Home About us Contact
|
Home About us Contact | ||
|
|
||
Effective Therapeutic Intervention (effective + therapeutic_intervention)
Selected AbstractsGenetic loss of D-amino acid oxidase activity reverses schizophrenia-like phenotypes in miceGENES, BRAIN AND BEHAVIOR, Issue 1 2010V. Labrie Reduced function of the N -methyl- d -aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. The NMDAR contains a glycine binding site in its NR1 subunit that may be a useful target for the treatment of schizophrenia. In this study, we assessed the therapeutic potential of long-term increases in the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic inactivation of its catabolic enzyme D-amino acid oxidase (DAO) in mice. The effects of eliminating DAO function were investigated in mice that display schizophrenia-related behavioral deficits due to a mutation (Grin 1D481N) in the NR1 subunit that results in a reduction in NMDAR glycine affinity. Grin 1D481N mice show deficits in sociability, prolonged latent inhibition, enhanced startle reactivity and impaired spatial memory. The hypofunctional Dao 1G181R mutation elevated brain levels of D-serine, but alone it did not affect performance in the behavioral measures. Compared to animals with only the Grin 1D481N mutation, mice with both the Dao1G181R and Grin 1D481N mutations displayed an improvement in social approach and spatial memory retention, as well as a reversal of abnormally persistent latent inhibition and a partial normalization of startle responses. Thus, an increased level of D-serine resulting from decreased catalysis corrected the performance of mice with deficient NMDAR glycine site activation in behavioral tasks relevant to the negative and cognitive symptoms of schizophrenia. Diminished DAO activity and elevations in D-serine may serve as an effective therapeutic intervention for the treatment of psychiatric symptoms. [source] Anticipatory grieving among parents living with a child with cancerJOURNAL OF ADVANCED NURSING, Issue 9 2010Ekhlas Al-Gamal al-gamal e. & long t. (2010) Anticipatory grieving among parents living with a child with cancer. Journal of Advanced Nursing,66(9), 1980,1990. Abstract Aim., This paper is a report of a comparative study of anticipatory grief of parents of children newly diagnosed with cancer and those whose children were diagnosed 6,12 months earlier. Background., Public perceptions of cancer as a fatal illness persist despite improved prognosis for children. Parents may experience feelings of despair, hopelessness, and worthlessness , the most common psychological expressions of anticipatory grief. With a focus on developing more effective therapeutic intervention, healthcare professionals have developed greater interest in the concept of anticipatory grief. Method., One hundred and forty parents, divided between ,newly diagnosed' and ,6,12 months after diagnosis' groups, were recruited in 2006 from two hospitals representative of the healthcare sector in Jordan. Structured interviews were conducted to assess anticipatory grief, using the Marwit and Meuser Caregiver Inventory: Childhood Cancer. Analysis was performed using t -tests. Results., Fewer than half of the parents in both groups reported being at peace with themselves and their situation in life. Parents of newly diagnosed children reported more severe anticipatory grief responses than those in the second group. No statistically significant differences were found in responses between mothers and fathers. Conclusion., Healthcare professionals should encourage parents to discuss negative feelings related to their child's illness and potential outcome. Hospital policies need to include the provision and promotion of support group services for parents, and nurses should encourage parents to exploit such services. [source] Functional ,glial' GLYT1 glycine transporters expressed in neuronsJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Luca Raiteri J. Neurochem. (2010) 114, 647,653. Abstract Glycine transporter 1 (GLYT1) and GLYT2 are the glycine transporters in CNS. While GLYT2 is largely expressed in glycinergic neurons, GLYT1 has long been considered to be exclusively present in glial cells. There is increasing evidence that significant amounts of the ,glial' transporter also exist on neurons, particularly on pre-synaptic nerve endings of glutamatergic neurons. The functions of ,neuronal GLYT1' may be manifold and are discussed in this review. Of major interest are the interactions between neuronal GLYT1 and glutamatergic receptors of the NMDA type the activity of which is modulated not only by astrocytic GLYT1 but also by neuronal GLYT1. Pathophysiological roles and therapeutic implications of neuronal GLYT1 are emerging from recent studies with genetically modified mice, particularly with animals lacking forebrain neuron-specific GLYT1 transporters. These mutant mice exhibit promnesic phenotypes reflecting enhancement of NMDA receptor function, as it occurs following administration of GLYT1 