bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pharmacokinetic and pharmacodynamic study of desmopressin: evaluating sex differences and the effect of pre-treatment with piroxicam, and further validation of an indirect response model
Authors: Odeberg Johanna Mercke , Callréus Torbjörn , Lundin Stefan , Roth E Bodil , Höglund Peter 
Published: October 2004

Abstract
Desmopressin is a synthetic vasopressin analogue mainly used in treatment of diabetes insipidus and nocturia. Studies in rats have revealed a sex difference in the response to a vasopressin infusion, which was diminished after treatment with an NSAID. This study was performed in man to investigate the influence of sex and concomitant treatment of piroxicam on the pharmacokinetics and dynamics of desmopressin, and to validate a previously described indirect response model. Eight healthy males and eight healthy females participated in the trial, which was conducted in a pharmacokinetic (PK) part followed by a pharmacodynamic (PD) part. Desmopressin was administered intravenously as a single dose (PK = dose 2 μg, PD = dose 0.2 μg). Piroxicam was administered to achieve steady state. The pharmacokinetic parameters of desmopressin were estimated and calculated by means of two-compartmental analysis. In the dynamic part a study design based on an oral hydration model was used. Parameters for urine flow and urine osmolality were estimated. Individual estimates of the pharmacokinetic parameters served as input to the indirect response model that subsequently was fitted to urine osmolality data. The pharmacokinetics of desmopressin after a fixed bolus injection was neither influenced by piroxicam nor sex of the subject. The pharmacodynamics of desmopressin showed a sex difference where females exhibited a more pronounced antidiuretic effect than males, which was statistically significant when the effects were submaximal (&gt;4.5 h after dose). The sex differences were diminished after pre-treatment with piroxicam, indicating a prostaglandin PGE2-mediated mechanism. The indirect response model was confirmed, although the modelling could not distinguish a sex difference, indicating a limitation of this model compared with traditional descriptive statistics.
The combination of modified antioxidant enzymes for anti-thrombotic protection of the vascular wall: the significance of covalent connection of superoxide dismutase and catalase activities
Authors: Maksimenko Alexander V , Golubykh Vladimir L , Tischenko Elena G 
Published: October 2004

Abstract
Vascular wall protection can be achieved by preventive attachment to the vascular wall of antioxidants and elimination/neutralization of toxic products after their disproportioning. For this purpose we have prepared covalent conjugates between the vascular wall glycosaminglycan chondroitin sulfate (CHS) and the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The following conjugates were obtained: SOD-CHS, CAT-CHS and SOD-CHS-CAT. Their anti-thrombotic activity was comparedin a rat model of arterial thrombosis by measuring the time of occlusion emergence and thrombus mass. It is noteworthy that the effectiveness of single bolus injections of SOD-CHS/CAT-CHS mixture was much lower than that of the bienzymic SOD-CHS-CAT conjugate. The conjugate SOD-CHS-CAT proved to be anti-thrombotically effective in doses two orders of magnitude lower than the native biocatalysts and an order of magnitude lower than SOD-CHS and CAT-CHS derivatives. For effective anti-thrombotic protection in oxidative conditions it is important to maintain the stable connection of SOD and CAT activity on the vascular wall and the large size of these conjugates. Covalent conjugate SOD-CHS-CAT is the best prospect for pharmaceutical development.
Red marine alga Bryothamnion triquetrum lectin induces endothelium-dependent relaxation of the rat aorta via release of nitric oxide
Authors: Lima Ricardo F , Criddle David N , Souza Emmanuel P , Sampaio Alexandre H , Nascimento Kyria S , Cavada Benildo S , Assreuy Ana Maria S 
Published: October 2004

