Therapeutic Strategies (therapeutic + strategy)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Therapeutic Strategies

  • alternative therapeutic strategy
  • attractive therapeutic strategy
  • common therapeutic strategy
  • current therapeutic strategy
  • different therapeutic strategy
  • effective therapeutic strategy
  • future therapeutic strategy
  • new therapeutic strategy
  • novel therapeutic strategy
  • possible therapeutic strategy
  • potential therapeutic strategy
  • promising therapeutic strategy
  • specific therapeutic strategy
  • useful therapeutic strategy

  • Selected Abstracts

    Therapeutic Strategies for Xenograft Rejection

    Ph.D., Shu S. Lin M.D.
    ABSTRACT The increasing demand for transplantable organs over the past several decades has stimulated the idea of using animal organs in lieu of cadaveric organs in clinical transplantation. Pigs are now considered to be the most suitable source of organs for transplantation because of their abundant availability, their appropriate size, their relatively short gestation period, and the recent development in the technology to genetically manipulate them. In the past few years, some of the seemingly complex immunologic responses in pig-to-primate transplantation have been elucidated. This progress has allowed us to focus our efforts on devising specific therapeutic strategies to overcome or prevent some of the responses that contribute to rejection of the xenograft. In this article, we review the various approaches that might allow clinical xenotransplantation to come to fruition. [source]

    Two Different Therapeutic Strategies in ICD Lead Defects: Additional Combined LeadVersus Replacement of the Lead

    Objectives: Implantation of an additional HV-P/S lead versus extraction of the defective HV-P/S lead and implantation of a new one is one possible therapeutic approach in cases of a defective high-voltage pace/sense lead (HV-P/S). No information is available on potential differences in clinical outcome in these different approaches. Methods: Between January 2000 and February 2006, 86 patients with HV-P/S lead defect received either an additional transvenous HV-P/S lead (n = 33, group 1) or the HV-P/S lead was replaced (n = 53, group 2). The duration of the initially implanted leads was significantly different in the two groups (7.4 ± 2.9; group 1 and 4.1 ± 3.4 years; group 2). The outcome of these two groups of patients was retrospectively analyzed. Results: Seventy-three patients [85%] survived until the end of follow-up of 29 ± 15 (group 1) and 33 ± 21 (group 2) months (P = ns), respectively. Thirteen patients died: six in group 1 and seven in group 2 (P = ns). Fourteen patients experienced perioperative complications (group 1: six; group 2: eight; P = ns). ICD system-related complications occurred in 22 patients (group 1: seven; group two: 15; P = ns). The event-free cumulative survival of patients with additional and replaced HV-P/S lead for postoperative events (including death) after 1, 2, and 3 years was 82%, 70%, 70%, and 86%, 81%, 66%, respectively (P = 0.93). Conclusions: Implantation of an additional HV-P/S lead or replacement of the HV-P/S lead in case of HV-P/S lead failure is statistically not different concerning mortality and morbidity. There are no predictors for further lead defects. Implantation of an additional HV-P/S lead should not be recommended in young patients or patients with greater likelihood of living many years. Predictors for death were an age over 70 years and renal insufficiency. [source]

    Treatment of Skin Disease,Comprehensive Therapeutic Strategies

    David J. Eedy
    No abstract is available for this article. [source]

    Hyponatremia in Heart Failure: Revisiting Pathophysiology and Therapeutic Strategies

    Amir Kazory MD
    Hyponatremia is frequently encountered in patients with heart failure (HF), and its association with adverse outcomes is well-established in this population. While hyponatremia is an independent marker for severity of HF, it is not certain whether it has a causal impact on the progression of the disease. There are no universally accepted consensus guidelines regarding therapeutic strategies for HF-associated hyponatremia and volume overload; current societal guidelines do not address management of this complication. Whereas thiazide diuretics are known to induce or worsen hyponatremia in this setting through a number of mechanisms, loop diuretics can be considered a readily available first-line pharmacologic therapy. Consistent with pathophysiology of the disease and mechanisms of action of loop diuretics, available clinical evidence supports such an approach provided that patients can be closely monitored. Use of vasopressin receptor antagonists is an emerging therapeutic strategy in this setting, and the efficacy of these agents has so far been shown in a number of clinical studies. These agents can be reserved for patients with HF in whom initial appropriate loop diuretic therapy fails to improve serum sodium levels. Copyright © 2010 Wiley Periodicals, Inc. [source]

    Videotaped Focus Groups: Transforming a Therapeutic Strategy Into a Research Tool

