Promising Treatment (promising + treatment)

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Distribution within Medical Sciences

Terms modified by Promising Treatment

  • promising treatment option

  • Selected Abstracts

    Naltrexone and Cue Exposure With Coping and Communication Skills Training for Alcoholics: Treatment Process and 1-Year Outcomes

    ALCOHOLISM, Issue 11 2001
    Peter M. Monti
    Background: Promising treatments for alcoholics include naltrexone (NTX), cue exposure combined with urge-specific coping skills training (CET), and communication skills training (CST). This study investigated the effects of combining these elements as treatment adjuncts. Methods: A 2 2 design investigated the effects of CET combined with CST, as compared with an education and relaxation control treatment, during a 2-week partial hospital program (n= 165) followed by 12 weeks of NTX (50 mg/day) or placebo during aftercare (n= 128). Drinking outcomes were assessed at 3, 6, and 12 months after discharge from the partial hospital. Process measures included urge, self-efficacy (confidence about staying abstinent in risky situations), and self-reported coping skills. Medically eligible alcohol-dependent patients were recruited. Results: Among those compliant with medication on at least 70% of days, those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months. CET/CST-condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6- and 12-month follow-ups than patients in the control treatment. Interactions of medication with behavioral treatments were not significant. Process measures showed that NTX resulted in lower weekly urge ratings, and those in CET/CST used more of the prescribed coping skills after treatment, reported fewer cue-elicited urges, and reported more self-efficacy in a posttest role-play test. Drinking reductions at 3, 6, and 12 months correlated with more use of coping skills, lower urge, and higher self-efficacy. Conclusions: The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX. They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year. The value of the urge-specific and general coping skills and of self-efficacy and urge constructs was demonstrated in their association with drinking outcomes. [source]

    Practitioner Review: Assessment and treatment of refugee children and adolescents who have experienced war-related trauma

    Kimberly A. Ehntholt
    Background:, Increasingly clinicians are being asked to assess and treat young refugees, who have experienced traumatic events due to war and organised violence. However, evidence-based guidance remains scarce. Method:, Published studies on the mental health difficulties of refugee children and adolescents, associated risk and protective factors, as well as effective interventions, particularly those designed to reduce war-related post-traumatic stress disorder (PTSD) symptoms, were identified and reviewed. The findings are summarised. Results:, Young refugees are frequently subjected to multiple traumatic events and severe losses, as well as ongoing stressors within the host country. Although young refugees are often resilient, many experience mental health difficulties, including PTSD, depression, anxiety and grief. An awareness of relevant risk and protective factors is important. A phased model of intervention is often useful and the need for a holistic approach crucial. Promising treatments for alleviating symptoms of war-related PTSD include cognitive behavioural treatment (CBT), testimonial psychotherapy, narrative exposure therapy (NET) and eye movement desensitisation and reprocessing (EMDR). Knowledge of the particular needs of unaccompanied asylum-seeking children (UASC), working with interpreters, cross-cultural differences, medico-legal report writing and the importance of clinician self-care is also necessary. Conclusion:, More research is required in order to expand our limited knowledge base. [source]

    Treatment of opioid dependence in adolescents and young adults with extended release naltrexone: preliminary case-series and feasibility

    ADDICTION, Issue 9 2010
    Marc J. Fishman
    ABSTRACT Background Opioid dependence is an increasing problem among adolescents and young adults, but in contrast to the standard in the adult population, adoption of pharmacotherapies has been slow. Extended-release naltrexone (XR-NTX) is a promising treatment that has been receiving increasing interest for adult opioid dependence. Clinical chart abstractions were performed on a convenience sample of 16 serial adolescent and young adult cases (mean age 18.5 years) treated for opioid dependence with XR-NTX who attended at least one out-patient clinical follow-up visit. Case descriptions Of these 16 cases, 10 of 16 (63%) were retained in treatment for at least 4 months and nine of 16 (56%) had a ,good' outcome defined as having substantially decreased opioid use, improvement in at least one psychosocial domain and no new problems due to substance use. Conclusions These descriptive results suggest that XR-NTX in the treatment of adolescents and young adults with opioid dependence is well tolerated over a period of 4 months and feasible in a community-based treatment setting, and associated with good outcomes in a preliminary, small non-controlled case-series. This probably reflects an overall trend towards greater adoption of medication treatments for this population. [source]

    A case series investigating acceptance and commitment therapy as a treatment for previously treated, unremitted patients with anorexia nervosa

