bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicentric, placebo‐controlled, double‐blind clinical trial of &beta;‐sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia
Authors: KLIPPEL K.F. , HILTL D.M. , SCHIPP B. ,   for the German BPH‐Phyto study group‡
Published: November 2003

Objective To report the results of a double‐blind, placebo‐controlled trial to evaluate Azuprostat® , a &beta;‐sitosterol, in patients with symptoms of outlet obstruction caused by benign prostatic hyperplasia (BPH).Patients and methods A randomized, double‐blind and placebo‐controlled clinical trial was conducted to assess the efficacy and safety of 130 mg free &beta;‐sitosterol (phytosterol) daily, using the international prostate symptom score (IPSS) as the primary outcome variable. In total, 177 patients with BPH were recruited for 6 months of treatment in 13 study centres. In addition to the relative difference in the IPSS, changes in quality of life, peak urinary flow rate (Qmax ) and post‐void residual urinary volume (PVR) were recorded. The drug used in the trial consisted of a chemically defined extract of phytosterols, derived for example from species of Pinus, Picea or Hypoxis, with &beta;‐sitosterol as the main component.Results There were significant (P<0.01) improvements over placebo in those treated with &beta;‐sitosterol; the mean difference in the IPSS between placebo and &beta;‐sitosterol, adjusted for the initial values, was 5.4 and in the quality‐of‐life index was 0.9. There were also significant improvements in the secondary outcome variables, with an increase in Qmax (4.5 mL/s) and decrease in PVR (33.5 mL) in favour of &beta;‐sitosterol when adjusted for the changes after placebo.Conclusion These results show that &beta;‐sitosterol is an effective option in the treatment of BPH.
Morphogenesis of the human lacrimal gland
Authors: De La Cuadra‐Blanco C. , Peces‐Peña M. D. , Mérida‐Velasco J. R. 
Published: November 2003

AbstractThe aim of this study was to determine the main stages of the lacrimal gland's developmental process in humans and to establish its precise morphogenetic timetable. Its onset is generally assumed to take place at O’Rahilly's stage 21, arising from an epithelial thickening of the superior extreme of the temporary conjunctival fornix. However, the present study points to a prior stage in the process: the presence of epithelial–mesenchymal changes in embryos at O’Rahilly's stage 19. The study was performed using light microscopy on serial sections of 37 human specimens: 23 embryos and 14 fetuses ranging from 15 to 137 mm crown–rump length (7–116 weeks of development). Three stages in lacrimal gland morphogenesis were identified: (1) the presumptive glandular stage, O’Rahilly's stages 19–20, characterized by a thickening of the superior fornix epithelium together with surrounding mesenchymal condensation; (2) the bud stage, generally assumed to be the first manifestation of glandular origin, characterized initially by the appearance of nodular formations in the region of the superior conjunctival fornix and concluding with the appearance of lumina within the epithelial buds; and (3) the glandular maturity stage, weeks 9–16, the period in which the gland begins to take on the morphology of adulthood.
Expression of fibroblast growth factor‐2 (FGF‐2) in early stages (days 3–11) of the development of the avian lung, Gallus gallus variant domesticus: an immunocytochemical study
Authors: Maina J. N. , Madan A. K. , Alison B. 
Published: November 2003

AbstractIn the avian lung, the bronchial system forms from epithelial (endodermal) cells. The intrapulmonary primary bronchus is the focal point of airway development. It originates secondary bronchi (SB) along its proximal–distal extent and parabronchi (tertiary bronchi) arise from and connect the SB. From as early as day 3.5, fibroblast growth factor‐2 (FGF‐2) is diffusely expressed in the epithelial and mesenchymal cells. Up‐regulation of FGF‐2 in discrete areas of the developing lung seem to set the growth rate, trajectories followed, areas appropriated, three‐dimensional symmetry and coupling of the airways. Expressed early in development and persisting into the incubation period, FGF‐2 may be involved in the formation of the avian lung. Morphogenetic differences between the avian and the mammalian lungs may explain the existing structural contrarieties.
Microscopic analysis of the cellular events during scatter factor/hepatocyte growth factor‐induced epithelial tubulogenesis
Authors: Williams M. J. , Clark P. 
Published: November 2003

