bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis
Authors: Petri Susanne , Kiaei Mahmoud , Damiano Maria , Hiller Andrew , Wille Elizabeth , Manfredi Giovanni , Calingasan Noel Y. , Szeto Hazel H. , Beal M. Flint 
Published: July 2006

AbstractReactive oxygen species (ROS) play a major role in the pathogenesis of neurodegenerative diseases. They are important contributors to necrotic and apoptotic cell death. A major proportion of cellular ROS is generated at the inner mitochondrial membrane by the respiratory chain. In the present study, we investigated a novel peptide antioxidant (SS‐31) targeted to the inner mitochondrial membrane for its therapeutic effects both in vitro and in vivo in the G93A mouse model of amyotrophic lateral sclerosis (ALS). SS‐31 protected against cell death induced by hydrogen peroxide in vitro in neuronal cells stably transfected with either wild‐type or mutant Cu/Zn superoxide dismutase (SOD1). Daily intraperitoneal injections of SS‐31 (5 mg/kg), starting at 30 days of age, led to a significant improvement in survival and motor performance. In comparison with vehicle‐treated G93A mice, SS‐31‐treated mice showed a decreased cell loss and a decrease in immunostaining for markers of oxidative stress in the lumbar spinal cord. This further enhances the concept that pharmacological modification of oxidative stress is a therapeutic option for the treatment of ALS.
Parkinsonism genes: culprits and clues
Authors: Abeliovich Asa , Flint Beal M. 
Published: July 2006

AbstractParkinson's disease (PD) is characterized by a unique clinical constellation that includes: slowness, rigidity, gait difficulty, and tremor at rest. Pathological studies have linked this presentation to the loss of midbrain dopamine neurons (Gelb et al. 1999) although other neuronal populations are also targeted in PD. Epidemiological data implicate both genetic and environmental factors in the etiology of the disease. The identification of a series of genes that underlie relatively rare, familial forms of Parkinsonism (a clinical term that encompasses ‘sporadic’ PD, familial Parkinson's‐like forms, as well as other related syndromes) has brought excitement to the field. Three of the mutated familial Parkinsonism (FP) genes: Parkin, DJ‐1, and PINK1, typically present with apparent autosomal recessive inheritance and are implicated in mitochondria and oxidative stress‐related survival pathways. Two other FP genes: α‐Synuclein (αSyn) and LRRK2, present in an autosomal dominant pattern and are associated with prominent intracellular protein inclusions. A series of recent publications suggest novel pathways that may link the FP genes.
Oligodendroglial metabotropic glutamate receptors are developmentally regulated and involved in the prevention of apoptosis
Authors: Luyt Karen , Váradi Anikó , Durant Claire F. , Molnár Elek 
Published: July 2006

AbstractOligodendrocytes (OLs) are responsible for axon myelination and are the principal cells targeted in preterm white matter injury. The cellular and molecular mechanisms involved in white matter development and immature OL injury are incompletely understood. Metabotropic glutamate receptors (mGluRs) modulate neuronal development and survival, and have recently been identified in oligodendrocyte progenitor cells (OPCs). Using the highly homogeneous CG‐4 OPC line and O4 marker‐immunoselected primary OLs, we established the differentiation stage‐specific expression profile of mGluR3 and mGluR5 mRNAs and proteins in the oligodendroglial lineage and type‐2‐astrocytes (ASTs). Our quantitative analysis indicated no changes in mGluR3, but a significant down‐regulation of mGluR5a mRNA and protein expression during differentiation of OPCs into OLs or ASTs. The down‐regulation of mGluR5a had functional consequences, with significantly fewer OLs and ASTs than OPCs responding to the group I mGluR agonist (RS)‐3,5‐dihydroxyphenylglycine with intracellular Ca2+concentration oscillations. Neither stimulation nor inhibition of mGluR3 or mGluR5 altered OPC migration, suggesting that these receptors do not play prominent roles in the regulation of OPC motility. The activation of mGluR5 completely protected OPCs and substantially reduced staurosporine‐induced apoptosis in OLs. This suggests that the down‐regulation of mGluR5 in premyelinating OLs is likely to contribute to their increased vulnerability, and that the targeting of mGluR5 may be a potential therapeutic strategy for future development.
Mesotrypsin, a brain trypsin, activates selectively proteinase‐activated receptor‐1, but not proteinase‐activated receptor‐2, in rat astrocytes
Authors: Wang Yingfei , Luo Weibo , Wartmann Thomas , Halangk Walter , Sahin‐Tóth Miklós , Reiser Georg 
Published: July 2006

