bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the nitric oxide and cyclo‐oxygenase pathway in mesenteric resistance vessels of normotensive and spontaneously hypertensive rats
Authors: Le Marquer‐Domagala F. , Finet M. 
Published: July 2006

The double perfused mesentery was used to compare arterial and venous KCl‐ and acetylcholine (ACh)‐induced responses in tissues taken from normotensive (WKY) and spontaneously hypertensive rats (SHR), in the presence or absence of inhibitors of nitric oxide (NO) synthase (NG‐nitro‐L‐arginine (L‐NOARG) and NG‐nitro‐L‐arginine methyl ester (L‐NAME)) and cyclo‐oxygenase (indomethacin, mefenamic acid).
KCl (20 to 120 mM K+) caused concentration‐dependent increases in arterial and venous perfusion pressures. The maximal arterial effects were significantly higher in the SHRs than in the WKY, with no differences in the venous pressor responses.
L‐NAME and L‐NOARG (100 μM) had no effect on the basal perfusion pressures in tissues from either WKY or SHRs, and mefenamic acid only induced a significant reduction of the basal perfusion pressures in the venous mesenteric vessels isolated from WKY.
L‐NAME and L‐NOARG (100 μM) potentiated the pressor responses to KCl to the same extent in the venous and arterial beds derived from WKY and SHR, while indomethacin and mefenamic acid (5 μM) only significantly decreased these responses in WKY.
Acetylcholine (ACh)‐induced relaxations (1 nM to 10 μM) were significantly higher in arterial beds of WKY than in SHR, without differences in the venous relaxant responses.
L‐NAME (100 μM) inhibited ACh‐induced relaxations in arterial and venous beds from both groups of rats. Mefenamic acid was without effect on ACh‐induced relaxations in either the arterial or the venous beds from WKY and SHR.
In conclusion, the liberation of NO in the perfused mesenteric vasculatures requires an active tone and no dysfunction of NO synthase activity is functionally apparent in the mesenteries isolated from SHRs. The cyclo‐oxygenase pathway is only implicated in the KCl‐induced responses of tissues derived from WKY, but not in the vasodilatations induced by ACh in either the arterial or the venous vasculatures from WKY and SHR.
Attenuation of precipitated morphine withdrawal symptoms by acute i.c.v. administration of a group II mGluR agonist
Authors: Fundytus Marian E. , Coderre Terence J. 
Published: July 2006

We previously showed that chronic i.c.v. antagonism of metabotropic glutamate receptors (mGluRs) concurrently with s.c. morphine significantly attenuated precipitated withdrawal symptoms. Conversely, acute i.c.v. injection of a selective group II mGluR antagonist just before the precipitation of withdrawal exacerbated abstinence symptoms.
In the present study, we showed that acute i.c.v. administration of the non‐selective mGluR agonist 1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD), as well as the group II selective agonist (2S,1′R,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG‐IV), significantly attenuated the severity of precipitated withdrawal symptoms.
From these results we hypothesize that chronic opioid treatment may indirectly induce a desensitization of group II mGluRs, which contributes to the development of dependence.
In‐hospital cardiac arrest is associated with use of non‐antiarrhythmic QTc‐prolonging drugs
Authors: De Bruin Marie L. , Langendijk Pim N. J. , Koopmans Richard P. , Wilde Arthur A. M. , Leufkens Hubert G. M. , Hoes Arno W. 
Published: July 2006

