bluuebunny/crossref_metadata_2025_split huggingface dataset:
Food does not affect the pharmacokinetics of solifenacin, a new muscarinic receptor antagonist: results of a randomized crossover trial
Authors: Uchida Taisuke , Krauwinkel Walter J. , Mulder Hans , Smulders Ronald A. 
Published: June 2004

Aim  To determine the effect of food ingestion on the pharmacokinetic profile of solifenacin succinate (YM905; Vesicare®), a new bladder selective muscarinic receptor antagonist for the treatment of overactive bladder, a chronic disease usually caused by involuntary detrusor muscle contractions during bladder filling.Methods  A randomized, two‐period, crossover study in two groups of 12 healthy men (aged 18–45 years, body weight 60–100 kg, body mass index ≤30). A single 10‐mg dose of solifenacin was administered to the first group in the fasting state during period 1 and in the fed state during period 2, and to the second group in the fed state during period 1 and in the fasting state during period 2 (10 mg is two times the suggested starting dose). There was a 14‐day washout between treatment periods. Parameters obtained included Cmax, AUClast, and AUC0–inf, as well as t1/2, tmax, and tlag.Results  One subject withdrew during the first period for personal reasons. No statistically or clinically significant pharmacokinetic differences occurred between subjects in the fed and fasting states. All geometric mean ratios were close to 1 (Cmax, 1.033; AUClast, 1.068; AUC0–inf, 1.040). The 90% confidence intervals (CIs) fell in the predefined no‐food‐effect boundaries of 0.8–1.25 (Cmax, 0.953–1.120; AUClast, 0.990–1.153; AUC0–inf, 0.976–1.109). The mean difference in t1/2 was − 3.8 h (90% CI 7.6– 0.0). There were no significant differences between the fed and fasting states with regard to tmax and tlag (P > 0.05).Conclusions  The pharmacokinetics of oral solifenacin was not affected by food ingestion, suggesting that this drug may be administered with or without food. The results observed in this investigation are consistent with those of previous studies of solifenacin.
Clinical pharmacology of clemastine in healthy dogs
Authors: HANSSON H. , BERGVALL K. , BONDESSON U. , HEDELAND M. , TÖRNEKE K. 
Published: June 2004

Abstract  The pharmacokinetic properties of clemastine were investigated in six healthy dogs and compared with the effect of the drug recorded as inhibition of wheal formation induced by intradermal injections of histamine. Clemastine clearance was high (median: 2.1 L h−1 kg−1) and the volume of distribution large (13.4 L kg−1). The half‐life after intravenous administration was 3.8 h and the plasma protein binding level in vitro was 98%. After oral administration, the bioavailability was only 3%. Given intravenously, clemastine (0.1 mg kg−1) inhibited wheal formation completely for 7 h, whereas the effect after oral administration (0.5 mg kg−1) was minor. The data show that most dosage regimens suggested in the literature for the oral administration of clemastine to dogs are likely to give too low a systemic exposure of the drug to allow effective therapy.
A randomized, controlled study to evaluate the steroid sparing effect of essential fatty acid supplementation in the treatment of canine atopic dermatitis
Authors: SÆVIK BENTE K. , BERGVALL KERSTIN , HOLM BIRGIT R. , SAIJONMAA‐KOULUMIES LEENA E. , HEDHAMMAR ÅKE , LARSEN STIG , KRISTENSEN FLEMMING 
Published: June 2004

Abstract A randomized, double blind, placebo‐controlled multicentre clinical trial of 12 weeks’ duration was undertaken in 60 dogs with atopic dermatitis to evaluate the steroid sparing effect of essential fatty acid supplementation. The dogs were randomly assigned to receive either a combination of borage seed oil and fish oil or a placebo, in addition to prednisolone tablets. All dogs received a standardized basal diet. Owners of the dogs recorded pruritus daily using a 10 cm visual analog scale and the dosage of prednisolone was established based on the pruritus score, according to written instructions. The dosage of prednisolone and the use of any concurrent treatment (shampoo and/or ear‐cleanser) were recorded by the owner on a daily basis. The investigators graded the skin lesions at days 0, 42 and 84. The use of prednisolone during the test period was lower in the active group, but the difference was not statistically significant (P = 0.32). The test period was sequentially divided into 43–84, 50–84, 57–84, 64–84, 71–84 and 78–84 days. On day 64, the difference between the active group and the placebo group reached statistical significance (P = 0.04) with an increasing difference towards the end of the study. A statistically significant reduction in the pruritus scores and the total clinical scores from day 0 to day 84 was apparent in both groups (P < 0.0001). At the end of the study, both the pruritus score and the total clinical score were lower in the active group. Our findings indicate a steroid sparing effect of essential fatty acid supplementation in canine atopic dermatitis and, furthermore, that there is a time lag before the effect is attained.
Frequent and occasional species and the shape of relative‐abundance distributions
Authors: Ulrich Werner , Ollik Marcin 
Published: June 2004