Abstract
We have investigated the vascular relaxant effects of the lectin from a red marine alga Bryothamnion triquetrum (BTL), in particular, the endothelial-dependency and the participation of a specific glycoprotein-binding site. BTL (1–100 μg mL−1) was applied to rat isolated aortic rings, with or without endothelium, tonically precontracted with phenylephrine (0.1 μm). Endothelium-dependent relaxation was assessed in the presence of indometacin (10 μm), l-nitro arginine methyl ester (L-NAME, 100 μm) and tetraethylammonium (TEA, 500 μm). For the involvement of the glycoprotein-binding site, BTL was assayed in presence of mucin (300 μg mL−1) or N-acetyl d-glucosamine (GlcNAc; 300 μg mL−1), a specific and non-specific lectin-binding sugar, respectively. BTL fully and concentration dependently relaxed preparations that possessed an intact endothelium (IC50 (concn producing 50% contraction) = 12.1 ± 1.6 μg mL−1), whereas no significant relaxation was observed in endothelial-denuded tissue. L-NAME, but not indometacin or TEA, completely inhibited the lectin relaxation, suggesting the involvement of nitric oxide (NO). The lectin in association with mucin, but not with GlcNAc, inhibited BTL-induced relaxation, implicating the involvement of the lectin binding site. Our data suggest that the relaxant effect of the red marine alga Bryothamnion triquetrum lectin on isolated aorta occurs via interaction with a specific lectin-binding site on the endothelium, resulting in a release of NO.
Induction of apoptosis in human breast adenocarcinoma MCF-7 cells by prodelphinidin B-2 3,3′-di-O-gallate from Myrica rubra via Fas-mediated pathway
Authors: Kuo Po-Lin , Hsu Ya-Ling , Lin Ta-Chen , Lin Liang-Tzung , Lin Chun-Ching 
Published: October 2004

Abstract
Myrica rubra Sieb et Zucc. (Myricaceae) is well known as a rich source of tannins. Prodelphinidin B-2 3,3′-di-O-gallate (PB233′OG) is a proanthocyanidin gallate that has been reported to exhibit anti-oxidant and antiviral activity. In this study, we evaluated the anti-proliferative activity of PB233′OG isolated from the bark of M. rubra in human breast adenocarcinoma MCF-7 cells. To identity the anti-cancer mechanism of PB233′OG, we assayed its effect on apoptosis, cell cycle distribution, and levels of p53, p21/WAF1, Fas/APO-1 receptor and Fas ligand. The results showed that PB233′OG induced apoptosis of MCF-7 cells without mediation of p53 and p21/WAF1. We suggest that Fas/Fas ligand apoptotic system is the main pathway of PB233′OG-mediated apoptosis of MCF-7 cells. Our study reports here for the first time that the activity of the Fas/Fas ligand apoptotic system may participate in the anti-proliferative activity of PB233′OG in MCF-7 cells.
Microsphere-liposome complexes protect adenoviral vectors from neutralising antibody without losses in transfection efficiency, in-vitro
Authors: Steel Jason C , Cavanagh Heather M A , Burton Mark A , Kalle Wouter H J 
Published: October 2004

Abstract
Adenoviral vectors have been commonly used in gene therapy protocols but the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced, which limits further administration. This study examines the effectiveness of a novel combination of microspheres and liposomes for the shielding of adenovirus from neutralising antibodies in an in-vitro setting. We show that liposomes are effective in the protection of adenovirus from neutralising antibody and that the conjugation of these complexes to microspheres augments the level of protection. This study further reveals that previously neutralised adenovirus may still be transported into the cell via liposome-cell interactions and is still capable of expressing its genes, making this vector an effective tool for circumvention of the humoral immune response. We also looked at possible side effects of using the complexes, namely increases in cytotoxicity and reductions in transfection efficiency. Our results showed that varying the liposome:adenovirus ratio can reduce the cytotoxicity of the vector as well as increase the transfection efficiency. In addition, in cell lines that are adenoviral competent, transfection efficiencies on par with uncomplexed adenoviral vectors were achievable with the combination vector.
Investigation into the mast cell stabilizing activity of nature-identical and synthetic indanones
Authors: Frankish Neil , Farrell Ronan , Sheridan Helen 
Published: October 2004

Abstract
As part of an ongoing search for novel molecules with therapeutic potential we examined the mediator release inhibition activity of a number of indanones and their derivatives. The aldol condensation product 18 was approximately twice as potent as disodium cromoglycate as an inhibitor of compound 48/80-stimulated histamine release from rat peritoneal mast cells. The activity of this class of dimeric indanone compound is significantly higher than controls and may represent a new class of mast cell stabilizing agents. Compound 18 has been selected for further biological evaluation of its mast cell stabilization profile.
Corni fructus as the major herb of Die-Huang-Wan for lowering plasma glucose in Wistar rats
Authors: Liou Shorong-Shii , Liu I-Min , Hsu Sheng-Fa , Cheng Juei-Tang 
Published: October 2004

