			Home About us Contact

Therapeutic Mechanisms (therapeutic + mechanism)

Distribution by Scientific Domains

Medical Sciences	84%

Selected Abstracts

Distress, Dissociation, and Embodied Experience: Reconsidering the Pathways to Mediumship and Mental Health

ETHOS, Issue 1 2005
REBECCA SELIGMAN
This article explores the biocultural bases of spirit possession mediumship in the Afro-Brazilian religion, Candomblé. After a brief review of the literature, the article moves beyond the biomedical and social-structural explanations that have dominated the theoretical landscape, by attempting to construct an etiology of mediumship that is traced through the interface of individual characteristics with the cultural belief system that forms their context. Data were collected from a total of 71 individuals over the course of a year-long field study in Salvador, Brazil. Analyses of social ethnography, life history and semistructured interviews along with results from psychological inventories, suggest that altered states of consciousness should not be considered the central and defining element of mediumship. An alternative model is proposed, in which the combination of social conditions and somatic susceptibilities causes certain individuals to identify with the mediumship role, and predisposes them to dissociate. However in the context of Candomblé, dissociation is not a pathological experience, but rather a therapeutic mechanism, learned through religious participation, that benefits individuals with a strong tendency to somatize. [source]

Basis of occlusive therapy in psoriasis: correcting defects in permeability barrier and calcium gradient

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2001
Sang Min Hwang MD
Background Although occlusive dressings have great potential in the management of psoriasis vulgaris, the therapeutic mechanism is not completely understood. Occlusion artificially restores and corrects the defective barrier in psoriasis plaques. Additionally, occlusion is know to normalize the epidermal calcium gradients in hyperproliferative murine skin models. Methods To investigate the basis of the therapeutic effect of occlusion on psoriatic plaques, we investigated the ultrastructural morphology of intercorneocyte lipid layers, lamellar bodies, and calcium gradient in chronic plaque-type psoriasis after occlusion with a water vapor-impermeable membrane. The specimens were processed for electron microscopy using: (i) ruthenium tetroxide postfixation; and (ii) ion-capture cytochemistry for calcium localization. Results Occlusion for 7 days resulted in a nearly mature pattern of intercellular multilamellar structures, re-establishment of the near-normal epidermal calcium gradient, and disappearance of calcium precipitates from the stratum corneum interstices. Conclusions The normalization of the permeability barrier and epidermal calcium gradient may play important roles in the therapeutic effects of occlusive dressings in chronic plaque-type psoriasis. [source]

Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma model

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009
Seung-Hyung Kim
Abstract Objectives This study aimed to investigate the effect of piperine on airway hyper-responsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, immunoglobulin E and histamine production in a murine model of asthma. Methods Asthma was induced in Balb/c mice by ovalbumin sensitization and inhalation. Piperine (4.5 and 2.25 mg/kg) was orally administered 5 times a week for 8 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was determined and samples of bronchoalveolar lavage fluid, lung cells and serum were collected for further analysis. Key findings Piperine-treated groups had suppressed eosinophil infiltration, allergic airway inflammation and airway hyperresponsiveness, and these occurred by suppression of the production of interleukin-4, interleukin-5, immunoglobulin E and histamine. Moreover, polymerase chain reaction products for thymus and activation regulated chemokine from lung cell RNA preparations were decreased in the piperine-treated group compared with control groups, although transforming growth factor-, products were increased in the piperine-treated group. Conclusions The results suggest that the therapeutic mechanism by which piperine effectively treats asthma is based on a reduction of Th2 cytokines (interleukin-4, interleukin-5), eosinophil infiltration, and by marked reduction of thymus and activation regulated chemokine, eotaxin-2 and interleukin-13 mRNA expression (especially transcription of nuclear factor-, dependent genes) in lung tissue, as well as reduced interleukin-4, interleukin-5 and eotaxin levels in bronchoalveolar lavage fluid, and histamine and ovalbumin-specific immunoglobulin E production in serum. [source]

Specific immunotherapy of experimental myasthenia gravis by a novel mechanism

ANNALS OF NEUROLOGY, Issue 4 2010
Jie Luo PhD
Objective Myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG), are antibody (Ab)-mediated autoimmune diseases, in which autoantibodies bind to and cause loss of muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. To develop a specific immunotherapy of MG, we treated rats with ongoing EAMG by intraperitoneal injection of bacterially-expressed human muscle AChR constructs. Methods Rats with ongoing EAMG received intraperitoneal treatment with the constructs weekly for 5 weeks beginning after the acute phase. Autoantibody concentration, subclassification, and specificity were analyzed to address the underlying therapeutic mechanism. Results EAMG was specifically suppressed by diverting autoantibody production away from pathologically relevant specificities directed at epitopes on the extracellular surface of muscle AChRs toward pathologically irrelevant epitopes on the cytoplasmic domain. A mixture of subunit cytoplasmic domains was more effective than a mixture containing both extracellular and cytoplasmic domains or than only the extracellular domain of ,1 subunits. Interpretation Therapy using only cytoplasmic domains, which lack pathologically relevant epitopes, avoids the potential liability of boosting the pathological response. Use of a mixture of bacterially-expressed human muscle AChR cytoplasmic domains for antigen-specific immunosuppression of myasthenia gravis has the potential to be specific, robust, and safe. ANN NEUROL 2010;67:441,451 [source]

Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates,

ANNALS OF NEUROLOGY, Issue 3 2009
Stefano Pluchino MD
Objective Transplanted neural stem/precursor cells (NPCs) display peculiar therapeutic plasticity in vivo. Although the replacement of cells was first expected as the prime therapeutic mechanism of stem cells in regenerative medicine, it is now clear that transplanted NPCs simultaneously instruct several therapeutic mechanisms, among which replacement of cells might not necessarily prevail. A comprehensive understanding of the mechanism(s) by which NPCs exert their therapeutic plasticity is lacking. This study was designed as a preclinical approach to test the feasibility of human NPC transplantation in an outbreed nonhuman primate experimental autoimmune encephalomyelitis (EAE) model approximating the clinical and complex neuropathological situation of human multiple sclerosis (MS) more closely than EAE in the standard laboratory rodent. Methods We examined the safety and efficacy of the intravenous (IV) and intrathecal (IT) administration of human NPCs in common marmosets affected by human myelin oligodendrocyte glycoprotein 1-125,induced EAE. Treatment commenced upon the occurrence of detectable brain lesions on a 4.7T spectrometer. Results EAE marmosets injected IV or IT with NPCs accumulated lower disability and displayed increased survival, as compared with sham-treated controls. Transplanted NPCs persisted within the host central nervous system (CNS), but were also found in draining lymph nodes, for up to 3 months after transplantation and exhibited remarkable immune regulatory capacity in vitro. Interpretation Herein, we provide the first evidence that human CNS stem cells ameliorate EAE in nonhuman primates without overt side effects. Immune regulation (rather than neural differentiation) is suggested as the major putative mechanism by which NPCs ameliorate EAE in vivo. Our findings represent a critical step toward the clinical use of human NPCs in MS. Ann Neurol 2009;66:343,354 [source]

Equine laminitis: cryotherapy reduces the severity of the acute lesion

EQUINE VETERINARY JOURNAL, Issue 3 2004
A. W. Van Eps
Summary Reasons for performing study: The hypometabolic and vasoconstrictive effects of cryotherapy could prevent the development of laminitis. Objectives: To use distal limb cryotherapy to prevent laminitis induced by alimentary carbohydrate overload. Methods: Laminitis was induced in 6 Standardbred horses that had one front limb continuously cooled in an ice/water mixture. Lameness evaluation, blinded lamellar histological grading and analysis for lamellar matrix metalloproteinase-2 (MMP-2) mRNA expression were used to evaluate the severity of laminitis. Results: Cryotherapy was well tolerated and effective in cooling the feet. In each horse no lameness was observed in the treated limbs. Laminitis histology scores in the treated limbs were significantly less than those of the corresponding untreated forelimbs (P<0.05). Laminitis histology scores in the treated limbs were also significantly less than those of the untreated limbs (fore- and hind) as a group (P<0.05). Expression of MMP-2 mRNA in the iced feet was significantly (P<0.05) less than that detected in the untreated feet. Conclusions: Cryotherapy, when applied to one foot, markedly reduced the severity of acute laminitis in this study. We propose that vasoconstriction (preventing delivery of haematogenous trigger factors) and hypometabolism (reduction in lamellar MMP activity) were the primary therapeutic mechanisms. Potential relevance: Although further research is needed, we suggest cryotherapy as a potentially effective prophylactic strategy in horses at risk of developing acute laminitis. [source]

Prevention of embolic stroke by catheter ablation of atrial fibrillation

EUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2008
C. Stöllberger
Background and purpose:, Radiofrequency-catheter-ablation of atrial fibrillation is now commonly performed. Aim of this short review is to summarize questions and uncertainties concerning radiofrequency ablation of atrial fibrillation with respect to therapeutic mechanisms, long-term efficacy and stroke-prevention. Results:, The majority of atrial fibrillation patients is too old for radiofrequency ablation. Candidates for radiofrequency ablation belong to a subgroup with a low embolic risk. The radiofrequency ablation procedure itself may increase the embolic risk, and at present it is uncertain how long this embolic risk persists after the procedure. Conclusion:, We doubt if radiofrequency ablation prevents embolism in atrial fibrillation. [source]

Interpersonal psychotherapy for borderline personality disorder: Possible mechanisms of change

JOURNAL OF CLINICAL PSYCHOLOGY, Issue 4 2006
John C. Markowitz
This article describes the rationale for applying interpersonal psychotherapy (IPT) to the treatment of patients who have borderline personality disorder and explains the adaptation of standard IPT to that end. The authors describe the preliminary stages of adapting IPT for a pilot study to test its feasibility and potential efficacy and speculate on potentially therapeutic mechanisms for IPT in treating patients who have borderline personality disorder. © 2006 Wiley Periodicals, Inc. J Clin Psychol 62: 431,444, 2006. [source]

Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2008
W. E. W. ROEDIGER
Summary Background, Factors initiating human ulcerative colitis (UC) are unknown. Dysbiosis of bacteria has been hypothesized to initiate UC but, to date, neither the nature of the dysbiosis nor mucosal breakdown has been explained. Aim, To assess whether a dysbiosis of anaerobic nitrate respiration could explain the microscopic, biochemical and functional changes observed in colonocytes of UC. Methods, Published results in the gastroenterological, biochemical and microbiological literature were reviewed concerning colonocytes, nitrate respiration and nitric oxide in the colon in health and UC. A best-fit explanation of results was made regarding the pathogenesis and new treatments of UC. Results, Anaerobic nitrate respiration yields nitrite, nitric oxide (NO) and nitrous oxide. Colonic bacteria produce NO and UC in remission has a higher lumenal NO level than control cases. NO with sulphide, but not NO alone, impairs ,-oxidation, lipid and protein synthesis explaining the membrane, tight junctional and ion channel changes observed in colonocytes of UC. The observations complement therapeutic mechanisms of those probiotics, prebiotics and antibiotics useful in treating UC. Conclusions, The prolonged production of bacterial NO with sulphide can explain the initiation and barrier breakdown, which is central to the pathogenesis of UC. Therapies to alter bacterial nitrate respiration and NO production need to evolve. The production of NO by colonic bacteria and that of the mucosa need to be separated to pinpoint the sequential nature of NO damage in UC. [source]

The power of cueing to circumvent dopamine deficits: A review of physical therapy treatment of gait disturbances in Parkinson's disease

MOVEMENT DISORDERS, Issue 6 2002
Tamar C. Rubinstein MSc
Abstract Gait disturbances are among the primary symptoms of Parkinson's disease (PD) and contribute significantly to a patient's loss of function and independence. Standard treatment includes antiparkinsonian drugs, primarily levodopa. In addition to the standard drug regime, physical therapy is often prescribed to help manage the disease. In recent years, there have been promising reports of physical therapy programs combined with various types of sensory cueing for PD. In this brief review of the literature, we summarize the evidence regarding the clinical efficacy of different physical therapy programs for PD, specifically with respect to improving gait. We also discuss the potential therapeutic mechanisms of sensory cueing and review the studies that have used cueing in the treatment of gait in PD. This review of the literature shows two key findings: (1) despite its relatively long history, the evidence supporting the efficacy of conventional physical therapy for treatment of gait in PD is not strong; and (2) although further investigation is needed, sensory cueing appears to be a powerful means of improving gait in PD. © 2002 Movement Disorder Society [source]

Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates,

Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms

BIPOLAR DISORDERS, Issue 8 2008
Alan G Mallinger
Objectives:, Attenuation of protein kinase C (PKC) is a mechanism common to both established (lithium, valproate) and some novel (tamoxifen) antimanic agents. Verapamil, although primarily known as a calcium channel blocker, also has PKC inhibitory activity. Verapamil has shown antimanic activity in some but not all studies. Therefore, we investigated verapamil, used alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. Methods:, Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n = 45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n = 10) or continued-lithium (n = 8). Phase 2 nonresponders (n = 10) were assigned to combined verapamil/lithium in Phase 3. Results:, Response in Phase 2 did not differ significantly between verapamil and continued-lithium. During Phase 3, response to combined treatment was significantly better than overall response to monotherapy in Phase 2 (Fisher's Exact test, p = 0.043). Mania ratings improved during combined treatment in Phase 3 by 88.2% (linear mixed model analysis, F = 4.34, p = 0.013), compared with 10.5% improvement during Phase 2. Conclusions:, In this preliminary investigation, verapamil monotherapy did not demonstrate antimanic efficacy. By contrast, the combination of verapamil plus lithium was highly efficacious. Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium. This effect may be mediated by additive actions on PKC inhibition, which may be an important mechanism for antimanic agents in general. [source]

Direct suppression of autoreactive lymphocytes in the central nervous system via the CB2 receptor

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008
B N Dittel
The cannabinoid system is now recognized as a regulator of both the nervous and immune systems. Although marijuana has been used for centuries for the treatment of a variety of disorders, its therapeutic mechanisms are only now being understood. The best-studied plant cannabinoid, ,9 -tetrahydrocannabinol (THC), produced by Cannabis sativa and found in marijuana, has shown evidence of being immunosuppressive in both in vivo and in vitro. Since THC binds to at least two receptors that are differentially expressed by the immune and nervous systems, it has not been possible to clearly discriminate the biological effects it exerts in the two systems. In addition, endogenous cannabinoids have also been described that bind to both receptors and exert both neuronal and immune modulatory activity. The generation of mice deficient in specific cannabinoid receptors has facilitated studies to discriminate cannabinoid-specific functions. This review focuses on the function of the cannabinoid receptor 2 (CB2), primarily expressed in the immune system, in regulating T cell effector functions associated with autoimmune inflammation in the central nervous system (CNS). British Journal of Pharmacology (2008) 153, 271,276; doi:10.1038/sj.bjp.0707493; published online 8 October 2007 [source]