bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic scaling of SJ‐8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, by species‐invariant time methods
Authors: Shin Beom S. , Kim Dong H. , Cho Chang Y. , Park Si K. , Chung Sun G. , Cho Eui H. , Lee Sun H. , Joo Jeong H. , Kwon Ho S. , Lee Kang C. , Yoo Sun D. 
Published: May 2003

AbstractThis study examined the pharmacokinetic disposition of SJ‐8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, in mice, rats, rabbits and dogs after i.v. administration. The serum concentration‐time curves of SJ‐8029 were best described by tri‐exponential equations in all these animal species. The mean Cl, Vss and t1/2 were 0.3 l/h, 0.1 l and 63.2 min in mice, 1.5 l/h, 1.6 l and 247.7 min in rats, 13.8 l/h, 39.6 l and 245.9 min in rabbits, and 29.2 l/h, 44.6 l and 117.4 min in dogs, respectively. Based on animal data, the pharmacokinetics of SJ‐8029 were predicted in humans using simple allometry and also by several species‐invariant time transformations using kallynochron, apolysichron and dienetichron times. The human pharmacokinetic parameters of Cl, Vss and t1/2 predicted by the simple allometry and various species‐invariant time methods were 50.4–145.0 l/h, 369.0–579.8 l and 242.0–1448.3 min, respectively. These preliminary parameter values may be useful in designing early pharmacokinetic studies of SJ‐8029 in humans. Copyright © 2003 John Wiley & Sons, Ltd.
Time dependent pharmacokinetics of albendazole in human
Authors: Mirfazaelian A. , Rouini M. R. , Dadashzadeh S. 
Published: May 2003

AbstractThe pharmacokinetics of the main metabolites of albendazole (albendazole sulphoxide (ABZ‐SO) and albendazole sulphone (ABZ‐SO2)) were studied in 12 healthy human volunteers in a double blind design on the first and last days of oral administration of 800 mg albendazole daily for 15 days.No significant differences were observed in Cmax, Tmax and Vd/F of ABZ‐SO, whereas the AUC, AUMC and T1/2 of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. There were also no significant differences in the Cmax, Tmax, Vd/F and T1/2 of ABZ‐SO2, whereas the AUC and AUMC of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing.These observations suggest time dependent pharmacokinetics of albendazole (observed for ABZ‐SO and ABZ‐SO2), which was explained on the basis of the induction of enzymes involved in the metabolism of ABZ‐SO (albendazole sulphoxide) to metabolites other than albendazole sulphone in multiple dosing. Copyright © 2003 John Wiley & Sons, Ltd.
Lack of interaction between HEPP, a new antiepileptic agent, and carbamazepine in rabbits
Authors: García A. Luis , Medina R. Liz , Pérez M. Rodolfo , Jung C. Helgi 
Published: May 2003

AbstractThe effect of the combination of a new anticonvulsant drug HEPP and carbamazepine (CBZ) on the pharmacokinetics of HEPP and CBZ was investigated using rabbits as an animal model. The study was performed in 18 male New Zealand white rabbits which were randomly divided into three groups, according to a balanced incomplete block design of three treatments and two periods. Plasma concentrations for HEPP and CBZ were assayed using HPLC methods. The results showed that the pharmacokinetic parameters Cmax, AUC and t1/2 were not statistically different when HEPP was administered alone and with CBZ, (AUC0−α 82.86±19.40 vs 83.24±12.56 µg h ml−1; t 1 2 β 3.40±0.29 vs 3.36±0.45 h; Cmax 18.93±2.99 vs 19.79±2.68 micro;g ml−1 and Tmax 1.27±0.16 vs 1.22±0.11 h for HEPP alone and HEPP plus CBZ respectively. Evaluation of the pharmacokinetic parameters of CBZ showed, AUC0−inf 61.5±21.7 vs 67.4±23.8 µg h ml−1; t12 4.60±1.54 vs 4.41±1.35 h; Cmax 8.45±3.83 vs 8.70±2.59 micro;g ml−1 when the drug was administered alone and CBZ plus HEPP, respectively. Our data indicate that there is no effect on the pharmacokinetics of either HEPP or CBZ, when they are administered simultaneously. Copyright © 2003 John Wiley & Sons, Ltd.
Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects
Authors: Wójcicki Jerzy , Jaroszynska Maria , Droździk Marek , Pawlik Andrzej , Gawrońska‐Szklarz Barbara , Sterna Rozalia 
Published: May 2003