AimsQTc interval‐prolonging drugs have been linked to cardiac arrhythmias, cardiac arrest and sudden death. In this study we aimed to quantify the risk of cardiac arrest associated with the use of non‐antiarrhythmic QTc‐prolonging drugs in an academic hospital setting.MethodsWe performed a case–control study in which patients, for whom intervention of the advanced life support resuscitation team was requested for cardiac arrest between 1995 and 2003 in the Academic Medical Centre, Amsterdam, were compared with controls regarding current use of non‐antiarrhythmic QTc‐prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusting for potential confounding factors.ResultsA statistically significant increased risk of cardiac arrest (OR 2.1, 95% CI 1.2, 3.5) was observed in patients who received QTc‐prolonging drugs (42/140). The risk was more pronounced in patients receiving doses > 1 defined daily dose (OR 2.5, 95% CI 1.1, 5.9), patients taking > 1 QTc‐prolonging drug simultaneously (OR 4.8, 95% CI 1.6, 14) and patients taking pharmacokinetic interacting drugs concomitantly (OR 4.0, 95% CI 1.2, 13).ConclusionsUse of non‐antiarrhythmic QTc‐prolonging drugs in hospitalized patients with several underlying disease is associated with an increased risk of cardiac arrest. The effect is dose related and pharmacokinetic drug–drug interactions increase the risk substantially. Physicians caring for inpatients should be made aware of the fact that these non‐antiarrhythmic drugs may be hazardous, so that potential risks can be weighed against treatment benefits and additional cardiac surveillance can be requested, if necessary.
Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance
Authors: Anderson Brian J. , Allegaert Karel , Van den Anker John N. , Cossey Veerle , Holford Nicholas H. G. 
Published: July 2006

What is already known about this subject• Effects of size, renal function, age (postnatal age, gestational age and postmenstrual age) as predictors of vancomycin clearance in premature neonates are established, but the relative contribution of each component remains poorly quantified, largely because these variables are closely correlated.• We have quantified the covariates contributing to vancomycin clearance population parameter variability in order to establish the major covariates required for dosing predictions. Size, standardized using allometric models, was the primary covariate used in our analysis.What this study adds• Size explained 49.8%, postmenstrual age 18.2% and renal function 14.1% of clearance variability.• Descriptors of the relationship between age and clearance in premature neonates vary.• The use of a variable slope sigmoidal model to describe the relationship between clearance and postmenstrual age predicted an adult clearance of 3.79 l h−1 70 kg−1 (95% confidence interval 2.76, 4.98) from premature neonatal data.AimTo identify and quantify factors describing the variability of vancomycin clearance in premature neonates.MethodsPopulation pharmacokinetics were estimated (NONMEM) in 214 neonates [postmenstrual age (PMA) 30.4 weeks, range 24–34 weeks; postnatal age 11.9 days, range 1–27 days; weight 1.30 kg, range 0.42–2.6 kg] using therapeutic drug monitoring data. Covariate analysis included weight, PMA, serum creatinine, use of inotropes or ibuprofen, positive blood culture and respiratory support. A one‐compartment linear disposition model with zero order input and first‐order elimination was used to describe the data (604 observations).ResultsThe population estimate for volume of distribution (V) was 39 l 70 kg−1 (coefficient of variation 19.4%). Clearance (CL) increased from 0.897 l h−1 70 kg−1 at 24 weeks PMA to 2.02 l h−1 70 kg−1 by 34 weeks PMA. The between‐subject variability for CL was 18.6% and the between‐occasion variability was 12.2%. The use of ibuprofen reduced clearance, but this effect was attributable to reduced renal function. Overall, 82% of the variability of CL was predictable. Size explained 49.8%, PMA 18.2% and renal function 14.1%. The use of a variable slope sigmoidal model to describe the relationship between clearance and PMA predicted an adult clearance of 3.79 l h−1 70 kg−1 (95% confidence interval 2.76, 4.98).ConclusionsSize, renal function and PMA are the major contributors to clearance variability in premature neonates. The small (18%) unexplained variability in clearance suggests target concentration intervention is unnecessary if size, age and renal function are used to predict the dose. Extrapolation to an adult clearance from neonatal data is possible using allometric size models and a function describing clearance maturation.
Pharmacokinetics, safety and tolerance of single‐ and multiple‐dose adefovir dipivoxil in healthy Chinese subjects
Authors: Sun De‐qing , Wang Hai‐sheng , Ni Mei‐yuan , Wang Ben‐jie , Guo Rui‐chen 
Published: July 2006