inhibitors. Inactivation of neuronal GLYT1 in the forebrain may represent an effective therapeutic intervention for the treatment of schizophrenia. [source] Median Arcuate Ligament Syndrome,A Novel Treatment Using an Intrathecal Morphine Pump to Relieve Intractable Visceral PainPAIN PRACTICE, Issue 2 2008Oren T. Guttman MD ,,Abstract Purpose: Median arcuate ligament syndrome, which presents with intractable visceral pain, is difficult to both diagnose and treat. This case report describes the first use of an intrathecal morphine pump as an effective therapeutic intervention. Clinical features: We describe a 39-year-old female who presented with a four-year history of misdiagnosed debilitating abdominal pain. After multiple failed attempts at medical management and surgeries, a trial of intrathecal narcotics provided significant relief. Six months after insertion of an intrathecal morphine pump, the patient was pain-free and had resumed all activities of daily living. Conclusion: The use of an intrathecal narcotic pump should be considered for treatment of patients with intractable visceral pain secondary to median arcuate ligament syndrome.,, [source] Prevention of red cell alloimmunization by CD25 regulatory T cells in mouse modelsAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2007Jin Yu Transfusion therapy is currently an effective therapeutic intervention in a number of diseases, including sickle cell disease. However, its use is complicated by a high incidence of red blood cell (RBC) alloimmunization in the transfusion recipients. The identification of T regulatory cells (Tregs) among the CD4+ CD25+ T cell subset as key regulators of peripheral tolerance in mice as well as humans has opened an exciting era in the prevention and treatment of autoimmune disease and for improving organ transplantation. However, their potential in inducing transfusion tolerance remains to be explored. We used red cells from mice transgenic for human glycophorin A blood group antigen as donor cells and transfused wild-type mice to induce alloantibodies, as an experimental system to study RBC alloimmunization. We found that depletion with anti-CD25 enhanced the alloantibody production, indicating that CD25 Tregs play an important role in regulation of alloantibody responses. More importantly, adoptive transfer of purified population of CD4+CD25+ but not CD4+CD25, cells from naļve mice prevented the induction of IgG and IgM alloantibody production in transfusion recipients, with a concomitant reduction in activated splenic B cells and macrophages. Similarly, adoptive transfer of purified populations of CD4+CD25+ cells from naļve mice into naļve syngeneic recipients inhibited the anti-Ig response to rat RBCs in the recipients but transfer of control CD4+CD25, cells did not. Altogether, our results demonstrate that Tregs participate in the control of transfusion-associated RBC alloantibody responses, opening up the possibility that Treg immunotherapy may be exploited for suppressing transfusion immunization events. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Proteomic profiling for cancer progression: Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell linesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2005Eiko Hayashi Abstract Tumor development and progression consist of a series of complex processes involving multiple changes in gene expression (Paolo et al. Physiol. Rev., 1993, 73, 161,195; Lance et al. Cell., 1991, 64, 327,336). Tumor cells acquire an invasive and metastatic phenotype that is the main cause of death for cancer patients. Therefore, for early diagnosis and effective therapeutic intervention, we need to detect the alterations associated with transition from benign to malignant tumor cells on a molecular basis. To unravel alterations concerned with tumor progression, the proteomic approach has attracted great attention because it can identify qualitative and quantitative changes in protein composition, including post-translational modifications. In this study, we performed proteomic differential display analysis for the expression of intracellular proteins in the regressive cancer cell line QR-32 and the inflammatory cell-promoting progressive cancer cell line QRsP-11 of murine fibrosarcoma by two-dimensional gel electrophoresis and mass spectrometry using an Agilent 1100 LC/MSD Trap XCT. We found 11,protein spots whose expression was different between QR-32 and QRsP-11 cells and identified nine proteins, seven of which, calreticulin precursor, tropomyosin,1 , chain, annexin,A5, heat shock protein (HSP)90-,, HSP90-,, PEBP, and Prx,II, were over-expressed, and two, Anp32e and HDGF, which were down-regulated. The results suggest an important complementary role for proteomics in identification of molecular abnormalities in tumor progression. [source] Combinatorial treatments enhance recovery following facial nerve crush,,THE LARYNGOSCOPE, Issue 8 2010Nijee Sharma BS Abstract Objectives/Hypothesis: To investigate the effects of various