Home About us Contact
|
Home About us Contact | ||
|
|
||
Potential Clinical Applications (potential + clinical_application)
Selected AbstractsMiniaturization of Fluorescence Microscopes Using Fibre OpticsEXPERIMENTAL PHYSIOLOGY, Issue 6 2002Fritjof Helmchen In both medical research and diagnostics characterization of biological tissue on the cellular level relies on high-resolution optical microscopy. In most cases, however, tissue is excised for microscopic investigation, in part because conventional microscopes are bulky instruments. Imaging of cells in the intact living organism has been difficult. Over the last decade several groups have developed miniature confocal microscopes that use fibre optics to deliver light to the specimen and to measure either reflected or excited fluorescence light. In addition, two-photon excitation recently has been employed in a small portable ,fibrescope'. A potential clinical application of these microscope probes is their endoscopic use for optical biopsy of inner organs or guidance of conventional biopsy. As a mobile research tool they may permit imaging of neuronal activity in the brain of awake, behaving animals. Here, we review technological approaches to build miniaturized fluorescence microscopes and discuss their potential applications. [source] Mesenchymal stem cell interaction with a non-woven hyaluronan-based scaffold suitable for tissue repairJOURNAL OF ANATOMY, Issue 5 2008G. Pasquinelli Summary The fabrication of biodegradable 3-D scaffolds enriched with multipotent stem cells seems to be a promising strategy for the repair of irreversibly injured tissues. The fine mechanisms of the interaction of rat mesenchymal stem cells (rMSCs) with a hyaluronan-based scaffold, i.e. HYAFF®11, were investigated to evaluate the potential clinical application of this kind of engineered construct. rMSCs were seeded (2 × 106 cells cm,2) on the scaffold, cultured up to 21 days and analysed using appropriate techniques. Light (LM), scanning (SEM) and transmission (TEM) electron microscopy of untreated scaffold samples showed that scaffolds have a highly porous structure and are composed of 15-µm-thick microfibres having a rough surface. As detected by trypan blue stain, cell adhesion was high at day 1. rMSCs were viable up to 14 days as shown by CFDA assay and proliferated steadily on the scaffold as revealed by MTT assay. LM showed rMSCs in the innermost portions of the scaffold at day 3. SEM revealed a subconfluent cell monolayer covering 40 ± 10% of the scaffold surface at day 21. TEM of early culture showed rMSCs wrapping individual fibres with regularly spaced focal contacts, whereas confocal microscopy showed polarized expression of CD44 hyaluronan receptor; TEM of 14-day cultures evidenced fibronexus formation. Immunohistochemistry of 21-day cultures showed that fibronectin was the main matrix protein secreted in the extracellular space; decorin and versican were seen in the cell cytoplasm only and type IV collagen was minimally expressed. The expression of CD90, a marker of mesenchymal stemness, was found unaffected at the end of cell culture. Our results show that HYAFF®11 scaffolds support the adhesion, migration and proliferation of rMSCs, as well as the synthesis and delivery of extracellular matrix components under static culture conditions without any chemical induction. The high retention rate and viability of the seeded cells as well as their fine modality of interaction with the substrate suggest that such scaffolds could be potentially useful when wide tissue defects are to be repaired as in the case of cartilage repair, wound healing and large vessel replacement. [source] Osteogenesis induced by extracorporeal shockwave in treatment of delayed osteotendinous junction healingJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2010Ling Qin Abstract Healing at the osteotendinous junction (OTJ) is challenging in orthopedic surgery. The present study aimed to test extracorporeal shockwave (ESW) in treatment of a delayed OTJ healing. Twenty-eight rabbits were used for establishing a delayed healing (DH) model at patella-patellar-tendon (PPT) complex after partial patellectomy for 4 weeks and then were divided into DH and ESW groups. In the ESW group, a single ESW treatment was given at postoperative week 6 to the PPT healing complex. The samples were harvested at week 8 and 12 for radiographic and histological evaluations with seven samples for each group at each time point. Micro-CT results showed that new bone volume was 1.18 ± 0.61,mm3 in the ESW group with no measurable new bone in the DH group at postoperative week 8. Scar tissue formed at the OTJ healing interface of the DH group, whereas ESW triggered high expression of VEGF in hypertrophic chondrocytes at week 8 and regeneration of the fibrocartilage zone at week 12 