AbstractThe lipophilic beta‐adrenoreceptor antagonist propranolol and hydrophilic atenolol have been studied to define their pharmacokinetic and pharmacodynamic characteristics in obese patients. A total of 43 subjects were allocated into three study groups: (1) healthy, lean, normolipaemic volunteers, (2) obese normolipaemic subjects, and (3) obese patients with lipid disorders. A crossover method with an interval of 2 weeks was applied for oral 80 mg propranolol and oral 100 mg atenolol administration. Heart rate as well as systolic and diastolic blood pressure were recorded during 24 h. At each time‐point of measurement blood serum concentration of propranolol and atenolol were evaluated. Pharmacokinetic parameters of the drugs were calculated using a one‐compartment open model for extravascular administration. There were no statistically significant differences in blood serum concentrations of propranolol between the studied groups. The concentrations of atenolol were significantly lower in both normolipaemic and hyperlipidaemic obese subjects. A trend towards increase in Vd/F and Cl/F of propranolol in obese patients with hyperlipidaemia were noted. In the case of water‐soluble atenolol, the AUC, Cmax, Cl/(F×BW) were significantly lower in obese hyperlipidaemic and normolipaemic patients in comparison with lean subjects. The pharmacodynamic effects of propranolol and atenolol in obese and lean subjects were of similar magnitude. The observed differences between obese and non‐obese persons were clinically not relevant. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of length of sampling schedule and washout interval on magnitude of drug carryover from period 1 to period 2 in two‐period, two‐treatment bioequivalence studies and its attendant effects on determination of bioequivalence
Authors: Dhariwal Kuldeep , Jackson Andre 
Published: May 2003

AbstractThe relationships between post‐dosing blood sampling schedules and length of washout interval on the percent of drug carryover into period 2, in a two‐treatment, two‐period, crossover bioequivalence study was investigated. Observed simulations were done using a two‐compartment model with a beta half‐life of 100 h, sampling to 200 and 300 h, followed by 1 to 4 washout half‐lives. These data were compared with simulations with sampling for 200 and 300 h and no carryover between periods (i.e. true data) and used to establish the per cent carryover. Pseudo‐observed concentration period 2 data were also generated for an experimental amiodarone bioequivalence study by adding either 5%, 10% or 50% of the period 2 Cmax value to the observed concentrations of selected subjects (i.e. those with longest half‐lives) to give a pseudo‐plasma concentration profile. Further investigation via simulation was done by including or excluding subjects with time 0 concentrations of 1%–10% of period 2 Cmax. The simulated data indicated that up to a 3% carryover of AUC into the second period of a bioequivalence study had no effect on the power of the 90% CI for AUC and Cmax. For amiodarone, second period pre‐dose drug concentrations equal to as much as 50% of the observed period 2 Cmax value had less effect on the 90% CI (i.e. compared with the true data) for AUC and Cmax than did subject deletion. Copyright © 2003 John Wiley & Sons, Ltd.
Revisiting the role of retinoid signaling in skeletal development
Authors: Weston Andrea D. , Hoffman Lisa M. , Underhill T. Michael 
Published: May 2003

AbstractSeveral years ago, it was discovered that an imbalance of vitamin A during embryonic development has dramatic teratogenic effects. These effects have since been attributed to vitamin A's most active metabolite, retinoic acid (RA), which itself profoundly influences the development of multiple organs including the skeleton. After decades of study, researchers are still uncovering the molecular basis whereby retinoids regulate skeletal development. Retinoid signaling involves several components, from the enzymes that control the synthesis and degradation of RA, to the cytoplasmic RA‐binding proteins, and the nuclear receptors that modulate gene transcription. As new functions for each component continue to be discovered, their developmental roles appear increasingly complex. Interestingly, each component has been implicated in skeletal development. Moreover, retinoid signaling comes into play at distinct stages throughout the developmental sequence of skeletogenesis, highlighting a fundamental role for this pathway in forming the adult skeleton. Consistent with these roles, manipulation of the retinoid signaling pathway significantly affects the expression of the skeletogenic master regulatory factors, Sox9 and Cbfa1. In addition to the fact that we now have a greater understanding of the retinoid signaling pathway on a molecular level, much more information is now available to begin placing retinoid signaling within the context of other factors that regulate skeletogenesis. Here we review these recent advances and describe our current understanding of how retinoid signaling functions to coordinate skeletal development. We also discuss future directions and clinical implications in this field. Birth Defects Research (Part C) 69:156–173, 2003. © 2003 Wiley‐Liss, Inc.
Morphogenesis and dysmorphogenesis of the appendicular skeleton
Authors: Shum Lillian , Coleman Cynthia M. , Hatakeyama Yuji , Tuan Rocky S. 
Published: May 2003

