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Vivo Findings (vivo + finding)
Selected AbstractsCharacterization of Bves expression during mouse development using newly generated immunoreagentsDEVELOPMENTAL DYNAMICS, Issue 6 2006Travis K. Smith Abstract Bves (blood vessel/epicardial substance) is a transmembrane protein postulated to play a role in cell,cell interaction/adhesion. It was independently isolated by two groups as a gene product highly enriched in the developing heart. Disagreement exists about its expression during development. Most notably, the expression of Bves in non-muscle cells is disputed. Determining the expression profile of Bves is a critical initial step preceding the characterization of protein function in development and in the adult. We have generated new monoclonal antibodies against mouse Bves and used these immunoreagents to elucidate Bves expression in development. As expected, we detect Bves in myocytes of the developing heart throughout development. In addition, skeletal and smooth muscle cells including those of the coronary system express Bves. Finally, specific, but not all, epithelial derivatives of the three germ layers are stained positively with these monoclonal antibodies. Protein expression in cultured epithelial and muscle cell lines corroborate our in vivo findings. Taken together, these results demonstrate the expression of Bves in a wide range of epithelial and muscle cells during mouse embryogenesis and indicate a broad function for this protein in development, and show that these newly generated reagents will be invaluable in further investigation of Bves. Developmental Dynamics 235:1701,1708, 2006. © 2006 Wiley-Liss, Inc. [source] Impaired formation of the inner retina in an AChE knockout mouse results in degeneration of all photoreceptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004Afrim H. Bytyqi Abstract Blinding diseases can be assigned predominantly to genetic defects of the photoreceptor/pigmented epithelium complex. As an alternative, we show here for an acetylcholinesterase (AChE) knockout mouse that photoreceptor degeneration follows an impaired development of the inner retina. During the first 15 postnatal days of the AChE,/, retina, three major calretinin sublaminae of the inner plexiform layer (IPL) are disturbed. Thereby, processes of amacrine and ganglion cells diffusely criss-cross throughout the IPL. In contrast, parvalbumin cells present a nonlaminar IPL pattern in the wild-type, but in the AChE,/, mouse their processes become structured within two ,novel' sublaminae. During this early period, photoreceptors become arranged regularly and at a normal rate in the AChE,/, retina. However, during the following 75 days, first their outer segments, and then the entire photoreceptor layer completely degenerate by apoptosis. Eventually, cells of the inner retina also undergo apoptosis. As butyrylcholinesterase (BChE) is present at a normal level in the AChE,/, mouse, the observed effects must be solely due to the missing AChE. These are the first in vivo findings to show a decisive role for AChE in the formation of the inner retinal network, which, when absent, ultimately results in photoreceptor degeneration. [source] Prostaglandin E synthase in the pathophysiology of arthritisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2005Fumiaki Kojima Abstract Prostaglandin E synthase (PGES) is a recently identified terminal enzyme that acts downstream of cyclooxygenase and catalyzes the conversion of prostaglandin (PG) H2 to PGE2. At least three isozymes have been cloned so far, which are called membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES. Among them, mPGES-1 is induced by various inflammatory stimuli in some cells and tissues. Induction of mPGES-1 in the component of articular tissues of patients with rheumatoid arthritis and osteoarthritis has been demonstrated in vitro. Recent studies using adjuvant induced arthritis model have shown the increase of mPGES-1 expression resulted in the increase of PGE2 production at the sites of inflammation. In addition, reports of mPGES-1-deficient mice clearly suggest the role of mPGES-1 in the process of chronic inflammation such as collagen-induced arthritis and collagen antibody induced arthritis in vivo. Thus, recent in vitro and in vivo findings suggest that mPGES-1 may be a novel therapeutic target for arthritis. This paper introduces recent advances in research about the role of PGES in the pathophysiology of arthritis. [source] Statins and progressive renal diseaseMEDICINAL RESEARCH REVIEWS, Issue 1 2002Michele Buemi Abstract Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans. © 2001 John Wiley & Sons, Inc. Med Res Rev, 22, No. 1, 76,84, 2002 [source] Polychromatic Light Similar to the Terrestrial Solar Spectrum Without its UV Component Stimulates DNA Synthesis in Human Peripheral Blood Lymphocytes In Vivo and In VitroPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2006Natalya A. Zhevago ABSTRACT Immunosuppressive effects of the minor component of the terrestrial solar spectrum, UV radiation, have been substantiated over the past several years. This raises the question of what influence the dominant part of the solar spectrum,visible and IR light,would have on the human immune system. In the present randomized, placebo-controlled double-blind study a small area of the body surface of volunteers was irradiated with polychromatic light (480,3400 nm), simulating the significant part of the terrestial sunlight irradiance spectrum and its power density. An average 2.5-fold to three-fold increase in spontaneous