bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cathepsin B mRNA and protein expression following contusion spinal cord injury in rats
Authors: Ellis Rebecca C. , Earnhardt J. Nicole , Hayes Ronald L. , Wang Kevin K.W. , Anderson Douglas K. 
Published: July 2005

AbstractWe provide the first data that cathepsin B (Cath B), a lysosomal cysteine protease, is up‐regulated following contusion‐spinal cord injury (SCI). Following T12 laminectomy and moderate contusion, Cath B mRNA and protein expression profiles were examined from 2 to 168 h post‐injury in rats using real‐time PCR and immunoblots, respectively. Contusion injury significantly increased [mRNA]Cath B in the injury site and adjacent segments over sham injury levels. While the largest [mRNA]Cath B induction (20‐fold over naive) was seen in the injury site, the caudal segment routinely yielded [mRNA]Cath B levels greater than 10‐fold over naive. Interestingly, sham injury animals also experienced mRNA induction at several time points at the injury site and in segments rostral and caudal to the injury site. Contusion injury also significantly elevated levels of Cath B proenzyme protein (37 kDa) over sham injury in the injury site (48, 72 and 168 h post‐injury). Furthermore, significant protein increases of single and double chain Cath B (both active forms) occurred at the injury site at 72 and 168 h post‐injury. Similar significant increases in Cath B protein levels were seen in areas adjacent to the injury site. The induction of Cath B mRNA and protein expression following contusion injury is previously undescribed and suggests that Cath B may potentially be involved in the secondary injury cascade, perhaps for as long as 1 week post‐injury.
Improvement of embryonic dopaminergic neurone survival in culture and after grafting into the striatum of hemiparkinsonian rats by CEP‐1347
Authors: Boll Jette Bisgaard , Geist Marie Aavang , Kaminski Schierle Gabriele S. , Petersen Karina , Leist Marcel , Vaudano Elisabetta 
Published: July 2005

AbstractTransplantation of embryonic nigral tissue ameliorates functional deficiencies in Parkinson's disease (PD). A main constraint of neural grafting is the poor survival of dopaminergic neurones grafted into patients. Studies in rats indicated that many grafted neurones die by apoptosis. CEP‐1347 is a mixed‐lineage‐kinase (MLK) inhibitor with neuroprotective action in several in vitro and in vivo models of neuronal apoptosis. We studied the effect of CEP‐1347 on the survival of embryonic rat dopaminergic neurones in culture, and after transplantation in hemiparkinsonian rats. CEP‐1347 and the alternative MLK inhibitor CEP‐11004 significantly increased the survival of dopaminergic neurones in primary cultures from rat ventral mesencephalon and in Mn2+‐exposed PC12 cells, a surrogate model of dopaminergic lethal stress. Moreover, combined treatment of the grafting cell suspension and the host animal with CEP‐1347 significantly improved the long‐term survival of rat dopaminergic neurones transplanted into the striatum of hemiparkinsonian rats. Also, the protective effect of CEP‐1347 resulted in an increase in total graft size and in enhanced fibre outgrowth. Thus, treatment with CEP‐1347 improved dopaminergic cell survival under severe stress and might be useful to improve the positive outcome of transplantation therapy in PD and reduce the amount of human tissue required.
Morphological and biochemical changes of neurofilaments in aged rat sciatic nerve axons
Authors: Uchida Atsuko , Tashiro Tomoko , Komiya Yoshiaki , Yorifuji Hiroshi , Kishimoto Takeo , Hisanaga Shin‐ichi 
Published: July 2005