    M. I. Berman
    Abstract The aim of the present study was to evaluate the effectiveness of Acceptance and Commitment Therapy (ACT) for treatment of anorexia nervosa (AN) using a case series methodology among participants with a history of prior treatment for AN. Three participants enrolled; all completed the study. All participants had a history of 1,20 years of intensive eating disorder treatment prior to enrollment. Participants were seen for 17,19 twice-weekly sessions of manualized ACT. Symptoms were assessed at baseline, post-treatment and 1-year follow-up. All participants experienced clinically significant improvement on at least some measures; no participants worsened or lost weight even at 1-year follow-up. Simulation modelling analysis (SMA) revealed for some participants an increase in weight gain and a decrease in eating disorder symptoms during the treatment phase as compared to a baseline assessment phase. These data, although preliminary, suggest that ACT could be a promising treatment for subthreshold or clinical cases of AN, even with chronic participants or those with medical complications. Copyright 2009 John Wiley & Sons, Ltd and Eating Disorders Association. [source]

    Schnitzler syndrome: response to anakinra in two cases and a review of the literature

    Christian Schuster MD
    Background, Schnitzler syndrome is a rare disease characterized by a chronic urticarial eruption and monoclonal gammopathy, as well as clinical and laboratory signs of inflammation. The pathophysiology is still unknown, although various autoantibody-mediated mechanisms have been described. Complete remission of symptoms has been reported recently in patients with Schnitzler syndrome treated with anakinra, an interleukin-1 receptor antagonist. Methods, Two patients with Schnitzler syndrome treated with anakinra therapy are presented. Results, We report two cases of nearly complete remission of symptoms in Schnitzler syndrome after the initiation of anakinra therapy, and the first observation of a relapse under continuous daily anakinra therapy. A review of the published literature on the treatment of Schnitzler syndrome with anakinra is presented. Conclusions, Based on published data, monotherapy with anakinra is currently the most promising treatment for Schnitzler syndrome, because it is able to induce complete remission of symptoms. [source]

    Treatment of pediculosis capitis with thiabendazole: a pilot study

    Mohammad Reza Namazi MD
    Background, Despite the improvement of health standards, head lice infestation remains a problem worldwide. In addition, there is increasing evidence that head lice are becoming resistant to common pediculocides. Aim, To test the potential effectiveness of thiabendazole, a potent and broad-spectrum antiparasitic and scabicidal agent, for the treatment of pediculosis capitis. Methods, Twenty-three female patients, aged 7,12 years, who had active head lice infestation, were treated with oral thiabendazole, 20 mg/kg twice daily for 1 day, with repeat treatment after 10 days. Results, On the 11th day, meticulous hair examination showed that 21 patients had responded to treatment [91%; 95% confidence interval (CI), 71,98%], with 14 showing complete responsiveness (61%; 95% CI, 40,78%). The only adverse reactions observed were nausea and mild dizziness, which occurred in four patients, three of whom took the drug on an empty stomach. Conclusions, Thiabendazole may be a promising treatment for head lice infestation. The primary action of this drug seems to be the inhibition of parasite microtubule polymerization by binding to ,-tubulin. In addition, thiabendazole may interfere with the synaptic transmission of lice through its probable cholinergic effect. As pediculosis capitis is a very communicable disease, the unresponsiveness to thiabendazole could largely be attributed to new infestations during the drug-free interval. Therefore, massive and simultaneous rather than individual and isolated treatments should be used to achieve the epidemiologic control of this ectoparasitosis. As this is a preliminary study, the performance of double-blind, randomized controlled trials on this subject is warranted. Thiabendazole, either alone or in combination with other agents, may prove to be of particular use in areas in which head lice show resistance to common pediculocides. [source]

    Virtual reality exposure therapy for active duty soldiers,

    Greg M. Reger
    Abstract Virtual reality exposure (VRE) therapy is a promising treatment for a variety of anxiety disorders and has recently been extended to the treatment of posttraumatic stress disorder (PTSD). In this article, the authors briefly review the rationale for VRE and its key processes. They illustrate the treatment with an active-duty Army soldier diagnosed with combat-related PTSD. Six sessions of VRE were provided using an immersive simulation of a military convoy in Iraq. Self-reported PTSD symptoms and psychological distress were reduced at posttreatment relative to pretreatment reports, as assessed by the PTSD Checklist,Military Version and the Behavior and Symptom Identification Scale,24. The case outcomes parallel those reported in the research with other disorders and suggest the applicability of VRE in treating active duty soldiers with combat-related PTSD. 2008 Wiley Periodicals, Inc. J Clin Psychol: In Session 64:1,7, 2008. [source]