    NURSING FORUM, Issue 1 2000
    Dayle Hunt Joseph RN
    Focus groups have become a popular method of collecting data for research projects. The addition of using a videotaped approach has broad implications for researchers, as it allows constant replay of the session. Although on the surface this approach seems straightforward and easy to use, the authors caution that this is not an approach for the novice. Investigators planning to use a focus group method must be well versed in group process. There is an unpredictable nature to the focus group process, and researchers need to prepare for the inevitable mishaps that lead to lost opportunities for data collection. [source]

    Reactive species and early manifestation of insulin resistance in type 2 diabetes

    L. E. Fridlyand
    The early stages of type 2 diabetes mellitus are characterized by the development of insulin resistance (IRe) in muscle cells and adipocytes with the concomitant loss of ,-cell compensation. We have extensively reviewed the literature related to metabolic and signalling pathways of reactive oxygen species (ROS) in regard to the coordinated development of oxidative stress and IRe. We considered the hypothesis that oxidative stress leads to IRe in muscle cells and adipocytes, but found that the data are more consistent with the hypothesis that the cellular mechanisms that protect against oxidative stress per se are capable of creating an ROS-dependent insulin-resistant state. Furthermore, ROS-induced mitochondrial dysfunction can lead to disruptions of lipid metabolism, increasing the intracellular lipid content, and, in addition, contribute to lipid-dependent IRe in myocytes. Together, these two ROS-activated pathways to IRe can contribute to a global state of profound resistance to insulin action. Therapeutic strategies should, therefore, be directed towards reducing insulin resistance without an increase in ROS production or concentration. Pharmacological or other approaches to IRe that result in the activation of mitochondrial biogenesis in particular could be highly beneficial in the prevention or treatment of both insulin resistance and type 2 diabetes. [source]

    Does increasing dose improve efficacyin patients with poor antidepressantresponse: a review

    E. Corruble
    Objective: Therapeutic strategies in depressed patients with no or partial response to adequate first-line antidepressant medication remain a matter of concern. This paper focuses on the strategy of dose increase. Method: This review was based on a systematic Medline search of papers dealing with antidepressant dose issues in major depression since the 1960s. Results: The strategy of dose increase is poorly studied in clinical trials. Conclusion: Until this strategy is better studied, caution is advised in its use. However, antidepressants for which this strategy seems to be the most relevant are tricyclic drugs and serotonin and noradrenaline reuptake inhibitors. These results are discussed both in terms of therapeutic strategies for the clinician and in terms of clinical research. [source]

    Use of ristocetin cofactor activity in the management of von Willebrand disease

    HAEMOPHILIA, Issue 2001
    B.M. Ewenstein
    von Willebrand disease (vWD), the most common of the hereditary bleeding disorders, arises from quantitative or qualitative defects in von Willebrand factor (vWF). vWF is a multimeric plasma protein that plays a key role in primary and secondary haemostasis. In the current classification scheme, vWD is divided into six subtypes that are based on the nature of the vWF defect. Therapeutic strategies depend on the accurate identification of these subtypes. In most clinical situations, desmopressin is effective treatment for the great majority of patients with mild (type 1) disease, while replacement therapy with factor VIII/vWF concentrates that contain high levels of vWF activity is required for most type 2 and nearly all type 3 vWD patients. Several factor VIII/vWF replacement products are available, one of which (Humate P) has been approved for the treatment of vWD by the US Food and Drug Administration. Preliminary results of recent studies support the hypothesis that treatment with factor VIII/vWF concentrates based upon the content of vWF activity as reflected in the ristocetin cofactor assay is practicable, safe and efficacious. The establishment of optimal treatment regimens with respect to dose intensity and duration will require further study. [source]

    Anticoagulation After Coronary Artery Surgery in Patients With Polycythemia Vera: Report of Two Cases

    Bilgehan Sava, Oz M.D.
    Normalization of the hematocrit and elevated platelet counts is obligatory to reduce the thrombotic risk of patients with PV. Therapeutic strategies include phlebotomy, myelosuppressive agents, and, more recently, interferon-,. In addition, appropriate antiplatelet therapy should be administered to prevent life-threatening complications and reducing the viscosity of the blood. Although aspirin is widely preferred in such patients, this monodrug therapy or combined with clopidogrel as an alternative approach might not be enough, especially after coronary artery surgery. Therefore, warfarin should be added to anticoagulant therapy. This short report describes the use of warfarin, associated with aspirin and clopidogrel as an anticoagulant regimen after coronary artery bypass surgery in two cases with polycythemia vera. We believe that a combination of warfarin with other oral antiplatelet agents may be more effective in preventing the coronary artery bypass graft thrombosis. [source]

