKOTA S. K. , ISAZA R. , DUNKER F. , RIDDLE H. , PELOQUIN C. A.
Published: October 2005

This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty‐three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20–30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0–24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with Tmax at or before 2 h regardless of the method of drug administration. Cmax at a mean dose of 25.6 (±4.6) mg/kg was 19.6 (±9.5 μg/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 ± 4.2 mg/kg, Cmax was 25% (4.87 ± 4.89 μg/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 ± 15.2 mg/kg yielded Cmax of 12.3 ± 6.3 μg/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher Cmax and lower inter‐subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved Cmax values are below the recommended 20–50 μg/mL range.
Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration
Authors: DAVIS J. L. , SALMON J. H. , PAPICH M. G.
Published: October 2005

The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high‐pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half‐life (t1/2) of 2.02 h and volume of distribution [Vd(ss)] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (Cmax) was 3.47 μg/mL and an apparent half‐life (t1/2) of 1.64 h. Bioavailability was approximately 5.0%. The AUCISF:AUCplasma ratio was 80.55% which corresponded to the percentage protein‐unbound drug in the plasma (77.07%). The t1/2 in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 ± 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 μg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram‐positive bacteria (MIC ≤ 0.5 μg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.
Pharmacokinetics and i.m. bioavailability of ceftiofur in Asian elephants (Elephas maximus)
Authors: DUMONCEAUX G. , ISAZA R. , KOCH D. E. , HUNTER R. P.
Published: October 2005

Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3‐week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean Cmax following i.m. administration was 1.63 μg/mL with a corresponding Tmax of 0.55 h. Following i.v. administration, the median Vd(ss) was 0.51 L/kg and a median Clp of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen.
Peritoneal clearance of homocysteine with icodextrin or standard glucose solution exchange
Authors: CZUPRYNIAK ANETA , NOWICKI MICHAL , CHWATKO GRAZYNA , JANDER ANNA , BALD EDWARD
Published: October 2005

Background:  The aim of the study was to assess plasma homocysteine concentration in peritoneal dialysis patients, and to compare the effect of different peritoneal solutions (glucose‐based and icodextrin‐based) on peritoneal clearance of homocysteine.

Methods:  The study group comprised 10 chronic peritoneal dialysis patients; the control group comprised 15 healthy, age‐matched non‐obese subjects with normal renal function. Patients with vitamin B12 or folate deficiency were excluded. In all subjects, plasma homocysteine and dialysis adequacy parameters were assessed at baseline. The clearance study was carried out with 2.27% glucose and 7.5% icodextrin solutions (12‐h dwell time).

Results:  Mean dialysate concentration of homocysteine was similar for both glucose and icodextrin solutions (8.3 ± 3.2 and 8.4 ± 1.9 µmol/L, respectively), but homocysteine clearance was significantly higher for icodextrin than glucose solution (1.82 ± 0.57 vs 1.39 ± 0.53 mL/min per 1.73 m2P = 0.01). Net ultrafiltration after icodextrin solution was also higher than after glucose solution (599 ± 136 mL vs 134 ± 337 mL, P < 0.01). A correlation between total plasma level of homocysteine and its peritoneal clearance was found (r = 0.69; P = 0.03).

Conclusion:  It appears that peritoneal elimination of homocysteine depends primarily on its plasma concentration. Icodextrin‐based solution for peritoneal dialysis seems to be more efficient in homocysteine elimination than a standard glucose‐based solution.
Arthroscopic Verification of Ultrasonographic Diagnosis of Meniscal Pathology in Dogs
Authors: Mahn Matthew M. , Cook James L. , Cook Cristi Reeves , Balke Michael T.
Published: October 2005

Objective—To determine the clinical usefulness of ultrasonography for diagnosis of meniscal pathology in dogs.

Study Design—Double‐blind prospective study.

Animals—Dogs (n=10) with lameness localized to the stifle.

Materials and Methods—Sonographic examination of each affected stifle was performed by 1 ultrasonographer unaware of specific historical and clinical data for the dog. Sonographic findings were recorded, but not reviewed until study completion. Arthroscopic examination of the affected stifle was performed within 48 hours of ultrasonography by 1 surgeon unaware of ultrasonographic findings. Arthroscopic findings were recorded, but not reviewed until study completion. Two investigators compared the ultrasonographic and arthroscopic findings at study completion to determine the sensitivity, specificity, positive predictive value, and negative predictive value.