    Review article: omega-3 fatty acids , a promising novel therapy for non-alcoholic fatty liver disease

    Aliment Pharmacol Ther,31, 679,692 Summary Background, Non-alcoholic fatty liver disease affects 10,35% of the adult population worldwide; there is no consensus on its treatment. Omega-3 fatty acids have proven benefits for hyperlipidaemia and cardiovascular disease, and have recently been suggested as a treatment for non-alcoholic fatty liver disease. Aims, To review the evidence base for omega-3 fatty acids in non-alcoholic fatty liver disease and critically appraise the literature relating to human trials. Methods, A Medline and PubMed search was performed to identify relevant literature using search terms ,omega-3', ,N-3 PUFA', ,eicosapentaenoic acid', ,docosahexaenoic acid', ,non-alcoholic fatty liver disease' and ,NAFLD'. Results, Omega-3 fatty acids are important regulators of hepatic gene transcription. Animal studies demonstrate that they reduce hepatic steatosis, improve insulin sensitivity and reduce markers of inflammation. Clinical trials in human subjects generally confirm these findings, but have significant design inadequacies. Conclusions, Omega-3 fatty acids are a promising treatment for non-alcoholic fatty liver disease which require to be tested in randomized placebo-controlled trials. [source]

    Continuous changes in the optical properties of liver tissue during laser-induced interstitial thermotherapy

    Joerg P. Ritz MD
    Abstract Background and Objective Laser-induced thermotherapy (LITT) is a promising treatment for irresectable liver tumors. To predict the effects of laser applications and to optimize treatment planning in LITT, it is essential to gain knowledge about light distribution in tissue, tissue optical properties (absorption, scattering, anisotropy, penetration depth), and their continuous changes during therapy. Study Design/Materials and Methods Measurements of optical properties were performed with a double integrating-sphere system and a laser diode (830 nm). Porcine liver tissue samples were examined in a native state (35C) and after exposure to different temperatures (45C to 80C). Results Rising temperature was accompanied by a decrease in the absorption coefficient and anisotropy factor and an increase in the scattering coefficient. These changes were only significant in the temperature range of 50 to 65C (P,<,0.01). The optical penetration depth decreased from 3.1mm in the native state to 1.7mm at 65C (P,<,0.01). Above 65, there was no significant change in the tissue optical properties. Conclusions The optical properties of liver tissue change significantly under the influence of tissue heating, resulting in a decreased optical penetration depth. These changes occur mainly in the temperature range of 50C to 65C, corresponding to protein denaturation. To ensure a safe and effective procedure, an adjustment of the laser power to the actual penetration depth is recommended during therapy. Lasers Surg. Lasers Surg. Med. 28:307,312, 2001. 2001 Wiley-Liss, Inc. [source]

    Oncoproteomics of hepatocellular carcinoma: from cancer markers' discovery to functional pathways

    Stella Sun
    Abstract Hepatocellular carcinoma (HCC) is a heterogeneous cancer with no promising treatment and remains one of the most prevailing and lethal malignancies in the world. Researchers in many biological areas now routinely identify and characterize protein markers by a mass spectrometry-based proteomic approach, a method that has been commonly used to discover diagnostic biomarkers for cancer detection. The proteomic research platforms span from the classical two-dimensional polyacrylamide gel electrophoresis (2-DE) to the latest Protein Chip or array technology, which are often integrated with the MALDI (matrix-assisted laser-desorption ionization), SELDI (surface-enhanced laser desorption/ionization) or tandem mass spectrometry (MS/MS). New advances on quantitative proteomic analysis (e.g. SILAC, ICAT, and ITRAQ) and multidimensional protein identification technology (MudPIT) have greatly enhanced the capability of proteomic methods to study the expressions, modifications and functions of protein markers. The present article reviews the latest proteomic development and discovery of biomarkers in HCC that may provide insights into the underlying mechanisms of hepatocarcinogenesis and the readiness of biomarkers for clinical uses. [source]

    Response to Cardiac Resynchronization Therapy: Is It Time to Expand the Criteria?

