Chaperonins in disease: mechanisms, models, and treatments.

Chaperonins are oligomeric proteins that assist in the folding of nascent or denatured proteins. Bacterial chaperonins are strongly immunogenic and can cause tissue pathology. They have been implicated in infection, autoimmune disease, and idiopathic or multifactorial diseases, such as arthritis and atherosclerosis. Chaperonin 60 proteins are also involved in prion diseases. In the past few years, much progress has been made in unravelling the involvement of various bacterial and mammalian chaperonin 60 (Cpn 60 or hsp 60) proteins in such diseases, and in proposing mechanisms for their biological actions, although we are still some way from a full understanding of chaperonin action that might lead to immunotherapeutic approaches. This review focuses on the current knowledge of the roles of Cpn 60 in the pathology of infectious and immune diseases, and discusses models for the actions of this molecule. Some potential therapeutic strategies will also be reviewed.     

Bipolar disorder: causes, contexts, and treatments

Bipolar disorder is a chronic and often devastating illness that may go undiagnosed because of its complex and diverse presentation. Clinicians can provide psychological treatments, in conjunction with pharmacotherapy, that can reduce the frequency, severity, and duration of manic and depressive episodes. Because bipolar disorder is characterized by high degrees of comorbidity and high rates of medical complications, the clinician will frequently need to implement other treatments targeted to comorbid conditions, such as panic, generalized anxiety, substance abuse, and personality disorders. This article introduces the issue of Journal of Clinical Psychology: In Session devoted to the treatment of bipolar disorder. We describe the cognitive styles and personal vulnerabilities that pose greater risk for bipolar disorder. Three evidence-based psychological treatments (interpersonal social rhythm therapy, family-focused treatment, and cognitive-behavioral therapy) and current pharmacological treatments are examined and illustrated. Finally, we review the effectiveness and practice implications of a variety of treatments for this severe and underresearched disorder.     

Osteoarthritis: understanding the pathophysiology,genetics, and treatments

Risk factors for developing osteoarthritis include age, previous joint injury, obesity, and a genetic predisposition. An imbalance of joint functioning initiates the disease process, which is then worsened through biochemical changes in the collagen in the joint. Joint pain is the cardinal clinical presentation. Radiographic and lab testing do not correlate well with the disease; therefore, diagnosis is made by clinical findings. Treatment focuses on maintaining joint function through the use of directed activity, physical therapy, and medications.     

Role of nanostructures in allergy: Diagnostics,treatments and safety

Nanotechnology is science, engineering and technology conducted at the nanoscale, which is about 1–100 nm. It has led to the development of nanomaterials, which behave very differently from materials with larger scales and can have a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition and functionalization of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers and nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalization with ligands, which provide the desired interaction with the immunological system, that is dendritic cell receptors to activate and/or modulate the response, as well as specific IgE, or effector cell receptors. However, undesired issues related to toxicity and hypersensitivity responses can also happen and would need evaluation. There are wide panels of accessible structures, and controlling their physico-chemical properties would permit obtaining safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment. The application of dendrimeric antigens, nanoallergens and nanoparticles in allergy diagnosis is very promising since it can improve sensitivity by increasing specific IgE binding, mimicking carrier proteins or enhancing signal detection. Additionally, in the case of immunotherapy, glycodendrimers, liposomes, polymers and nanoparticles have shown interest, behaving as platforms of allergenic structures, adjuvants or protectors of allergen from degradation or having a depot capacity. Taken together, the application of nanotechnology to allergy shows promising facts facing important goals related to the improvement of diagnosis as well as specific immunotherapy.     

