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Irreversible Changes (irreversible + change)
Selected AbstractsHyaluronidase reduces human breast cancer xenografts in SCID miceINTERNATIONAL JOURNAL OF CANCER, Issue 2 2002Svetlana Shuster Abstract A hyaluronan-rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti-cancer strategy. Hyaluronan interaction with its CD44 receptor and the resulting signal transduction events may be among the mechanisms for hyaluronan-associated cancer progression. We have shown previously that hyaluronidase treatment of breast cancer cells in vitro not only eradicates hyaluronan but also modifies expression of CD44 variant exons of tumor cells. We now determine if such effects occur in vivo and if it is accompanied by tumor regression. SCID mice bearing xenografts of human breast carcinomas were given intravenous hyaluronidase. Tumor volumes decreased 50% in 4 days. Tumor sections showed decreased hyaluronan. Intensity of staining for CD44s was not affected, whereas staining for specific CD44 variant exon isoforms was greatly reduced in residual tumors. Necrosis was not evident. Hyaluronidase, used previously as an adjunct in cancer treatment, presumably to enhance penetration of chemotherapeutic drugs, may itself have intrinsic anti-cancer activity. Removing peritumor hyaluronan appears to cause an irreversible change in tumor metabolism. Continuous hyaluronan binding to CD44 variant exon isoforms may also be required to stabilize inherently unstable isoforms that participate perhaps in tumor progression. Further investigation is required to confirm a cause and effect relationship between loss of hyaluronan, changes in CD44 variant exon expression and tumor reduction. If confirmed, hyaluronidase may provide a new class of anti-cancer therapeutics and one without toxic side effects. © 2002 Wiley-Liss, Inc. [source] Restoration of Protein Synthesis in Heart and Skeletal Muscle After Withdrawal of AlcoholALCOHOLISM, Issue 4 2004Thomas C. Vary Abstract: Background: The rate of protein synthesis is diminished after chronic alcohol consumption through changes in both mRNA translation initiation and elongation. It remains unknown how long adverse effects of alcohol on protein synthesis persist after withdrawal from ethanol. Methods: We examined the effect of removal of alcohol from the diet of rats for 72 hr after chronic alcohol exposure (16 weeks) on rates of protein synthesis and potential mechanisms for controlling mRNA translation in heart, skeletal muscle, and liver. Rates of protein synthesis were measured after intravenous infusion of [3H]-l-phenylalanine. The formation of active eukaryotic initiation factor (eIF)4E·eIF4G complex, the cellular content of eukaryotic elongation factor (eEF)1A and eEF2, and the phosphorylation state of eEF2 and S6K1 were measured in each tissue. Results: Withdrawal of alcohol from the diet restored protein synthesis in heart and skeletal muscle to values obtained in pair-fed control rats not exposed to alcohol. However, the organ weight and protein content per muscle was not affected by withdrawal of alcohol from the diet. In both heart and skeletal muscle, the restoration of protein synthesis correlated with reversal of defects in the formation of active eIF4E·eIF4G complex and eEF1A content. Myocardial eEF2 content was also restored to control values after withdrawal of alcohol from the diet. In the gastrocnemius, there was a decrease in the cellular content of eEF2. The lower eIF2 content may have been counterbalanced by an increased activity of eEF2 through a reduction in the phosphorylation state of eEF2 allowing protein synthesis to proceed unimpeded. Conclusions: These studies indicate that changes in protein metabolism observed during chronic alcohol intake are reversible and do not, at this stage, represent an irreversible change in cardiac or skeletal muscle. [source] Statistical Mechanical Modeling of Protein AdsorptionMATERIALWISSENSCHAFT UND WERKSTOFFTECHNIK, Issue 12 2003P. R. Van TasselArticle first published online: 5 JAN 200 Abstract We present rationale for and a derivation of a statistical mechanical model of protein adsorption. Proteins are modeled as rigid geometric objects adsorbing initially in a reversible manner and subsequently undergoing an irreversible change in shape to a permanently adsorbed state. Both adsorption and shape change occur subject to energetic interactions with previously adsorbed proteins. We evaluate the model quantitatively for proteins with disk-shaped projections within the scaled particle theory and compare the predictions to experimental measurements taken via optical waveguide lightmode spectroscopy. [source] Non-viral gene therapy for diabetic retinopathyDRUG DEVELOPMENT RESEARCH, Issue 11 2006*Article first published online: 9 FEB 200, Toshiyuki Oshitari Abstract Diabetic retinopathy results from vascular abnormalities, such as an increase in the permeability of retinal vessels, and retinal neurodegeneration, which are irreversible changes that occur early in the course of diabetic retinopathy. To block the vascular and neuronal complications associated with the development and progression of diabetic retinopathy, a reasonable strategy would be to prevent the increased vascular permeability and to block the neuronal cell death. The purpose of this review is to present the non-viral strategies being used to block the neurovascular abnormalities