postoperatively. The accelerated osteogenesis could be explained by acceleration of endochondral ossification. In conclusion, ESW was able to induce osteogenesis at OTJ with delayed healing with enhanced endochondral ossification process and regeneration of fibrocartilage zone. These findings formed a scientific basis to potential clinical application of ESW for treatment of delayed OTJ healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:70,76, 2010 [source] Protective effects of the Alisma orientalis extract on the experimental nonalcoholic fatty liver diseaseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2006Xuezhi Hong The aim of this investigation was to evaluate the efficacy of Alisma orientalis methanolic extract (AOME) on the experimental nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet. Rats were fed with high-fat diet for six weeks and then gavaged the AOME for another six weeks. Typical pathological symptoms of NAFLD occurred in the high-fat diet rats. Administration with the AOME (150,300 and 600 mg kg,1) markedly decreased the serum and liver lipids; the high level of fasting serum glucose was reduced and insulin resistance was improved. The AOME treatment was also helpful in preventing the oxidative stress by lessening lipid peroxidation and activating antioxidant enzymes. Markers of the liver injury, aminotransferase abnormalities and hepatomegaly were improved and morphological changes, such as liver steatosis, mixed inflammation and collagen deposition, were lessened in rats treated with the AOME. These results suggested that the AOME showed hepatoprotective effects on NAFLD and may be a potential clinical application for treatment of this chronic liver disease. [source] Protective effects of melatonin against myocardial injury induced by isoproterenol in ratsJOURNAL OF PINEAL RESEARCH, Issue 2 2003Mahmut Acikel Abstract: This study was performed to determine whether melatonin could have a protective effect against myocardial injury (MI) induced by isoproterenol (ISO) in rats. Twenty-four rats were divided into three treatment groups: (1) control (n = 8): saline solution. (2) ISO (n = 8): ISO only. (3) melatonin + ISO (n = 8). Melatonin (10 mg/kg/day, i.p.) was administered 30 min before the initiation of ISO (150 mg/kg/day, s.c.). Drugs and saline were given at 14:00 hr for two consecutive days. At the end of the second day, blood samples were taken from the abdominal aorta shortly after the rats were anesthetized for the purpose of measuring cardiac troponins T (cTnT) and I (cTnI); hearts were removed, preserved and examined microscopically. Additionally, based on the histological changes in myocardial tissue, the rats were divided into three groups: no change, mild changes and moderate and/or marked changes. The mean cTnT and cTnI values were significantly increased in ISO group compared with control group [(1.29 ± 0.22 ng/mL versus 0.46 ± 0.07 ng/mL, P < 0.0001) and (0.56 ± 0.11 ng/mL versus 0.21 ± 0.01 ng/mL, P < 0.001)], respectively, and were significantly reduced in the ISO + melatonin group (0.65 ± 0.06 ng/mL for cTnT and 0.25 ± 0.01 ng/mL for cTnI) compared with the ISO only group (P < 0.01), respectively. cTnT and cTnI values were significantly increased in rats with moderate and/or marked cardiac changes compared with hearts where there were mild changes and no change (P < 0.05). ISO + melatonin group showed less histological changes than the ISO group (P < 0.01). In conclusion, this study revealed a protective effect of melatonin against ISO-induced MI in rats, and its potential clinical application in the treatment of MI. [source] Growth inhibitory effects of pegylated IFN ,-2b on human liver cancer cells in vitro and in vivoLIVER INTERNATIONAL, Issue 8 2006Hirohisa Yano Abstract: Purpose: We investigated the effects of pegylated IFN-,2b (PEG-IFN-,2b) on the growth of human liver cancer cells. Methods: The effect of PEG-IFN-,2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN-, receptor-2 (IFNAR-2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG-IFN-,2b. After HAK-1B cells were transplanted into nude mice, various doses of PEG-IFN-,2b or IFN-,2b were administered, and tumor volume, weight, histology, and IFNAR-2 expression were examined. Results: PEG-IFN-,2b inhibited the growth of nine cell lines with apoptosis in a dose- and time-dependent manner. Continuous contact with PEG-IFN-,2b induced time-dependent growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-,2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG-IFN-,2b was significantly stronger than that of non-PEG-IFN-,2b in vivo. Conclusions: Continuous contact with PEG-IFN-,2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-,2b for the prevention and treatment of HCC. [source] A novel visual analogue scale (VAS) device: an instrument based on the VAS