AbstractCartilage patterning and differentiation are prerequisites for skeletal development through endochondral ossification (EO). Multipotential mesenchymal cells undergo a complex process of cell fate determination to become chondroprogenitors and eventually differentiate into chondrocytes. These developmental processes require the orchestration of cell–cell and cell–matrix interactions. In this review, we present limb bud development as a model for cartilage patterning and differentiation. We summarize the molecular and cellular events and signaling pathways for axis patterning, cell condensation, cell fate determination, digit formation, interdigital apoptosis, EO, and joint formation. The interconnected nature of these pathways underscores the effects of genetic and teratogenic perturbations that result in skeletal birth defects. The topics reviewed also include limb dysmorphogenesis as a result of genetic disorders and environmental factors, including FGFR, GLI3, GDF5/CDMP1, Sox9, and Cbfa1 mutations, as well as thalidomide‐ and alcohol‐induced malformations. Understanding the complex interactions involved in cartilage development and EO provides insight into mechanisms underlying the biology of normal cartilage, congenital disorders, and pathologic adult cartilage. Birth Defects Research (Part C) 69:102–122, 2003. Published 2003 Wiley‐Liss, Inc.
Hyaluronan and CD44: Strategic players for cell–matrix interactions during chondrogenesis and matrix assembly
Authors: Knudson Cheryl B. 
Published: May 2003

AbstractEmbryonic induction, soluble and insoluble factors, receptors, and signal transduction are orchestrated for the morphogenesis of the cartilage elements. The interaction of cells with the extracellular matrix (ECM) may lead to altered cellular response to morphogens based on the formation of new adhesive contacts, or the uncoupling of cell–matrix interactions. Hyaluronan's influence on cell behavior, and its intimate association with cells are accomplished by a wide variety of specific binding proteins for hyaluronan. The temporal expression of the hyaluronan receptor CD44 (which is expressed as several alternatively spliced variants) may be strategic to many of these cell–matrix interactions during chondrogenesis. CD44 expression is temporally coincident with the reduction of intercellular spaces at the regions of future cartilage deposition. The spatial organization of CD44 at the cell surface may function to establish or regulate the structure of the pericellular matrix dependent on a hyaluronan scaffold. As the ECM is modified during embryogenesis, the cellular response to inductive signals may be altered. An uncoupling of chondrocyte–hyaluronan interaction leads to chondrocytic chondrolysis. Thus, consideration of cell–matrix interactions during chondrogenesis, in the light of our current understanding of the temporal and spatial expression of signaling morphogens, should become a promising focus of future research endeavors. Birth Defects Research (Part C) 69: 174–196, 2003. © 2003 Wiley‐Liss, Inc.
Development of synovial joints
Authors: Archer Charles W. , Dowthwaite Gary P. , Francis‐West Philippa 
Published: May 2003

AbstractSynovial joints arise through two main processes. In long bone elements, cartilaginous differentiation occurs across the locations of the prospective joints that then segment secondarily. This process occurs through the development of a noncartilaginous region known as the interzone. The interzone becomes an important signaling center to the opposing elements, which can regulate growth through such factors as GDF‐5. The interzone also expresses bone morphogenetic proteins (BMPs) and their antagonists, such as noggin. Overexpression of BMPs, or the loss of noggin leads to joint fusions. The interzone also expresses Wnt‐14, which appears to be specific for this region in the developing anlagen, and regulates its nonchondrogenic nature. Cavitation of the joint follows, driven by selective high‐level synthesis of hyaluronan by interzone cells and presumptive synovial cells. In addition, as the interzone disperses during cavity enlargement, data are now accruing that suggest that both the synovium and articular cartilage develop from this population. Finally, the development of articular cartilage progresses through appositional growth driven by a progenitor/stem cell subpopulation that resides in the articular surface. The individual elements of the skeleton are connected together at regions termed joints or articulations. Classically, there are three broad categories of joints: immovable joints (syntharthroses); mixed articulations, in which the range of movement is limited (amphiarthroses); and the movable, or synovial, joints (diarthroses). This review concentrates on the development of the synovial joints. Birth Defects Research (Part C) 69:144–155, 2003. © 2003 Wiley‐Liss, Inc.
Comparison of qualitative and quantitative analyses of age‐related changes in clivus bone marrow on MR imaging
Authors: Bayramoǧlu Alp , Aydingöz Üstün , Hayran Mutlu , Öztürk Hakan , Cumhur Meserret 
Published: June 2003