Abstract
Die-Huang-Wan is a mixture of six herbs used to lower plasma glucose by increasing insulin secretion in normal rats. Die-Huang-Wan contains the herbs dioscorea (Dioscoreae rhizoma), cornus (Corni fructus), alisma (Rhizoma alismatis), holelen (Poria), rehmannia (Rehmanniae radix) and tree peony bark (Moutan radicis cortex). The present study was designed to clarify the major herb contributing to the plasma glucose-lowering action of Die-Huang-Wan in rats. A decrease in plasma glucose was not observed in Wistar rats treated with the cornus-deleted formula of Die-Huang-Wan; however, the action was retained in the other herb-deleted formulas containing cornus. In normal rats, the decrease in plasma glucose and increase in plasma insulin concentrations were dependent on the dose of cornus and were similar to those produced by Die-Huang-Wan. Treatment of Wistar rats with each of the other five herbs separately did not result in a decrease in plasma glucose. Moreover, the increase in plasma insulin or reduction in plasma glucose resulting from cornus treatment was blocked by atropine or 4-diphenylacetoxy-N-methylpiperidine methiodide mustard, indicating mediation of muscarinic M3 receptors similar to that caused by Die-Huang-Wan. These results suggest that cornus is the major contributor to the plasma glucose-lowering action in Die-Huang-Wan in normal rats.
Role of the carboxylic group in the antispasmodic and vasorelaxant action displayed by kaurenoic acid
Authors: Ambrosio Sergio R , Tirapelli Carlos R , Coutinho Silvia T , de Oliveira Dionéia C R , de Oliveira Ana M , Da Costa Fernando B 
Published: October 2004

Abstract
The present work describes the investigation of the role of the carboxylic group in the structure-activity relationship of the diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid, KA) in inhibiting rat aorta contraction. For this purpose the methylation of the C-19 carboxyl group of KA was carried out. The effects of the obtained ent-methyl-kaur-16-en-19-oate (KAMe) were compared with those induced by KA. Vascular reactivity experiments showed that KA (50 and 100 μm) concentration-dependently inhibited KCl-induced contraction in both endothelium-intact and denuded rat aortic rings. On the other hand, KAMe attenuated KCl-induced contraction at 100 μm, but not at 50 μm. KA also reduced CaCl2-induced contraction in Ca2+-free solution containing KCl (30 mM). Again, KAMe produced a less accentuated reduction in CaCl2-induced contraction than that induced by the acid KA. KAMe (1–450 μm) concentration-dependently relaxed KCl-pre-contracted rings (percentages of relaxation 82.57±1.65 and 70.55±4.71, respectively) with denuded endothelium. Similarly, the relaxation induced by KA on phenylephrine (Phe)-pre-contracted rings (73.06±3.68%) was more pronounced than that found for KAMe (53.68±4.75%). Pre-incubation of denuded rings for different periods with KA and KAMe showed that the equilibrium periods required by each compound to achieve its maximal inhibitory response on KCl-induced contraction are different. Collectively, our results provide functional evidence that methylation of the C-19 carboxyl group of KA reduces but does not abolish the antispasmodic activity displayed by KA. Additionally, we showed that the equilibrium period is a critical step for the inhibitory effect displayed by kaurane-type diterpenes.
Hepatoprotective activity of Terminalia catappa L. leaves and its two triterpenoids
Authors: Gao Jing , Tang Xinhui , Dou Huan , Fan Yimei , Zhao Xiaoning , Xu Qiang 
Published: October 2004