designed to quantify the subjective visual experienceOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 3 2004Jonathan S. Pointer Abstract Purpose :,To evaluate a novel device intended to facilitate the direct quantification of the subjective visual experience. The design principle is based on that of the visual analogue scale (VAS) technique but obviates the need for subsequent measurement unlike the administration of the conventional paper VAS. Methods :,The visual experience of 134 normally sighted 17,40-year-olds was quantified using (in randomised sequence) a paper VAS and the novel VAS device. A notional 100-point scale was utilised in either case, and the extreme descriptive anchors for both instruments were ,dreadful' and ,perfect'. Results :,The degree of clinical agreement between the two alternative VAS techniques was very high. A small bias (mean = +0.7 VAS units: 95% confidence interval 0.3,1.2 units) towards the paper VAS was evident in these data, an outcome of no clinical significance or impediment as regards the substitution of the novel device for the conventional paper-based approach. Conclusions :,The moving of a bead along a wire is shown to be a clinically and statistically reliable alternative procedure to the pen-marking of a conventional paper VAS for the evaluation of the recent subjective visual experience, provided that the same minimum/maximum descriptive anchors are used for either instrument. The instant quantification of the VAS score afforded by the novel technique introduced here broadens the potential clinical application of this technique. [source] Human papillomavirus integration: detection by in situ hybridization and potential clinical applicationTHE JOURNAL OF PATHOLOGY, Issue 1 2004Mark F Evans Abstract Human papillomaviruses (HPVs) are accepted as a necessary cause of cervical neoplasia. However, the benefits of testing simply for high-risk HPV types are limited because of their high prevalence in intraepithelial lesions of all grades, the majority of which regress if left untreated. One factor considered to be of key importance for the progression of intraepithelial lesions to invasive disease is integration of HPV into the host cell genome. Although questions remain about the prevalence of integration amongst pre-invasive lesions, sensitive in situ hybridization techniques utilizing tyramide reagents may aid determination of the significance of HPV infection by enabling routine detection of both high-risk HPV and its physical status. This will provide important data relevant not only to our understanding of the biology of HPV-associated neoplasia, but also potentially to clinical testing for HPV. Copyright © 2003 John Wiley & Sons, Ltd. [source] Candidate's Thesis: Platelet-Activating Factor,Induced Hearing Loss: Mediated by Nitric Oxide?,THE LARYNGOSCOPE, Issue 12 2003Chung-Ku Rhee MD Abstract Objectives/Hypothesis Platelet-activating factor (PAF)in middle ear effusion is thought to induce hearing loss. The purpose of this study is to investigate the role of nitric oxide (NO) in the mechanism of PAF-induced hearing loss by studying the effects of PAF application on the round window membrane (RWM) with and without PAF-antagonist NO-blocker. Study Design Longitudinal study on randomized guinea pigs using PAF to induce hearing loss. Methods Guinea pigs were divided into four groups: PBS, PAF, PAF-antagonist, and L-NAME. The PBS group received phosphate buffered saline (PBS) and the PAF groups received 10, 20, and 40 ,g of PAF soaked into gelfoam and placed on the RWM. PAF-antagonist (WEB 2170) and NOS inhibitor NG-nitro-l-arginine-methylester (L-NAME) were injected intraperitoneally prior to PAF 20 ,g application on the RWM. The following three tests were performed on each animal group: Hearing was tested with an auditory brainstem response (ABR) test over 24 hours. At the end of 24 hours, cochlear hair cells were examined by scanning electron microscopy (SEM) and immunohistochemistry was carried out on the cochlea to test the expression of inducible nitric oxide synthase (iNOS). Results The PAF group developed significant elevation of ABR threshold and cochlear hair cell damage in the SEM group as compared with the PBS control group. The PAF-antagonist (WEB 2170) and the L-NAME groups did not show significant elevation of ABR threshold and cochlear hair cell damage compared with the group administered PAF 20 ,g, but in the PAF-antagonist group, the elevation of ABR threshold was significant compared with that of the PBS control group, whereas it was not significant compared with the PBS group in the L-NAME group. Strong expression of iNOS on cochlea was observed in the PAF group and lighter expression was seen in PBS, WEB 2170, and L-NAME groups. Conclusions This study demonstrated that PAF placed on the RWM induced hearing loss and