    Molecular markers and determinants of prostate cancer metastasis

    Rahul V. Gopalkrishnan
    Although intensely studied, the molecular and biochemical determinants of prostate cancer development and progression remain ill-defined. Moreover, current markers and methodologies cannot distinguish between a tumor that will remain indolent and not impinge on patient survival, versus a tumor with aggressive traits culminating in metastatic spread and death. Once prostate cancer is confirmed the most significant threat to a patient's survival and quality of life involves tumor metastasis. Radical surgery notwithstanding, prostate cancer accounts for 10% of all cancer-related deaths primarily arising through development of metastasis. Metastasis markers demonstrating an acceptable level of reliability are an obvious necessity if disproportionate and costly treatment is to be avoided and a reasonably accurate determination of clinical prognosis and measure of successful response to treatment is to be made. Therapeutic strategies that specifically inhibit metastatic spread are not presently possible and may not become available in the immediate future. This is because, while localized tumorigenesis has been relatively amenable to detection, analysis and treatment, metastasis remains a relatively undefined, complex and underexplored area of prostate cancer research. New findings in the field such subclasses of genes called metastasis suppressors and cancer progression suppressors, have opened up exciting avenues of investigation. We review current methodological approaches, model experimental systems and genes presently known or having potential involvement in human prostate cancer metastasis. © 2001 Wiley-Liss, Inc. [source]

    Enhancing spiritual well-being among suicidal African American female survivors of intimate partner violence

    Natalie C. Arnette
    Spirituality has been identified as one component of a culturally competent therapeutic intervention for African American women. The present study was designed to investigate the ability of factors, such as level of hopelessness and the use of positive religious coping strategies, to predict spiritual well-being over time. Seventy-four low-income African American women were administered self-report questionnaires measuring hopelessness, use of religious coping strategies, and two domains of spiritual well-being. Path analysis indicated that hopelessness, existential well-being, religious well-being, and positive religious coping are correlated with one another. Further, lower levels of hopelessness predict increases in existential well-being over time; higher levels of positive religious coping predict increases in religious well-being over time. Results were consistent with the study hypotheses and highlight the need to attend to predictors of spiritual well-being when implementing culturally relevant interventions with abused, suicidal African American women. Therapeutic strategies for reducing hopelessness and enhancing positive religious coping to improve spiritual and existential well-being are presented; such strategies will ensure the interventions are more culturally competent. © 2007 Wiley Periodicals, Inc. J Clin Psychol 63: 909,924, 2007. [source]

    Therapeutic management of recurrent hepatitis C after liver transplantation

    Rosângela Teixeira
    Abstract Recurrent hepatitis C ranges from minimal damage to cirrhosis developing in a few months or years in a substantial proportion of transplant recipients. Different virus, host and donor factors are involved in the pathogenesis of recurrence, but many are poorly understood. Therapeutic strategies can be utilized in the pre-, peri- or posttransplantation setting. Antiviral therapy using interferon and ribavirin and modifying immunosuppression are the main strategies to prevent progression disease. The efficacy of interferon and ribavirin is limited and side effects, reduction/withdrawal are frequent. Current sustained virological response rates are approximately 28%. An optimal immunosupppression regimen has not been established. The choice of calcineurin inhibitors has not clearly been shown to affect histological hepatitis C virus (HCV) but higher cumulative exposure to corticosteroids to treat acute rejection is associated with more severe recurrence. The manner in which the doses of immunosuppression are modified has more influence on HCV recurrence than the use of a specific drug per se. Debate about the influence of immunosuppressive regimens on HCV recurrence is ongoing. Potential antifibrotic therapy and new agents targeting HCV infection and replication are emerging and are anticipated to be added to our armentarium in battling recurrent HCV post-LT. [source]

    Therapeutic strategies against TGF-, signaling pathway in hepatic fibrosis

    Xingjun Liu
    Abstract: Hepatic fibrosis is the common wound-healing response to chronic liver injury. In this process, activation of hepatic stellate cells is characteristic of cell proliferation and migration, production of collagen and other extracellular matrix (ECM) molecules, and contraction after transforming into myofibroblasts. It has been shown that the fibrogenic process is prominently regulated by transforming growth factor-,1 (TGF-,1) and that the specific blockade of TGF-,1/Smad3 signaling may therapeutically intervene the fibrosis of various tissues. In this review, we attempt to integrate recent advances in the understanding of the mechanisms underlying TGF-,1/Smad3 pathway modulation of ECM gene expression in the context of liver fibrosis, discuss intervention strategies targeting the blockade of related signal pathways, and look into novel ways to the safe and efficacious prevention and treatment of hepatic fibrosis. [source]