combinatorial treatments, consisting of a tapering dose of prednisone (P), a brief period of nerve electrical stimulation (ES), and systemic testosterone propionate (TP) on improving functional recovery following an intratemporal facial nerve crush injury. Study Design: Prospective, controlled animal study. Methods: After a right intratemporal facial nerve crush, adult male Sprague-Dawley rats were divided into the following eight treatment groups: 1) no treatment, 2) P only, 3) ES only, 4) ES + P, 5) TP only, 6) TP + P, 7) ES + TP, and 8) ES + TP + P. For each group n = 4,8. Recovery of the eyeblink reflex and vibrissae orientation and movement were assessed. Changes in peak amplitude and latency of evoked response, in response to facial nerve stimulation, was also recorded weekly. Results: Brief ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. Also, ES or TP treatments enhanced recovery of some functional parameters more than P treatment. When administered alone, none of the three treatments improved recovery of complete facial function. Only the combinatorial treatment of ES + TP, regardless of the presence of P, accelerated complete functional recovery and return of normal motor nerve conduction. Conclusions: Our findings suggest that a combinatorial treatment strategy of using brief ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. Administration of P neither augments nor hinders recovery. Laryngoscope, 2010 [source] Hypertrophic osteoarthropathy in two children with cholestatic hepatic diseaseACTA PAEDIATRICA, Issue 8 2005M Katsicas Abstract Aim: To describe two children with hypertrophic osteoarthropathy associated with cholestatic hepatic disease. Both patients suffered from chronic progressive cholestatic liver disease and developed digital clubbing, polyarthritis and periosteal reaction. In one of them, clinical and radiological features normalized after liver transplant. Conclusion: Hepatic hypertrophic osteoarthropathy is a rare disabling condition that responds poorly to conservative management, while liver transplantation appears to be the only effective therapeutic intervention. [source] Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trialJOURNAL OF VIRAL HEPATITIS, Issue 3 2009L. Alvarez-Lajonchere Summary., Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is available against this pathogen and therapeutic treatments currently in use are of limited efficacy. In the present study, the immunogenicity of the therapeutic vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120, was evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4, 8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to previous treatment with interferon (IFN) plus ribavirin. Interestingly, following the final immunization, neutralizing antibody responses against heterologous viral pseudoparticles were modified in eight individuals, including six de novo responders. In addition, 73% of vaccinees exhibited specific T cell proliferative response and T cell IFN-gamma secretory response 24 weeks after primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed de novo cellular immune response against HCV core and the number of patients (46.7% at the end of treatment) with cellular immune response against more than one HCV structural antigen increased during vaccination (P = 0.046). In addition, despite persistent detection of HCV RNA, more than 40% percent of vaccinated individuals improved or stabilized liver histology, particularly reducing fibrosis, which correlated with cellular immune response against more than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising candidate for effective therapeutic interventions based on its ability for enhancing the immune response in HCV chronically infected individuals. [source] Toward the discovery of new biomarkers of hepatocellular carcinoma by proteomicsLIVER INTERNATIONAL, Issue 2 2007Enrique Santamarķa Abstract Primary liver cancer is the fifth most frequent neoplasm and the third most common cause of cancer-related death, with more than 500 000 new cases diagnosed yearly. The outcome for hepatocellular carcinoma (HCC) patients still remains dismal, partly because of our limited knowledge of its molecular pathogenesis and the difficulty in detecting the disease at its early stages. Therefore, studies aimed at the definition of the mechanisms associated with HCC progression and the identification of new biomarkers leading to early diagnosis and more effective therapeutic interventions are urgently needed. Proteomics is a rapidly expanding discipline that is expected to change the way in which diseases will be diagnosed, treated, and monitored in the near future. In the last few years, HCC has been extensively investigated using different proteomic approaches on HCC cell lines, animal models, and human tumor tissues. In this review, state-of-the-art technology on proteomics is overviewed, and recent advances in liver cancer proteomics and their clinical projections are discussed. [source] | |||||||||||||