cochlear hair cell damage. The PAF-antagonists and L-NAME prevented the PAF-induced hearing loss and inhibited iNOS expression in the cochlea. These findings suggest that the PAF-induced hearing loss caused by cochlear hair cell damage may have been mediated by NO. PAF-antagonists and L-NAME may have future therapeutic implications in preventing sensorineural hearing loss associated with chronic otitis media. The results of this study have significant potential clinical application. [source] Models for Estimating Bayes Factors with Applications to Phylogeny and Tests of MonophylyBIOMETRICS, Issue 3 2005Marc A. Suchard Summary Bayes factors comparing two or more competing hypotheses are often estimated by constructing a Markov chain Monte Carlo (MCMC) sampler to explore the joint space of the hypotheses. To obtain efficient Bayes factor estimates, Carlin and Chib (1995, Journal of the Royal Statistical Society, Series B57, 473,484) suggest adjusting the prior odds of the competing hypotheses so that the posterior odds are approximately one, then estimating the Bayes factor by simple division. A byproduct is that one often produces several independent MCMC chains, only one of which is actually used for estimation. We extend this approach to incorporate output from multiple chains by proposing three statistical models. The first assumes independent sampler draws and models the hypothesis indicator function using logistic regression for various choices of the prior odds. The two more complex models relax the independence assumption by allowing for higher-lag dependence within the MCMC output. These models allow us to estimate the uncertainty in our Bayes factor calculation and to fully use several different MCMC chains even when the prior odds of the hypotheses vary from chain to chain. We apply these methods to calculate Bayes factors for tests of monophyly in two phylogenetic examples. The first example explores the relationship of an unknown pathogen to a set of known pathogens. Identification of the unknown's monophyletic relationship may affect antibiotic choice in a clinical setting. The second example focuses on HIV recombination detection. For potential clinical application, these types of analyses must be completed as efficiently as possible. [source] Preparation of extracellular domain 3 of human VEGF receptor-2 and the monitoring of its real-time binding to VEGF by biosensorsBIOTECHNOLOGY PROGRESS, Issue 6 2009Juan Zhang Abstract Vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in stimulating the proliferation of endothelial cells and improving the permeability of blood vessels, which is involved in tumor angiogenesis, a process that is essential for tumor growth and metastasis. In this study, we describe a method for high yield of recombinant extracellular domain 3 (KDR3) of human VEGFR-2 in an Escherichia coli system with further purification by cation exchange chromatography and immobilized metal affinity chromatography (IMAC). The biological activity of recombinant KDR3 was performed by sequestering VEGF in HUVEC proliferation assay. The real-time binding of human VEGF to immobilized KDR3 was monitored by a label-free biosensor, Optical waveguide lightmode spectroscopy (OWLS). Under the given experimental conditions, the association rate constant ka was 4.2 × 103 M,1 s,1 and the dissociation rate kd was 5.1 × 10,3 s,1. The dissociation constant KD was then calculated to be 1.2 × 10,6 M. The obtained values will serve as baseline parameters for the design of improved versions of recombinant soluble VEGF receptors and the evaluation of developed anti-KDR antibodies. In addition, such a scenario established by the use of OWLS will potentiate the kinetic study of ligand/receptor and antigen/antibody. The receptor discussed here, which block VEGF binding to cell membrane KDR, have potential clinical application in the treatment of cancer and other diseases where pathological angiogenesis is involved. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Clinical applications of laser scanning cytometryCYTOMETRY, Issue 3 2002Attila Tárnok Abstract This study reviews existing and potential clinical applications of laser scanning cytometry (LSC) and outlines possible future developments. LSC provides a technology for solid phase cytometry. Fluorochrome-labeled specimens are immobilized on microscopic slides that are placed on a conventional epifluorescence microscope and analyzed by one or two lasers. Data comparable to flow cytometry are generated. In addition, the position of each event is recorded, a feature that allows relocalization and visualization of each measured event. The major advantage of LSC compared with other cytometric methods is the combination of two features: (a) the minimal clinical sample volume needed and (b) the connection of fluorescence data