    Gene-based treatment of motor neuron diseases,

    MUSCLE AND NERVE, Issue 3 2006
    Thais Federici PhD
    Abstract Motor neuron diseases (MND), such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are progressive neurodegenerative diseases that share the common characteristic of upper and/or lower motor neuron degeneration. Therapeutic strategies for MND are designed to confer neuroprotection, using trophic factors, anti-apoptotic proteins, as well as antioxidants and anti-excitotoxicity agents. Although a large number of therapeutic clinical trials have been attempted, none has been shown satisfactory for MND at this time. A variety of strategies have emerged for motor neuron gene transfer. Application of these approaches has yielded therapeutic results in cell culture and animal models, including the SOD1 models of ALS. In this study we describe the gene-based treatment of MND in general, examining the potential viral vector candidates, gene delivery strategies, and main therapeutic approaches currently attempted. Finally, we discuss future directions and potential strategies for more effective motor neuron gene delivery and clinical translation. Muscle Nerve, 2005 [source]

    Evolving concepts of management of febrile neutropenia in children with cancer

    PEDIATRIC BLOOD & CANCER, Issue 2 2002
    Elmar Orudjev MD
    Abstract Background Recent investigations of febrile neutropenia in pediatric cancer patients have identified subsets of low-risk patients who can be managed with less antibiotic therapy than previously recommended standards. Methods and Materials PubMed and Medline were searched for prospective trials and reviews of febrile neutropenia in children. Magnitude and duration of fever and neutropenia, comorbidities, and therapeutic strategies were examined. Results Twenty-seven prospective trials and five reviews were identified. The child with cancer and low-risk febrile neutropenia is clinically well and afebrile within 24,96 hr of antibiotic therapy and has evidence of marrow recovery with a rising phagocyte count. Disqualifying comorbidities include leukemia at diagnosis or in relapse, uncontrolled cancer, age under 1 year, medical condition(s) that would otherwise require hospitalization and social or economic conditions that may potentially compromise access to care or compliance. Therapeutic strategies include parenteral or oral antibiotics in the hospital with early discharge or parenteral antibiotics in the outpatient setting followed by oral or parenteral therapy and daily reassessment. Although as many as 25% of low-risk patients require modification of therapy and/or hospitalization, life-threatening or fatal infection is exceptional. Conclusion One-third to one-half the children with febrile neutropenia are at low-risk of serious infection. In the context of clinic trials, they can be safely managed with inpatient or outpatient strategies that maintain close follow-up and reduce the burden of antibiotic therapy. Adoption of these alternative strategies as the standard of care should proceed with caution guided by written protocols. Med Pediatr Oncol 2002;39:77,85. © 2002 Wiley-Liss, Inc. [source]

    The role of bacteriolysis in the pathophysiology of inflammation, infection and post-infectious sequelae

    APMIS, Issue 11 2002
    Review article
    The literature dealing with the biochemical basis of bacteriolysis and its role in inflammation, infection and in post-infectious sequelae is reviewed and discussed. Bacteriolysis is an event that may occur when normal microbial multiplication is altered due to an uncontrolled activation of a series of autolytic cell-wall breaking enzymes (muramidases). While a low-level bacteriolysis sometimes occurs physiologically, due to "mistakes" in cell separation, a pronounced cell wall breakdown may occur following bacteriolysis induced either by beta-lactam antibiotics or by a large variety of bacteriolysis-inducing cationic peptides. These include spermine, spermidine, bactericidal peptides defensins, bacterial permeability increasing peptides from neutrophils, cationic proteins from eosinophils, lysozyme, myeloperoxidase, lactoferrin, the highly cationic proteinases elastase and cathepsins, PLA2, and certain synthetic polyamino acids. The cationic agents probably function by deregulating lipoteichoic acid (LTA) in Gram-positive bacteria and phospholipids in Gram-negative bacteria, the presumed regulators of the autolytic enzyme systems (muramidases). When bacteriolysis occurs in vivo, cell-wall- and -membrane-associated lipopolysaccharide (LPS (endotoxin)), lipoteichoic acid (LTA) and peptidoglycan (PPG), are released. These highly phlogistic agents can act on macrophages, either individually or in synergy, to induce the generation and release of reactive oxygen and nitrogen species, cytotoxic cytokines, hydrolases, proteinases, and also to activate the coagulation and complement cascades. All these agents and processes are involved in the pathophysiology of septic shock and multiple organ failure resulting from severe microbial infections. Bacteriolysis induced in in vitro models, either by polycations or by beta-lactams, could be effectively inhibited by sulfated polysaccharides, by D-amino acids as well as by certain anti-bacteriolytic antibiotics. However, within phagocytic cells in inflammatory sites, bacteriolysis tends to be strongly inhibited presumably due to the inactivation by oxidants and proteinases of the bacterial muramidases. This might results in a long persistence of non-biodegradable cell-wall components causing granulomatous inflammation. However, persistence of microbial cell walls in vivo may also boost innate immunity against infections and against tumor-cell proliferation. Therapeutic strategies to cope with the deleterious effects of bacteriolysis in vivo include combinations of autolysin inhibitors with combinations of certain anti-inflammatory agents. These might inhibit the synergistic tissue- and- organ-damaging "cross talks" which lead to septic shock and to additional post-infectious sequelae. [source]

