1,721,061 research outputs found
Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/motor neuron disease
No full textBACKGROUND:Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neuromuscular disease characterized by progressive muscle weakness resulting in paralysis, which might be treated with ciliary neurotrophic factor.
OBJECTIVES: The objective of this review was to examine the efficacy of ciliary neutrophic factor in amyotrophic lateral sclerosis.
SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (searched June 2003) for randomized trials, MEDLINE (from January 1966 to October 2003) and EMBASE (from January 1980 to October 2003), checked the reference lists of papers identified and contacted the authors of studies identified to get additional unpublished results.
SELECTION CRITERIA: We considered the following selection criteria: Types of studies: randomized controlled clinical trials; Types of participants: adults with a diagnosis of either probable or definite amyotrophic lateral sclerosis according to the El Escorial criteria; Types of interventions: treatment with ciliary neurotrophic factor for at least six months, in a placebo-controlled randomized format; Types of outcome measures Primary: survival; Secondary: muscle strength, respiratory function, changes in bulbar functions, changes in quality of life, proportion of patients with adverse side effects (such as cough, asthenia, nausea, anorexia, weight loss and increased salivation).
DATA COLLECTION AND ANALYSIS: We identified two randomized trials. The data were extracted and examined independently by the reviewers. Some missing data were obtained from investigators.
MAIN RESULTS: Two trials, with a total population of 1,300 amyotrophic lateral sclerosis patients treated with subcutaneous injections of recombinant human ciliary neurotrophic factor, were examined in this review. The methodological quality of these trials was considered adequate. No significant difference was observed between ciliary neurotrophic factor and placebo groups for survival, the primary outcome measure. The relative risk was 1.07 (95% CI 0.81 to 1.41). No significant differences between the groups were observed for most of the secondary outcomes. However, a significant increase of the incidence of several adverse events was noted in groups treated with higher doses of CNTF.
REVIEWERS' CONCLUSIONS: Ciliary neurotrophic factor treatment has no effect on amyotrophic lateral sclerosis progression. At high concentration, several side effects were observed. A combination of ciliary neurotrophic factor with other neurotrophic factors (as suggested by results on animal models), and more efficient delivery methods should be tested
Phorbol esters and PKC signaling regulate proliferation, vimentin cytoskeleton assembly and glutamine synthetase activity of chick embryo cerebrum astrocytes in culture
No full textHMSCs from UCB: isolation, characterization and determination of osmotic properties for optimal cryopreservation
Full text linkIn tissue engineering, storing of biological material represents a fundamental step to bring cell-based medical devices to market on demand - Karlsson and Toner (2000) and more recently Fadda et al. (2009). Compared to other methods, freezing to cryogenic temperatures allows long shelf lives and genetic stability (Karlsson and Toner, 2000). Unfortunately, cryopreserved cells are damaged by the cryopreservation process itself (Mazur, 2004). This loss (up to 50 %) can be tolerated for some cell lineages, but it's unacceptable for others, as the human Mesenchymal Stem Cells (hMSCs) from Umbilical Cord Blood (UCB), whose collection and isolation is known to be difficult (Bieback et al., 2004). In this case, an optimal cryopreservation protocol is mandatory. Due to the high number of trials actually required for experimental optimization, mathematical modelling is considered a practical solution. To this aim, the osmotic properties need to be first estimated in order to determine the volume of residual intra-cellular water left by osmosis to form lethal ice or glass. In this work, the hMSCs from UCB of three different donors, after informed consent, have been isolated by a density gradient centrifugation method. The successful isolation has been verified through phenotypic cytofluorimetric analysis, and adipogenesis/osteogenesis capability differentiations. Osmotic properties, namely inactive cell volume, water and CPA (DMSO) permeabilities, have been determined by means of experimental runs carried out under hypertonic conditions (obtained with the addition of sucrose or DMSO), at three different temperatures. Cells volumes excursions have been measured by a potenziometric device (Coulter Counter) under equilibrium and dynamic conditions. Linear and non-linear regression analyses have been carried out to determine the adjustable parameters by means of the two parameters bi-compartimental model by Kleinahns (1998), as applied to a single-sized cell population (i.e. identical cells with size equal to the average). It is found that, the inactive volume fraction of hMSC from UCB apparently changes (increase) when DMSO is used instead of sucrose, thus limiting cell volume excursion during swelling. It is hypothesized that, a cell volume control system is activated during swelling, probably due to the action of ion pumps
Muscarinic receptor subclasses in retinal cultures: effect of corticosterone.