AbstractProteinase‐activated receptors (PARs), a subfamily of G protein‐coupled receptors, which are activated by serine proteases, such as trypsin, play pivotal roles in the CNS. Mesotrypsin (trypsin IV) has been identified as a brain‐specific trypsin isoform. However, its potential physiological role concerning PAR activation in the brain is largely unknown. Here, we show for the first time that mesotrypsin, encoded by the PRSS3 (proteinase, serine) gene, evokes a transient and pronounced Ca2+ mobilization in both primary rat astrocytes and retinal ganglion RGC‐5 cells, suggesting a physiological role of mesotrypsin in brain cells. Mesotrypsin mediates Ca2+ responses in rat astrocytes in a concentration‐dependent manner, with a 50% effective concentration (EC50) value of 25 nm. The maximal effect of mesotrypsin on Ca2+ mobilization in rat astrocytes is much higher than that observed in 1321N1 human astrocytoma cells, indicating that the activity of mesotrypsin is species‐specific. The pre‐treatment of cells with thrombin or the PAR‐1‐specific peptide TRag (Ala‐pFluoro‐Phe‐Arg‐Cha‐HomoArg‐Tyr‐NH2, synthetic thrombin receptor agonist peptide), but not the PAR‐2‐specific peptide, reduces significantly the mesotrypsin‐induced Ca2+ response. Treatment with the PAR‐1 antagonist SCH79797 confirms that mesotrypsin selectively activates PAR‐1 in rat astrocytes. Unlike mesotrypsin, the two other trypsin isoforms, cationic and anionic trypsin, activate multiple PARs in rat astrocytes. Therefore, our data suggest that brain‐specific mesotrypsin, via the regulation of PAR‐1, is likely to be involved in multiple physiological/pathological processes in the brain.
Sustained brain‐derived neurotrophic factor up‐regulation and sensorimotor gating abnormality induced by postnatal exposure to phencyclidine: comparison with adult treatment
Authors: Takahashi Makoto , Kakita Akiyoshi , Futamura Takashi , Watanabe Yuichiro , Mizuno Makoto , Sakimura Kenji , Castren Eero , Nabeshima Toshitaka , Someya Toshiyuki , Nawa Hiroyuki 
Published: July 2006

AbstractBrain‐derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression and the behavioral effects. Both single and repeated phencyclidine injections into adult rats induced BDNF up‐regulation in the corticolimbic system and a decrease in prepulse inhibition, both of which were transient. In contrast, subchronic postnatal administration increased BDNF protein and mRNA levels in the hippocampus and entorhinal cortex, which were sustained until 8 weeks of age. In parallel, the postnatal rats treated with phencyclidine developed a persistent decrease in prepulse inhibition at the adult stage. The chronic BDNF increase appeared to contribute to the prepulse inhibition abnormality, as subchronic BDNF infusion into the hippocampus of normal rats mimicked the prepulse inhibition deficits. This study suggests that phencyclidine exposure during brain development induces sustained BDNF up‐regulation in the limbic system with a biological link to sensorimotor gating deficits.
N‐Arachidonyl‐glycine inhibits the glycine transporter, GLYT2a
Authors: Wiles Amy L. , Pearlman Rhonda‐Jo , Rosvall Mari , Aubrey Karin R. , Vandenberg Robert J. 
Published: July 2006

AbstractN‐arachidonyl‐glycine is one of a series of N‐arachidonyl‐amino acids that are derived from arachidonic acid. N‐arachidonyl‐glycine is produced in a wide range of tissues with greatest abundance in the spinal cord. Here we report that N‐arachidonyl‐glycine is a reversible and non‐competitive inhibitor of glycine transport by GLYT2a, but has little effect on glycine transport by GLYT1b or γ‐amino butyric acid transport by GAT1. It has previously been reported that the activity of GLYT2a is down‐regulated by protein kinase C and therefore we investigated whether the actions of N‐arachidonyl‐glycine on GLYT2a are mediated by second messenger systems that lead to the activation of protein kinase C. However, the protein kinase C inhibitor, staurosporine, had no effect on the actions of N‐arachidonyl‐glycine on GLYT2a. Thus, the actions of N‐arachidonyl‐glycine are likely to be mediated by a direct interaction with the transporter. We have further defined the pharmacophore by investigating the actions of other N‐arachidonyl amino acids as well as the closely related compounds arachidonic acid, anandamide and R1‐methanandamide. Arachidonic acid, anandamide and R1‐methanandamide have no effect on glycine transport, but N‐arachidonyl‐l‐alanine has similar efficacy at GLYT2a to N‐arachidonyl‐glycine, and N‐arachidonyl‐γ‐amino butyric acid is less efficacious. These observations define a novel recognition site for the N‐arachidonyl amino acids.
Identification of a new functional target of haloperidol metabolite: implications for a receptor‐independent role of 3‐(4‐fluorobenzoyl) propionic acid
Authors: Kim Hyeon Soo , Song Minseok , Yumkham Sanatombi , Choi Jang Hyun , Lee Taehoon , Kwon Joseph , Lee Sung Jae , Kim Jong‐In , Lee Kang‐Woo , Han Pyung‐Lim , Shin Seung Woo , Baik Ja‐Hyun , Kim Yong Sik , Ryu Sung Ho , Suh Pann‐Ghill 
Published: July 2006