AimsTo assess the pharmacokinetics, safety and tolerance of single‐ and multiple‐dose adefovir dipivoxil (ADV) in healthy Chinese subjects.MethodsForty‐two healthy subjects were randomized into 5, 10, 20, 40 and 60‐mg dose groups for safety assessment. Nine and 10 healthy males were enrolled for a single‐dose pharmacokinetic profile and assessment of the effect of food on the pharmacokinetics of adefovir (PMEA), respectively. Another 10 healthy subjects were enrolled for a multiple‐dose safety assessment and pharmacokinetic profile. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters, and pharmacokinetics were assessed by determining PMEA concentrations with a validated LC‐MS/MS method.ResultsNo serious adverse events occurred. The pharmacokinetic parameters of PMEA following ADV 10, 20 and 40 mg were: geometric mean [95% confidence interval (CI)] for AUC0−24 h 227 (205, 253), 423 (361, 506) and 686 (585, 828) µg l−1 h, Cmax 23.0 (20.7, 27.3), 47.4 (42.8, 53.2) and 83.6 (72.6, 97.4) µg l−1, arithmetic mean (95% CI) for t1/2 6.8 (6.3, 7.3), 7.4 (6.7, 8.1) and 7.7 (6.5, 8.9) h, median value (range) for tmax 1.00 (1.00–2.00), 0.75 (0.75–2.50) and 1.00 (0.75–2.00) h, respectively. The steady‐state pharmacokinetics parameters were similar to those following a single dose. The AUC of PMEA was unaffected by food.ConclusionADV is safe and well tolerated in healthy Chinese subjects. The mean Cmax of PMEA is proportional to dose, but the linearity of AUC needs further study. There is no accumulation following multiple doses of ADV and the extent of absorption of PMEA is unaffected by food.
Effect ofABCB1(MDR1) haplotypes derived from G2677T/C3435T on the pharmacokinetics of amlodipine in healthy subjects
Authors: Kim Kyoung‐Ah , Park Pil‐Whan , Park Ji‐Young 
Published: July 2006

AimWe aimed to investigate the effect of theABCB1gene on the pharmacokinetics of amlodipine.MethodsBased on polymorphisms of theABCB1gene at positions 2677 and 3435, 26 healthy male participants were divided into three groups: subjects with 2677GG/3435CC (n = 9), 2677GT/3435CT (n = 9) and 2677TT/3435TT (n = 8). After a single‐dose administration of 5 mg amlodipine, plasma concentrations of amlodipine were measured and its pharmacokinetic characteristics were compared according toABCB1genotype.ResultsThe area under the plasma concentration–time curve was significantly lower in subjects with 2677TT/3435TT (140.8 ± 35.6 ng h−1 ml−1) and 2677GT/3435CT (149.8 ± 40.1 ng h−1 ml−1) than in those with 2677GG/3435CC (208.6 ± 39.2 ng h−1 ml−1) [95% confidence interval (CI) on the difference, 2677GG/3435CCvs.2677GT/3435CT 12.0, 105.6,P < 0.01; 2677GG/3435CCvs.2677TT/3435TT 19.6, 116.0,P < 0.01; 2677GT/3435CTvs.2677TT/3435TT − 39.2, 57.2,P > 0.05]. The peak plasma concentrations were highest in subjects with 2677GG/3435CC (3.8 ± 0.5 ng ml−1), lower in subjects with 2677GT/3435CT (3.2 ± 0.5 ng ml−1) and 2677TT/3435TT (2.7 ± 0.5 ng ml−1) in rank and showed a significant difference between those with 2677GG/3435CC and with 2677TT/3435TT (95% CI on the difference 0.4, 2.0,P < 0.01). However, the oral clearance was higher in subjects with 2677TT/3435TT (37.7 ± 10.2 l h−1) than in those with 2677GT/3435CT (35.7 ± 9.9 l h−1) and with 2677GG/3435CC (24.8 ± 5.4 l h−1) and exhibited a significant difference betweenABCB1genotype groups (95% CI on the difference, 2677GG/3435CCvs.2677GT/3435CT − 21.5, − 0.3,P < 0.05; 2677GG/3435CCvs.2677TT/3435TT − 23.8, − 2.0,P < 0.05).ConclusionAmlodipine pharmacokinetics was affected by the genetic polymorphisms of theABCB1gene in humans. These findings may provide a plausible explanation for interindividual variation in the disposition of amlodipine, although our study could not explain the exact mechanism(s) by which the polymorphicABCB1gene paradoxically reduces the plasma levels of amlodipine. Further evaluation is thus warranted.
Intraoperative haemodynamic stability in patients with phaeochromocytoma – minimally invasive vs conventional open surgery
Authors: Weismann Dirk , Fassnacht Martin , Weinberger Fabian , Hamelmann Wulf , Diehl Saskia , Lorenz Kerstin , Baerlehner Eckhard , Reincke Martin , Beuschlein Felix , Knoefel Wolfram , Nies Christoph , Hahner Stefanie , Allolio Bruno 
Published: July 2006