No full textWe have previously shown that exogenously administered corticosterone affects muscarinic receptor binding in the chick embryo retina. Analysis with the selective antagonist pirenzepine has shown that both muscarinic receptor subclasses M1 and M2 are present in treated retinas. On the contrary, only M2 is detectable in controls. Moreover, receptor affinity for agonists is modified by hormone treatment. Since these studies did not show whether or not the hormone directly influences retinal cells, a similar study was performed on retinal tissue cultures. Cells were treated at day 5 in vitro for 24 hr with 1.10(-8) M corticosterone. Scatchard analysis of results obtained with 3H-quinuclidinyl benzilate (3H-QNB) binding showed no difference between treated and control cultures. However, displacement experiments demonstrated that both M1 and M2 were present in treated cultures, whereas controls had only M2. Also, receptor affinity for the agonist carbachol was modified, as already observed with in vivo studies. In addition, a new phenomenon was observed: treated cultures had a significantly higher number of cells. The possibility that the hormone can prevent cell death or stimulate cell mitosis is considered
Protein kinase C-epsilon is a developmentally regulated, neuronal isoform in the chick embryo central nervous system
No full textDifferential regulation of phospholipases C and D by phorbol esters and the physiological activators carbachol and glutamate in astrocytes from chicken embryo cerebrum and cerebellum
No full textGamma aminobutyric acid (GABA) modulators for amyotrophic lateral sclerosis/motor neuron disease
No full textImbalance of gamma amynobutyric acid (GABA) and related modulators has been indicated as an important factor in the pathogenesis of amyotrophic lateral sclerosis (ALS). In this context, the role and mechanism of action of gabapentin and baclofen (GABA agonistI). This is the first systematic review addressing the benefit of gabapentin or baclofen by means of clinical trials for the treatment of ALS
Developmentally regulated expression and localization of dystrophin and utrophin in the human fetal brain
No full textExpression of pituitary adenylate cyclase-activating polypeptide (PACAP)receptors and PACAP in human fetal retina
No full textSpecific receptors for pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide with neuroregulatory and neurotrophic functions, have recently been identified in the retinas of different mammalian species. In the present study, expression of PACAP receptors and PACAP was investigated in the retinas of 12-18-week human embryos. Radioligand binding studies showed that the two forms of PACAP with 38 and 27 amino acids (PACAP 38 and PACAP 27, respectively) displaced the binding of 125I-PACAP 27 with IC50 values in the picomolar range, whereas functional receptor assays demonstrated that the two peptides were potent and effective stimulators of adenylyl cyclase activity. In contrast, vasoactive intestinal peptide (VIP) and human peptide histidine-isoleucine, which are homologous to PACAP, displayed lower affinities for the 125I-PACAP 27 binding site and were much less potent stimulators of cyclic AMP formation. Glucagon and secretin were inactive in both receptor assays. The expression of specific PACAP receptors was further investigated by reverse transcription-polymerase chain reaction technique, which showed the presence of mRNAs coding for PACAP type I and for nonselective PACAP type II (both VIP1 and VIP2) receptors. By the same technique, expression of PACAP mRNA was also detected. These data indicate that the developing human retina synthesizes PACAP and that the peptide may act on retinal cells by predominantly stimulating PACAP type I receptors coupled to cyclic AMP formation
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