bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative bioavailability and effect studies on metoprolol* administered as ordinary and slow‐release tablets in single and multiple doses
Authors: Regärdh Carl‐Gunnar , Johnsson Gillis , Jordö Lars , Sölvell Lennart 
Published: July 2010

Abstract: The bioavailability, plasma levels and pharmacological effects of 100 mg of metoprolol tartrate administered as an ordinary tablet and as two different slow‐release (SR) preparations were compared in healthy volunteers after single and multiple doses in one series of experiments. In another the urinary excretion of metoprolol and total radioactivity during 72 hours were determined after single doses of 50 mg of metoprolol‐(3H) tartrate in solution and in two SR tablets with different dissolution rates. Administration of metoprolol in SR form reduced the peak plasma levels and delayed the time to reach the peak in comparison with the ordinary tablet. The areas under the plasma concentration curves (AUC) after single doses and between two doses in steady state were almost identical for the SR tablets and the ordinary one. Administration of metoprolol in SR form did not significantly influence the urinary recovery of metoprolol (about 3% of the dose) or the fraction of the radioactive dose excreted via the kidney (>97% for each preparation).The elimination half‐life determined from the post‐absorptive phase of the ordinary tablet was 4.0±0.6 hours. The effect on the exercise heart rate and the blood pressure declined at the same constant rate in the post‐absorptive phase and the rate was virtually identical for the different types of tablets. The time for 50% reduction of the maximum effect was about 8 hours. Both of the effect variables were linearly related to the log plasma concentration for the ordinary tablet and the relationships could be described by the same regression line. No significant correlation between the effects and the plasma levels was obtained for the SR tablets. Despite substantial differences between the peak plasma levels of the ordinary tablet and the SR preparations, both types of tablets induced about the same maximum effects on exercise heart rate and systolic blood pressure and only slightly higher effects were recorded at the end of the dosage interval for the SR tablets.
Toxicological studies on metoprolol *
Authors: Bodin Nils‐Olof , Flodh Hans , Magnusson Göran , Malmfors Torbjörn , Nyberg Jan‐Anders 
Published: July 2010

Abstract:This paper presents a review of the toxicological studies in animals on metoprolol ‐ a cardioselective β‐blocking agent. Studies after single administration were performed in mice, rats and dogs. LD50‐values were calculated for the rodents while maximum tolerated dose was estimated for the dogs. Studies after repeated administration for up to 6 months were performed in rats and dogs. Reproduction studies were performed in rats and rabbits.The studies performed on metoprolol so far have not revealed any toxic effect other than the acute effects observed after administration of single, high doses.
Metabolism of metoprolol‐(3H) in man, the dog and the rat
Authors: Borg Karl Olof , Carlsson Enar , Hoffmann Kurt‐Jürgen , Jönsson Tor‐Erik , Thorin Hans , Wallin Boel 
Published: July 2010

Abstract:The main urinary metabolites of metoprolol‐(3H) in man, the dog and the rat were identified by gas chromatography and mass spectrometry by comparison with synthesized reference compounds. The amounts of the different metabolites in urine were determined by radio‐gas chromatography. In man metoprolol was metabolized by oxidative deamination, O‐dealkylation with subsequent oxidation and aliphatic hydroxylation into three main urinary metabolites which together accounted for 85% of the total urinary excretion. In the dog and the rat the same metabolites could be recovered but in different relative abundances.The inhibition of cardiovascular effects of isoprenaline by the metabolites and a presumed metabolite was studied and compared with the effects of metoprolol. Two of the compounds blocked the isoprenaline responses but they were 2–8 times less potent than metoprolol. The metabolites showed a significantly lower acute toxicity in mice than metoprolol.
Effects of Isoprenaline and Dibutyryl‐C‐AMP on the Electrical and Mechanical Activity of the Rabbit Myometrium
Authors: Nesheim Britt‐Ingjerd , Sigurdsson Stefan B. 
Published: July 2010