Results—Two of the 10 dogs had bilateral stifle evaluation. Twenty‐four lateral and medial menisci, with normal and abnormal findings, were examined. The sensitivity and specificity for ultrasonographic diagnosis were 90.0% and 92.9%, respectively; positive and negative predictive values were 90.0% and 92.9%, respectively.

Conclusions—Ultrasonography is highly specific and sensitive for diagnosing bucket handle tears of the medial meniscus in dogs.

Clinical Relevance—Ultrasonographic evaluation of menisci in dogs is a noninvasive method for accurately and efficiently diagnosing pathology, determining the need for surgical intervention, and providing comprehensive information to clients.
Canine Sacroiliac Luxation: Anatomic Study of Dorsoventral Articular Surface Angulation and Safe Corridor for Placement of Screws Used for Lag Fixation
Authors: Shales Chris J. , Langley‐Hobbs Sorrel J.
Published: October 2005

Objective— To define a safe corridor in the dorsoventral plane to facilitate placement of screws inserted in lag fashion within the sacral body for fixation of sacroiliac fracture–luxation injuries in dogs.

Study Design— Anatomic study.

Sample Population— Cadaveric canine sacra.

Methods— Canine sacra (n=45) were used for a radiographic study to define a safe corridor in the dorsoventral plane for placement of screws inserted in lag fashion for fixation of sacroiliac luxation in the dog. The defined safe corridor allowed drilling to a depth of 65% of the sacral width to ensure screw purchase of ≥60%. Effects of positioning and measurement techniques were evaluated.

Results— Eighty‐seven safe corridors were measured. The mean articular surface was 100±4.52° from horizontal. Mean maximum, optimum, and minimum safe corridor drill angles were 111± 4.57°, 100±4.70°, and 89±5.17°, respectively, from the articular surface. Predicted surgeon error of ±4° was used to define the safe corridor for use clinically.

Conclusions— In 91% of sacra, a drill angle of 100±4° would remain ventral to the vertebral canal. Twelve sacra (14%) were at risk of penetration of the pelvic canal. A drill angle of 97±4° avoids penetration of the vertebral canal in all sacra measured but risks ventral exit from the body in 30% of sacra studied.

Clinical Relevance— A drill angle of 97° from the articular surface is recommended for insertion of screws for lag fixation of canine sacroiliac luxation.
Comparison of Perioperative Analgesic Protocols for Dogs Undergoing Tibial Plateau Leveling Osteotomy
Authors: Hoelzler Michael G. , Harvey Ralph C. , Lidbetter David A. , Millis Darryl L.
Published: October 2005

Objective—To compare effects of 3 commonly used perioperative analgesic protocols (epidural injection, intra‐articular injection, and intravenous [IV] injection) for management of postoperative pain in dogs after tibial plateau leveling osteotomy (TPLO).

Study Design—Prospective, randomized clinical trial.

Animals—Fifty‐six healthy dogs with naturally occurring cranial cruciate ligament rupture.

Methods—Dogs were premedicated with IV hydromorphone and acepromazine and were randomly assigned to receive either E (preoperative epidural injection with morphine and bupivacaine), IA (pre‐ and postoperative intra‐articular injections of bupivacaine), or C (neither epidural morphine and bupivacaine, nor intra‐articular bupivacaine). All dogs were administered hydromorphone (0.05 mg/kg IV) at extubation and as needed to maintain comfort postoperatively. Patients were observed and monitored continuously for 24 hours and discomfort was assessed using visual analog pain scores (VASs), multifactorial pain scores (MPSs), and response to a pressure nociceptive threshold (PNT) measuring device. Time to 1st dose and the total doses of hydromorphone required to achieve adequate comfort for each dog were recorded.

Results—No differences in measured indices of postoperative pain were observed between dogs of each treatment group; VAS (P=.190), MPS (P=.371), and PNT (P=.160). Time to 1st analgesic intervention was longer for Group E compared with Group C (P=.005) and longer for Group IA compared with Group C (P=.032). Although time to 1st intervention between Groups E and IA were longer for Group E, differences were not significant. To provide an adequate level of comfort, more analgesic interventions were administered to dogs in Group C compared with dogs in group E (P=.015). On average, more hydromorphone was administered to Group C compared with Group IA (P=.072) and to Group IA compared with Group E (P=.168), but statistical significance was not reached for these data.