    Corticosteroids in the treatment of multiple sclerosis

    K. M. Myhr
    Background ,, Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS) that usually is clinically characterized by repeated subacute relapses followed by remissions. Therapeutic strategies include corticosteroid treatment of relapses and immunomodulatory- or immunosuppressive treatment to prevent new relapses and progression of disability. Objectives ,, To review the evidences for the use of corticosteroids in the treatment of relapses in MS as well as its possible disease modifying potential. Materials & Methods ,, Available literature from PubMed search and personal experiences on corticosteroid treatment in multiple sclerosis were reviewed. Results ,, High dose short-term oral or intravenous methylprednisolone for 3-5 days speed up recovery from relapses, but the treatment has no influence on the occurrence of new relapses or long-term disability. There is also some evidence that pulsed treatment with methylprednisolone have beneficial long-term effects in multiple sclerosis. Conclusion ,, Relapses with moderate to serious disability should be treated with high dose intravenous or oral methylprednisolone. More data is needed to determine long-term disease modifying effects of corticosteroids. [source]

    Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype-associated gene expression signatures

    CANCER, Issue 16 2009
    Chiara Braconi MD
    Abstract BACKGROUND: The presence of vascular invasion in hepatocellular cancer (HCC) correlates with prognosis, and is a critical determinant of both the therapeutic approach and the recurrence or intrahepatic metastases. The authors sought to identify candidate therapeutic agents capable of targeting the invasive phenotype in HCC. METHODS: A gene expression signature associated with vascular invasion derived from 81 human cases of HCC was used to screen a database of 453 genomic profiles associated with 164 bioactive molecules using the connectivity map. Candidate agents were identified by their inverse correlation to the query gene signature. The efficacy of the candidate agents to target invasion was experimentally verified in PLC/PRF-5 and HepG2 HCC cells. RESULTS: The gene signature associated with vascular invasion in HCC comprised of 47 up-regulated and 26 down-regulated genes. Computational bioinformatics analysis revealed several putative candidates, including resveratrol and 17-allylamino-geldanamycin (17-AAG). Both of these agents reduced HCC cell invasion at noncytotoxic concentrations. 17-AAG, a heat shock protein 90 (HSP-90) inhibitor, was shown to modulate the expression of several diverse cancer-associated genes, including ADAMTS1, part of the query signature, and maspin, an HSP-90,associated protein with a tumor suppressor role in HCC. CONCLUSIONS: Candidates for further evaluation as therapies to limit invasion in HCC have been identified using a computational bioinformatics analysis of phenotype-associated gene expression. Phenotype targeting using genomic profiling is a rational approach for drug discovery. Therapeutic strategies targeting a defined cancer-associated phenotype can be identified without a detailed knowledge of individual downstream targets. Cancer 2009. © 2009 American Cancer Society. [source]

    Therapeutic strategies, immediate and mid-term outcomes in non-ST-segment elevation acute coronary syndromes with respect to age: A single-center registry of 488 consecutive patients

    Mario Leoncini M.D.
    Abstract Background: Elderly patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) may receive benefit from an early invasive strategy. However, aged patients often suffer from comorbidities that may contraindicate an invasive approach and affect prognosis adversely. The impact of comorbidities on an invasive approach to NSTE-ACS in the elderly has not been fully investigated. Hypothesis: This study sought to examine the outcome of an unselected population of patients with NSTE-ACS stratified according to age and treatment approach. Methods: The feasibility and efficacy of an invasive strategy for NSTE-ACS and the 6-month outcome were assessed in 253 unselected consecutive patients , 70 years (elderly) and compared with those of 235 unselected consecutive patients < 70 years. Results: Angiography was not performed in 69 patients (86% , 70 years) because of contraindications. In the whole population, the 6-month event rate was significantly higher in elderly compared with younger patients (22 vs. 14%; odds ratio 1.8, 95% confidence interval 1.1-2.9; p<0.02). This difference was driven by the high event rate observed in the elderly with contraindications to angiography (47 vs. 16% in the elderly treated invasively; p < 0.002). On the other hand, no significant difference was observed in the 6-month event rate between elderly and younger patients undergoing an invasive approach (16 vs. 13%; p=0.36). Contraindications to angiography,namely, creatinine , 1.5 mg/dl and elevated troponin I at admission,were the only independent predictors of 6-month outcome. Conclusions: The invasive approach was feasible in 77% of patients , 70 years. Those with contraindications to angiography showed a poor mid-term prognosis. The early invasive strategy was associated with more favorable outcomes regardless of age. [source]

    Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agents

    CANCER SCIENCE, Issue 11 2007
    Yoshio Honma
    A low concentration of differentiation inducers greatly enhances the in vitro and in vivo antiproliferative effects of interferon (IFN), in several human cancer cells. Among the differentiation inducers tested, the sensitivity of cancer cells to IFN, was most strongly affected by cotylenin A. Cotylenin A, which is a novel fusicoccane diterpene glycoside with a complex sugar moiety, affected the differentiation of leukemia cells that were freshly isolated from acute myelogenous leukemia patients in primary culture. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were early genes induced by the combination of cotylenin A and IFN, in carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFN, cooperatively induced apoptosis through the TRAIL signaling system. Combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells. In an analysis of various cancer cell lines, ovarian cancer cells were highly sensitive to combined treatment with cotylenin A and IFN, in terms of the inhibition of cell growth. This treatment was also effective toward ovarian cancer cells that were refractory to cisplatin, and significantly inhibited the growth of ovarian cancer cells as xenografts without apparent adverse effects. Ovarian cancer cells from patients were also sensitive to the combined treatment in primary cultures. Combined treatment with cotylenin A and IFN, may have therapeutic value in treating human cancers including ovarian cancer. (Cancer Sci 2007; 98: 1643,1651) [source]

    Study of the MR relaxation of microglia cells labeled with Gd-DTPA-bearing nanoparticles

    Emeline Julie Ribot
    Abstract Therapies involving cells as vehicles need to visualize in situ the trafficking of the cells concerned. This cellular imaging can be driven by cell contrast agent-based nanoparticle internalization and non-invasive MRI (magnetic resonance imaging) detection. Here, microglial cells, that would transport a suicide gene to a glioma, were incubated for different times, with various concentrations of silica nanoparticles on which numerous Gd-DTPA were grafted. The goal of this study was to investigate the repartition of cell-associated particles. MRI was used to quantitatively follow the particle uptake process. Fluorescence microscopy images showed that, although most of the nanoparticles were internalized, some remained adsorbed on the extracellular membrane surface. The cells were then submitted to various treatments: glycine to release bound nanoparticles and/or ultrasound to destroy the cell membranes. The R1 relaxation rates were measured at 4.7 T. R1 was maximal for 4,h of incubation, decreased after 8,h and remained stable for the 24 following hours. The magnetic resonance signal of ultrasonicated and glycine-treated cells made it possible to quantify the loss of bound nanoparticles after 8,h. Nevertheless, this release did not prevent cell detection since the internalized nanoparticles are enough concentrated to visualize the labeled cells even after 4 days of cell growth. These results highlight the compartmentalization of nanoparticles in microglia and the evolution of the MR signal of the labeled cells. This study could be of importance to interpret in vivo the MR signal changes that could occur after administration of such nanoparticle-labeled cells in therapeutic strategies. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Remission induction chemotherapy induces in vivo caspase-dependent apoptosis in bone marrow acute myeloid leukemia blast cells and spares lymphocytes

    CYTOMETRY, Issue 3 2006
    J.-P. Vial
    Abstract Background The goal of new therapeutic strategies is to adapt the treatment of acute myeloid leukemia (AML) patients to the prognostic and/or to the hematological response. Methods We analyzed in vivo apoptosis induction in blast cells and in lymphocytes of AML patients receiving remission induction treatment. Results We show, on 12 peripheral blood samples, that the increase of peripheral apoptotic blast cells cannot be considered as the earliest marker of the treatment efficiency, because the significant increase of apoptosis followed the white blood cell and the peripheral blast cell count reductions, probably due to an efficient clearance of circulating apoptotic cells. Furthermore, the study of 65 bone marrow samples at d15 showed that the treatment induced apoptosis of blast cells while sparing the lymphocytes. This apoptosis was evidenced both at the caspase and at the membrane levels using respectively fmk-VAD-FITC and Annexin V binding assays. We found that less than 50% of apoptosis, measured with the fmk-VAD-FITC, in the d15 residual bone marrow blast cells, correlated with lower disease-free survival probability. Conclusion More studies are needed in larger series and earlier during the remission induction treatment to confirm the possible prognostic significance of in vivo apoptosis induction. © 2006 International Society for Analytical Cytology [source]