AbstractMechanical and electrical responses of spontaneously contracting muscle strips from oestrogen dominated rabbit uterus were investigated by the sucrose gap method. The effects of isoprenaline and dibutyryl‐c‐AMP in the presence and absence of propranolol were tested. It has been shown previously that the β‐adrenoceptor agonist isoprenaline inhibits the spontaneously contracting uterus even in the presence of the β‐blocker propranolol. The rise in c‐AMP which is caused by isoprenaline, is, however, blocked by propranolol. The aim of this investigation was to study further the role of c‐AMP in the isoprenaline‐induced relaxation of the uterus.Isoprenaline (10‐6M) consistently abolished spikes and mechanical contractions, usually accompanied by hyperpolarization. Propranolol (3 × 10‐6M) markedly reduced the incidence of hyperpolarization, but did not affect the other actions of isoprenaline. Hyperpolarization does not seem to be a prerequisite for inhibition of uterine contraction. Dibutyryl‐c‐AMP mimicked the actions of isoprenaline. No positive evidence to support a hypothesis of a c‐AMP‐independent mechanism was found. Therefore a possible explanation of the results could be that isoprenaline increases c‐AMP in a small intracellular pool, mediating electrical and mechanical responses but not influenced by propranolol.
Effect of Melperone, Two of its Metabolites and Thiothixene on Central Monoamine Metabolism and Prolactin Levels in Rodents
Authors: Wiesel Frits‐Axel , Bjerkenstedt Lars , Skett Paul 
Published: July 2010

Abstract The effects of melperone and thiothixene on the concentrations of monoamine metabolites in brain and prolactin in the serum of rats and mice were determined. Both drugs increased brain concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in a dosedependent manner. 5‐Hydroxyindoleacetic acid (5‐HIAA) was unaffected. The effect of thiothixene was longer lasting and about 5 times greater than that of melperone. Melperone, but not thiothixene, increased levels of 3‐methoxy‐4‐hydroxyphenylethylene glycol (MOPEG). Several hours after administration of melperone, levels of HVA and MOPEG were diminished.Both drugs increased prolactin concentrations in rat serum. Thiothixene was about 10 times more potent than melperone.Of two urinary metabolites of melperone investigated, one caused the same qualitative effects on monoamine metabolism as melperone itself but with reduced potency. The other metabolite was ineffective.
Transport and Binding of Lidocaine By Lung Slices and Perfused Lung of Rats
Authors: Post C. , Andersson R.G.G. , Ryrfeldt Å. , Nilsson E. 
Published: July 2010

AbstractThe accumulation of radioisotopically labelled lidocaine was investigated in lung slices and perfused lungs of rats. Lidocaine was taken up by rat lung slices incubated in an oxygenated physiological solution (pH 7.4) at 37°.14C‐lidocaine accumulated in lung slices to a much greater extent than did3H‐sucrose, and the lidocaine space was approximately 7 times that of the extracellular space. No metabolism of lidocaine took place during the incubation period. The accumulation of lidocaine was inhibited by low temperature, while anaerobic conditions had no inhibitor effect. The uptake of lidocaine (0.028 mM) was slightly antagonized by high concentrations of Ca2+(10 mM).The isolated perfused lung model was used for studying the pulmonary absorption of lidocaine from the vascular bed. Lidocaine was rapidly extracted from the perfusion solution and the drug appeared to accumulate in at least two compartments. It seems that in the rat lung a portion of the lidocaine taken up had accumulated within the cells, while som of it may be fixed to the cell surfaces.
Effect of Fluoride on the Activity of Ornithine Decarboxylase in Normal and Fluoride Resistant LS Cells
Authors: Hongslo Jan K. , Alfheim Ingrid 
Published: July 2010

Abstract Renewal of growth medium caused an induction of ornithine decarboxylase (ODC) activity in LS cells grown in suspension culture. Addition of low concentrations of fluoride ions to the growth medium (up to 1.3 mM) resulted in a further increase in this induction of ODC‐activity, whereas addition of 6 mM fluoride caused an inhibition of the induction and resulted in reduced ODC‐activity as compared to controls.Since sodium fluoride had no stimulatory or inhibitory effect on the ODC‐activity assay, it is likely that the effect is exerted on the regulation of ODC‐activity in the cells. The effect of fluoride ions on the induction of ODC‐activity upon renewal of the growth medium was markedly less pronounced in fluoride resistant LS cells.
Terodiline inhibition of human bladder contraction. Effects in vitro and in women with unstable bladder
Authors: Rud T. , Andersson K.‐E. , Boye N. , Ulmsten U. 
Published: July 2010