and morphological information for the measured event. Since the introduction of LSC, numerous methods have been established for the analysis of cells, cellular compartments, and tissues. Although most cytometric methods use only two or three colors, the characterization of specimens with up to five fluorochromes is possible. Most clinical applications have been designed to determine ploidy and immunophenotype; other applications include analyses of tissue biopsies and sections, fluorescence in situ hybridization, and the combination of vital and nonvital information on a single-cell basis. With the currently available assays, LSC has proven its wide spectrum of clinical applicability in slide-based cytometry and can be introduced as a standard technology in multiple clinical settings. Cytometry (Clin. Cytometry) 50:133,143, 2002. © 2002 Wiley-Liss, Inc. [source] Glucagon-like peptide 1(GLP-1) in biology and pathologyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Juris J. Meier Abstract Post-translational proteolytic processing of the preproglucagon gene in the gut results in the formation of glucagon-like peptide 1 (GLP-1). Owing to its glucose-dependent insulinotropic effect, this hormone was postulated to primarily act as an incretin, i.e. to augment insulin secretion after oral glucose or meal ingestion. In addition, GLP-1 decelerates gastric emptying and suppresses glucagon secretion. Under physiological conditions, GLP-1 acts as a part of the ,ileal brake', meaning that is slows the transition of nutrients into the distal gut. Animal studies suggest a role for GLP-1 in the development and growth of the endocrine pancreas. In light of its multiple actions throughout the body, different therapeutic applications of GLP-1 are possible. Promising results have been obtained with GLP-1 in the treatment of type 2 diabetes, but its potential to reduce appetite and food intake may also allow its use for the treatment of obesity. While rapid in vivo degradation of GLP-1 has yet prevented its broad clinical use, different pharmacological approaches aiming to extend the in vivo half-life of GLP-1 or to inhibit its inactivation are currently being evaluated. Therefore, antidiabetic treatment based on GLP-1 may become available within the next years. This review will summarize the biological effects of GLP-1, characterize its role in human biology and pathology, and discuss potential clinical applications as well as current clinical studies. Copyright © 2005 John Wiley & Sons, Ltd. [source] Regulatory T cells for the prevention of graft- versus -host disease: Professionals defeat amateursEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2009Matthias Edinger Abstract CD4+CD25+ Treg are pivotal for the maintenance of self-tolerance and the adoptive transfer of Treg is envisaged for the treatment of autoimmune diseases and the induction of tolerance after allogeneic organ or stem cell transplantation. Owing to the paucity of natural Treg in peripheral blood, isolation of Treg for therapeutic purposes is cumbersome and not easily translatable into clinical trials. To circumvent such hurdles, many groups are exploring the de novo induction of Treg from conventional T cells for potential clinical applications. In this issue of the European Journal of Immunology, a paper examines the therapeutic efficacy of natural and induced Treg in a model of graft- versus -host disease and report that induced Treg rapidly lose their Treg features in an allogeneic environment and are unable to prevent disease. Thus, the stability of induced Treg is of major concern as discussed in this Commentary. [source] Neuropharmacology and therapeutic potential of cannabinoidsADDICTION BIOLOGY, Issue 1 2000Roger G. Pertwee Mammalian tissues contain at least two types of cannabinoid receptor, CB 1, found mainly on neurones and CB 2, found mainly in immune cells. Endogenous ligands for these receptors have also been identified. These endocannabinoids and their receptors constitute the endogenous cannabinoid system. Two cannabinoid receptor agonists, ,9 -tetrahydrocannabinol and nabilone, are used clinically as anti-emetics or to boost appetite. Additional therapeutic uses of cannabinoids may include the suppression of some multiple sclerosis and spinal injury symptoms, the management of pain, bronchial asthma and glaucoma, and the prevention of neurotoxicity. There are also potential clinical applications for CB 1 receptor antagonists, in the management of acute schizophrenia and cognitive/memory dysfunctions and as appetite suppressants. Future research is likely to be directed at characterizing the endogenous cannabinoid system more completely, at obtaining more conclusive clinical data about cannabinoids with regard to both beneficial and adverse effects, at developing improved cannabinoid formulations and