AbstractHaloperidol, a dopamine D2 receptor blocker, is a classical neuroleptic drug that elicits extrapyramidal symptoms. Its metabolites include 3‐(4‐fluorobenzoyl) propionic acid (FBPA) and 4‐(4‐chlorophenyl)‐4‐piperidinol (CPHP). Until now, the biological significance of these metabolites has remained largely unknown. Here, we report that the administration of FBPA to mice effected a suppression of locomotor activity and induced catalepsy in a manner similar to that observed with haloperidol, whereas CPHP had no significant effects. Neither of these two metabolites, however, exhibited any ability to bind to the dopamine D2 receptor. FBPA blocked dopamine‐induced extracellular signal‐regulated kinase 1/2 phosphorylation, and it specifically affected mitogen‐activated protein kinase kinase (MEK)1/2 activity in hippocampal HN33 cells. Moreover, FBPA was capable of direct interaction with MEK1/2, and inhibited its activity in vitro. We demonstrated the generation of haloperidol metabolites within haloperidol‐treated cells by mass spectrometric analyses. Collectively, our results confirm the biological activity of FBPA, and provide initial clues as to the receptor‐independent role of haloperidol.
Bone response adjacent to calcium phosphate electrostatic spray deposition coated implants: an experimental study in goats
Authors: Manders Peter J .D. , Wolke Joop G. C. , Jansen John A. 
Published: July 2006

AbstractBackground: A new technique to deposit calcium phosphate (CaP) coatings onto titanium substrates has been developed recently. This electrostatic spray deposition (ESD) technique seems to be very promising. It appears to have clinical advantages such as an inexpensive and simple set‐up, high deposition efficiency and the possibility to synthesize layers with a defined surface morphology.Objective: The aim of this study was to examine biological properties and osteoconductivity of ESD CaP coatings when inserted into the femoral condyle of a goat.Material and methods: Twenty‐four implants with two gaps, i.e. 1 or 2 mm, were inserted into the femoral condyles of six goats. The implants were coated on one side with either a commercially available plasma‐sprayed hydroxyapatite (HAPS) coating or an ESD carbonate apatite (CAESD) coating. The other side of the implant was always left uncoated (Ti). Twelve weeks after implantation the animals were sacrificed and the characteristics of bone ingrowth and bone contact were evaluated.Results: At 3 months, histological and quantitative histomorphometrical measurements demonstrated more bone ingrowth and bone contact for coated sites as compared with uncoated sites. Statistical testing revealed that for both the 1 and 2 mm gaps HAPS (plasma‐sprayed hydroxyapatite) as well as CAESD (ESD carbonate apatite) ‐coated surfaces always had a significantly higher (P<0.05) amount of bone contact than uncoated Ti surfaces. On HAPS surfaces always significantly more bone was present than on CAESD surfaces. Further statistical testing revealed a significant difference in bone ingrowth between the HAPS as well as CAESD and Ti 1+2 mm gap specimens (P<0.05). Further, HAPS 1 mm gaps showed more bone ingrowth than CAESD 1 mm gaps. No significant difference existed between HAPS and CAESD 2 mm gaps.Conclusion: On the basis of our observations, we conclude that the used ESD technique is a promising new method to deposit CaP coatings onto titanium substrates. On the other hand, plasma‐spray HA‐coated implants have a still more favourable effect on the bone response.
Comparison between jaw bone augmentation by means of a stiff occlusive titanium membrane or an autologous hip graft: a retrospective clinical assessment
Authors: Molly Liene , Quirynen Marc , Michiels Katleen , Steenberghe Daniel van 
Published: July 2006