AbstractTerodiline, a drug with anticholinergic and calcium antagonistic properties, effectively relaxed carbachol‐contracted, isolated human bladder preparations. In the concentrations used, terodiline displaced to the right the concentration‐response curve obtained on cumulative addition of carbachol. The maximum response was slightly reduced only at the highest terodiline concentration used (5μM), suggesting a mainly competitive antimuscarinic effect. Nine patients, aged 12–78 years, suffering from urge urinary incontinence were investigated by simultaneous urethro‐cystometry before and after treatment with terodiline 12.5 mg twice or three times daily for 10 days. The patients reported subjective improvement with almost no side effects. Objectively, the number of uninhibited bladder contractions and the amplitude of the contractions decreased. The bladder capacity was almost doubled. There were no marked effects on bladder and urethral pressures at rest, and only two of the investigated patients had slight residual urine after treatment.The results suggest that terodiline is a promising alternative to existing drugs for inhibition of undesired detrusor activity.
Complete Programme for Acute Toxicity Testing — not only LD50 Determination.
Authors: Dayan A. 
Published: July 2010

Abstract The objective of any experimenter should be to obtain the maximum amount of useful information in the most economical manner possible. In this context,‘useful’ means study both of the principal or anticipated actions of the compound under examination, and also detection of additional responses to it. For efficient evaluation, including greater statistical rigour, a continuous or graded response and quantitative measurement is preferable, although much can be done by simply analysis of the presence or absence of responses, even if these are complex or dependent upon subjective criteria. Consistency of experimental conditions, and of diagnostic criteria are essential, whether in single, exploratory or comparative tests.Acute toxicity tests, like other experiments, should be designed pragmatically, therefore, confirming to the properties of the substance under examination, but also with general or holistic coverage, albeit less specific, to detect unanticipated actions. Greater or lesser weight may be given to these two classes of method, depending on whether the test is done as part of a general screen of a previously unknown substance, or as a specific control measure done to assay one particular property. Extrapolation of the results to man or other species is only possible with the caution proper to any experiment done under restricted and highly artificial conditions, but the value of acute toxicity data has often been shown by experience gained in man.
Correlation between cytotoxicity in vitro and LD50‐values.
Authors: Ekwall B. 
Published: July 2010

Abstract Previous studies of the correlation between cytotoxicity in vitro and LD50 in rodents have shown a good correspondence for small groups of substances, such as antibiotics, metals, and solvents, but a poor correspondence for other small groups of substances, such as drugs and pesticides, as well as for larger groups of heterogeneous chemicals. The generally poor correlation may be the result of the joint operation of three factors: 1. The existence of organ‐specific toxicity. 2. The pharmacokinetics in whole animals. 3. Methodological problems disturbing a basically equivalent in vitro/in vivo toxicity.We have made further studies of the correlation for altogether 95 drugs. The type of human and mouse systemic lethal poisoning was compared with the cytotoxicity divided by the i.v. LD50 in the mouse and approximate i.v. LD in man, called Specific Indices (SI1d). A minority of the drugs had an organ‐specific lethal action which was corresponding to high SI1d of 100 or more for all drugs. A majority of the drugs (80%) had a known or possible lethal interference with basal functions of animal and human tissues correlated to low SI1d of 1–10. At lethal dosage most of the latter drugs induce a non‐specific CNS depression, which was interpreted as the systemic reaction to basal cytotoxicity of chemicals reaching brain cells.Tissue culture tests of cytotoxicity seem to be relevant for the lethal action of most chemicals in man. Comparisons of in vitro/in vivo toxic dosage (SI1d) and concentrations might be used to screen the selectivity of lethal action of chemicals, and to select chemicals interfering with basal cell functions for further studies in vitro.It will be difficult to replace animal testing by cell tests in toxicity evaluation because of the organ‐specific toxicity and characteristic pharmacokinetics of many substances. However, initial standard in vitro cytotoxicity tests combined with subsequent approximative LD50 tests coupled to pharmacokinetic studies in the animals could produce data discriminating organ‐specific from basal cell toxicity. The toxic mechanisms of the probable majority of common chemicals with a basal cytotoxicity at lethal dosage could then be analysed in tissue culture, which would increase the precision of analysis, as well as saving animal lives.
Acute toxicity testing in cultures of mouse neuroblastoma cells.
Authors: Walum E. , Peterson A. 
Published: July 2010