modes of administration for use in the clinic and at devising clinical strategies for separating out the sought-after effects of CB 1 receptor agonists from their psychotropic and other unwanted effects. [source] Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applicationsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Allen P. Anandarajah Abstract Focal bone loss around inflamed joints in patients with autoimmune disease, such as rheumatoid arthritis, remains a serious clinical problem. The recent elucidation of the RANK/RANK-ligand/OPG pathway and its role as the final effector of osteoclastogenesis and bone resorption has brought a tremendous understanding of the pathophysiology of inflammatory bone loss, and has heightened expectation of a novel intervention. Here, we review the etiology of inflammatory bone loss, the RANK/RANK-ligand/OPG pathway, and the clinical development of anti-RANK-ligand therapy. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] Stem cells and pulmonary metamorphosis: New concepts in repair and regenerationJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005Jason M. Aliotta Adult stem cells are likely to have much more versatile differentiation capabilities than once believed. Numerous studies have appeared over the past decade demonstrating the ability of adult stem cells to differentiate into a variety of cells from non-hematopoietic organs, including the lung. The goal of this review is to provide an overview of the growth factors which are thought to be involved in lung development and disease, describe the cells within the lung that are believed to replace cells that have been injured, review the studies that have demonstrated the transformation of bone marrow-derived stem cells into lung cells, and describe potential clinical applications with respect to human pulmonary disease. © 2005 Wiley-Liss, Inc. [source] Estimation of Acute Fluid Shifts Using Bioelectrical Impedance Analysis in HorsesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2007C. Langdon Fielding Background: Multi-frequency bioelectrical impedance analysis (MF-BIA) has been used to evaluate extracellular fluid volume (ECFV), but not fluid fluxes associated with fluid or furosemide administration in horses. If able to detect acute changes in ECFV, MF-BIA would be useful in monitoring fluid therapy in horses. Hypothesis: The purpose of this study was to evaluate the ability of MF-BIA to detect acute fluid compartment changes in horses. We hypothesized that MF-BIA would detect clinically relevant (10,20%) changes in ECFV. Animals: Six healthy mares were used in the study. Methods: This is an original experimental study. Mares were studied in 3 experiments: (1) crystalloid expansion of normally hydrated subjects, (2) furosemide-induced dehydration followed by crystalloid administration, and (3) acute blood loss followed by readministration of lost blood. MF-BIA measurements were made before, during, and after each fluid shift and compared to known changes in volume calculated based on the intravenous fluids that were administered in addition to urinary fluid losses. Mean errors between MF-BIA estimated change and known volume change were compared using nonparametric analysis of variance. Estimated ECFV pre- and post-fluid administration similarly were compared. The level of statistical significance was set at P < .05. Results: Results of the study revealed a statistically significant change in ECFV and total body water during crystalloid expansion and dehydration. Statistically significant changes were not observed during blood loss and administration. Mean errors between MF-BIA results and measured net changes were small. Conclusions and Clinical Importance: MF-BIA represents a practical and accurate means of assessing acute fluid changes during dehydration and expansion of ECFV using isotonic crystalloids with potential clinical applications in equine critical care. [source] The mechanisms of tumor suppressor effect of glucocorticoid receptor in skinMOLECULAR CARCINOGENESIS, Issue 8 2007Dmitry Chebotaev Abstract Glucocorticoid hormones exert a tumor suppressor effect in different experimental models, including mouse skin carcinogenesis. The glucocorticoid control of cellular functions is mediated via the glucocorticoid receptor (GR), a well-known transcription factor that regulates genes by DNA-binding dependent transactivation, and DNA-binding independent transrepression through negative interaction with other transcription factors. In this perspective, we analyze known mechanisms that underlie the anticancer effect of GR signaling, including effects on cell growth, differentiation, apoptosis, and angiogenesis. We also discuss a novel mechanism for the tumor suppressor effect of the GR in skin: through the regulation of the number and status of follicular