SummaryObjective  There is conflicting evidence, whether or not minimally invasive adrenalectomy (MA) is associated with an increased perioperative cardiovascular instability in phaeochromocytomas compared to conventional open adrenalectomy (CA).Design and patients  In a retrospective analysis of 49 patients with phaeochromocytoma we compared 27 cases of MA to 22 cases of CA by assessing intraoperative haemodynamic parameters and perioperative complications. Patients undergoing MA for adrenocortical adenomas (aldosteronomas n = 15, inactive adenomas n = 13) served as controls. Additionally, we investigated the effect of phenoxybenzamine (POB) pretreatment on intraoperative cardiovascular stability in 42 patients (ranked by maximum daily POB‐dose) by comparing the highest (n = 10) with the lowest (n = 10) POB dose quartile (0·32 ± 0·2 and 2·17 ± 0·6 mg/kg/day, P < 0·001).Results  In phaeochromocytomas we found no significant difference in intraoperative haemodynamic parameters or complications when comparing MA with CA. In comparison to adrenocortical adenomas, MA in phaeochromocytomas was associated with a significantly higher maximum systolic BP (188 ± 29 vs 154 ± 22 mmHg, P < 0·001), more frequent hypertensive episodes (1[0–4]vs 0[0–1], P < 0·001), more episodes of systolic BP > 200 mmHg (0[0–4]vs 0[0–1], P = 0·03) and a higher demand for intraoperative fluids (3194 ml vs 1750 ml, P < 0·001). Most haemodynamic parameters did not differ significantly between high‐dose POB pretreatment and low‐dose POB pretreatment, but high‐dose POB pretreatment was associated with a significantly higher intraoperative heart rate (120 ± 19·5 vs 94 ± 15·2 min−1, P < 0·01).Conclusion  There is no significant difference in haemodynamic stability between MA and CA in phaeochromocytomas, but it is significantly inferior when compared to MA for cortical adenomas. We could not detect a beneficial effect of high‐dose compared to low‐dose POB pretreatment on intraoperative cardiovascular stability.
Testicular function after 131I therapy for hyperthyroidism
Authors: Ceccarelli Claudia , Canale Domenico , Battisti Paolo , Caglieresi Carolina , Moschini Cecilia , Fiore Emilio , Grasso Lucia , Pinchera Aldo , Vitti Paolo 
Published: July 2006