AbstractCultured mouse neuroblastoma cells (C1300) may be used as models for nerve cells since they have a number of properties in common with their normal counterpartsin vivo.In order to test the possibility of using C1300 cells as alternativeto experimental animals when testing for acute toxicity, cells (clone 41A3) were exposed to a number of common chemicals (CH3HgCl, CdCl2HgCl2ppDDT, n‐butanol, benzene, dioxan, n‐propanol, aceton and t‐butanol). The toxic effect was quantified by measuring the degree of cell detachment in the cultures. The concentrations of chemicals that caused 25% of the total cell number to detach (TD25) were used for comparison with LD50values.In spite of the very simplified situation in culture, where the toxicity of a substance is little or not at all influenced by factors like penetration, storage, metabolism and excretion a good correlation (corr. coeff. 0,98) was obtained between TD25values and LD50values. Good correlations betweenin vitroandin vivotests have also been reported by others. One possible explanation to these findings could be simplifiedin vivotoxicokinetics of these substances when tested in high doses for general effects like animal death. If so, simplein vitrotests may be used for predicting acute toxicity of certain groups of substances.
Clinical evaluation of three toothbrush models tested by schoolchildren
Authors: Stroski ML , de Souza Dal Maso AM , Wambier LM , Chibinski ACR , Pochapski MT , Santos FA , Wambier DS 
Published: July 2010

To cite this article:

Int J Dent Hygiene
9, 2011; 149–154 DOI: 10.1111/j.1601‐5037.2010.00476.x. Stroski ML, de Souza Dal Maso AM, Wambier LM, Chibinski ACR, Pochapski MT, Santos FA, Wambier DS. Clinical evaluation of three toothbrush models tested by schoolchildren.Abstract:  Aim:  The aim of this single‐blind cross‐over study was to compare the performance of three different toothbrush models in the control of dental biofilm and maintaining a healthy gingival condition.Methods:  Twenty‐seven schoolchildren (aged 9–10 years) participated in the study. Three toothbrushes with different bristle arrangements were used: T1 – bristles on the same plane, straight arrangement; T2 – bristles on different planes, straight arrangement; T3 – bristles on different planes, straight and circular arrangement. The participants were then randomly divided into three groups for brushing with one of the three toothbrushes. Each experimental period lasted 15 days each, with three daily brushings and a 7‐day washout interval was used between periods. The oral hygiene and gingival bleeding indices were recorded by a single, calibrated examiner blind to the brush used. Bristle wear was measured with a digital calliper at the end of each period. The data were analysed using parametric (anova and Student’s t‐test) and non‐parametric (Cochran’s Q and McNemar) tests.Results:  The toothbrushes achieved similar results (P > 0.05) for the clinical parameters investigated. The three models exhibited a similar degree of bristle wear (P > 0.05).Conclusion:  The arrangement of the bristles had little influence over the removal of biofilm and gingival conditions. Thus, there is no clinical justification for replacing conventional toothbrushes with more expensive models.
Feeding of very low birth weight infants born to HCMV‐seropositive mothers in Germany, Austria and Switzerland
Authors: Buxmann Horst , Falk Maike , Goelz Rangmar , Hamprecht Klaus , Poets Christian F , Schloesser Rolf L 
Published: July 2010

AbstractAim:  To evaluate the enteral feeding practice of preterm infants <32 weeks (W) gestational age (GA) or <1500 g birth weight (BW) from human cytomegalovirus (HCMV)‐seropositive mothers in Germany, Austria and Switzerland.Methods:  This prospective cross‐sectional study included all neonatal units (NU) admitting preterm infants <32W or <1500 g BW in Germany, Austria and Switzerland. In June and July 2009, an anonymized questionnaire was sent via e‐mail, asking whether mothers of the above patients were screened for HCMV, and about the enteral feeding protocol for preterm infants <32W GA or <1500 g BW from HCMV‐seropositive mothers.Results:  During the study period, 58.6% of the questionnaires (123/210) from Germany, 50% (13/26) from Austria and 50% (6/12) from Switzerland were returned, yielding a total of 6232 preterm infants for analysis. Formula was given to the mentioned preterm infants in 28.5% (35/123) of the German NUs but not in Austria or Switzerland. Untreated breast milk was given in 66.6% (4/6) of the Swiss, 14.6% (18/123) of the German and no Austrian NU. Long‐term pasteurized breast milk was given in 32.5% (40/123) of the German and 38.5% (5/13) of the Austrian NUs, but not in Switzerland. Short‐term pasteurized breast milk was given only in 5.7% (7/123) of German NUs. Freeze‐thawed breast milk was given in Germany (4.9%; 6/123), Austria (61.5%; 8/13) and Switzerland (16.7%; 1/6).Conclusion:  Preterm infants <32W GA or <1500 g BW born to HCMV‐seropositive mothers are fed according to different regimes in German‐speaking countries. About 28.5% of the German VLBW‐infants receive formula, which is not recommended.
Structure, location and interactions of G‐quadruplexes
Authors: Huppert Julian L. 
Published: July 2010