AbstractWe have made a detailed comparison of neurofilaments (NFs) in the axons of the sciatic nerves between young and aged rats. In young rats, NF density was similar between proximal and distal sciatic nerve, but it became higher in the proximal region of sciatic nerve of aged rats. In accordance with this morphological change, NF protein content decreased dramatically in the middle region of the sciatic nerves of aged rats. The ratio of NF‐M to NF‐H in aged rats was lower than that in young rats at the proximal region of sciatic nerves and further decreased in the distal region of sciatic nerve. We analyzed transcription and axonal transport of NF proteins in motor neurons in spinal cord which are the major constituents of sciatic nerve axons. Of the transcripts of the NF subunits, NF‐M mRNA was particularly reduced in aged rats. Examination of slow axonal transport revealed that the transport rate for NF‐M was slightly faster than that for NF‐H in young rats, but slightly slower in aged rats. A decrease in both the synthesis and transport rate of NF‐M with aging may contribute to the relative reduction in NF‐M in the aged rat sciatic nerve. Although the relationship between NF packing and reduced NF‐M is not clear at present, these changes in NFs may be associated with age‐dependent axonal degeneration diseases.
The contributions of excitotoxicity, glutathione depletion and DNA repair in chemically induced injury to neurones: exemplified with toxic effects on cerebellar granule cells
Authors: Fonnum F. , Lock E. A. 
Published: July 2005

AbstractSix chemicals, 2‐halopropionic acids, thiophene, methylhalides, methylmercury, methylazoxymethanol (MAM) and trichlorfon (Fig. 1), that cause selective necrosis to the cerebellum, in particular to cerebellar granule cells, have been reviewed. The basis for the selective toxicity to these neurones is not fully understood, but mechanisms known to contribute to the neuronal cell death are discussed. All six compounds decrease cerebral glutathione (GSH), due to conjugation with the xenobiotic, thereby reducing cellular antioxidant status and making the cells more vulnerable to reactive oxygen species. 2‐Halopropionic acids and methylmercury appear to also act via an excitotoxic mechanism leading to elevated intracellular Ca2+, increased reactive oxygen species and ultimately impaired mitochondrial function. In contrast, the methylhalides, trichlorfon and MAM all methylate DNA and inhibit O6‐guanine‐DNA methyltransferase (OGMT), an important DNA repair enzyme. We propose that a combination of reduced antioxidant status plus excitotoxicity or DNA damage is required to cause cerebellar neuronal cell death with these chemicals. The small size of cerebellar granule cells, the unique subunit composition of their N‐methyl‐d‐aspartate (NMDA) receptors, their low DNA repair ability, low levels of calcium‐binding proteins and vulnerability during postnatal brain development and distribution of glutathione and its conjugating and metabolizing enzymes are all important factors in determining the sensitivity of cerebellar granule cells to toxic compounds.The chemical formulae of the six xenobiotics and one metabolite dichlorvos discussed in the text.image
Phosphorylation of extracellular‐regulating kinase in NMDA receptor antagonist‐induced newly generated neurons in the adult rat dentate gyrus
Authors: Okuyama Noriko , Takagi Norio , Kawai Takayuki , Miyake‐Takagi Keiko , Takeo Satoshi 
Published: July 2005

AbstractNeurogenesis in the adult brain is promoted by various stimulations. NMDA receptor blockade enhances neurogenesis in the hippocampal dentate gyrus. There is no agreed conclusion, however, as to whether newly generated neurons after NMDA receptor blockade obtain functional properties. We investigated the functional maturation of newly generated neurons after NMDA receptor blockade. In the dentate gyrus, 80% of newly generated cells differentiated into the phenotype of mature neurons at 29 days after the single intraperitoneal injection of an NMDA receptor antagonist MK‐801. The number of newly generated neurons after MK‐801 treatment was significantly greater than that in the saline‐treated group. The neurogenic basic helix‐loop‐helix transcription factor NeuroD protein in the dentate gyrus after MK‐801 treatment was expressed transiently in proliferative cells, but not in mature neurons. To determine functional properties of newly generated neurons, we administered NMDA to the lateral ventricle. As an in vivo response, we assessed extracellular‐regulating kinase (ERK) phosphorylation. The newly generated neurons showed ERK phosphorylation by NMDA administration as seen in surrounding mature neurons. The number of newly generated neurons, which responded to NMDA receptor stimulation, increased with time after MK‐801 treatment. The present study provides evidence that newly generated neurons in the adult hippocampus after NMDA receptor blockade acquire biochemical function in vivo.
Anorectal Malformations: Does Healthcare Meet the Needs?
Authors: Hartman Esther E , Sprangers Mirjam A. G , Visser Mechteld R. M , Oort Frans J , Hanneman Marianne J. G , van Heurn L W. Ernest , de Langen Zacharias J , Madern Gerard C , Rieu Paul N. M. A , van der Zee David C , Looyaard N , Aronson Daniel C 
Published: July 2005