Conclusions—In this study population, significant differences were seen in time to 1st hydromorphone dose between Groups E and IA compared with Group C. As well, more supplemental analgesia was administered to Group C compared with Group E to maintain the same level of postoperative comfort. Although differences between Groups E and IA tended to favor the epidural group, differences were minimal and not statistically significant.

Clinical Relevance—Our results suggest that regardless of analgesic protocol, measured indices of pain in dogs after TPLO can be minimized if dogs are continuously observed and appropriately supplemented with parenteral opioids. However, the frequency of postoperative opioid dosing can be minimized and may be a factor when contemplating supplementary use of epidural or intra‐articular injections as part of a balanced analgesic approach.
Antebrachial Fractures in Four Captive Polar Bears (Ursus maritimus)
Authors: Lin Rebecca C. , Engeli Emmanuel , Prowten Allan W. , Erb Hollis N. , Ducharme Norm G. , Goodrich Laurie R.
Published: October 2005

Objective—To identify common risk factors for antebrachial fractures of captive polar bears and to evaluate outcome after fracture repair.

Study Design—Retrospective study.

Animals—Four captive polar bears.

Methods—United States zoological collections were surveyed to determine the prevalence of fractures in captive polar bears. Medical records of captive polar bears that had antebrachial fractures were reviewed for signalment, history, physical and radiographic findings, fracture management, postoperative care, and outcome. Serum samples from healthy bears and bears with antebrachial fractures were assayed for 25‐hydroxyvitamin D (25‐OHD) concentrations.

Results—Nineteen fractures (12 polar bears) occurred from 1974 to 2002; 12 fractures involved the antebrachium. Management of 4 antebrachial fractures was reviewed; 3 were repaired by internal fixation and 1 by external coaptation. Fractures healed and bears were returned to exhibit on average 3 months postfracture. Of 11 serum samples assayed for 25‐OHD concentrations, 6 were below normal, 1 was low normal and 4 were within normal reference intervals. The 7 bears with subnormal or low normal values were housed in 2 zoos. Subnormal vitamin D concentrations were identified in 2 of 3 bears with fractures.

Conclusions—Fracture disease is not uncommon in captive polar bears. Additional research is necessary to explore the role of nutrition in polar bear fracture disease.

Clinical Relevance—Internal fixation of antebrachial fractures is feasible and reasonably well tolerated in captive polar bears.
Comparison of Three Methods for Arthrodesis of the Distal Intertarsal and Tarsometatarsal Joints in Horses
Authors: Zubrod Chad J. , Schneider Robert K. , Hague Brent A. , Ragle Claude A. , Gavin Patrick R. , Kawcak Chris E.
Published: October 2005

Objective—To evaluate the effects of diode laser surgery (LS), surgical drilling (SD), and intraarticular sodium monoiodoacetate (MIA) as methods for fusing the distal intertarsal (DIT) and tarsometatarsal (TMT) joints in horses.

Study Design—Experimental study.

Animals—Adult horses (15) without radiographic signs of osteoarthritis (OA) of the DIT and TMT joints.

Methods—Group 1 (n=3) had LS performed bilaterally on DIT and TMT joints; 1 horse was evaluated for 1 week and 2 horses were evaluated for 2 weeks. Group 2 (n=6) had LS on DIT and TMT joints of 1 tarsus and MIA administration into the contralateral DIT and TMT joints and were evaluated for 6 months. Group 3 (n=6) had LS performed on DIT and TMT joints of 1 tarsus and SD of the contralateral DIT and TMT joints and were evaluated for 12 months. Postoperative comfort, lameness, radiography, microradiography, and histology scores were compared using repeated measures ANOVA, and paired or 2 sample t‐tests; significance was set atP<.05.

Results—LS caused the least postoperative morbidity. In group 2, horses were less lame in 4 LS‐treated limbs and 2 MIA‐treated limbs at 6 months when compared with the contralateral limb. In group 3, horses were less lame in 5 LS‐treated limbs and 1 SD‐treated limb at 6 and 12 months compared with the contralateral limb. On microradiography, 11 MIA joints and 2 LS joints had bone bridging the joint at 6 months whereas 8 SD joints and 5 LS joints had bone bridging at 12 months. Significantly more joint space was bridged by bone in MIA‐ (51.4%) and SD (46.2%)‐treated joints compared with LS joints at 6 (30.6%) and 12 (28.5%) months, respectively (P<.05).