AbstractScatter factor/hepatocyte growth factor (SF/HGF), a large multifunctional polypeptide growth and motility factor, is known to play important roles during embryonic development, adult tissue growth and repair. In an established three‐dimensional type I collagen model, SF/HGF induces Madin–Darby canine kidney (MDCK) epithelial cysts to form long, branching tubules (tubulogenesis). In addition, the composition of the surrounding extracellular matrix (ECM) has been shown to modulate SF/HGF‐induced morphogenesis, where tubulogenesis was completely abrogated in Matrigel basement membrane. Many cellular events that occur during SF/HGF‐mediated remodelling, and its modulation by the ECM, remain unclear. We have investigated these mechanisms through microscopic examination of the time‐course of SF/HGF‐induced responses in MDCK cysts cultured in type I collagen or Matrigel. We found that early responses to SF/HGF were matrix‐independent. Changes included increased paracellular spacing between normally closely apposed lateral membranes, and the formation of filopodial processes, indicating a partial motile response. Cell–cell contact was maintained, with the persistence of cell junctions. Therefore, while one or a number of ECM components are preventing SF/HGF‐primed cells from undergoing an invasive and/or migratory programme, non‐permissive matrices are not preventing SF/HGF signalling to the cell. Later matrix‐dependent responses, which occurred in type I collagen but not Matrigel, included the formation of basal protrusions that comprise two or more neighbouring cells, which extend to form nascent tubules. Modified polarity of cells comprising the basal protrusions was evident, with a marker for the apical membrane being found in the same region as adherens junctions and desmosomes, typically localized at lateral membranes. We propose a model for SF/HGF‐induced tubulogenesis in which tubules form from basal protrusions of adjacent cells. This mechanism of in vitro tubule formation has many similarities to reported in vivo epithelial tubulogenesis.
Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25‐Dx expression in the rat spinal cord
Authors: Labombarda F. , Gonzalez S. L. , Deniselle M. C. Gonzalez , Vinson G. P. , Schumacher M. , De Nicola A. F. , Guennoun R. 
Published: November 2003

AbstractProgesterone provides neuroprotection after spinal cord injury, but the molecular mechanisms involved in this effect are not completely understood. In this work, expression of two binding proteins for progesterone was studied in intact and injured rat spinal cord: the classical intracellular progesterone receptor (PR) and 25‐Dx, a recently discovered progesterone membrane binding site. RT‐PCR was employed to determine their relative mRNA levels, whereas cellular localization and relative protein levels were investigated by immunocytochemistry. We observed that spinal cord PR mRNA was not up‐regulated by estrogen in contrast to what is observed in many brain areas and in the uterus, but was abundant as it amounted to a third of that measured in the estradiol‐stimulated uterus. In male rats with complete spinal cord transection, levels of PR mRNA were significantly decreased, while those of 25‐Dx mRNA remained unchanged with respect to control animals. When spinal cord‐injured animals received progesterone treatment during 72 h, PR mRNA levels were not affected and remained low, whereas 25‐Dx mRNA levels were significantly increased. Immunostaining of PR showed its intracellular localization in both neurons and glial cells, whereas 25‐Dx immunoreactivity was localized to cell membranes of dorsal horn and central canal neurons. As the two binding proteins for progesterone differ with respect to their response to lesion, their regulation by progesterone, their cellular and subcellular localizations, their functions may differ under normal and pathological conditions. These observations point to a novel and potentially important role of the progesterone binding protein 25‐Dx after injury of the nervous system and suggest that the neuroprotective effects of progesterone may not necessarily be mediated by the classical progesterone receptor but may involve distinct membrane binding sites.
NGF activates the phosphorylation of MAP1B by GSK3β through the TrkA receptor and not the p75NTRreceptor
Authors: Goold Robert G. , Gordon‐Weeks Phillip R. 
Published: November 2003