epithelial stem cells (SC), which are a target cell population for skin carcinogenesis. Our studies on keratin5.GR transgenic animals that are resistant to skin carcinogenesis, demonstrated that the GR diminishes the number of follicular epithelial SCs, reduces their proliferative and survival potential and affects the expression of follicular SC "signature" genes. The analysis of global effect of the GR on gene expression in follicular epithelial SCs, basal keratinocytes, and mouse skin tumors provided an unexpected evidence that gene transrepression by GR plays an important role in the maintenance of SC and in inhibition of skin carcinogenesis by this steroid hormone receptor. It is known that antiinflammatory effect of glucocorticoids is chiefly mediated by GR transrepression. Thus, our findings suggest the similarity between the mechanisms of antiinflammatory and anticancer effects of the GR signaling. We discuss the potential clinical applications of our findings in light of drug discovery programs focused on the development of selective GR modulators that preferentially induce GR transrepression. © 2007 Wiley-Liss, Inc. [source] Catchlike property of skeletal muscle: Recent findings and clinical implicationsMUSCLE AND NERVE, Issue 6 2005Stuart Binder-Macleod PhD Abstract The catchlike property of skeletal muscle is the force augmentation produced by the inclusion of an initial, brief, high-frequency burst of two to four pulses at the start of a subtetanic low-frequency stimulation train. Catchlike-inducing trains take advantage of the catchlike property of skeletal muscle and augment muscle performance compared with constant-frequency trains, especially in the fatigued state. Literature spanning more than 30 years has provided comprehensive information about the catchlike property of skeletal muscle. The pattern of the catchlike-inducing train that maximizes muscle performance is fairly similar across different muscles of different species and under various stimulation conditions. This review summarizes the mechanisms of the catchlike property, factors affecting force augmentation, techniques used to identify patterns of catchlike-inducing trains that maximize muscle performance, and potential clinical applications to provide a historical and current perspective of our understanding of the catchlike property. Muscle Nerve, 2005 [source] Human adipose-derived stem cells: isolation, characterization and applications in surgeryANZ JOURNAL OF SURGERY, Issue 4 2009Michelle Locke Abstract The ideal stem cell for use in functional tissue engineering needs to be abundantly available, harvested with minimal morbidity, differentiated reliably down various pathways and able to be transplanted safely and efficaciously. Adult human adipose tissue contains a population of mesenchymal stem cells, termed ,adipose-derived stem cells' (ASC), which seem to fulfil most, if not all, of these criteria. ASC can be harvested readily, safely, and in relative abundance by modern liposuction techniques. They are capable of differentiating into other mesenchymal tissue types, including adipocytes, chondrocytes, myocytes and osteoblasts. They also show angiogenic properties, with recent evidence of a potential role in healing radiotherapy-damaged tissue, possibly due to their secretion of vascular endothelial growth factor. Similarly, they may have a role in healing chronic wounds, and as such are being investigated in phase 1 trials for their ability to aid healing of recurrent Crohn's fistulae. Subsequently they have a wide range of potential clinical uses in all fields of surgery. This article reviews the current and potential clinical applications of ASC in relation to surgery, as well as methods for their isolation, differentiation and molecular characterization. [source] Binase and other microbial RNases as potential anticancer agentsBIOESSAYS, Issue 8 2008Alexander A. Makarov Some RNases possess preferential cytotoxicity against malignant cells. The best known of these RNases, onconase, was isolated from frog oocytes and is in clinical trials as anticancer therapy. Here we propose an alternative platform for anticancer therapy based on T1 RNases of microbial origin, in particular binase from Bacillus intermedius and RNase Sa from Streptomyces aureofaciens. We discuss their advantages and the most promising directions of research for their potential clinical applications. BioEssays 30:781,790, 2008. © 2008 Wiley Periodicals, Inc. [source] Erythropoietin administration protects against functional impairment and cell death after ischaemic renal injury in pigsBJU INTERNATIONAL, Issue 1 2007COLIN J. FORMAN OBJECTIVE To determine whether the administration of erythropoietin at the time of ischaemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration and promotes renal functional recovery, as