Four‐stranded G‐rich DNA structures called G‐quadruplexes have been the subject of increasing interest recently. Experimental and computational techniques have been used to implicate them in important biological processes such as transcription and translation. In this minireview, I discuss how they form, what structures they adopt and with what stability. I then discuss the computational approaches used to predict them on a genomic scale and how the information derived can be combined with experiments to understand their biological functions. Other minireviews in this series deal with G‐quadruplex nucleic acids and human disease [Wu Y & Brosh RM Jr (2010) FEBS J] and making sense of G‐quadruplex and i‐motif function in oncogene promoters [Brooks TA et al. (2010) FEBS J].
Ruthenium plaque radiation therapy for iris and iridociliary melanomas
Authors: Razzaq Lubna , Keunen Jan E.E. , Schalij‐Delfos Nicoline E. , Creutzberg Carien L. , Ketelaars Martijn , de Keizer Rob J.W. 
Published: July 2010

Abstract.Purpose:  To determine the long‐term effects of ruthenium‐106 plaque radiation therapy for iris and iridociliary melanomas in terms of tumour regression and complications.Methods:  Between 1 November 1997 and 31 December 2007, 36 patients with an iris or iridociliary melanoma were treated with Ruthenium‐106 (Ru‐106) ophthalmic plaque radiation therapy. The median follow‐up was 6.5 years with a range of 2–11 years. The mean tumour apex dose was 151.5 Gy. Main outcome measures were local tumour control and radiation‐related ocular complications.Results:  The mean age of the patients at the time of treatment was 54 years (range 14–82). The tumours had a median largest basal dimension of 4.8 mm (range 3–11) and a prominence of 2.3 mm (range 0.8–5), with a median involvement of three clock hours (range 1–6). The tumours were confined to the iris in 14 patients (39%), extended into the anterior ciliary body in 12 (33%), while the anterior ciliary body tumour extended into the iris in ten patients (28%). Tumours regressed in all patients (100%) with a mean regression of 80% of the original tumour size at 7 years of follow‐up. Radiation‐related complications included corneal erosions on the first postoperative day in nine patients (25%), cataract in four of 11 patients free of cataract before treatment (36%) and postradiation glaucoma in one patient (3%). Visual acuity of 20/200 or worse was present in one of 20 patients (5%) at 6 years of follow‐up. Local recurrences occurred in two patients (5%), 2 and 5 years after the radiation therapy respectively, and both underwent enucleation. Distant metastases occurred in one of these enucleated patients (3%) 2 years after treatment.Conclusion:  Ru‐106 plaque radiation therapy for iris and iridociliary melanoma resulted in good local tumour control and preservation of visual acuity with few and treatable side‐effects.
Trailing Edge Noise Model Validation and Application to Airfoil
Optimization
Authors: Bertagnolio F. , Madsen H. Aa. , Bak C. 
Published: July 2010

Abstract
The aim of this article is twofold. First, an existing trailing edge noise model is validated by comparing with airfoil surface pressure fluctuations and far field sound pressure levels measured in three different experiments. The agreement is satisfactory in one case but poor in two other cases. Nevertheless, the model reproduces the main tendencies observed in the measurements with respect to varying flow conditions. Second, the model is implemented into an airfoil design code that is originally used for aerodynamic optimization. An existing wind turbine airfoil is optimized in order to reduce its noise emission, trying at the same time to preserve some of its aerodynamic and geometric characteristics. The new designs are characterized by less cambered airfoils and flatter suction sides. The resulting noise reductions seem to be mainly achieved by a reduction in the turbulent kinetic energy across the boundary layer near the trailing edge and to a lesser extent by a smaller boundary layer displacement thickness.