AbstractWe have recently shown that nerve growth factor (NGF) induces the phosphorylation of the microtubule‐associated protein 1B (MAP1B) by activating the serine/threonine kinase glycogen synthase kinase 3β (GSK3β) in a spatio‐temporal pattern in PC12 cells that correlates tightly with neurite growth. PC12 cells express two types of membrane receptor for NGF: TrkA receptors and p75NTRreceptors, and it was not clear from our studies which receptor was responsible. We show here that brain‐derived neurotrophic factor, which activates p75NTRbut not TrkA receptors, does not stimulate GSK3β phosphorylation of MAP1B in PC12 cells. Similarly, NGF fails to activate GSK3β phosphorylation of MAP1B in PC12 cells that lack TrkA receptors but express p75NTRreceptors (PC12 nnr). Chick ciliary ganglion neurons in culture lack TrkA receptors but express p75NTRand also fail to show NGF‐dependent GSK3β phosphorylation of MAP1B, whereas in rat superior cervical ganglion neurons in culture, NGF activation of TrkA receptors elicits GSK3β phosphorylation of MAP1B. Finally, inhibition of TrkA receptor tyrosine kinase activity in PC12 cells and superior cervical ganglion neurons with K252a potently and dose‐dependently inhibits neurite elongation while concomitantly blocking GSK3β phosphorylation of MAP1B. These results suggest that the activation of GSK3β by NGF is mediated through the TrkA tyrosine kinase receptor and not through p75NTRreceptors.
P‐glycoprotein in blood–brain barrier endothelial cells: interaction and oligomerization with caveolins
Authors: Jodoin Julie , Demeule Michel , Fenart Laurence , Cecchelli Roméo , Farmer Sarah , Linton Kenneth J. , Higgins Christopher F. , Béliveau Richard 
Published: November 2003

AbstractP‐glycoprotein (P‐gp), an adenosine triphosphate (ATP)‐binding cassette transporter which acts as a drug efflux pump, is highly expressed at the blood–brain barrier (BBB) where it plays an important role in brain protection. Recently, P‐gp has been reported to be located in the caveolae of multidrug‐resistant cells. In this study, we investigated the localization and the activity of P‐gp in the caveolae of endothelial cells of the BBB. We used an in vitro model of the BBB which is formed by co‐culture of bovine brain capillary endothelial cells (BBCEC) with astrocytes. Caveolar microdomains isolated from BBCEC are enriched in P‐gp, cholesterol, caveolin‐1, and caveolin‐2. Moreover, P‐gp interacts with caveolin‐1 and caveolin‐2; together, they form a high molecular mass complex. P‐gp in isolated caveolae is able to bind its substrates, and the caveolae‐disrupting agents filipin III and nystatin decrease P‐gp transport activity. In addition, mutations in the caveolin‐binding motif present in P‐gp reduced the interaction of P‐gp with caveolin‐1 and increased the transport activity of P‐gp. Thus, P‐gp expressed at the BBB is mainly localized in caveolae and its activity may be modulated by interaction with caveolin‐1.
Nuclear factor κB nuclear translocation as a crucial marker of brain response to interleukin‐1. A study in rat and interleukin‐1 type I deficient mouse
Authors: Nadjar Agnès , Combe Chantal , Layé Sophie , Tridon Viviane , Dantzer Robert , Amédée Thierry , Parnet Patricia 
Published: November 2003

AbstractThe signalling pathways that mediate early central effects of interleukin‐1 (IL‐1) during the acute phase reaction have been poorly elucidated. Interaction of IL‐1β to its specific receptor interleukin‐1 receptor type I (IL‐1RI) leads to nuclear factor kappa B (ΝFκB) nuclear translocation and a robust transcriptional activation of inhibitor of kappa B alpha (IκBα) within the rat brain. Indeed, we demonstrated that IL‐1RI expressed in blood brain barrier (BBB) cells and in circumventricular organs (CVOs) is crucial for p65‐NFκB translocation induced by peripheral injection of IL‐1β. Moreover, it has been previously shown that monitoring IκBα mRNA synthesis is an effective tool to investigate the activity of the transcription factor NFκB into the CNS. However in the present study we observed time‐related and cell‐type differences between IκBα mRNA synthesis and p65‐NFκB translocation. This indicates that the expression of IκBα mRNA does not strictly parallel p65‐NFκB nuclear translocation, suggesting that these markers are not interchangeable to investigate NFκB activity but must be studied together. Thus, we hypothesize that IL‐1β reached the brain across the CVOs that lack a BBB and endothelial cells all over the brain and interacted with its receptors to induce NFκB translocation. The study of the consequences of the impairment of NFκB pathway activation in in vivo experimentation should bring important clues about the precise role of this transcription factor.
Effects of tasting technique – sequential tasting vs. mixed tasting – on perception of dry white wine and blue mould cheese
Authors: Nygren Ingemar T. , Gustafsson Inga‐Britt , Johansson Lisbeth 
Published: November 2003