Clinical Relevance—SD and MIA resulted in more bone bridging of the distal 2 tarsal joints, than LS. However, LS seemingly caused less pain and discomfort to horses in the immediate postoperative period; horses were generally less lame in the LS limb. More laser energy may need to be applied to these joints to promote fusion; however, it may also have beneficial effects beyond fusion. Further research on horses with OA of the distal 2 tarsal joints is needed to determine whether LS can cause soundness without facilitating bony fusion.
Effects of melatonin on the thermoregulatory responses to intermittent exercise
Authors: Atkinson Greg , Holder Anna , Robertson Caroline , Gant Nicholas , Drust Barry , Reilly Thomas , Waterhouse Jim
Published: October 2005

Abstract: We examined the effects of a single 2.5‐mg dose of melatonin on the thermoregulatory and circulatory responses to intermittent exercise at a room temperature of 27.2 ± 0.4°C (mean ± S.D.), a relative humidity of 55 ± 3% (mean ± S.D.), and a light intensity of 200–300 lux. In a double‐blind cross‐over study, six male participants ingested either melatonin or placebo at 11:45 hr. Participants then rested in a semi‐supine position for 75 min and completed an intermittent running protocol for 66 min at alternating intensities of 40, 60 and 80% of maximal oxygen uptake. Rectal and mean skin temperature, heart rate, blood pressure, skin blood flow, subjective alertness and sleepiness, ratings of perceived exertion (RPE) and thermal strain were recorded. No effects of melatonin were found on these variables measured during the resting period (P > 0.10). During exercise, melatonin was found to moderate the increase in rectal temperature by approximately 0.25°C (P = 0.050) and magnify the increase in skin blood flow (P = 0.047). Postexercise systolic blood pressure was 7.8 ± 2.5 mmHg (mean ± S.D.) lower than before the exercise in the melatonin trial; a change which differed significantly to that in the placebo trial (P = 0.018). Melatonin did not influence subjective alertness and sleepiness before or after exercise and did not change the responses of mean skin temperature, RPE and thermal strain during the exercise (P > 0.10). In summary it is apparent that a 2.5‐mg dose of melatonin has hypothermic, but not soporific, effects during 66 min of intermittent exercise performed under moderate heat stress. Whether such effects improve endurance athletic performance in hot conditions remains to be confirmed. Our data also suggest that postexercise systolic hypotension is more marked after ingestion of melatonin.
Comparison of the impact of melatonin on chronic ethanol‐induced learning and memory impairment between young and aged rats
Authors: Baydas Giyasettin , Yasar Abdullah , Tuzcu Mehmet
Published: October 2005

Abstract:  Chronic alcohol exposure causes functional and structural changes in nervous system which have all been associated with learning and memory impairments. Furthermore, alcohol consumption has been shown to alter the pattern of neural cell adhesion molecules (NCAM) which are involved in memory processes. In the current work, we investigated the effects of melatonin on learning and memory deficits induced by alcohol exposure in young and aged rats. A group of young rats (3 months old) were administered ethanol for 45 days and half of them were co‐treated with melatonin. Similar treatments were performed in the aged (19 months old) rats. Morris water maze test and passive avoidance task were used to assess cognitive performance. Lipid peroxidation (LPO) and glutathione (GSH) levels were determined to characterize the level of oxidative stress in the hippocampus and cortex. NCAM levels were determined by Western blotting in the hippocampal homogenates. There was a significant elevation in LPO levels and a reduction in GSH levels in aged and alcohol‐exposed rats. Furthermore, both young and aged rats displayed some cognitive impairment when given with alcohol for 45 days. Co‐administration of melatonin with ethanol significantly reduced LPO and elevated GSH levels while improving the learning and memory deficits induced by ethanol; the aged rats exhibited a greater response to melatonin supplementation. Moreover, melatonin modulated NCAM expression in hippocampus. Present findings indicate that exposure to ethanol induces learning and memory deficits probably by generating reactive oxygen species and downregulating NCAM 180 in hippocampus of aged rats. Melatonin improves learning and memory deficits and the behavioral responses of rats to melatonin supplementation are age dependent.
Successively postadministered melatonin prevents disruption of hepatic antioxidant status in rats with bile duct ligation
Authors: Ohta Yoshiji , Imai Yoichiro , Matsura Tatsuya , Yamada Kazuo , Tokunaga Kenji
Published: October 2005