Abstract
The aim of this study was to evaluate the effect of the chloroform extract of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCI4)-induced acute liver damage and D-galactosamine (D-GaIN)-induced hepatocyte injury. Moreover, the effects of ursolic acid and asiatic acid, two isolated components of TCCE, on mitochondria and free radicals were investigated to determine the mechanism underlying the action of TCCE on hepatotoxicity. In the acute hepatic damage test, remarkable rises in the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (5.7- and 2.0-fold) induced by CCI4 were reversed and significant morphological changes were lessened with pre-treatment with 50 and 100 mg kg−1 TCCE. In the hepatocyte injury experiment, the increases in ALT and AST levels (1.9- and 2.1-fold) in the medium of primary cultured hepatocytes induced by D-GaIN were blocked by pre-treatment with 0.05, 0.1, 0.5 gL−1 TCCE. In addition, Ca2+-induced mitochondrial swelling was dose-dependently inhibited by 50–500 μm ursolic acid and asiatic acid. Both ursolic acid and asiatic acid, at concentrations ranging from 50 to 500 μm, showed dose-dependent superoxide anion and hydroxyl radical scavenging activity. It can be concluded that TCCE has hepatoprotective activity and the mechanism is related to protection of liver mitochondria and the scavenging action on free radicals.
Griseofulvin micronization and dissolution rate improvement by supercritical assisted atomization
Authors: Reverchon E , Porta G Della , Spada A , Antonacci A 
Published: October 2004

Abstract
Supercritical assisted atomization (SAA) was used to micronize griseofulvin (GF), selected as a model compound, to verify the performance of this innovative process. SAA is based on the solubilization of supercritical carbon dioxide in a liquid solution containing the drug. The ternary mixture is then sprayed through a nozzle and microparticles are formed as a consequence of the enhanced atomization. Precipitation temperature and drug concentration in the liquid solution were studied to evaluate their influence on morphology and size of precipitated particles. A good particle size control was obtained and GF spherical particles with mean diameters ranging from 0.5 to 2.5 μm were produced with a narrow particle size distribution. Processed GF was characterized by high-performance liquid chromatography-UV/vis, headspace-gas chromatography-flame ionization detection, differential scanning calorimetry, BET and X-ray analyses. No drug degradation was observed and a solvent residue (acetone) less than 800 ppm was measured. GF microparticles showed good stability and surface areas ranging from about 4 to 6 m2 g−1; moreover, the micronized drug retained the crystalline habit. GF capsules were formulated with starch and used to compare the dissolution rate of SAA-processed and conventional jet-milled drug. A faster dissolution and a better reproducibility of the dissolution profile were observed for SAA-processed GF.
Metabolism of the dihydropyridine calcium channel blockers mebudipine and dibudipine by isolated rat hepatocytes
Authors: Bohlooli S , Mahmoudian M , Skellern G G , Grant M H , Tettey J N A 
Published: October 2004

Abstract
The prototype 1,4-dihydropyridine (1,4-DHP) nifedipine, indicated for the management of hypertension and angina pectoris, has drawbacks of rapid onset of vasodilating action and a short half-life. Several newer analogues have been designed to offset these problems and these include mebudipine and dibudipine. These analogues contain t-butyl substituents that have been selected to alter the fast metabolism without altering pharmacological activity. In this study, the metabolism of mebudipine and dibudipine by isolated rat hepatocytes has been investigated. These compounds were extensively metabolized in 2 h by oxidative pathways, analogous to those known for nifedipine, and by O-glucuronidation after hydroxylation of the t-butyl substituents. The in-vitro half-lives of mebudipine (22 ± 7.1 min) and dibudipine (40 ± 9.8 min) were significantly longer than that of nifedipine (5.5 ± 1.1 min), which was investigated in parallel in this study. These newer 1,4-DHPs address the problem of the short half-life of nifedipine and have potential for further development in view of their comparable potency to nifedipine.
In-vitro vasodilatory activity of the hexanic extract of leaves and stems from Piper truncatum Vell. in rats
Authors: Raimundo Juliana Montani , de Almeida Roberta Ramos , Velozo Leosvaldo Salazar Marques , Kaplan Maria Auxiliadora Coelho , Gattass Cerli Rocha , Zapata-Sudo Gisele 
Published: October 2004