it does in rodent models, in a higher mammalian model. MATERIALS AND METHODS The model of IRI involved unilateral nephrectomy in pigs, followed a week later by renal artery occlusion for 1 h, followed by reperfusion for 5 days. Pigs were randomized to receive erythropoietin 5000 units/kg intravenously at the time of ischaemia, followed by 1000 units/kg subcutaneously daily, or no treatment (six pigs each). Renal function and structure were analysed; blood and urine were collected daily to determine serum creatinine level, blood urea nitrogen, and creatinine clearance. Animals were killed after 5 days to obtain the injured kidneys. The kidneys were examined histologically for evidence of cellular mitosis, apoptosis and necrosis. RESULTS Erythropoietin significantly abrogated renal dysfunction after IRI compared with controls at 12 h after injury; the mean (sem) creatinine clearance (as a percentage of baseline) for IRI was 68.2 (6)% vs erythropoietin-IRI 94.9 (8.9)% (P = 0.027), although by 36 h this was no longer significant, with values of 73.8 (12.7)% vs 95.9 (12)%, respectively (P = 0.23). Erythropoietin also significantly reduced the amount of cell death on histological analysis after 5 days of reperfusion, with a median (range) for IRI of 5.5 (1,45) vs erythropoietin-IRI of 1.5 (0,4) (P = 0.043). CONCLUSION This study confirms the potential clinical applications of erythropoietin as a novel therapeutic agent in patients at risk of IRI. [source] S-nitrosothiols as selective antithrombotic agents , possible mechanismsBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2010MP Gordge S-nitrosothiols have a number of potential clinical applications, among which their use as antithrombotic agents has been emphasized. This is largely because of their well-documented platelet inhibitory effects, which show a degree of platelet selectivity, although the mechanism of this remains undefined. Recent progress in understanding how nitric oxide (NO)-related signalling is delivered into cells from stable S-nitrosothiol compounds has revealed a variety of pathways, in particular denitrosation by enzymes located at the cell surface, and transport of intact S-nitrosocysteine via the amino acid transporter system-L (L-AT). Differences in the role of these pathways in platelets and vascular cells may in part explain the reported platelet-selective action. In addition, emerging evidence that S-nitrosothiols regulate key targets on the exofacial surfaces of cells involved in the thrombotic process (for example, protein disulphide isomerase, integrins and tissue factor) suggests novel antithrombotic actions, which may not even require transmembrane delivery of NO. [source] Emerging strategies for exploiting cannabinoid receptor agonists as medicinesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009Roger G Pertwee Mandarin translation of abstract Medicines that activate cannabinoid CB1 and CB2 receptor are already in the clinic. These are Cesamet® (nabilone), Marinol® (dronabinol; ,9 -tetrahydrocannabinol) and Sativex® (,9 -tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol® can also be prescribed to stimulate appetite, while Sativex® is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB2 receptors; or (v) ,multi-targeting'. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed. Mandarin translation of abstract [source] Short wavelength automated perimetryACTA OPHTHALMOLOGICA, Issue 6 2001John M. Wild ABSTRACT. Short Wavelength Automated Perimetry (SWAP) utilizes a blue stimulus to preferentially stimulate the blue cones and a high luminance yellow background to adapt the green and red cones and to saturate, simultaneously, the activity of the rods. This review describes the theoretical aspects of SWAP, highlights current limitations associated with the technique and discusses potential clinical applications. Compared to white-on-white (W-W) perimetry, SWAP is limited clinically by: greater variability associated with the estimation of threshold, ocular media absorption, increased examination duration and an additional learning effect. Comparative studies of SWAP and W-W perimetry have generally been undertaken on small cohorts of patients. The conclusions are frequently unconvincing due to limitations for SWAP in the delineation of abnormality and of progressive field loss. SWAP is almost certainly able to identify glaucomatous visual field loss in advance of that by W-W perimetry although the incidence of progressive field loss is similar between the two techniques. Increasing evidence suggests that functional abnormality with SWAP is preceded by structural abnormality of the optic nerve head and/or the retinal nerve fibre layer. SWAP appears to be beneficial in the detection of diabetic macular oedema and possibly in some neuro-ophthalmic disorders. [source] | |||||||||||||