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Significant Preservation (significant + preservation)
Selected AbstractsAlzheimer's Disease: Current Pharmacotherapy in the Context of Patient and Family NeedsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5s2 2003David S. Geldmacher MD The objective of this paper is to review current evidence and treatment patterns for pharmacotherapy in Alzheimer's disease (AD), with an emphasis on outcomes considered important to patients and families. The sources for the information are the peer-reviewed literature, Food and Drug Administration-approved package labeling for acetylcholinesterase inhibitors (AChEIs), expert opinions expressed at the First Annual Dementia Congress, and clinical experience. Three AChEI agents are in routine use in the United States. They are considered part of the standard of care for patients with mild-to-moderate AD. There are differences in metabolism, pharmacokinetics, side effects, and ease of use that may influence the prescriber's choice of agent and dosage. The three approved agents have similar outcomes in cognition and global clinician ratings of effectiveness in double-blind placebo controlled trials. Persistent therapy with effective doses of AChEIs is associated with reduced risk for, or delayed, nursing home placement, which is a stated priority of AD caregivers. Agents from this class of drugs have also been shown to be associated with statistically significant preservation of daily function and benefits in treatment of adverse behaviors in AD. Numerous additional choices are available to the clinician for pharmacotherapy of adverse behaviors. Community-based psychoeducational support is also of value to caregivers. [source] Risedronate Preserves Trabecular Architecture and Increases Bone Strength in Vertebra of Ovariectomized Minipigs as Measured by Three-Dimensional Microcomputed Tomography,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2002Babul Borah Ph.D. Abstract Risedronate reduces the risk of new vertebral fractures up to 70% within 1 year of treatment in patients with osteoporosis. Both increases in bone mass and preservation of bone architecture are thought to contribute to antifracture effects. Our objectives were to determine the effects of risedronate on trabecular bone mass and architecture and to determine the relative contributions of mass and architecture to strength in the vertebra of ovariectomized (OVX) minipigs. The minipigs were OVX at 18 months of age and were treated daily for 18 months with either vehicle or risedronate at doses of 0.5 mg/kg per day or 2.5 mg/kg per day. The three-dimensional (3D) bone architecture of the L4 vertebral cores of Sinclair S1 minipigs was evaluated by 3D microcomputed tomography (,CT). Compared with the OVX control, the vertebral bone volume (bone volume/tissue volume [BV/TV]) was higher in both treated groups (p < 0.05). The architectural changes were more significant at the 2.5-mg/kg dose and were more prevalent at the cranial-caudal ends compared with the midsection. At the higher dose, the trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity were higher, and marrow star volume (Ma.St.V) and trabecular separation (Tb.Sp) were lower (p < 0.05). The trabecular separation variation index(TSVI), a new measure to approximate structural variations, was smaller in the 2.5-mg/kg-treated group (p < 0.05). In this group, a significant preservation of trabeculae orthogonal to the cranial-caudal axis was confirmed by a decrease in the degree of anisotropy (DA) and an increase in the percent Cross-strut (%Cross-strut; p < 0.05). Both normalized maximum load (strength) and normalized stiffness of the same vertebral cores were higher in the 2.5-mg/kg risedronate group compared with the OVX group (p < 0.05). BV/TV alone could explain 76% of the variability of the bone strength. The combination of bone volume and architectural variables explained >90% of the strength. The study showed that risedronate preserved trabecular architecture in the vertebra of OVX minipigs, and that bone strength is tightly coupled to bone mass and architecture. [source] Increased expression of glial cell line-derived neurotrophic factor protects against oxidative damage-induced retinal degenerationJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Aling Dong Abstract Oxidative damage contributes to retinal cell death in patients with age-related macular degeneration or retinitis pigmentosa. One approach to treatment is to identify and eliminate the sources of oxidative damage. Another approach is to identify treatments that protect cells from multiple sources of oxidative damage. In this study, we investigated the effect of increased expression of glial cell line-derived neurotrophic factor (GDNF) in three models of oxidative damage-induced retinal degeneration. Double transgenic mice with doxycycline-inducible expression of GDNF in the retina were exposed to paraquat, FeSO4, or hyperoxia, all sources of oxidative damage and retinal cell death. Compared to controls, mice with increased expression of GDNF in the retina showed significant preservation of retinal function measured by electroretinograms, reduced thinning of retinal cell layers, and fewer TUNEL-positive cells indicating less retinal cell death. Mice over-expressing GDNF also showed less staining for acrolein, nitrotyrosine, and 8-hydroxydeoxyguanosine, indicating less oxidative damage to lipids, proteins, and DNA. This suggests that GDNF did not act solely to allow cells to tolerate higher levels of oxidative damage before initiation of apoptosis, but also reduced damage from oxidative stress to critical macromolecules. These data suggest that gene transfer of Gdnf should be considered as a component of therapy for retinal degenerations in which oxidative damage plays a role. [source] Combined hematopoietic and lentiviral gene-transfer therapies in newborn Twitcher mice reveal contemporaneous neurodegeneration and demyelination in Krabbe diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2009F. Galbiati Abstract This study characterized the therapeutic benefits of combining hematogenous cell replacement with lentiviral-mediated gene transfer of galactosylceramidase (GALC) in Twitcher mice, a bona fide model for Krabbe disease. Bone marrow cells and GALC-lentiviral vectors were administered intravenously without any preconditioning to newborn Twitcher pups before postnatal day 2. Treated Twitchers survived up to 4 months of age. GALC activity remained less than 5% of normal values