SummaryObjective  Radioiodine‐131 is commonly used for treatment of hyperthyroidism but there are few available data on the effects of this treatment on male gonadal function. The untoward effects of 131I have been mainly studied in male patients treated with high doses for thyroid cancer. In the present work we studied the absorbed radiation dose to the testes and testicular function in hyperthyroid men after 131I treatment.Patients and measurements  Nineteen male hyperthyroid patients were enrolled in the study before 131I therapy. Seventeen of the patients had Graves’ disease and two had toxic adenoma. The study was subdivided into two parts: a dosimetric and a clinical study. Six patients were enrolled for the dosimetric study and 13 for the clinical study. The β dose delivered to the testes was evaluated by the Medical Internal Radiation Dose (MIRD) method. The γ dose was measured by thermoluminescent dosimeters (TLDs) placed on the skin overlying the inferior poles of the testes for 3 weeks after therapy. The clinical evaluation included hormone determination, ultrasound (US) of the testes and sperm analysis. Patients were followed up for 12 months after 131I therapy.Results  In the dosimetric study, the β dose absorbed in the testes was 12·5 ± 8·8 mGy (range 29–15 mGy) and the γ dose was 15·8 ± 5·3 mGy (range 24–11 mGy). The total dose to the testes for administered activity unit was 39 ± 14 µGy/MBq (range 27–86 µGy/MBq). In the clinical study, FSH did not change significantly after 131I treatment for the majority of patients. Serum testosterone (T) and the T/LH ratio were significantly reduced 45 days after treatment and returned to basal levels after 12 months. Ten out of 15 hyperthyroid patients (67%) had low sperm motility before treatment. A significant increase in progressive motility was observed after 131I therapy (Friedman test χ2 = 12·65, P = 0·01). Conversely, there was no significant variation in sperm concentration and percentage of normal forms after 131I.Conclusions  After 131I therapy, germinal epithelium and Leydig cell function undergo only marginal changes, which may have some significance in subjects with a pre‐existing fertility impairment.
Impairment of GH responsiveness to combined GH‐releasing hormone and arginine administration in adult patients with Prader‐Willi syndrome
Authors: Grugni G. , Marzullo P. , Ragusa L. , Sartorio A. , Trifirò G. , Liuzzi A. , Crinò A. ,   on behalf of the Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology
Published: July 2006

SummaryObjective It is unclear if poor health outcomes of adult patients with Prader‐Willi syndrome (PWS) are influenced by GH deficiency (GHD). Few studies have been focused on PWS adults, but further information on the concomitant role of obesity on GH/IGF‐I axis function is needed. The aim of our study was to investigate the prevalence of GHD in a large group of adult subjects with genetically confirmed PWS.Design and subjects We studied the GH response to a combined administration of GHRH (1 µg/kg i.v. at 0 minutes) and arginine (ARG) (30 g i.v., infused from 0 to 30 minutes) as well as the baseline IGF‐I levels, in a group of 44 PWS adults (18 males, 26 females) aged 18–41·1 years. The same protocol was carried out in a control group of 17 obese subjects (7 males, 10 females) aged 21·8–45·8 years.Measurements Blood samples were taken at −15 and 0 minutes and then 30, 45, 60, 90 and 120 minutes after GHRH administration. Serum GH and total IGF‐I concentrations were measured by chemioluminescence. Statistical analysis was performed by Student'st‐test for unpaired data, and using analysis of variance for parametric and nonparametric (Mann–Whitney test) data, where appropriate. The relationship between pairs of variables was assessed by Pearson's correlation. Independent variables influencing GH secretion were tested by multiple linear regression analysis.Results The GH response to GHRH + ARG was significantly lower in PWS patients (GH peak (mean ± SE) 8·4 ± 1·2 µg/l; AUC: 471·4 ± 77·8 µg/l/h) than obese subjects (GH peak 15·7 ± 2·9 µg/l,P < 0·02; AUC 956 ± 182·9 µg/l/h,P < 0·005). When considered individually, 17 of 44 PWS individuals (38·6%) were severely GHD, according to the cut‐off limit of 4·1 µg/l for obese individuals, and low IGF‐I‐values were present in 33 PWS patients. Moreover, impaired GH response was combined with subnormal IGF‐I levels in all PWS patients with GHD.Conclusions Adult subjects with PWS had a reduced responsiveness to GHRH + ARG administration associated with reduced IGF‐I levels. In addition, a severe GHD for age was demonstrated in a significant percentage of PWS subjects. These findings are in agreement with the hypothesis that a complex derangement of hypothalamus‐pituitary axis occurred in PWS, and suggested that impaired GH secretion is not an artefact of obesity.
Effects of Cation Properties on Sol‐gel Transition and Gel Properties of κ‐carrageenan
Authors: Lai V.M.F. , Wong P.A.‐L. , Lii C.‐Y. 
Published: July 2006