    Background: Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10,40% of patients do not respond to this treatment and are labeled as nonresponders. Given that there is a lack of consensus on how to define response to CRT, the purpose of this viewpoint is to discuss currently used definitions and their shortcomings, and to provide recommendations as to how an expansion of the criteria for CRT response may be useful to clinicians. Methods and Results: Analysis of the literature and case reports indicates that the majority of established measures of CRT response, including New York Heart Association functional class and echocardiographic, hemodynamic, and neurohormonal parameters, are poor associates of patient-reported symptoms and quality of life. Moreover, the potential moderating role of psychological factors in determining health outcomes after CRT has largely been neglected. Conclusions: It is recommended to routinely assess health status after CRT with a disease-specific questionnaire in standard clinical practice and to examine its determinants, including psychological factors such as personality traits and depression. This may lead to improved (secondary) treatment and prognosis in CHF patients treated with CRT. [source]

    Successful Treatment of T-cell Post-Transplant Lymphoproliferative Disorder with the Retinoid Analog Bexarotene

    Donald E. Tsai
    T-cell post-transplant lymphoproliferative disorder (PTLD) is a rare life threatening complication of organ transplantation. It is usually resistant to treatment with reduction in immunosuppression or chemotherapy and carries a poor prognosis. We report on a combined kidney and pancreas transplant patient with Epstein,Barr virus (EBV) positive T-cell PTLD that had recurred after chemotherapy and reduction in immunosuppression. The patient was successfully treated with bexarotene, a novel synthetic retinoid analog, achieving a complete clinical response. Bexarotene may be a promising treatment for T-cell PTLD. [source]

    Should being aged over 70 years hinder penile prosthesis implantation?

    BJU INTERNATIONAL, Issue 6 2009
    Amr Al-Najar
    OBJECTIVE To assess the satisfaction profiles following penile prosthesis surgery in patients with erectile dysfunction (ED) in their seventh decade of life. PATIENTS AND METHODS In all, 174 patients received, for the first time, a penile prosthesis between 1990 and 2007 in our department. Among these, 35 patients were aged ,70 years at prosthesis implantation. Of these, 18 patients were still alive at the time of follow-up. Using a telephone survey, patients were asked to answer the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) as well as the International Index of Erectile Dysfunction (IIEF). Another question in the survey was developed by the authors based on a comprehensive review of the literature, which assessed the usefulness of the device for the patient and the degree of their usage. This was formulated as follows: How many times per 2 weeks do you have a sexual intercourse? RESULTS In all, 15 of 18 patients were either very or somewhat satisfied (83%). At follow-up 11 out of 15 (73%) patients were using their prosthesis regularly. The mean IIEF and EDITS scores were 21.80 and 75.20, respectively. CONCLUSION A penile prosthesis remains a highly promising treatment in older patients with a similar satisfaction rate to those published for younger patients. Thus, the motivation of the patient and not the age of the patient should be the main determinant factor in this surgical procedure. [source]

    Late lethal hepatitis B virus reactivation after rituximab treatment of low-grade cutaneous B-cell lymphoma

    G. Perceau
    Summary The chimeric anti-CD20 monoclonal antibody, rituximab, is a promising treatment for cutaneous B-cell lymphomas. Classically used in combination with a multiagent-chemotherapy regimen, it can sometimes give excellent results alone. Because of its selective action on B lymphocytes, it is considered a moderate immunosuppressant in terms of infection. We describe a woman with relapsed cutaneous follicular centre B-cell lymphoma and secondary lymph-node involvement treated with rituximab alone, which induced a complete remission. One year later, she experienced a fatal hepatitis B virus (HBV) reactivation. Several such HBV reactivations were reported after combined rituximab and multiagent chemotherapy for B-cell lymphomas. This is the first case of HBV reactivation occurring during the year following rituximab monotherapy in the absence of any other immunosuppressive factor. [source]

    Successful treatment with infliximab and methotrexate of pyostomatitis vegetans associated with Crohn's disease

    G. Bens
    Summary A 35-year-old woman with severe fistulizing Crohn's disease presented with pyostomatitis vegetans affecting both the mouth and the vulva. The coalescing pustules transformed within several days into vegetating lesions on areas of inflammation. Microbial assessments revealed no pathogenic agent. Histology showed neutrophilic microabscesses, but no granulomas. Three injections of infliximab and maintenance therapy with methotrexate resulted in rapid and complete regression of both the pyostomatitis vegetans and the Crohn's disease. Infliximab and methotrexate may be a promising treatment for the rare cases of pyostomatitis vegetans associated with Crohn's disease. [source]

    Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis

    CANCER, Issue 2 2002
    Phase I study
    Abstract BACKGROUND Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) combined with cytoreductive surgery (CS) has been proposed as a new multimodal treatment mainly for carcinomatosis of gastrointestinal origin. To evaluate whether this regimen could be used for other tumor types, the authors conducted a Phase I study on HIIC with doxorubicin and cisplatin in patients with peritoneal carcinomatosis or sarcomatosis. PATIENTS AND METHODS Thirty-one patients with peritoneal carcinomatosis or sarcomatosis (PCS) were enrolled for the study. After completion of CS, HIIC was administered with drug doses that were increased for each consecutive cohort following a three-patient cohort scheme. Thereafter, the accrual was stopped when Grade 4 locoregional or systemic toxicity was observed. The maximum tolerated dose (MTD) was considered the dose in the previous triplet. Drug pharmacokinetics and procedure costs also were analyzed. RESULTS After CS, residual tumors were not present or measured less than or equal to 3 mm (in dimension) in all cases. Maximum tolerated dose was 15.25 and 43.00 mg L,1 for doxorubicin and cisplatin, respectively. The perfusate/plasma area under the curve ratios were favorable for both drugs, at 162 113 and 20.6 6.0, respectively, for doxorubicin and cisplatin. Doxorubicin levels in the peritoneum were higher than in tumor or normal tissue samples. There were no postoperative deaths. Surgery-related complications were observed in 25% of cases. Findings at cost analysis showed that the length of stay in the operation room and intensive care unit were the major cost drivers. CONCLUSIONS Cytoreductive surgery combined with HIIC is an expensive but feasible therapeutic approach for locally advanced abdominal tumors. Because our preliminary findings for local disease control are encouraging, a Phase II study is now advisable to verify the activity of this promising treatment. Cancer 2002;94:492,9. 2002 American Cancer Society. [source]

    Dendritic cells pulsed with ,-fetoprotein and mutant P53 fused gene induce bi-targeted cytotoxic T lymphocyte response against hepatic carcinoma

    CANCER SCIENCE, Issue 7 2008
    Jun Ren
    Dendritic cell (DC)-based immunotherapy is rapidly emerging as a promising treatment in cancer therapy. We had previously shown that DC pulsed with either defined mRNA of tumor antigen (Ag) such as ,-fetoprotein (AFP), or total RNA of hepatocellular carcinoma (HCC) could elicit Ag-specific cytotoxic T lymphocyte (CTL) response. Therefore, we suggested a novel DC-based therapeutic method, in which DCs derived from CD34+ cells enriched peripheral blood mononuclear cells were pulsed with liposome-coated AFP and mutant P53 (mtP53) fused gene pEGFP-C3/AFP-mtP53 to induce bi-targeted specific CTL responses against HCC. Three different genotype HCC cell lines, HepG2 (human histocompatibility leukocyte antigens (HLA) A2 positive, AFP expressing positive, P53 expressing negative), SMMC7721 (HLA A2 positive, neither AFP nor P53 expressing positive), and HMCC97 (HLA A2 positive, both AFP and P53 expressing positive) were selected as targets for CTL responses. An important finding was that DCs pulsed with the liposome-coated fused gene could evoke more intensive bi-targeted Ag-specific CTL responses against HMCC97 than DCs pulsed with either AFP or P53 single gene (P < 0.05). This experimental therapeutic model provides a new promising cytotherapeutic approach, in that DCs pulsed with the fused gene of different Ags might induce more extensive multitargeted antitumor immunity. (Cancer Sci 2008; 99: 1420,1426) [source]

    Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin) in neovascular age-related macular degeneration

    Philippe Bonnin
    Acta Ophthalmol. 2010: 88: 641,645 Abstract. Purpose:, Angiogenic inhibitors, alone or combined with other therapies, are believed to represent a promising treatment for neovascularization in age-related macular degeneration (wet AMD). They can maintain or improve visual acuity (VA), at least for the first 2 years. However, evolution to retinal atrophy cannot be ruled out and it may be useful to assess the effects of antiangiogenic therapy on retinal and choroidal circulation. Methods:, We carried out a pilot study in 15 patients with wet AMD. Time-averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before and 4 weeks after a single intravitreal injection of 1.25 mg bevacizumab in 0.05 ml. Patients underwent two ophthalmic examinations, before and 4 weeks after injection, including VA measurement and optical coherence tomography (OCT3) examination. Results:, In treated eyes, bevacizumab injection was followed by a significant improvement in VA (from 20/125 to 20/80; p = 0.0214), and a decrease in mean central macular thickness (from 392 96 ,m to 271 50 ,m; p = 0.0038). Mean BFV decreased by 10% in the CRA (p = 0.0226), 20% in the TPCA (p = 0.0026) and 20% in the OA (p = 0.0003). No effect was observed in fellow eyes. Conclusions:, Intravitreal bevacizumab acutely improved VA and reduced central macular thickness in wet AMD. Ultrasound imaging revealed that BFVs decreased in all retrobulbar arteries, suggesting that after local diffusion, bevacizumab exerts a short-term regional effect. Bevacizumab might therefore induce hypoperfusion of the whole eye, which may correspond to a vascular side-effect. [source]

