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Partial Protection (partial + protection)
Selected AbstractsIbotenate Injections into the Pre- and Parasubiculum Provide Partial Protection against Kainate-Induced Epileptic Damage in Layer III of Rat Entorhinal CortexEPILEPSIA, Issue 7 2001Tore Eid Summary: ,Purpose: A loss of neurons in layer III of the entorhinal cortex (EC) is often observed in patients with temporal lobe epilepsy and in animal models of the disorder. We hypothesized that the susceptibility of layer III of the EC to prolonged seizure activity might be mediated by excitatory afferents originating in the presubiculum. Methods: Experiments were designed to ablate the presubiculum unilaterally by focal ibotenate injections and to evaluate the effect of this deafferentation on the vulnerability of EC layer III neurons to the chemoconvulsant kainate (injected systemically 5 days later). Results: After treatment with kainate, 11 of the 15 rats preinjected with ibotenate showed clear-cut, partial neuroprotection in layer III of the EC ipsilateral to the ibotenate lesion. Serial reconstruction of the ibotenate-induced primary lesion revealed that entorhinal neurons were protected only in animals that had lesions in the pre- and parasubiculum, especially in the deep layers (IV,VI). Conclusions: The deep layers of the pre- and parasubiculum appear to control the seizure-induced damage of EC layer III. This phenomenon may be of relevance for epileptogenesis and for the pathogenesis of temporal lobe epilepsy. [source] Evaluation of a magnetic resonance biomarker of osteoarthritis disease progression: doxycycline slows tibial cartilage loss in the Dunkin Hartley guinea pigINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2009Jonathan Bowyer Summary The objective was to assess the effect of doxycycline treatment on a magnetic resonance imaging (MRI) biomarker of cartilage volume loss, and on matrix metalloproteinase (MMP) activity in a guinea pig osteoarthritis model. Guinea pigs (9 months old) were dosed with vehicle or doxycycline, 0.6, 3.0 mg/kg/day for 66 days. Fat-suppressed 3D gradient-echo MRI of the left knee was acquired pre- and post dosing. Change in medial tibial plateau (MTP) cartilage volume (MT.VC) was determined using image analysis. At termination, MTP cartilage was removed from knees and proteolytic MMP activity determined using a fluorescent peptide substrate assay. Vehicle-treated animals lost 20.5% (95% CI mean 25.6,15.1) MT.VC. The doxycycline (0.6 mg/kg/day) group lost 8.6% (P < 0.05, 95% CI 20.6 to ,5.3) whilst the 3.0 mg/kg/day group lost 10.0% (P < 0.05, 95% CI 13.9,6.0%). Endogenous levels of active MMPs were below limits of detection in all samples. However, doxycycline treatment ablated amino phenyl mercuric acid activated MMP-13 and MMP-8 levels, reduced MMP-9 levels by 65% and MMP-1 levels by 24%. Doxycycline treatment resulted in partial protection from MT.VC loss and was associated with complete reduction in MMP-13 and MMP-8, and partial reduction in MMP-9 activity. These data imply a role of MMPs in cartilage degeneration but incomplete protection suggests that additional doxycycline insensitive mechanisms are important in this model. The protective effect of doxycycline correlates with the clinical finding of lessened joint space narrowing, strengthens the utility of this animal model in identifying disease-modifying osteoarthritic drugs and supports the use of MRI biomarkers of cartilage loss. [source] GRA7 provides protective immunity in cocktail DNA vaccines against Toxoplasma gondiiPARASITE IMMUNOLOGY, Issue 9 2007E. JONGERT SUMMARY In a previous study, single-gene vaccination with GRA1, GRA7 or ROP2 was shown to elicit partial protection against Toxoplasma gondii. In this study, the contribution of each antigen in the evoked humoral and cellular immune responses was evaluated after vaccination with plasmid mixtures containing GRA1, GRA7 and ROP2. Cocktail DNA vaccinated mice developed high antibody titers against the antigens from two-gene DNA vaccine cocktails, but lower titres when immunized with the three-gene cocktail. High numbers of IFN-, secreting splenocytes were generated predominantly against GRA7. Brain cyst burden was reduced by 81% in mice vaccinated with the three-gene mixture and they were completely protected against acute toxoplasmosis. Similar high levels of brain cyst reductions were obtained after vaccination with cocktails composed of GRA1 and GRA7 (89% reduction), or GRA7 and ROP2 (79% reduction), but not with the cocktail composed of GRA1 and ROP2. In low dose single-gene vaccinations, IFN-, and strong protection could only be elicited by GRA7. Hence, the presence of GRA7 in the DNA vaccine formulation was important for optimal protection and this was correlated with GRA7-specific IFN-, production. We propose GRA7 as a main component in cocktail DNA vaccines for vaccination against T. gondii. [source] Accumulated p53 protein and UVA protection level of sunscreensPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2000S. Seité Nuclear p53 expression is a sensitive parameter for the detection of ultraviolet (UV)-induced skin damage, and it has been used as an endpoint to evaluate the effectiveness of sunscreens. In this study, we compared the protection provided by two sunscreens having identical sun protection factors (SPF) but different UVA protection factors (UVA-PF) measured by the persistent pigment darkening method (PPD). The SPF of the sunscreens was 7 and the UVA-PF were respectively 7 and 3. Nuclear p53 protein was quantified in human skin biopsies treated with sunscreens and exposed 8 times to 5 MED of solar simulated radiation (SSR). The results showed that both sunscreens offered only partial protection against the increased expression of nuclear p53 protein induced by repetitive SSR exposures. However, a significantly lower level of p53-positive cells was found in areas protected with the sunscreen having the higher UVA-PF compared to the other sunscreen protected areas. In order to verify whether the difference in efficacy of these products was due to the difference in UVA absorption capacity, we quantified epidermal p53 protein accumulation after 8 exposures to either UVA (320,400 nm) or UVA1 (340,400 nm). We showed that as with SSR, repetitive exposures to 12.5 and 25 J/cm2 of UVA or UVA1 induced a significant increase in p53-positive cells in the human epidermis. These results confirmed that SPF determined on the basis of an acute erythemal reaction does not predict the level of protection against cumulative damage. They also showed that the protection provided by two sunscreens with different UVA protection factors is different (based on nuclear p53 protein accumulation), and that the PPD method can distinguish varying levels of sunscreen efficacy against UVA-induced cell damage. [source] The diversity of FtsY-lipid interactionsBIOPOLYMERS, Issue 7 2010M. E. Reinau Abstract The bacterial signal recognition particle (SRP) receptor FtsY forms a complex with the SRP Ffh to target nascent polypeptide chains to the bacterial inner membrane. How FtsY interacts with lipids and associates to the membrane is unclear. Here, we show that vesicle binding leads to partial protection against proteolytic degradation and a change in secondary structure, which differs depending on whether the lipids are simple mixtures of zwitterionic and anionic lipids, mimics of Escherichia coli lipids, or lysolipids. Lipid binding alters the stability of FtsY. Thermal unfolding of FtsY in buffer shows two transitions, one occurring at ,60°C and the other at ,90°C. The thermal intermediate accumulating between 60 and 90°C has structural features in common with the state induced by binding to E. coli lipids. E. coli lipid extract induces a single transition around 70°C, anionic lipids have no effect while cooperative unfolding is completely removed in lysolipids. Thus, the lipid environment profoundly influences the dynamic properties of FtsY, leading to three different kinds of FtsY-lipid interactions with different effects on structure, proteolytic protection, and stability, and is driven both by hydrophobic and electrostatic interactions. Trypsin digestion experiments highlight the central role of the N-domain in lipid contacts, whereas the A- and G-domains appear to play a more minor part. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 595,606, 2010. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Macrocyclic Hexaureas: Synthesis, Conformation, and Anion BindingCHEMISTRY - A EUROPEAN JOURNAL, Issue 19 2009Denys Meshcheryakov Dr. Abstract Varied flexibility: Cyclic oligoureas are formed by using anions as templates. Linking of six xanthene and/or diphenyl ether fragments by urea groups leads to the formation of five macrocyclic compounds with a 48-membered ring with variable flexibility (see picture). Their interaction with anions shows a strong influence of acetate and chloride ions on the cyclization from four precursor molecules. Five macrocylic compounds XXXXXX, XXDXXD, XDXDXD, XDDXDD, and DDDDDD with 48-membered rings, in which six xanthene and/or diphenyl ether fragments are linked through six urea (-NH-C(O)-NH-) groups, have been synthesized. In the cyclization step, a linear diamine was allowed to react with the appropriate diisocyanate by using a [5+1] (i.e., "XDXDX+D" for XDXDXD), [4+2] (DDDDDD), or [3+3] (XDDXDD) procedure. Compounds XXXXXX and XXDXXD were prepared from two molecules of the dimeric amine XX and two molecules of the respective monomeric diisocyanate (X or D) in a [2+1+2+1] (or 2×[2+1]) reaction. The (nonoptimized) yields in the cyclization step ranged from 45 to 80,%. The linear precursor diamines or diisocyanates were obtained by analogous condensation reactions by using partial protection with a tert -butoxycarbonyl group. All the macrocyclic compounds and synthetic intermediates were characterized by 1H,NMR and mass spectra. Three different crystal structures were obtained for XDDXDD, which show the molecule in a more or less strongly folded conformation determined by intramolecular hydrogen bonding. The interaction of the hexaureas with selected anions was studied by 1H,NMR spectroscopy and UV absorption spectrophotometry. [source] | |||||||||||||