ABSTRACTObjectives:The first aim was to identify the types of healthcare services used by children, adolescents, and adults with anorectal malformation (ARM) in relation to the severity of their disease and to examine whether additional care was needed. The second aim was to evaluate specific areas in the healthcare system, including provided information, transfer from pediatric to adult care, and satisfaction with the provided care.Methods:Three hundred eighty‐six (61%) patients with ARM, ages 6 to 52, completed a questionnaire that assessed their use of healthcare services and the need for additional services. Also, questions were asked about specific areas in the healthcare system. Clinical and sociodemographic characteristics were extracted from medical records.Results:In the preceding 6 months 50% of the children, 24% of the adolescents, and 24% of the adults consulted a medical specialist. Compared with patients with a mild form of ARM in the age range of 6 to 16 years, the more severely afflicted patients visited medical professionals more often (18% vs. 32%). Particularly, adolescents in the age range of 12 to 16 years with a severe form of the disease more often visited the pediatric surgeon than their peers with a mild form (2% vs. 16%). Twenty‐three percent of the children, 7% of the adolescents, and 8% of the adults consulted a nonmedical professional. Twenty percent of the children, 13% of the adolescents, and 17% of the adults would have liked additional or more treatment of a nonmedical professional. In 6 months, 40% of the children, 24% of the adolescents, and 20% of the adults received treatment information. One third of the adult patients who were transferred to “adult” surgeons encountered transfer problems. Almost all patients were satisfied with the care provided.Conclusions:There is good access to medical healthcare services, especially for children. However, more psychosocial and paramedical care is considered necessary. As could be expected, children and adolescents with a severe form of the disease reported to have visited a medical specialist more often. Although healthcare for patients with ARM may be improved at certain points, most parents and patients were very satisfied with the care provided.
Human Hepatic Mitochondria Generate Reactive Oxygen Species and Undergo the Permeability Transition in Response to Hydrophobic Bile Acids
Authors: Sokol Ronald J , Dahl Rolf , Devereaux Michael W , Yerushalmi Baruch , Kobak Gregory E , Gumpricht Eric 
Published: July 2005

ABSTRACTObjectives:Hydrophobic bile acids accumulate in the liver during cholestasis and are believed to cause hepatocellular necrosis and apoptosis in part through induction of the mitochondrial permeability transition (MPT) and the mitochondrial generation of oxidative stress. The purpose of this study was to determine if human hepatic mitochondria respond to bile acids in this manner.Methods:The MPT was measured spectrophotometrically and morphologically in normal human liver mitochondria exposed to glycochenodeoxycholic acid (GCDC) with and without cyclosporin A, an inhibitor of the MPT, antioxidants, and tauroursodeoxycholic acid (TUDC). Hydroperoxide generation was measured by dichlorofluorescein fluorescence. Cytochrome c and apoptosis‐inducing factor were assessed by immunoblotting.Results:GCDC induced the MPT in a dose‐dependent manner, which was inhibited by cyclosporin A, alpha‐tocopherol, beta‐carotene, idebenone, and TUDC. GCDC stimulated reactive oxygen species generation and release of cytochrome c and apoptosis‐inducing factor, which were significantly inhibited by the antioxidants, cyclosporin A, and TUDC.Conclusions:Mitochondrial pathways of cell death are stimulated in human hepatic mitochondria exposed to GCDC consistent with the role of mitochondrial dysfunction in the pathogenesis of cholestatic liver injury. These results parallel those reported in rodents, supporting the extrapolation of mechanistic studies of bile acid toxicity from rodent to humans.
Are There Psychosocial Differences in Diagnostic Subgroups of Children with Recurrent Abdominal Pain?
Authors: Robins Paul M , Glutting Joseph J , Shaffer Stephen , Proujansky Roy , Mehta Devendra 
Published: July 2005