ABSTRACTRecently, three different models have been proposed to explain the distribution of abundances in natural communities: the self‐similarity model; the zero‐sum ecological drift model; and the occasional–frequent species model of Magurran and Henderson. Here we study patterns of relative abundance in a large community of forest Hymenoptera and show that it is indeed possible to divide the community into a group of frequent species and a group of occasional species. In accordance with the third model, frequent species followed a lognormal distribution. Relative abundances of the occasional species could be described by the self‐similarity model, but did not follow a log‐series as proposed by the occasional–frequent model. The zero‐sum ecological drift model makes no explicit predictions about frequent and occasional species but the abundance distributions of the hymenopteran species did not show the excess of rare species predicted by this model. Separate fits of this model to the frequent and to the occasional species were worse than the respective fits of the lognormal and the self‐similarity model.
The ‘species problem’ and testing macroevolutionary hypotheses
Authors: Isaac Nick J. B. , Purvis Andy 
Published: June 2004

ABSTRACTSpecies lists change for a variety of reasons, including new information and preferences for different species concepts. Uncertainty over species numbers is potentially damaging to tests of proposed correlates of species richness, particularly if taxonomic changes are biased toward some clades over others. We investigate the effects of this error and bias by testing the same suite of macroevolutionary hypotheses in seven different arrangements of primate taxonomy. This is the first time that the effects of the ‘species problem’ have been systematically investigated in this way. Primates are an excellent model system for examining the effects of taxonomic uncertainty: species numbers have doubled in the past two decades, with the fastest growth in the Neotropics. We found that different variables were significantly associated with species richness in each taxonomic arrangement. However, there were no significant differences among taxonomies in the regression slopes for any predictor variable. We found no tendency for significant correlations to occur in taxonomies with more species, suggesting that the results cannot be explained by a lack of power in the smaller taxonomies. The findings are discussed with reference to the wider implications for testing macroevolutionary hypotheses.
Human and Murine Serine‐Palmitoyl‐CoA Transferase
Authors: Weiss Bertram , Stoffel Wilhelm 
Published: June 2004

Serine palmitoyltransferase (SPT, EC 2.3.1.50) is the key enzyme in sphingolipid biosynthesis. It catalyzes the pyridoxal‐5’‐phosphate‐dependent condensation of L‐serine and palmitoyl‐CoA to 3‐oxo‐sphinganine. Human expressed‐sequence‐tag (EST) clones are similar to the two yeast genes for synthesis of long‐chain bases, LCB1 and LCB2, which are believed to encode two subunits of SPT [Buede, R., Pinto, W. J., Lester, R. L. & Dickson, R. C. (1991) J. Bacteriol. 173, 4325–5332; Nagiec, M. M., Baltisberger, J. A., Wells, G. B., Lester, R. L. & Dickson, R. C. (1994) Proc. Natl Acad. Sci. USA 91, 7899–7902]. We have cloned and characterized two complete human and murine cDNA sequences named hLCB1 & mLCB1 and hLCB2 & mLCB2, respectively, similar to the yeast LCB1 and LCB2 genes.Human embryonic kidney cells (HEK 293) transfected with murine sequences of LCB1 (mLCB1) and LCB2 (mLCB2) independently and in coexpression showed an overexpression of the transcripts on the mRNA and protein level. The enzymatic activity of cells expressing mLCB2 alone or coexpressed with mLCB1 was three times higher than the activity of untransfected HEK cells. mLCB1 expression was not required for the synthesis of 3‐oxo‐sphinganine in mammalian cells. Transcription/translation in vitro yielded mLCB1 (53 kDa) and mLCB2 (63 kDa). The two proteins do not contain a signal peptide nor are they glycosylated. The endogenous and overexpressed SPT activity were both sensitive to common SPT inhibitors. Labeling studies with [1‐14C]palmitic acid indicated that cell lines transfected with mLCB2 preferentially use the excess sphingoid bases for glucocerebroside and galactocerebroside synthesis. Our results provide conclusive genetic and biochemical evidence that the human and murine LCB2 genes described here encode serine palmitoyltransferase. Further studies will be required to unravel the function of the LCB1 gene in mammalian cells.
Flavin Adenine Dinucleotide and Flavin Mononucleotide Metabolism in Rat Liver
Authors: Barile Maria , Brizio Carmen , De Virgilio Caterina , Delfine Sebastiano , Quagliariello Ernesto , Passarella Salvatore 
Published: June 2004