ABSTRACT:The phase transition temperatures, rheological properties and gel‐network characteristics for gelation of κ‐carrageenan‐salt (NaCl, KCl and CaCl2) solutions and their aged gels were investigated. The effectiveness of increasing gelling and gel‐melting temperatures at the salt concentrations examined followed the sequence of K+ > Ca2+ > Na+. This sequence was also true for the gel strength and the melting enthalpy (DH) of the most crosslinked junction zones of aged gels at low salt concentrations. Nonetheless, a different order (Ca++ > K+ and Na+) was found for increasing storage modulus and gelation rate during early‐stage gelation, thermal hysteresis and the DH of aged gels in some salt‐carrageenan systems.
Metagenomic DNA fragments that affect Escherichia coli mutational pathways
Authors: Yang Hanjing , To Kam H. , Aguila Sharon J. , Miller Jeffrey H. 
Published: July 2006

SummaryA multicopy cloning approach was used to search for metagenomic DNA fragments that affect Escherichia coli mutational pathways. Soil metagenomic expression libraries were constructed with DNA samples prepared directly from soil samples collected from the UCLA Botanical Garden. Using frameshift mutator screening, we obtained a total of 26 unique metagenomic fragments that stimulate frameshift rates in an E. coli wild‐type host. Mutational enhancer strains such as an ndk‐deficient strain and a temperature sensitive mutS strain (mutS60) were used to further verify the mutator phenotype. We found that the presence of multiple copies of certain types of metagenomic DNA sequence repeats cause general genome instability in the wild‐type E. coli host and the effect can be suppressed by overproducing a DNA mismatch component MutL. In addition, we identified nine metagenomic mutator genes (designated as smu genes) that encode proteins that have not been linked to mutator phenotypes prior to this study including a putative RNA methyltransferase Smu10A. The strain overproducing Smu10A displays one prominent base substitution hotspot in the rpoB gene, which coincides with the base substitution hotspot we have observed in cells that are partially deficient in the proofreading function carried out by the DNA polymerase III epsilon subunit. Based on the structural conservation of DNA replication/recombination/repair machineries among microorganisms, this approach would allow us to both identify new mutational pathways in E. coli and to find genes involved in DNA replication, recombination or DNA repair from vast unculturable microbes.
Embryo Production in Dogs: from In Vitro Fertilization to Cloning
Authors: Luvoni GC , Chigioni S , Beccaglia M 
Published: July 2006

ContentsIncreased availability of canine embryos would be desirable to develop research and to apply assisted reproductive technologies in the treatment of infertility and in the improvement of reproductive performances in valuable Canids, both domestic and non‐domestic. Embryo production through in vitro fertilization and nuclear transfer has been technically achieved in the dog, and the transfer of cloned embryos has recently resulted in the birth of puppies. However, the efficiency of these technologies is still very limited. This is mainly because of the peculiar characteristics of the canine oocyte and the lack of its full acquisition of developmental competence in vitro. This paper discusses the latest results and aspects on which further research should be focused to provide advances in the field.