and phytohemagglutinin-induced DNA synthesis in peripheral blood lymphocytes (Lym) was revealed at 0.5,24 h after irradiation at a therapeutic dose (12 J/cm2) in subjects with low preirradiation levels of both processes. The in vivo findings were echoed in parallel in vitro experiments, when blood drawn from the same subjects was directly irradiated (2.4 J/cm2), or when the irradiated blood was mixed 1:10 with nonirradiated autolo-gous blood to model events in the circulation following transcutaneous blood photomodification. Our data suggest that exposure of the human body to polychromatic visible + IR light may photomodify blood in the dermal vasculature of the irradiated area to lead to an immediate transfer of the light-induced effects to Lym of the entire circulating blood, which can result in modulation of Lym functional state at the systemic level. [source] Apoptosis and Phagocytosis of Tissue-Dwelling Eosinophils in Sinonasal Polyps,THE LARYNGOSCOPE, Issue 1 2000Åke Davidsson MD Abstract Objective: Sinonasal polyps contain numerous tissue-dwelling eosinophils, but the mechanisms causing their accumulation, functional activities, and resolution are largely unknown. Study Design: Nasal polyp tissue from 14 patients was evaluated for cellular expression of CD95, CD68, and Annexin-V, for the degree of apoptosis, and for phagocytosis of eosinophils. Material and Methods: Histological sections were immunostained as single stains for CD95, CD68, and Annexin-V, and as an immunostaining for CD68 combined with a modified Vital New Red staining. The latter staining is specific for eosinophils. Other sections were stained by terminal d-UTP nick end labeling (TUNEL) assay and routinely stained for H&E. Evaluation of the amount of stained cells was performed by counting the average number in 10 randomly chosen high-power fields. The TUNEL positivity was in all cases confirmed with apoptotic morphology. Results: The inflammatory infiltrate consisted of numerous eosinophils but also a considerable amount of lymphocytes, mast cells, and macrophage-like CD68+ cells. CD95 was frequently expressed on eosinophils, on numerous other inflammatory cells, and also on morphologically apoptotic cells. Annexin-V-positive eosinophils were not as frequent as CD95+ cells, but numerous Annexin-V-positive eosinophils were found. CD68+ cells approximately equalled the number of eosinophils. The number of cells phagocytosing eosinophils varied between polyps. Apoptosis of eosinophils (as evaluated by TUNEL combined with apoptotic morphology) was a common finding in six of the polyps. Conclusions: Previous in vitro and ex vivo findings of CD95 on eosinophils are now supported by demonstration of CD95 on eosinophils in this in vivo study. This investigation revealed a switch of the membrane-bound phosphatidylserine of apoptotic cells, which is a novel observation. The study has demonstrated apoptosis of tissue-dwelling eosinophils, and that CD68+ macrophage-like cells phagocytose eosinophils within the sinonasal polyps. [source] Formulation and evaluation of chitosan microspheres of aceclofenac for colon-targeted drug deliveryBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2010S. K. Umadevi Abstract The objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span-85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies, in vitro and in vivo drug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41,80,µm. The swelling index was in the range 0.37,0.82 and the entrapment efficiency range was 51,75% for all the formulations. The optimised batch ACM13 released 83.6% at 8,h and 104% at 24,h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non-Fickian diffusion mechanism. The in vivo findings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti-inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis. Copyright © 2010 John Wiley & Sons, Ltd. [source] Interferon-,2a is sufficient for promoting dendritic cell immunogenicityCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005A. Tamir Summary Type I interferons (IFNs) are widely used therapeutically. IFN-,2a in particular is used as an antiviral agent, but its immunomodulatory properties are poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and therefore play a crucial role in initiating the adaptive phase of the immune response. We studied the effects of IFN-,2a on DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN-,2a induced phenotypic maturation of DCs and increased their allostimulatory capacity. When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-,2a, the production of interleukin (IL)-10 and IL-12 was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-,2a mainly induced IL-10 release. The production of IFN-, and IL-5 by the responder naive T cells was also amplified in response to IFN-,2a-treated DCs. Furthermore, IL-12 production by IFN-,2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody. Different results were obtained when DCs were treated simultaneously with IFN-,2a and other maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h later. Under these circumstances, IFN-,2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-,/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone. Altogether, this work suggests that IFN-,2a in isolation is sufficient to promote DC activation, however, other concomitant events, such as exposure to LPS during a bacterial infection, can inhibit its effects. These results clarify some of the in vivo findings obtained with IFN-,2a and have direct implications for the design of IFN-,-based vaccines for immunotherapy. [source] | |||||||||||||