In order to gain some insight into mitochondrial flavin biochemistry, rat liver mitochondria essentially free of lysosomal and microsomal contamination were prepared and their capability to metabolise externally added and endogenous FAD and FMN tested both spectroscopically and via HPLC.The existence of two novel mitochondrial enzymes, namely FAD pyrophosphatase (EC 3.6.1.18) and FMN phosphohydrolase (EC 3.1.3.2), which catalyse FAD→FMN and FMN→riboflavin conversion, respectively, is shown. They differ from each other and from extramitochondrial enzymes, as judged by their pH profile and inhibitor sensitivity, and can be separated in a partial FAD pyrophosphatase purification.Digitonin titration and subfractionation experiments show that FAD pyrophosphatase is located in the outer mitochondrial membrane and FMN phosphohydrolase in the intermembrane space. Since these enzymes can metabolise endogenous FAD and FMN, which are made available by using both Triton X‐100 and the effector oxaloacetate, a proposal is made that FAD pyrophosphatase and FMN phosphohydrolase play a major role in mitochondrial flavoprotein turnover.
Identification of Strictly Conserved Histidine and Arginine Residues as Part of the Active Site in Petunia hybrida Flavanone 3β‐Hydroxylase
Authors: Lukačin Richard , Britsch Lothar 
Published: June 2004

Flavanone 3β‐hydroxylase, involved in the biosynthesis of flavonoids, catechins, and anthocyanidins, is a non‐heme iron enzyme, dependent on Fe2+, molecular oxygen, 2‐oxoglutarate, and ascorbate, the typical cofactors of the class of 2‐oxoglutarate‐dependent dioxygenases.Sequence alignment analysis of various 2‐oxoglutarate‐dependent dioxygenases and related enzymes revealed eight amino acid residues that seem to be strictly conserved within this group of enzymes. Among these residues, two histidines (His220 and His278) and one aspartic acid (Asp222) were identified as part of the putative iron‐binding site and an arginine residue (Arg288) as part of the 2‐oxoglutarate binding site, by site‐directed mutagenesis and functional analysis of the mutated recombinant enzyme.The mutant genes were expressed in Escherichia coli to give soluble proteins whose molecular masses were in excellent agreement with the wild‐type enzyme. Four out of nine mutant enzymes, [Gln78]FHT, [Gln121]FHT, [Gln264]FHT and [Gln266]FHT, were enzymatically active with activities reduced to 26–57%, implying that the mutated amino acid residues are not essential for catalysis. Replacement of His220 by glutamine and Asp222 by asparagine remarkably reduced the catalytic activity to about 0.15% and 0.4%, respectively. The [Gln220]FHT and [Asn222]FHT enzymes showed a slightly increased Km value with respect to iron binding, as compared to the wild‐type enzyme. The most drastic effect on the reaction rate of flavanone 3β‐hydroxylase was achieved by mutating His278 to glutamine. The mutant had no detectable enzyme activity, indicating that His278 was essential for the catalytic reaction. The observed protection of purified enzyme from inactivation by diethylpyrocarbonate after the addition of cofactors provided further independent confirmation for the involvement of histidine residues in the active site.The substitution of Arg288 by lysine or glutamine induced a precipitous decrease in catalytic activity and a fivefold and 160‐fold increase in the Michaelis constants for 2‐oxoglutarate, respectively. In addition, the enzymatic activities of the latter two mutant enzymes showed a strong pH dependence in the weakly acidic as well as in the neutral pH range, unlike the wild‐type enzyme.These results clearly indicate that Arg288 probably contributes to the specific binding of 2‐oxoglutarate at the active site of the enzyme, most likely by providing a positive charge, properly located in order to interact with the (5‐carboxyl function of 2‐oxoglutarate. Furthermore, we conclude that His220, His278 and Asp222 constitute three of the possible ligands for iron binding in the active site of flavanone 3β‐hydroxylase.
Synthesis of Soybean Agglutinin in Bacterial and Mammalian Cells
Authors: Adar Rivka , Streicher Hansjörg , Rozenblatt Shmuel , Sharon Nathan 
Published: June 2004