Abstract
Several plants from the Brazilian Tropical Forest are used in folk medicine for treatment of hypertension and asthma. In this study, we investigated the effects of hexanic extracts of leaves (HLE) and stems (HSE) from Piper truncatum on the contractility of cardiac, vascular and tracheal smooth muscles. Twitches of cardiac muscles obtained with electrical stimulation were recorded before and after exposure to increasing concentrations of hexanic extracts. HLE and HSE respectively reduced significantly the amplitude of twitches to 57.05 ± 11.63 and 61.58 ±5.70% of control in the presence of 100 μg mL−1. Contractile response to a single concentration of adrenaline (epinephrine) was measured before and after exposure of rat aorta rings to HLE and HSE. Both extracts inhibited aorta contraction in a concentration-dependent manner. The concentration of 50% inhibitory effect (IC50) was 32.3 ± 13.8 and 47.0 ± 23.8 μg mL−1 for HLE and HSE, respectively, in aorta with intact endothelium. HLE and HSE also reduced the acetylcholine-precontracted trachea in a concentration-dependent manner with maximal effect observed at 250 and 350 μg mL−1, respectively. Vasodilatation and trachea relaxation induced by HLE and HSE could explain the use of Piper extracts to reduce blood pressure and bronchospasm.
Fenestration of the Lamina Terminalis as a Valuable Adjunct in Aneurysm Surgery
Authors: Andaluz Norberto , Zuccarello Mario 
Published: October 2004

Abstract

OBJECTIVE:
Hydrocephalus, vasospasm, and frontobasal injury are common complications after aneurysmal subarachnoid hemorrhage (SAH) from anterior communicating artery aneurysms. Previous studies have suggested that fenestration of the lamina terminalis (FLT) during surgery may be associated with reduced rates of shunt-dependent hydrocephalus and vasospasm. We report 106 patients affected by anterior communicating artery aneurysms and Fisher Grade 3 aneurysmal SAH and the affect of FLT on shunt-dependent hydrocephalus, vasospasm, and frontobasal injury.

METHODS:
During a 3-year period, 53 patients underwent FLT and 53 did not. We prospectively evaluated admission and discharge clinical grades, hydrocephalus at admission, occurrence of clinical vasospasm, need for interventional vasospasm therapy, frontobasal hypodensity incidence, and permanent ventriculoperitoneal shunting requirement. Follow-up ranged from 3 to 35 months (mean, 17.9 mo).

RESULTS:
Shunting incidence after aneurysmal SAH with hydrocephalus was 4.25% in patients who underwent FLT and 13.9% in patients who did not (P&lt; 0.001). Clinical cerebral vasospasm occurred in 29.6% of patients who underwent FLT and in 54.7% of patients who did not (P&lt; 0.001). Frontobasal hypodensity was identified postoperatively in 0% of patients who underwent FLT and in 5% of patients who did not. Good outcome was reported in 69.81% of patients who underwent FLT and in 33.96% of patients who did not (P&lt; 0.001). Poor outcome was associated with higher Hunt and Hess grades, need for ventricular drainage, elevated intracranial pressure, and multiple interventional vasospasm therapies. No complications were linked to FLT.

CONCLUSION:
FLT was associated with statistically significant decreases in shunting rates, incidence of vasospasm, and better outcomes. We recommend its routine use in patients with Fisher Grade 3 anterior communicating artery aneurysmal SAH.
Anatomy of the Anterior Temporal Lobe and the Frontotemporal Region Demonstrated by Fiber Dissection
Authors: Peuskens Diedrik , van Loon Johannes , Van Calenbergh Frank , van den Bergh Raymond , Goffin Jan , Plets Christian 
Published: October 2004

Abstract

OBJECTIVE:
The white matter structure of the anterior temporal lobe and the frontotemporal region is complex and not well appreciated from the available neurosurgical literature. The fiber dissection method is an excellent means of attaining a thorough knowledge of the three-dimensional structure of the white matter tracts. This study was performed to demonstrate the usefulness of the dissection technique in understanding the white matter anatomy and the effects of current surgical approaches on the subcortical structure of the region.

METHODS:
Seventeen brain specimens obtained at routine autopsy were dissected by use of Klingler's fiber dissection technique after preparation by fixation and freezing. The dissections were performed with an operating microscope and followed a stepwise pattern of progressive white matter dissection.

RESULTS:
The dissection is described in an orderly fashion showing the white matter tracts of the anterior temporal lobe and the frontotemporal region. An insight is gained into the three-dimensional course of the anterior loop of the optic radiation, the temporal stem, the anterior commissure, and the ansa peduncularis.

CONCLUSION:
The anterior temporal lobe and the frontotemporal region contain several important white matter tracts that can be uniquely understood by performing a white matter dissection of the region. Surgical procedures on the anterior temporal lobe differ substantially as to their repercussions on the subcortical white matter tract anatomy, as shown by the findings in this study.