AbstractObjectives: Patients in need of bone augmentation procedures can be treated with a traditional hip graft or by neogenesis under a stiff occlusive titanium membrane, custom‐fit on the basis of CT‐scan data.Material and methods: Eighteen patients treated by means of a hip graft (H) were compared with 11 patients using a full titanium membrane (M) for the rehabilitation of upper jaws. In the H group, 17 patients (62 implants) in the anterior region (Ha) and 14 patients (23 implants) in the posterior region (Hp) were included. In the M group, nine patients (30 implants) in the anterior region (Ma) and seven patients (16 implants) in the posterior region (Mp) were included.Results: In group Ha, the CFR was 13.3% after 14 years compared with group Ma where the CFR was 17.4% after 9 years. In group Hp, the CFR was 22.8% after 16 years compared with group Mp where the CFR was 23.4% after 6 years. The marginal bone loss for group Ha after 20 years was 2.7 mm, for group Ma it was not even 1 mm after 9 years; for group Hp, it was 2.5 mm after 15 years compared with less than 1 mm after 3 years in group Mp.Conclusions: The success rate of alveolar ridge augmentation therapy is lower than in a classical approach. These augmentation procedures, however, show acceptable results. The titanium membrane augmentation leads to less marginal bone loss probably because neo‐formed bone has a better chance to adapt its mineralization to occlusal forces encountered. This technique could offer improvement if membrane exposure can be avoided.
Nitric oxide synthesis inhibition alters rat cutaneous wound healing
Authors: Amadeu Thaís P. , Costa Andréa M. A. 
Published: July 2006

Background:  Nitric oxide (NO) is an important molecule that participates in wound repair, but its effects on cutaneous wound healing are not well understood. The aim of this study was to investigate the effects of NO synthesis blockade on rat cutaneous wound healing by the administration of NG‐nitro‐l‐arginine methyl ester (l‐NAME), a non‐selective inhibitor of NO synthases.Methods:  NO synthesis was inhibited by administration of l‐NAME (20 mg/kg/day) in drinking water. An excisional wound was done, and the animals were killed 7, 14, and 21 days later. Wound contraction and blood pressure were evaluated. The lesion and adjacent skin were formalin fixed and paraffin embedded. Mast cells were quantified, and vessels were evaluated using stereological methods.Results:  l‐NAME‐treated animals presented delayed wound contraction, alterations in collagen organization, and neoepidermis thickness. The inhibition of NO synthesis increased mast cell migration 7 days after wounding, but decreased 21 days after wounding. Volume density of vessels was decreased in l‐NAME‐treated animals, 21 days after lesion. Surface density of vessels was frequently smaller in l‐NAME‐treated animals than in controls.Conclusion:  The blockade of NO synthesis impaired cutaneous wound healing, acting in early and late phases of wound repair.
Lichenoid and granulomatous dermatitis associated with atypical mycobacterium infections
Authors: S. Breza Thomas , Magro Cynthia M 
Published: July 2006

Background:  Lichenoid and granulomatous dermatitis defines a distinctive pattern of cutaneous inflammation that may be part of the morphologic spectrum of idiopathic lichenoid reactions such as lichen planus and as well may be seen with lichenoid drug reactions, endogenous T‐cell dyscrasias and as a feature of certain systemic diseases especially Crohn's disease and rheumatoid arthritis.Results:  We encountered three cases of lichenoid and granulomatous dermatitis in which the basis was one of primary cutaneous Mycobacterium infection. In all three cases acid fast stains revealed pathogenic organisms and as well cultures were positive for Mycobacterium kansasii in one case and Mycobacterium marinum in another. Other features included a prominent perineural and periadnexal lymphocytic infiltrate.Conclusions:  The differential diagnosis of lichenoid and granulomatous dermatitis should also encompass primary cutaneous Mycobacterium infection in addition to the other more characteristic entities associated wtih this distinctive reaction pattern. Infection with Mycobacterium induces a TH1 dominant response which would hence produce an infiltrate.
Atypical pemphigus: discordance between clinicopathological findings and the antigenic profile in four cases
Authors: Herrero‐Gonzalez Josep E. , Mascaró José M. , Iranzo Pilar , Herrero Carmen 
Published: July 2006