AbstractMagnetic resonance (MR) imaging is capable of detecting a wide spectrum of diseases involving clivus bone marrow. To evaluate any pathology in this region, the normal MR signal intensity patterns according to age should be known. Assessment of clivus bone marrow is usually and more efficiently made visually (qualitatively) on routine MR imaging. To compare the qualitative and quantitative analyses of age‐related changes in clivus bone marrow on MR imaging, midsagittal T1‐weighted MR images of the clivus bone marrow were prospectively evaluated in 201 subjects. MR signal intensity patterns of clivus bone marrow were qualitatively graded from I to III according to the proportions of low and high signal intensity areas within the clivus (Grade I: predominantly hypointense, Grade III: predominantly hyperintense). Signal intensity measurements were also made from the clivus, pons, and the cerebrospinal fluid within the fourth ventricle. Grade I pattern was observed in 92% of the subjects in the first decade, whereas Grade III pattern was not seen in this decade; Grade I pattern was absent in all but one of the subjects over the age of 50. Mean values of clivus/pons and clivus/CSF signal intensity measurements gradually increased with age in both males and females. Comparison of these ratios in each gender showed statistically significant higher values for males (P < 0.05). Comparison of the qualitative and quantitative results showed that calculated mean values of intensity ratios for each grade were different from each other; however, there was an overlap of the ranges of signal intensity ratios for Grades II and III. Visual evaluation of the clivus bone marrow MR signal is validated with the quantitative assessment results. Statistically significant higher intensity ratios in males may reflect a difference between gender in the bone mineral content under the influence of sex hormones. Clin. Anat. 16:304–308, 2003. © 2003 Wiley‐Liss, Inc.
Bilateral asymmetric deficiency of the pectoralis major muscle
Authors: Mosconi Tony , Kamath Sylvia 
Published: June 2003

AbstractWe observed a rare, bilateral congenital deficiency of the pectoralis major muscle in a 72‐year‐old female cadaver in our gross anatomy dissection laboratory. The outward appearance of the anterior thoracic wall, which included well‐developed breasts, revealed no obvious abnormalities. Upon dissection, the following features were observed: 1) on the left side, the sternal portion of the sternocostal head of the pectoralis major muscle was absent, the costal portion of the sternocostal head and the clavicular head were both well developed, a normal pectoralis minor was present, and the deltoid and subclavius muscles were not hypertrophied as is often the case when the pectoralis major muscle is deficient; 2) on the right side, the entire pectoralis major muscle was absent and the pectoralis minor, deltoid, and coracobrachialis muscles were infiltrated with connective tissue and fat; and 3) on both sides, the lateral pectoral nerves were absent and the medial pectoral nerves were present. The absence of the lateral pectoral nerves suggests that the deficiencies in the pectoralis major muscles are congenital malformations resulting from a developmental failure of the embryonic muscles rather than a sequel to polio or Poland's syndrome. Clin. Anat. 16:346–349, 2003. © 2003 Wiley‐Liss, Inc.
Median nerve penetration by a muscular branch of the brachial artery
Authors: Roy T. S. 
Published: June 2003

AbstractArterial variations in the distal half of the arm are common (Anagnostopoulou and Venieratos 1999, J. Anat. 195:471–476). We observed a rare variant of a muscular branch of the brachial artery that penetrated the median nerve in the lower part of the arm. After its origin from the posteromedial surface of the brachial artery, the muscular branch passed through a nervous loop in the median nerve to enter and supply the brachialis muscle. At the site of arterial penetration, the nerve displayed perineurial thickening and increased fasciculation and interfascicular connective tissue. Three small branches of the artery supplied the nerve fascicles. We did not observe nerve compression or muscular changes, but the possibility of altered clinical symptoms produced by irritation from arterial pulsation cannot be ruled out. This variation may be clinically important because symptoms of median nerve compression arising from similar variations are often confused with more common causes, such as radiculopathy and carpal tunnel syndrome. Clin. Anat. 16:335–339, 2003. © 2003 Wiley‐Liss, Inc.
Duplicated inferior vena cava and crossed renal ectopia with abdominal aortic aneurysm: Preoperative anatomic studies facilitate surgery
Authors: Shaw M. B. K. , Cutress M. , Papavassiliou V. , White S. , Thompson M. , Sayers R. 
Published: June 2003