    Evaluating the severity of dermatologic disorders

    Sarah J. Grekin
    ABSTRACT Assessment of a patient's disease severity is an essential component of formulating therapeutic strategies. However, disorders of the skin are often not amenable to strict classification criteria, and the dermatologist relies upon personal thresholds of severity when assessing the patient's overall condition. A number of grading systems have arisen, primarily from the need for standardized end points in clinical trials; in some circumstances, these severity assessments may assist the clinician in the evaluation and treatment of dermatologic disease. In this review, we will summarize the results of available severity scores of frequently encountered dermatologic disorders and discuss their utility in the management of disease in a clinician's office. [source]

    Pediatric atopic dermatitis: should we treat it differently?

    Robert Sidbury
    ABSTRACT:, Atopic dermatitis is an extremely common childhood skin disease that can have far-reaching impact on patients and families. Pediatric patients, particularly infants, pose special concerns for parents and providers, and equal emphasis must be placed on both nonpharmacologic and prescription interventions. Concerns for adverse effects of prescription therapies and a universal parental fear of an undetected allergy are hallmarks of pediatric atopic dermatitis care. The purpose of the present study is to highlight important educational and therapeutic strategies designed to optimally care for this patient population. [source]

    Cutaneous infections in the elderly: diagnosis and management

    Jeffrey M. Weinberg
    ABSTRACT:, Over the past several years there have been many advances in the diagnosis and treatment of cutaneous infectious diseases. This review focuses on the three major topics of interest in the geriatric population: herpes zoster and postherpetic neuralgia (PHN), onychomycosis, and recent advances in antibacterial therapy. Herpes zoster in adults is caused by reactivation of the varicella-zoster virus (VZV) that causes chickenpox in children. For many years acyclovir was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Famciclovir and valacyclovir, newer antivirals for herpes zoster, offer less frequent dosing. PHN refers to pain lasting ,2 months after an acute attack of herpes zoster. The pain may be constant or intermittent and may occur spontaneously or be caused by seemingly innocuous stimuli such as a light touch. Treatment of established PHN through pharmacologic and nonpharmacologic therapy will be discussed. In addition, therapeutic strategies to prevent PHN will be reviewed. These include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy. Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and nondermatophyte molds. Onychomycosis is found more frequently in the elderly and in more males than females. There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candidal onychomycosis. Over the past several years, new treatments for this disorder have emerged which offer shorter courses of therapy and greater efficacy than previous therapies. The treatment of bacterial skin and skin structure infections in the elderly is an important issue. There has been an alarming increase in the incidence of gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant pneumococci. While vancomycin has been considered the drug of last defense against gram-positive multidrug-resistant bacteria, the late 1980s saw an increase in vancomycin-resistant bacteria, including vancomycin-resistant enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated. Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including postsurgical wound infections, severe carbunculosis, and erysipelas. With limited treatment options, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid and quinupristin/dalfopristin. [source]

    Microglia and inflammation: Impact on developmental brain injuries

    Li-Jin Chew
    Abstract Inflammation during the perinatal period has become a recognized risk factor for developmental brain injuries over the past decade or more. To fully understand the relationship between inflammation and brain development, a comprehensive knowledge about the immune system within the brain is essential. Microglia are resident immune cells within the central nervous system and play a critical role in the development of an inflammatory response within the brain. Microglia are critically involved with both the innate and adaptive immune system, regulating inflammation and cell damage within the brain via activation of Toll-like receptors, production of cytokines, and a myriad of other intracellular and intercellular processes. In this article, microglial physiology is reviewed along with the role of microglia in developmental brain injuries in humans and animal models. Last, microglial functions within the innate and adaptive immune system will be summarized. Understanding the processes of inflammation and microglial activation is critical for formulating effective preventative and therapeutic strategies for developmental brain injuries. MRDD Research Reviews 2006;12:105,112. © 2006 Wiley-Liss, Inc. [source]