ABSTRACTObjectives:To examine psychosocial differences in diagnostic subgroups of children with recurrent abdominal pain (RAP).Methods:Children meeting Apley's 1975 definition of RAP were divided according to physician ratings into three subgroups, based on the Rome II diagnostic criteria of functional gastrointestinal disorders: functional dyspepsia (n = 17), irritable bowel syndrome (n = 18), and functional abdominal pain (n = 27). Groups were compared using measures of (a) child psychopathology, (b) parent psychopathology, and (c) child pain, somatization, and functional disability.Results:Multivariate results from a discriminant function analysis demonstrated that children classified according to these criteria could not be differentiated with respect to parent reported child psychopathology or child pain, somatization, and functional disability. There were significant univariate differences, however, between groups on parental psychopathology (F = 4.39, P = 0.02); parents of children with functional dyspepsia reported greater parental psychopathology symptoms than the other two groups.Conclusions:This study provides a preliminary comparison of pain, somatization, functional impact, and psychopathology ratings in the Rome II diagnostic subclassifications of children with RAP. Further investigation utilizing larger sample sizes, pain measures specifying pain location, and parental modeling of somatic behavior is indicated to better understand potential similarities and differences between these subgroups.
Age‐Specific Questionnaires Distinguish GERD Symptom Frequency and Severity in Infants and Young Children: Development and Initial Validation
Authors: Deal Linda , Gold Benjamin D , Gremse David A , Winter Harland S , Peters Suzanne B , Fraga Polly D , Mack Michael E , Gaylord Stefanie M , Tolia Vasundhara , Fitzgerald Joseph F 
Published: July 2005

ABSTRACTTwo gastroesophageal reflux disease (GERD) symptom questionnaires were developed and tested prospectively in a pilot study conducted in infants (1 through 11 months) and young children (1 through 4 years) with and without a clinical diagnosis of GERD. A pediatric gastroenterologist made the clinical diagnosis of GERD. Parents or guardians at 4 study sites completed the questionnaires, providing information on the frequency and severity of symptoms appropriate to the 2 age cohorts. In infants, symptoms assessed were back arching, choking or gagging, hiccups, irritability, refusal to feed and vomiting or regurgitation. In young children, symptoms assessed were abdominal pain, burping or belching, choking when eating, difficulty swallowing, refusal to eat and vomiting or regurgitation. Respondents were asked to describe additional symptoms. Symptom frequency was the number of occurrences of each symptom in the 7 days before completion of the questionnaire. Symptom severity was rated from 1 (not at all severe) to 7 (most severe). An individual symptom score was calculated as the product of symptom frequency and severity scores. The composite symptom score was the sum of the individual symptom scores. The mean composite symptom and individual symptom scores were higher in infants (P < 0.001 and P < 0.05, respectively) and young children (P < 0.001 and P < 0.05, respectively) with GERD than controls. Vomiting/regurgitation was particularly prevalent in infants with GERD (90%). Both groups with GERD were more likely to experience greater severity of symptoms. We found the GERD Symptom Questionnaire useful in distinguishing infants and young children with symptomatic GERD from healthy children.
Testing the Association Between Gastroesophageal Reflux and Apnea in Infants
Authors: Mousa Hayat , Woodley Frederick W , Metheney Melissa , Hayes John 
Published: July 2005