The cDNA of soybean agglutinin (SBA), a glycoprotein lectin, obtained from the mRNA of soybean seeds at mid‐maturation, was cloned in a λgt 10 phage and subcloned in a pUC‐8 plasmid. Probing with a fragment of the lectin gene [Vodkin, L. O., Rhodes, P. R. & Goldberg, R. B. (1983) Cell 34, 1023–1031] afforded a clone of 1012 nucleotides containing the complete coding region of 858 nucleotides for the precursor to soybean agglutinin. The deduced amino acid sequence contains the 253 residues of the mature lectin and an hydrophobic N‐terminal signal peptide of 32 amino acids. Expression in Escherichia coli of the cDNA coding for the precursor to the lectin or for the mature lectin led to the accumulation of large quantities of inclusion bodies, from which mature SBA was isolated in small yield (up to 1 mg/1). It was identical with the native lectin in the hemagglutinating activity and carbohydrate specificity, N‐terminal sequence and oligomeric structure, but, because it was not glycosylated, its subunit mass was lower by 2 kDa. Our findings show that pre‐SBA is processed into the mature form in the bacteria, and that, contrary to what has been suggested [Nagai, K. & Yamaguchi, H. (1993) J. Biochem. (Tokyo) 113, 123–125], glycosylation is not essential for the folding of the lectin, nor for its subunit assembly into a biologically active tetramer.To obtain recombinant SBA in secreted form, the pre‐SBA cDNA was subcloned in pTM1 vector and the construct inserted into vaccinia virus. When monkey BS‐C‐1 cells were infected by the virus, using a double expression protocol, recombinant lectin was secreted into the growth medium, from which it was isolated by immunoaffinity chromatography at a yield similar to that from the bacteria. Except for its lower hemagglutinating activity, the product was indistinguishable from native SBA in all properties tested. It was also susceptible to digestion by endo‐β‐N ‐acetylglucosaminidase H or N‐glycanase which caused a decrease of 2 kDa in its subunit mass and gave the same results on lectin blot analysis, indicating that it too is a glycoprotein with a single oligomannose unit.
Creatine Kinase and Aspartate Aminotransferase in Cows as Indicators for Endometritis
Authors: Sattler T. , Fürll M. 
Published: June 2004

SummaryThe aim of the study was to prove a correlation between creatine kinase (CK; EC 2.7.3.2.) and aspartate aminotransferase (AST; EC 2.6.1.1.) activities in serum and the severity of endometritis. We (i) determined clinical and clinical–chemical (CK, AST, bilirubin) parameters on 87 cows with abomasal displacement (DA), (ii) measured CK, AST and glutamate dehydrogenase (GLDH; EC 1.4.1.2.) in serum and uterine tissue samples in 10 slaughter cows, and (iii) compared the serum reaction (CK, AST, bilirubin) of six healthy, non‐pregnant cows after an inter‐auterine application of a mild irritating 0.2% peroxyacetic acid (Uterofertil®) with that of four healthy cows after an intrauterine application of 0.9% sodium chloride solution. Uterine tissue contains high activities of CK (2940 ± 1140 U/g protein) and AST (159 ± 25 U/g protein). Cows with DA have increased serum CK and AST activities, which correlate with the degree of endometritis. The DA without endometritis also comes along with slightly increased CK (quartiles 181, 259 and 288 U/l) and AST (101, 138 and 199 U/l) activities. In pregnant cows these activities are higher than in non‐pregnant cows. Irritation of the uterus with Uterofertil® leads to increased serum CK but not AST. After the exclusion of evaluated CK as a result of muscular damage or hypocalcaemia, this enzyme can be used as a screening parameter in the diagnosis of endometritis. In each clinical case it is necessary to determine if increased AST activities are muscle‐, liver‐ or uterus‐dependent.
Inhalation Anaesthesia for Castration of Newborn Piglets: Experiences with Isoflurane and Isoflurane/N2O
Authors: Walker B. , Jäggin N. , Doherr M. , Schatzmann U. 
Published: June 2004