    Alcohol vs. mechanical delamination in the treatment of corneal erosion: an electron microscopic study

    Purpose To performed an electron microscopy study to investigate the cleavage plane and the efficacy of alcohol delamination in recurrent corneal erosion (RCE). Methods By electron microscopy we analysed the epithelium of: seven controls treated with mechanical debridment, seven controls treated with alcohol delamination, ten cases of traumatic RCE and seven RCE due to MDFP treated with alcohol delamination, with special regard to the epithelial cells and the cleavage plane. Moreover we analysed four corneas from penetrating keratoplastys that were treated by alcohol delamination on the bench and both the epithelium and stroma were studied. Results In traumatic RCE the basement membrane remained in situ, a precondition for quick epithelial healing . In MDFP the whole basement membrane was detached from the stroma and remained adherent to the epithelium, therefore after alcohol delamination the healing process should be different between MDFP and traumatic RCE. Conclusion The present findings give strenght to alcohol delamination as a promising treatment for RCE [source]

    Discovery of Adamantyl Ethanone Derivatives as Potent 11,-Hydroxysteroid Dehydrogenase Type,1 (11,-HSD1) Inhibitors

    CHEMMEDCHEM, Issue 7 2010
    Xiangdong Su Dr.
    Abstract 11,-Hydroxysteroid dehydrogenases (11,-HSDs) are key enzymes regulating the pre-receptor metabolism of glucocorticoid hormones. The modulation of 11,-HSD type,1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue-specific glucocorticoid action by regulating 11,-HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11,-HSD1. The most active compounds identified (52, 62, 72, 92, 103 and 104) display potent inhibition of 11,-HSD1 with IC50 values in the 50,70,nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in,vivo studies. Comparison of the publicly available X-ray crystal structures of human 11,-HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor. [source]

    Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylation in splenectomized rats

    Wen-Fei Tan
    Summary 1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3, (GSK-3,) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3, activity and expression of interleukin-1, (IL-1,), tumour necrosis factor-, (TNF-,) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3, inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3,, and increased IL-1, and TNF-, expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3, signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits. [source]

    Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: a randomized controlled trial

    ADDICTION, Issue 9 2009
    Anthony DeFulio
    ABSTRACT Context Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. Objective To determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Design Participants (n = 128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly and developed needed job skills during the first 6 months were hired as operators in a data entry business and assigned randomly to an employment-only (control, n = 24) or abstinence-contingent employment (n = 27) group. Setting A non-profit data entry business. Participants Unemployed welfare recipients who used cocaine persistently while enrolled in methadone treatment in Baltimore. Intervention Abstinence-contingent employment participants received 1 year of employment-based contingency management, in which access to employment was contingent upon provision of drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Main outcome measure Cocaine-negative urine samples at monthly assessments across 1 year of employment. Results During the 1 year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment-only participants [79.3% and 50.7%, respectively; P = 0.004, odds ratio (OR) = 3.73, 95% confidence interval (CI) = 1.60,8.69]. Conclusions Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance intervention, and is among the most promising treatments for drug dependence. Work-places could serve as therapeutic agents in the treatment of drug dependence by arranging long-term employment-based contingency management programs. [source]

    Extended indications for anti-tumor necrosis factor-, therapy

    Chong-Hyeon YOON
    Abstract Tumour necrosis factor-, is a pleiotropic cytokine which has a broad range of actions in inflammation, infection and immunity. TNF-, is supposed to play a crucial role in the pathogenesis of various autoimmune diseases. TNF-, blocking agents have been demonstrated to be highly effective in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile rheumatoid arthritis. TNF-, inhibitors also have been tried with other rheumatic diseases and have emerged as promising treatments. We here review the current evidences of effectiveness of the anti-TNF-, therapy in various autoimmune diseases. [source]