Abstract:  We have reported that orally administered melatonin exerts a therapeutic effect on cholestatic liver injury in rats treated with bile duct ligation (BDL) possibly through its antioxidant and anti‐inflammatory actions. Herein, we examined whether successively postadministered melatonin prevents the disruption of hepatic antioxidant status in BDL‐treated rats. Wistar rats with BDL were killed 5 and 13 days after BDL. Melatonin (10 or 100 mg/kg body weight) was orally administered to rats with and without BDL everyday for 8 days, starting 5 days after BDL. The hepatic concentrations of thiobarbituric acid reactive substances, an index of lipid peroxidation, and reduced glutathione increased 5 days after BDL and further increased at 13 days. Hepatic vitamin E concentration and catalase and Se‐glutathione peroxidase (Se‐GSH‐Px) activities were similarly reduced at 5 and 13 days after BDL. Hepatic ascorbic acid concentration and the hepatic activities of Cu,Zn‐ and Mn‐superoxide dismutases, glutathione reductase, and glucose‐6‐phosphate dehydrogenase decreased 13 days after BDL. Melatonin postadministered to BDL‐treated rats attenuated all these changes observed at 13 days after the treatment more effectively at the higher dose than at the lower dose. Melatonin administered to BDL‐untreated rats increased the hepatic Se‐GSH‐Px activity at both doses and the hepatic activities of Cu,Zn‐ and Mn‐superoxide dismutases at the higher dose. These results indicate that successively postadministered melatonin at pharmacological doses prevents the disruption of hepatic antioxidant status in rats with BDL through its direct and indirect antioxidant action, which may contribute to its therapeutic effect of BDL‐induced cholestatic liver injury.
Beneficial pleiotropic actions of melatonin in an experimental model of septic shock in mice: regulation of pro‐/anti‐inflammatory cytokine network, protection against oxidative damage and anti‐apoptotic effects
Authors: Carrillo‐Vico Antonio , Lardone Patricia J. , Naji Latifa , Fernández‐Santos José M. , Martín‐Lacave Inés , Guerrero Juan M. , Calvo Juan R.
Published: October 2005

Abstract:  Septic shock, the most severe problem of sepsis, is a lethal condition caused by the interaction of a pathogen‐induced long chain of sequential intracellular events in immune cells, epithelium, endothelium, and the neuroendocrine system. The lethal effects of septic shock are associated with the production and release of numerous pro‐inflammatory biochemical mediators including cytokines, nitric oxide and toxic oxygen and nitrogen radicals, together with development of massive apoptosis. As melatonin has remarkable properties as a cytokine modulator, antioxidant and anti‐apoptotic agent, the present study was designed to evaluate the possible protective effect of melatonin against LPS‐induced septic shock in Swiss mice. We observed that intraperitoneally (i.p.) administered‐melatonin (10 mg/kg) 30 min prior, and 1 hr after i.p. LPS injection (0.75 mg/animal) markedly protected mice from the LPS lethal effects with 90% survival rates for melatonin and 20% for LPS‐injected mice after 72 hr. The melatonin effect was mediated by modulating the release of pro‐/anti‐inflammatory cytokine levels, protection from oxidative damage and counteracting apoptotic cell death. Melatonin was able to partially counteract the increase in LPS‐induced pro‐inflammatory cytokine levels such as tumor necrosis factor‐α, IL‐12 and interferon‐γ at the local site of injection, while it increased the production of the anti‐inflammatory cytokine IL‐10 both locally and systemically. Furthermore, melatonin inhibited the LPS‐induced nitrite/nitrate and lipid peroxidation levels in brain and liver and counteracted the sepsis‐associated apoptotic process in spleen. In conclusion, we have demonstrated that melatonin improves the survival of mice with septic shock via its pleiotropic functions as an immunomodulator, antioxidant and anti‐apoptotic mediator.