AbstractAbdominal aortic aneurysm in association with duplication of the inferior vena cava and crossed renal ectopia is described for the first time. Preoperative imaging with computer‐aided tomography provided good visualization of the local anatomy, allowing the surgical approach to be adapted for the best access to the surgical site. A retroperitoneal approach was successfully used for repair of the abdominal aortic aneurysm. Clin. Anat. 16:355–357, 2003. © 2003 Wiley‐Liss, Inc.
Dual sensory innervation of the dorsum of the thumb
Authors: Madhavi C. , Holla S. J. 
Published: June 2003

AbstractThe value of the thumb has been described as being almost equal to the rest of the fingers combined (Decker and du Plessis, eds. 1986, Lee McGregor's synopsis of surgical anatomy. 12th ed. p 496). Normal hand function is dependent upon the integrity of both the sensory and motor innervation of the thumb. A thorough knowledge of normal and anomalous sensory innervation of the digits has clinical application because of the increased use of local anesthesia and developments in plastic surgery involving the skin of the digits. Herein is reported an unusual variation in the sensory innervation of the thumb in an adult cadaver. The normal innervation of the dorsum of the thumb is reviewed, and the clinical importance of this variation is discussed. Clin. Anat. 16:344–345, 2003. © 2003 Wiley‐Liss, Inc.
Anomalous flexor digiti minimi brevis in Guyon's canal
Authors: Madhavi C. , Holla S. J. 
Published: June 2003

AbstractIn an adult male cadaver, the flexor digiti minimi brevis, a muscle of the hypothenar eminence, was found to arise from the superficial transverse septum (between the superficially placed flexor carpi ulnaris, palmaris longus, and flexor carpi radialis muscles, and the deeply placed flexor digitorum superficialis muscle) in the distal fourth of the flexor aspect of the left forearm. The muscle exhibited two strata of muscle fibers at its origin. The superficial stratum was a thin layer of transversely running fibers confined to the forearm, which has not been previously reported. The deep stratum, a thick layer of longitudinally running fibers, formed the bulk of the muscle. It traversed Guyon's canal superficial to the ulnar nerve and vessels to reach the hypothenar eminence. Its course through Guyon's canal could be a cause for ulnar tunnel syndrome. The ulnar nerve trunk innervated not only the anomalous flexor digiti minimi brevis muscle, but also abductor digiti minimi and palmaris brevis. This may be due to the common phylogeny of these three muscles from the same muscle mass. Clin. Anat. 16:340–343, 2003. © 2003 Wiley‐Liss, Inc.
Lateral femoral cutaneous neuralgia: An anatomical insight
Authors: Dias Filho L.C. , Valença M.M. , Guimarães Filho F.A.V. , Medeiros R.C. , Silva R.A.M. , Morais M.G.V. , Valente F.P. , França S.M.L. 
Published: June 2003

AbstractA detailed anatomic study was carried out on the lateral femoral cutaneous nerve to better understand the etiology and treatment of lateral femoral cutaneous neuralgia. As it passed from the pelvis into the thigh, the lateral femoral cutaneous nerve ran through an “aponeuroticofascial tunnel,” beginning at the iliopubic tract and ending at the inguinal ligament; as it passed through the tunnel, an enlargement in its side‐to‐side diameter was observed, suggesting that the fascial structures proximal to the inguinal ligament may be implicated in the genesis of lateral femoral cutaneous neuralgia. The finding of pseudoneuromas at this location, distant from the inguinal ligament, supports this hypothesis. The anterior superior iliac spine is located approximately 0.7 cm from the lateral femoral cutaneous nerve and serves as the bony landmark for nerve localization. Within the first 3 cm of leaving the pelvis, the lateral femoral cutaneous nerve was observed deep to the fascia lata; therefore, surgical dissection within the subcutaneous fascia may be conducted with relative impunity near the anterior superior iliac spine just inferior to the inguinal ligament. In 36% of cases there was no posterior branch of the nerve, which is correlated to lateral femoral cutaneous neuralgia symptoms often being limited to the anterior branch region. An accessory nerve was found in 30% of cases. Clin. Anat. 16:309–316, 2003. © 2003 Wiley‐Liss, Inc.