AbstractThe object of this study was to evaluate by means of descriptive sensory analysis the effect of mixed tasting on the perception of dry white wine and blue mould cheese, and to establish whether the tasting technique (sequential vs. mixed tasting) significantly affects this perception. A Swedish blue mould cheese, Bredsjö Blå, and a French blue mould cheese, Roquefort Société, and five commercial types of dry white wine were used. The same panel, selected and trained according to ISO standards, as in Nygren et al. (2002, 2003) carried out the descriptive analyses by means of a mixed tasting technique. The panel scored the same attributes for both cheese and wine as in Nygren et al. (2002, 2003). In general, the original wine attribute scores decreased more by means of mixed tasting technique than by means of sequential, while few changes of the original cheese attribute scores were observed. Overall, mixed tasting gave greater decreasing changes than sequential tasting.
Valproate Suppresses Status Epilepticus Induced by 4‐Aminopyridine in CA1 Hippocampus Region
Authors: Martín Eduardo D. , Pozo Miguel A. 
Published: November 2003

Summary:  Purpose: We investigated the effects of valproate (VPA) on an in vivo model of status epilepticus (SE) induced by intrahippocampal application of 4‐aminopyridine (4‐AP). Methods: To induce continuous epileptiform activity without a clinical component, 4‐AP (100 mM) was slowly injected in the hippocampus of adult rats. Extracellular field potential from the CA1 region of the rat hippocampus was recorded to assess abnormal epileptiform activity. Once the SE seizures were induced by 4‐AP, the test drug was injected. In some experiments to test the ability of a drug to prevent the induction of SE, the drug was administered before 4‐AP injection. Results: Intrahippocampal injection of 4‐AP induced continuous epileptic activity without a clinical component that lasted >60 min. The intravenous injection of 400–600 mg/kg VPA rapidly (∼100 s) abolished the SE, and this effect persisted for ≥4 h in our experimental model. The intravenous injection of 100–300 mg/kg VPA did not abolish previously induced SE, but prevented the appearance of SE when applied before the induction of SE. The intravenous injection of 80 mg/kg phenytoin or carbamazepine did not abolish or prevent SE. Conclusions: We conclude that 4‐AP–induced SE was suppressed by VPA at 400–600 mg/kg, whereas minor doses (100–300 mg/kg) only prevent the 4‐AP–induced SE. Present results suggest the revisiting of VPA as a useful drug for the treatment of SE.
Seizure Outcome after Temporal Lobectomy in Temporal Lobe Cortical Dysplasia
Authors: Srikijvilaikul Teeradej , Najm Imad M. , Hovinga Collin A. , Prayson Richard A. , Gonzalez‐Martinez Jorge , Bingaman William E. 
Published: November 2003

Summary:  Purpose: To identify the temporal lobe cortical dysplasia (CD) histopathology classification subtype and determine the seizure outcome of patients who underwent temporal lobectomy with coincident CD. Methods: We reviewed the data of 28 patients with temporal lobe epilepsy who underwent surgery with pathologically verified CD at our institution from 1990 to 2000. The seizure outcome was assessed at a minimum of 1 year after surgery according to Engel's classification. Results: Of 28 patients who underwent surgery, nine (32.1%) had isolated CD, and 19 (67.9%) had CD and hippocampal sclerosis (CD&HS). Twenty‐six (92.9%) patients had histopathology subtype Ia (architectural abnormalities). Twenty (71.4%) patients were seizure free (Engel class I). Favorable seizure outcome (Engel class I, II) was achieved in 26 (92.9%) patients. No difference in seizure outcome was noted between patients with CD and CD&HS. Conclusions: The most common histopathologic subtype in patients with temporal lobe CD is type Ia (architectural abnormalities). Temporal lobectomy in temporal lobe epilepsy patients with CD can achieve favorable seizure outcome.
Knowledge of Epilepsy and Familiarity with This Disorder in the U.S. Population: Results from the 2002 HealthStyles Survey
Authors: Kobau Rosemarie , Price Patricia 
Published: November 2003

Summary:  Purpose: To assess perceptions of knowledge and experience with epilepsy and seizures in the U.S. population to develop communication campaigns to improve the public's understanding of epilepsy. In a national survey, focal points included the public's knowledge of the disorder, whether people know someone who has it, exposure to epilepsy‐related information, and knowledge about how to respond to a person having a seizure. Methods: The Epilepsy Program of the Centers for Disease Control and Prevention included nine items on an annual mail survey that targeted a representative sample of the U.S. population. Data were weighted to be representative of the U.S. population. χ2 analyses were performed, and standardized residuals were used to examine the associations between responses and demographic variables. Results: Responses were obtained from 4,397 persons. Despite the low prevalence of epilepsy, results indicate that about half of all persons have witnessed an epileptic seizure either in person or on television; about one third of all persons know someone with epilepsy, but relatively few are familiar with epilepsy, how to respond to a seizure, or with the Epilepsy Foundation. Conclusions: In general, the public has relatively little knowledge about epilepsy. Educational campaigns that inform the public about this disorder and about seizures should work through community settings to improve the general public's understanding of epilepsy.
Analysis of Cerebrospinal Fluid Glial Fibrillary Acidic Protein after Seizures in Children
Authors: Gurnett Christina A. , Landt Michael , Wong Michael 
Published: November 2003