Current,experimental, and future treatments in inflammatory bowel disease: a clinical review

Abstract

Inflammatory bowel diseases (IBDs) may result from dysregulated mucosal immune responses directed toward the resident intestinal microbiota. This review describes the hallmark immunobiology of Crohn’s disease and ulcerative colitis as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD. Conventional therapies include 5-aminosalicylic acid, glucocorticosteroids, thiopurines, and methotrexate. Since 1997, monoclonal antibodies have gained widespread use. These consist of antibodies directed against pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12, and IL-23, or anti-homing antibodies directed against α4β7 integrin. Emerging oral therapies include modulators of intracellular signal transduction such as Janus kinase inhibitors. Vitamin D may help to regulate innate and adaptive immune responses. Modulation of the intestinal microbiota, using live microorganisms (probiotics), substrates for the colonic microbiota (prebiotics), or fecal microbiota transplantation (FMT), is in development. Dietary supplements are in widespread use, but providing evidence for their benefit is challenging. Stem cell treatment and nervous stimulation are promising future treatments.     

Finding,evaluating, refining,and applying empirically supported treatments for children and adolescents

Structured child and adolescent treatments, tested through controlled clinical trials, have produced beneficial effects in hundreds of studies. By contrast, the limited pool or research on traditional clinical treatments raises doubts about their effectiveness. Thus, identification of empirically supported treatments may contribute something of real value to clinical practice and training. The Child Task Force report represents an important initial step in this direction. Here we offer both praise and critique, suggesting a number of ways the task force process and product may be improved. In addition, we suggest several ways to strengthen and enrich the clinical trials research available to the Task Force, emphasizing the need to test empirically supported treatments with referred youth in practice settings.     

Contemporary behavioral activation treatments for depression: procedures,principles, and progress

In the past decade, there has been renewed interest in the feasibility and efficacy of purely behavioral treatments for clinical depression. Emphasizing the functional aspects of depressive and nondepressive behavior, these treatments focus on the concept of behavioral activation, which guides implementation of procedures aimed at increasing patient activity and access to reinforcement. Although researchers have provided positive preliminary support for behavioral activation-based interventions, many fundamental issues concerning strategies, principles, and change processes involved in behavioral activation have yet to be addressed. In this paper, we compare and contrast contemporary behavioral activation interventions, explore strategies and process of change issues, clarify the basic behavioral principles underlying activation strategies, and outline questions that need to be addressed to improve outcomes and better understand the potential significance of behavioral activation as it pertains to the future of behavior therapy for depression.     

Effects of hypnotic, placebo, and salicylic acid treatments on wart regression

Subjects with warts on their hands and/or feet were randomly assigned to a hypnotic suggestion, topical salicylic acid, placebo, or no treatment control condition. Subjects in the three treated groups developed equivalent expectations of treatment success. Nevertheless, at the six-week follow-up interval only the hypnotic subjects had lost significantly more warts than the no treatment controls. Theoretical implications are discussed.     

Mechanisms and treatments for severe,steroid-resistant allergic airway disease and asthma

Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.     

Relative efficacy of pharmacological,behavioral, and combination treatments for enhancing academic performance

The role of stimulant drugs in facilitating academic performance in hyperactive (HA), learning disabled (LD), and hyperactive-learning disabled (HA-LD) children has been a matter of controversy for over a decade. The findings from 16 studies that compared the effects of medication and behavioral interventions on academic performance are reviewed with consideration for methodological issues and clinical implications. It was concluded that certain academically oriented behavioral interventions were clearly superior to medication and that there was only limited support for the notion stimulant drugs markedly enhance the efficacy of the former. Suggestions on how the procedures in and the findings from these studies might apply to the clinical decision-making process are presented.     

Animal systems in the development of treatments for Alzheimer's disease: challenges,methods, and implications

Substantial resources and effort have been invested into the development of therapeutic agents for Alzheimer's disease (AD) with mixed and limited success. Research into the etiology of AD with animal models mimicking aspects of the disorder has substantially contributed to the advancement of potential therapies. Although these models have shown utility in testing novel therapeutic candidates, large variability still exists in terms of methodology and how the models are utilized. No model has yet predicted a successful disease-modifying therapy for AD. This report reviews several of the widely accepted transgenic and nontransgenic animal models of AD, highlighting the pathological and behavioral characteristics of each. Methodological considerations for conducting preclinical animal research are discussed, such as which behavioral tasks and histological markers may be associated with the greatest insight into therapeutic benefit. An overview of previous and current therapeutic interventions being investigated in AD models is presented, with an emphasis on factors that may have contributed to failure in past clinical trials. Finally, we propose a multitiered approach for investigating candidate therapies for AD that may reduce the likelihood of inappropriate conclusions from models and failed trials in humans.     