Background:  The diagnosis of pemphigus vulgaris and pemphigus foliaceus is usually based on clinical, histological, and immunofluorescence (IF) findings. In recent years, the antigenic profile of both diseases has been further defined by immunobiochemical techniques (ELISA, immunoblot, and immunoprecipitation).Methods:  A retrospective study of 40 pemphigus patients was performed to determine the clinical, histological, and antigenic profile in patients with pemphigus followed at our Department. Charts review, clinical data, histological and IF findings, and antigenic analysis by ELISA were performed in all patients.Results:  In most patients, there was a perfect correlation between the clinical and histological findings and their antigenic profile. In four patients (10%), clinicopathological features and antigenic findings were discordant.Conclusion:  The antigenic profiles in pemphigus do not always correlate with the clinical diagnosis. Therefore, clinical and histological features should be considered as the mainstay for the diagnosis of pemphigus.
Sparganosis in wild‐caught baboons (Papio cynocephalus anubis)
Authors: Nobrega‐Lee M. , Hubbard G. , LoVerde P. , Carvalho‐Queiroz C. , Conn D.B. , Rohde K. , Dick E.J. , Nathanielsz P. , Martin D. , Siler‐Khodr T. , Schlabritz‐Loutsevitch N. 
Published: July 2006

AbstractBackground  Sparganosis is the infection of a paratenic host with the plerocercoid metacestode of Spirometra spp. A 12‐year‐old captive, pregnant, wild‐caught baboon from Tanzania had multiple subcutaneous nodules.Methods  Examination of the biopsied nodules revealed the presence of viable metacestodes. The histological morphology of the metacestodes was consistent with the genus Spirometra and other pseudophyllidean cestodes. Since species of Spirometra produce growth hormones that are active in mammals, we measured fetal and placental growth and hormone levels. Blood samples were taken from the mother and the cesarean‐derived fetus for hematological, biochemical, and hormonal analyses and to test for the presence of antispargana antibodies.Results  Baboon placental weight and fetal hematological, biochemical, and morphometric parameters were within normal ranges. Antibody titers to spargana did not differ significantly between mother (1.08 OD405) and fetus (0.91 OD405). Baboon maternal insulin‐like growth factor and growth hormone values were also within the normal range. Estradiol and progesterone analysis in four of these animals (antibody titers ranged from 0.71 to 1.7 OD405) showed no statistically significant difference with age‐ or phase‐matched cycle parameters compared with antibody‐negative females.Conclusions  Based on the results that have been obtained, sparganosis did not appear to affect the endocrinological profile of pregnant and cycling female baboons.
Blockage of urine by intravesical ejaculate in cynomolgus monkeys
Authors: Chandolia R.K. , Luetjens C.M. , Wistuba J. , Semjonow A. , Pühse G. , Nieschlag E. 
Published: July 2006

AbstractBackground  The present communication reports intravesical semen coagulation and formation of a larger precipitate in two Cynomolgus monkeys.Methods  Ultrasound of the urinary bladder and light microscopy of intravesical coagulates.Results  These monkeys suffered from complete blockage of urine output and surgery was required to remove the sperm mass. Microscopic examination of the urine revealed millions of sperm as a cause of the mass and the blockage of urine output.Conclusions  Retrograde ejaculation of sperm may cause coagulation of ejaculates in the bladder of the cynomolgus monkey Macaca fascicularis. However, involvement of sperm mass in blockage of urine passage has not been described in this species.
Laser burn wound healing in naso‐labial region of fetal and neonatal mice
Authors: Nakasone A , Shibata S , Suzuki S , Yamashita Y , Ohyama K 
Published: July 2006

Objective:  To investigate the characteristics of wound healing in the mouse naso‐labial region in both the fetal and neonatal stages, histological and immunohistochemical analyses were performed using a newly established laser burn wound healing system.Materials and methods:  Fetal mice at embryonic day 14 (E 14) were wounded as a model of fetal wound healing. To compare it, neonatal mice at day 5 after birth (d 5) were adopted as a model of neonatal wound healing. The healing process was examined by van Gieson staining and immunohistochemistry for fibronectin and tenascin.Results:  Relatively large damage remained after wound healing even in fetal mice. In both types of wound healing, rapid regeneration of muscle tissues were observed. Fibronectin and tenascin immunostaining was detected not only in wound healing region, but also in the endomysium of regenerating muscle tissues. Especially, tenascin showed a restricted expression pattern.Conclusions:  Rapid regeneration of muscle tissues in the naso‐labial region in both the fetal and neonatal mice seemed to leave relatively large damage even in the fetal wound healing. Contracted force exerted by muscle tissues may be a reason for this phenomenon. Fibronectin and tenascin were closely related to the wound healing process including muscle regeneration in this region.