and neuronal cell death that are observed in the early stages of diabetic retinopathy in order to prevent the onset or the progression of the diabetic retinopathy. Some of the non-viral gene therapeutic techniques being used are electroporation of selected genes, injections of antisense oligonucleotides, and injections of small interference RNAs. The results obtained by these methods are discussed as is the potential of these therapeutic strategies to prevent the onset or the progression of the neurovascular abnormalities in diabetic retinopathy. Drug Dev. Res. 67:835,841, 2006. © 2007 Wiley-Liss, Inc. [source] Multiple stressors and regime shifts in shallow aquatic ecosystems in antipodean landscapesFRESHWATER BIOLOGY, Issue 2010JENNY DAVIS Summary 1. Changes in land management (land use and land cover) and water management (including extraction of ground water and diversion of surface waters for irrigation) driven by increases in agricultural production and urban expansion (and fundamentally by population growth) have created multiple stressors on global freshwater ecosystems that we can no longer ignore. 2. The development and testing of conceptual ecological models that examine the impact of stressors on aquatic ecosystems, and recognise that responses may be nonlinear, is now essential for identifying critical processes and predicting changes, particularly the possibility of catastrophic regime shifts or ,ecological surprises'. 3. Models depicting gradual ecological change and three types of regime shift (simple thresholds, hysteresis and irreversible changes) were examined in the context of shallow inland aquatic ecosystems (wetlands, shallow lakes and temporary river pools) in southwestern Australia subject to multiple anthropogenic impacts (hydrological change, eutrophication, salinisation and acidification). 4. Changes in hydrological processes, particularly the balance between groundwater-dominated versus surface water-dominated inputs and a change from seasonal to permanent water regimes appeared to be the major drivers influencing ecological regime change and the impacts of eutrophication and acidification (in urban systems) and salinisation and acidification (in agricultural systems). 5. In the absence of hydrological change, urban wetlands undergoing eutrophication and agricultural wetlands experiencing salinisation appeared to fit threshold models. Models encompassing alternative regimes and hysteresis appeared to be applicable where a change from a seasonal to permanent hydrological regime had occurred. 6. Irreversible ecological change has potentially occurred in agricultural landscapes because the external economic driver, agricultural productivity, persists independently of the impact on aquatic ecosystems. 7. Thematic implications: multiple stressors can create multiple thresholds that may act in a hierarchical fashion in shallow, lentic systems. The resulting regime shifts may follow different models and trajectories of recovery. Challenges for ecosystem managers and researchers include determining how close a system may be to critical thresholds and which processes are essential to maintaining or restoring the system. This requires an understanding of both external drivers and internal ecosystem dynamics, and the interactions between them, at appropriate spatial and temporal scales. [source] Chronic neuropathic pain: mechanisms, drug targets and measurementFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Nanna B. Finnerup Abstract Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems. Preclinical research provides several promising targets for treatment such as sodium and calcium channels, glutamate receptors, monoamines and neurotrophic factors; however, treatment is often insufficient. A mechanism-based treatment approach is suggested to improve treatment. Valid and reliable tools to assess various symptoms and signs in neuropathic pain and knowledge of drug mechanisms are prerequisites for pursuing this approach. The present review summarizes mechanisms of neuropathic pain, targets of currently used drugs, and measures used in neuropathic pain trials. [source] Displacement and recovery of the vesical neck position during pregnancy and after childbirth,NEUROUROLOGY AND URODYNAMICS, Issue 3 2007Jacobus Wijma Abstract Aims (i) To describe the displacement and recovery of the vesical neck position during pregnancy and after childbirth and (ii) to discriminate between compliance of the vesical neck supporting structures with and without pelvic floor contraction. Methods We focussed on the biomechanical properties of the vesical neck supporting structures during pregnancy and after childbirth by calculating the compliance and the hysteresis as a result from of abdominal pressure measurements and simultaneous perineal ultrasound. Results This study shows that compliance of the supporting structures remains relatively constant during pregnancy and returns to normal values 6 months after childbirth. Hysteresis, however, showed an increase after childbirth, persisting at least until 6 months post partum. Conclusions Vaginal delivery may stretch and or load beyond the physiological properties of the pelvic floor tissue and in this way may lead to irreversible changes in tissue properties which play an important role in the urethral support continence mechanism. Neurourol. Urodynam. 26:372,376, 2007. © 2007 Wiley-Liss, Inc. [source] | ||||||||||