in the nervous system for the first 2 months after treatment and reached ,30% in long-term-surviving mice. Long-term reconstitution of GALC activity in the nervous system was provided primarily by infiltrating macrophages and to a lesser extent by direct lentiviral transduction of neural cells. Treated Twitchers had significant preservation of myelin, with a G-ratio (ratio of the axon diameter to the diameter of the myelinated fiber) in sciatic nerve myelin of 0.75 ± 0.08 compared with 0.85 ± 0.10 in untreated mutants. Although treated mutants had improved locomotor activities during their long-term survival, they died with symptoms of progressive neurological degeneration, indistinguishable from those seen in untreated Twitchers. Examination of long-lived Twitchers showed that treated mutants were not protected from developing degeneration of axons throughout the neuroaxis. These results suggest that GALC deficiency not only affects myelinating glia but also leads to neuronal dysfunction. The contemporaneous neuropathology might help to explain the limited efficacy of current gene and cell therapies. © 2009 Wiley-Liss, Inc. [source] Laminar variation in neuronal viability and trophic dependence in neocortical slicesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2001Mary M. Niblock Abstract Organotypic slices are used frequently in studies of central nervous system development and function because they provide excellent experimental access with significant preservation of cellular context and relationships. Within a slice, however, a variety of factors may cause individual classes of neurons to respond differently to the culture environment. Differences in deafferentation, cellular maturation, trophic dependence and ongoing naturally occurring cell death may produce changes in the neuronal population that are transparent to the experimenter but that could affect experimental results significantly. In this study, we examined the distribution and prevalence of cell death among neurons in each cortical layer in organotypic slices. In addition, we assessed the ability of several neurotrophic factors to ameliorate neuronal death in each cortical layer. Within the first 24 hr in culture, there was striking laminar variation in the extent of neuronal death in culture, which could not be accounted for by the pattern of programmed cell death in vivo. In addition, neurons in the six layers of the neocortex differed in the degree to which they could be rescued by neurotrophic factors. These data suggest that differential neuronal death and rescue are important considerations in studies utilizing organotypic slices and may represent particularly confounding variables in studies of effects of trophic factors in such preparations. J. Neurosci. Res. 65:455,462, 2001. © 2001 Wiley-Liss, Inc. [source] Dissecting the molecular architecture and origin of Bayash Romani patrilineages: Genetic influences from South-Asia and the BalkansAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2009Irena Martinovi, Klari Abstract The Bayash are a branch of Romanian speaking Roma living dispersedly in Central, Eastern, and Southeastern Europe. To better understand the molecular architecture and origin of the Croatian Bayash paternal gene pool, 151 Bayash Y chromosomes were analyzed for 16 SNPs and 17 STRs and compared with European Romani and non-Romani majority populations from Europe, Turkey, and South Asia. Two main layers of Bayash paternal gene pool were identified: ancestral (Indian) and recent (European). The reduced diversity and expansion signals of H1a patrilineages imply descent from closely related paternal ancestors who could have settled in the Indian subcontinent, possibly as early as between the eighth and tenth centuries AD. The recent layer of the Bayash paternal pool is dominated by a specific subset of E1b1b1a lineages that are not found in the Balkan majority populations. At least two private mutational events occurred in the Bayash during their migrations from the southern Balkans toward Romania. Additional admixture, evident in the low frequencies of typical European haplogroups, J2, R1a, I1, R1b1b2, G, and I2a, took place primarily during the early Bayash settlement in the Balkans and the Romani bondage in Romania. Our results indicate two phenomena in the Bayash and analyzed Roma: a significant preservation of ancestral H1a haplotypes as a result of considerable, but variable level of endogamy and isolation and differential distribution of less frequent, but typical European lineages due to different patterns of the early demographic history in Europe marked by differential admixture and genetic drift. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source] 2121: Sustained neuroprotection after a single intravitreal injection of PGJ2 in a rodent model of NAIONACTA OPHTHALMOLOGICA, Issue 2010V TOUITOU Purpose Prostaglandin-J2 (PGJ2) has been proposed as a potential neuroprotective agent. We wanted to evaluate the toxicity/efficacy of a single intravitreal (IVT) injection of PGJ2 in a rodent model of nonarteritic anterior ischemic optic neuropathy (NAION). Methods We used the laser-activated rose Bengal induction method to produce AION in Long-Evans rats. We evaluated IVT-PGJ2 retinal and ON toxicity. Following induction, PGJ2 was IVT-injected in the treatment-group. IVT phosphate-buffered-saline (PBS) was used as control. Functional studies (VEP) were performed at baseline and at 7days post-treatment. Structural studies included immunohistochemical (IHC), electron microscopic (EM) analysis of the optic nerve (ON), and stereologic analysis of retinal ganglion cell (RGC) numbers at30 day 30. Results Toxicity: IVT PGJ2 (5 eyes) did not induce any significant functional/structural changes in the retina or ON of treated animals compared with animals injected with PBS (5 eyes) 30 days post-injection. Efficacy: After a single IVT-injection, day7 VEPs in the PGJ2-treatment group (n=7) had amplitudes 103.6% of baseline, whereas the PBS-treated group (n=6) had VEPs that were 42.4% of the baseline. 30days post-stroke, EM of ON from the treatment-group demonstrated significant preservation of axons and decreased demyelination. Stereological RGCcounts confirmed significant (p<0.04) RGC preservation in PGJ2-treated animals (1462.6 cells/µm2) compared w the stroke+PBS group (1156.5 cells/µm2). Conclusion A single IVT of PGJ2 preserves RGCs and their axons, and provides sustained neuroprotection for at least 1 month following initial ischemic event. [source] | |||||||||||||