Summary:  Purpose: To evaluate pediatric seizure patients for astrocytic injury by measuring cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP), determine risk factors for GFAP elevation after seizures, and compare seizure‐induced astrocyte injury with neuronal injury by concurrent measurement of CSF neuron‐specific enolase (NSE). Methods: CSF obtained from pediatric patients (n = 52) within 24 h of seizure was assayed for GFAP and NSE. Retrospective chart review was performed for seizure type, duration, and etiology. Results: Overall, children with seizures had elevated CSF GFAP compared with controls (p = 0.0075), but no elevation of NSE (p = 0.1437). No effect of seizure type or etiology was found, but a significant positive effect of seizure duration (p = 0.0010) and status epilepticus (p = 0.0296) was seen on CSF GFAP. Individually, seven children (13%) had elevated GFAP (>440 pg/ml); in five children, the increased GFAP was not accompanied by elevations in NSE (<12 ng/ml). Five children with elevated GFAP had symptomatic etiologies for their seizures, but the etiology of one child with elevated GFAP was cryptogenic, and one had febrile seizures. Conclusions: Elevation of CSF GFAP after seizures suggests that astrocytic injury may occur in a subgroup of children, primarily in the context of prolonged seizures and symptomatic etiologies. Increased GFAP levels may occur in patients with normal NSE, suggesting that GFAP may be a more sensitive marker of brain injury in some cases.
Physiology of Human Cortical Neurons Adjacent to Cavernous Malformations and Tumors
Authors: Williamson Anne , Patrylo Peter R. , Lee Sunghoon , Spencer Dennis D. 
Published: November 2003

Summary:  Purpose: Focal neocortical seizures can be associated with a number of specific pathologies including supratentorial tumors and cavernous malformations (CMs), both of which are highly epileptogenic. Methods: To begin to address the question of whether these lesions have different mechanisms of epileptogenesis, we used intracellular recordings from neurons adjacent to intracerebral neoplasms and cerebral CMs. Developmental anomalies were not included in this study. Results: Neurons adjacent to CMs had a greater propensity to show large (>5 mV), complex spontaneous synaptic events than did neurons neighboring neoplastic substrates (50 vs. 4.7% of cells and 75 and 8% of patients, respectively; p < 0.004; p < 0.05). Both spontaneous excitatory and inhibitory events were noted. In contrast, in tissue adjacent to tumors, low‐amplitude (<3 mV) spontaneous excitatory activity predominated. Neurons neighboring CMs also exhibited more excitable responses to synaptic stimulation, with multiple action potentials riding on prolonged excitatory postsynaptic potentials (EPSPs) being evoked in 71% of these cells, versus 32% of cells from the tumor group; p < 0.05. In studies using hippocampal tissue, we noted a similar pattern of spontaneous activity in tissue adjacent to CMs. Conclusions: These data suggest that CMs may induce seizure activity via a different pathophysiologic mechanism(s) than glial tumors.
Recurrent Nonstatus Generalized Seizures Alter the Developing Chicken Brain
Authors: Gong Zhao , Obenaus André , Li Nan , Sarty Gordon E. , Kendall Edward J. 
Published: November 2003

Summary:  Purpose: Noninvasive magnetic resonance imaging was used to assess the evolution of seizure‐induced pathology in epileptic, carrier, and normal chickens. Our objective was to determine whether repetitively evoked seizures in an epileptic fowl model of generalized seizures resulted in altered brain development. Methods: Data were obtained from seizure and control groups at 45, 90, and 180 days after hatching. Results: At 180 days, apparent diffusion coefficient (ADC) values in the optic tectum and archistriatum of the stimulated epileptic chicks were reduced, whereas ADC values in the nonstimulated group remained unchanged. The mean brain volume of epileptic chickens from the stimulated group was smaller than that from the nonstimulated group at 90 and 180 days. Conclusions: These findings establish that recurrent seizures modify the brain matrix.