ABSTRACTBackground:There is controversy regarding the association between gastroesophageal reflux and apnea. The controversy is further confused by the variety of ways reflux is detected, the varying methods of data analysis and the heterogeneity of subjects studied.Objectives:To determine if apnea is associated with reflux and to determine whether the association differs with acid or non acid reflux.Methods:We prospectively evaluated infants with apparent life‐threatening events or apnea by simultaneous pneumography, esophageal pH and multichannel intraluminal impedance monitoring. Apneic events and reflux frequency, duration, acidity and height were recorded. Apneic events were considered to be temporally linked to gastroesophageal reflux when they occurred during a gastroesophageal reflux episode or within 5 minutes after clearance of the refluxate. Data described with frequency tables, scatterplots and time series graphs were analyzed by regression analysis and χ2 testing.Results:Twenty‐five infants (10 males) aged 1 to 19 months were studied for up to 24 hours. Of 527 total apneic episodes, only 80 (15.2%) were temporally linked with gastroesophageal reflux: 37 (7.0%) with acid reflux and 43 (8.2%) with non‐acid reflux. Scatterplots revealed no significant correlation between apnea and frequency or duration of reflux episodes. Individual χ2 analyses within subjects found limited associations between reflux and apnea. Regression analyses showed a significant association between apnea and reflux in 4 of 25 subjects.Conclusions:We found little evidence for an association between apnea and total reflux, acid reflux or non‐acid reflux. There was no difference between acid gastroesophageal reflux and non‐acid gastroesophageal reflux in the frequency association with apnea. Either a χ2 statistic for each subject or R2 value computed from a lagged regression model for each subject can be used as an index of association in patient evaluation.
Equivalent lung deposition of budesonide in vivo: a comparison of dry powder inhalers using a pharmacokinetic method
Authors: Lähelmä Satu , Kirjavainen Merja , Kela Marjo , Herttuainen Jukka , Vahteristo Mikko , Silvasti Matti , Ranki‐Pesonen Marjut 
Published: July 2005

AimsThe aim of this study was to compare lung deposition of budesonide administered from two dry powder inhalers, Giona® Easyhaler® 200 µg/dose and Pulmicort® Turbuhaler® 200 µg/dose by utilizing a pharmacokinetic method.MethodsThis was an open, randomized, crossover study in 33 healthy subjects. The study consisted of four treatment periods separated by at least 4 wash‐out days. Equivalence in lung deposition was assessed after a single inhaled 1000 µg (5 × 200 µg) dose of budesonide from Giona® Easyhaler® and from Pulmicort® Turbuhaler®. Concomitant oral charcoal administration (40 g) was used to prevent gastrointestinal (GI) absorption of budesonide. The efficacy of the charcoal was studied after oral administration of a budesonide 2 mg capsule. The subjects were trained to inhale the study drugs with controlled flow rates, which resulted in an equal pressure drop (4 kPa) across both inhalers. Venous blood samples for the determination of budesonide concentrations in plasma were drawn before and at predetermined time points up to 8 h after drug administration. Budesonide concentrations in plasma were determined using liquid chromatography‐tandem mass spectrometry. Several pharmacokinetic parameters were estimated, the area under the budesonide concentration in plasma vs time curve from dosing to infinity (AUC(0, ∞)) being the primary response variable. Equivalence in lung deposition was concluded if the 90% confidence interval (CI) for the Easyhaler® : Turbuhaler® ratio of AUC(0, ∞) fell within the limits of 0.8–1.25.ResultsThe mean AUC(0,∞) value after Easyhaler® treatment was 3.48 (standard deviation (SD) 0.93) ng ml−1 h and after Turbuhaler® treatment 3.46 (1.13) ng ml−1 h. The Easyhaler® : Turbuhaler® AUC(0, ∞) ratio was 1.02 and the 90% CI was from 0.96 to 1.09. The mean Cmax values (SD) for budesonide in plasma after Easyhaler® and Turbuhaler® treatments were 1.22 (0.41) ng ml−1 and 1.29 (0.44) ng ml−1, respectively. There was no statistically significant difference (P = 0.39) between the median tmax for Easyhaler® (30 min) and Turbuhaler® treatment (23 min). Charcoal impaired the GI absorption of budesonide by 96%. The occurrence of adverse events was similar during both treatments.ConclusionsThe results show that the lung deposition of budesonide from Giona® Easyhaler® 200 µg/dose and Pulmicort® Turbuhaler® 200 µg/dose dry powder inhalers is equivalent. The charcoal block used to prevent GI absorption of swallowed budesonide was found to be effective.