SummaryThe aim of this study was to evaluate the inhalation anaesthesia with isoflurane and isoflurane/N2O by mask induction for routine castration of piglets under 14 days of age. Material and Methods: Eighty‐five male piglets aged between 4 and 12 days were used in a matched pair test. Two piglets of the same litter with the same weight were selected. One was castrated with, the other without anaesthesia. Induction was performed with either isoflurane (group ISO) or isoflurane/nitrous oxide (group ISO/N2O) in oxygen through a modified bain‐breathing system. Induction time was 90 and 60 s for group ISO and group ISO/N2O, respectively. The disappearance of the palpebral reflex was recorded. The reaction of the piglets during castration was judged according to a scoring system separately for both testicles during skin incision and dissection of the spermatic cord. The scores were added and mean values were calculated. Total anaesthesia time, castration time and quality of recovery was recorded. Blood was collected from all piglets immediately after castration for measurement of ACTH and beta‐endorphin values. Statistical analysis were performed by the Kruskal–Wallis test for nonparametric data and one‐wayanova(NCSS 2000, Kaysville, UT, USA). Results: Induction of anaesthesia proved to be smooth in all cases. The palpebral reflex disappeared after 36.5 s in group ISO/N2O versus 51 s in group ISO. Mean castration scores were 0.6 in group ISO and 0 in group ISO/N2O, whereas 7.7 in piglets with no anaesthesia. These scores were significantly different. Mean anaesthesia time was 128 s (30–390) for group ISO and 123 s (70–220) for group ISO/N2O. No deaths occured. The differences in the levels of ACTH andβ‐endorphins in the blood plasma in the different groups showed no statistical difference. Discussion: This study demonstrates that isoflurane or isoflurane/N2O anaesthesia by mask induction proves to be a safe, short and reliable method in piglets undergoing castration. Reaction to the castration procedure were significantly reduced. Stress hormone values were not different between the groups because of a large individual difference.
German Assessments of British‐Australian Relations, 1901–1914
Authors: Overlack Peter 
Published: June 2004

“The Federal Government does not have the most basic grasp of military matters”.Consul‐General Dr Georg Irmer, November 1909An examination of how Australia's closest colonial neighbour in 1901 viewed the event of Federation and its implications for British Imperial unity and regional defence contributes much to the continuing debate over the development of an Australian national identity. Germany in its Pacific colonies had a direct strategic and financial interest in how the new entity would present and project itself in the region. While the more superficial assessment of Australia's defence capability made by Germans was largely correct, the underlying assumptions of the fragility of Imperial unity and that in wartime Dominion concerns would be placed before Imperial ones were incorrect. While the enthusiastic reception Australian Federation received in German eyes was based on a tangible reality in the new Commonwealth, the political and military implications drawn from it clearly were not, and the consequences of this had catastrophic results for Germany in the Pacific in August 1914.
Chronic lymphocytic leukaemia in a pot‐bellied pig
Authors: Gill M. S. , Mauldin G. E. , LeBlanc C. J. , Sod G. A. 
Published: June 2004

AbstractAn 11‐year‐old, neutered male, Vietnamese pot‐bellied pig was admitted for routine dental and foot care. As a part of routine geriatric evaluation, blood was submitted for a complete blood count and serum biochemical analysis. The blood count revealed a marked leucocytosis due to lymphocytosis. Further diagnostic evaluation, including abdominal and thoracic radiography, abdominal ultrasonography and blood lymphocyte immunophenotyping confirmed a diagnosis of chronic lymphocytic leukaemia of T‐cell origin. Treatment was initiated with oral prednisone and cyclophosphamide. The pig did well on treatment for about 1 month after discharge but was then euthanized.
Effect of Tapered Grafts on Hemodynamics and Flow Rate in Dialysis Access Grafts
Authors: Krueger Ulf , Huhle Almuth , Krys Kerstin , Scholz Hans 
Published: June 2004

Abstract: Aim:  Aside from the high incidence of venous stenosis, high‐output failure and peripheral steal syndromes remain serious problems of vascular access. Meanwhile commercial tapered grafts are available to address this topic, but little is known about its effect neither on graft flow nor on hemodynamics.Methods:  Anastomotic models were constructed using a clear silicon elastomer. The arterial anastomosis was shaped in two ways: 1) like a direct connection of artery and 7‐mm graft and 2) with a 4‐mm diameter segment between artery and graft. Hemodynamic measurements were performed in a pulsatile flow circuit to simulate blood flow at physiological conditions. Flow patterns were obtained by direct dye injection. Additionally, the correlation between the length of narrow segment and mean arterial pressure was investigated.Results:  In all models using a 4‐mm segment, the oscillating anastomotic vortex was disappeared. This vortex was shifted to the area behind the well‐rounded expansions of the graft demonstrating a new separation region, but the flow direction was constant during the whole simulated cycle. At identical pressure rates and waveforms the length of narrow segment determined the graft flow rate directly (e.g., at mean pressure 100 mm Hg, flow reduction up to 28% in 4‐mm segments, and up to 55% in 3‐mm segments).Conclusion:  These findings indicate that taper is an important consideration in the design of vascular access grafts.