    Adult bone marrow,derived stem cells for organ regeneration and repair

    Florian Tögel
    Abstract Stem cells have been recognized as a potential tool for the development of innovative therapeutic strategies. There are in general two types of stem cells, embryonic and adult stem cells. While embryonic stem cell therapy has been riddled with problems of allogeneic rejection and ethical concerns, adult stem cells have long been used in the treatment of hematological malignancies. With the recognition of additional, potentially therapeutic characteristics, bone marrow,derived stem cells have become a tool in regenerative medicine. The bone marrow is an ideal source of stem cells because it is easily accessible and harbors two types of stem cells. Hematopoietic stem cells give rise to all blood cell types and have been shown to exhibit plasticity, while multipotent marrow stromal cells are the source of osteocytes, chondrocytes, and fat cells and have been shown to support and generate a large number of different cell types. This review describes the general characteristics of these stem cell populations and their current and potential future applications in regenerative medicine. Developmental Dynamics 236:3321,3331, 2007. © 2007 Wiley-Liss, Inc. [source]

    Neural stem cells for the treatment of disorders of the enteric nervous system: Strategies and challenges

    Maria-Adelaide Micci
    Abstract The main goal of this review is to summarize the status of the research in the field of stem cells transplantation, as it is applicable to the treatment of gastrointestinal motility. This field of research has advanced tremendously in the past 10 years, and recent data produced in our laboratories as well as others is contributing to the excitement on the use of neural stem cells (NSC) as a valuable therapeutic approach for disorders of the enteric nervous system characterized by a loss of critical neuronal subpopulations. There are several sources of NSC, and here we describe therapeutic strategies for NSC transplantation in the gut. These include using NSC as a relatively nonspecific cellular replacement strategy in conditions where large populations of neurons or their subsets are missing or destroyed. As with many other recent "breakthroughs" stem cell therapy may eventually prove to be overrated. However, at the present time, it does appear to provide the hope for a true cure for many currently intractable diseases of both the central and the peripheral nervous system. Certainly more extensive research is needed in this field. We hope that our review will encourage new investigators in entering this field of research ad contribute to our knowledge of the potentials of NSC and other cells for the treatment of gastrointestinal dysmotility. Developmental Dynamics 236:33,43, 2007. © 2006 Wiley-Liss, Inc. [source]

    Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives

    Ruth B. Caldwell
    Abstract Retinal neovascularization and macular edema are central features of diabetic retinopathy, the major cause of blindness in the developed world. Current treatments are limited in their efficacy and are associated with significant adverse effects. Characterization of the molecular and cellular processes involved in vascular growth and permeability has led to the recognition that the angiogenic growth factor and vascular permeability factor vascular endothelial growth factor (VEGF) plays a pivotal role in the retinal microvascular complications of diabetes. Therefore, VEGF represents an exciting target for therapeutic intervention in diabetic retinopathy. This review highlights the current understanding of the mechanisms that regulate VEGF gene expression and mediate its biological effects and how these processes may become altered during diabetes. The cellular and molecular alterations that characterize experimental models of diabetes are considered in relation to the influence of high glucose-mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's actions under hyperglycemic induction. Finally, potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological effects in the diabetic retina are considered. Copyright © 2003 John Wiley & Sons, Ltd. [source]

    Treatment of diabetic nephropathy in its early stages

    Giacomo Deferrari
    Abstract Diabetic nephropathy is one of the most frequent causes of end-stage renal disease (ESRD), and, in recent years, the number of diabetic patients entering renal replacement therapy has dramatically increased. The magnitude of the problem has led to numerous efforts to identify preventive and therapeutic strategies. In normoalbuminuric patients, optimal glycemic control (HbA1c lower than 7.5%) plays a fundamental role in the primary prevention of ESRD [weighted mean relative risk reduction (RRR) ,37% for metabolic control versus trivial renoprotection for intensive anti-hypertensive therapy or ACE-inhibitors (ACE-I)]. In the microalbuminuric stage, strict glycemic control probably reduces the incidence of overt nephropathy (weighted mean RRR ,50%), while blood pressure levels below 130/80 mmHg are recommended according to the average blood pressure levels obtained in various studies. In normotensive patients, ACE-I markedly reduce the development of overt nephropathy almost regardless of blood pressure levels; in hypertensive patients, ACE-I are less clearly active (weighted mean RRR ,23% versus other drugs), whereas angiotensin-receptor blockers (ARB) appear strikingly renoprotective. Once overt proteinuria appears, it is uncertain whether glycemic control affects the progression of nephropathy. In type 1 diabetes, various anti-hypertensive treatments, mainly ACE-I, are effective in slowing down the progression of nephropathy; in type 2 diabetes, two recent studies demonstrate that ARB are superior to conventional therapy or calcium channel blockers (CCB). In clinical practice, pharmacological tools are not always used to the best benefit of the patients. Therefore, clinicians and patients need to be educated regarding the renoprotection of drugs inhibiting the renin-angiotensin system (RAS) and the overwhelming importance of achieving target blood pressure. Copyright © 2003 John Wiley & Sons, Ltd. [source]