Electromagnetic hypersensitive Finns: Symptoms,perceived sources and treatments,a questionnaire study

The aim was to analyze the subjective experiences of Finns who describe themselves as suffering from electromagnetic hypersensitivity (EHS), their symptoms, self-perceived sources of the health complaints and the effectiveness of medical and complementary alternative therapies. A total of 395 questionnaires were mailed to self-diagnosed EHS persons. Of the participants 345 belonged to a Finnish self-help group and 50 came from outside of the group. The return rate of the study was 52.1% (206) and 80.9% of the respondents were women. Before the onset of EHS the most common health complaints were different types of allergies (35.1%, 68). During the acute phase of EHS the most common symptoms were nervous system related: “stress” (60.3%, 117), “sleeping disorders” (59.3%, 115) and “fatigue” (57.2%, 111). The sources that were most often reported to have triggered EHS were: “personal computers” (50.8%, 94) and “mobile phones” (47.0%, 87). The same devices were also claimed to cause the most symptoms during the acute phase. After the acute phase of EHS had passed, the respondents still claimed to react to these same digital and wireless devices while their reactions to basic electrical appliances were reduced. According to 76% of 157 respondents the reduction or avoidance of electromagnetic fields (EMF) helped in their full or partial recovery. The best treatments for EHS were given as: “dietary change” (69.4%), “nutritional supplements” (67.8%) and “increased physical exercise” (61.6%). The official treatment recommendations of psychotherapy (2.6%) and medication (?4.2%) were not significantly helpful. According to the present results the official treatment protocols should take better account the EHS person's own experiences. The avoidance of electromagnetic radiation and fields effectively removed or lessened the symptoms in EHS persons.     

Empirically supported treatments of disease-related symptoms in pediatric psychology: asthma, diabetes, and cancer.

OBJECTIVE: To review empirical studies of psychological treatments for (1) reducing physical symptoms in children and adolescents with asthma, (2) improving glycemic control in children and adolescents with diabetes, and (3) reducing chemotherapy side effects in children and adolescents with cancer. METHODS: We identified peer-reviewed studies of effects of psychological treatments for asthma symptoms, diabetes symptoms, and side effects of cancer chemotherapy through computerized databases (i.e., PSYCHLIT and MEDLINE). Treatment approaches are evaluated with respect to meeting criteria for being "promising," "probably efficacious," or "well-established" based on the Chambless criteria (Chambless et al., 1996). RESULTS: Two well-established treatments (EMG biofeedback for children with emotionally triggered asthma and imagery with suggestion for children undergoing chemotherapy) and two probably efficacious treatments (relaxation for children with emotionally triggered asthma and distraction with relaxation for children undergoing chemotherapy) were identified. Additional research is needed to evaluate the efficacy of treatments for diabetes-related symptoms. CONCLUSIONS: Future research would be enhanced by identifying characteristics of children who are likely to respond to psychological treatment as an adjunctive strategy for symptom management and by clearly elucidating mechanisms of effect of various interventions.     

Empirically supported treatments for panic disorder: costs, benefits, and stepped care

Treatment outcome findings suggest that cognitive-behavioral therapy (CBT) and pharmacotherapy offer similar short-term treatment gains for panic disorder and that CBT may afford more optimal maintenance of treatment gains without the need for ongoing treatment. However, efficacy is not the only consideration for patients, and because of limited health care resources, evaluation of the cost-benefit ratio of these treatments is important. In this article, the authors review estimates of the relative efficacy, acceptability, tolerability, and costs of these treatments; empirically examine the costs and outcome of cognitive-behavioral and pharmacologic interventions as they are delivered in an outpatient clinic specializing in these treatments; and comment on how these data inform a stepped care model of treatment. Analysis of the "services" data indicated that CBT was at least equal to pharmacotherapy in terms of pretreatment severity and acute treatment outcome and that CBT is an especially cost-effective treatment option.