Mast cell degranulation and calcium influx are inhibited by an Echinacea purpurea extract and the alkylamide dodeca-2E,4E-dienoic acid isobutylamide.

ETHNOPHARMACOLOGICAL RELEVANCE: Native Americans used plants from the genus Echinacea to treat a variety of different inflammatory conditions including swollen gums, sore throats, skin inflammation, and gastrointestinal disorders. Today, various Echinacea spp. preparations are used primarily to treat upper respiratory infections. AIM OF THE STUDY: The goal of this study was to evaluate the effects of an ethanolic E. purpurea (L) Moench root extract and the alkylamide dodeca-2E,4E-dienoic acid isobutylamide (A15) on mast cells, which are important mediators of allergic and inflammatory responses. Inhibition of mast cell activation may help explain the traditional use of Echinacea. MATERIALS AND METHODS: A15 was evaluated for its effects on degranulation, calcium influx, cytokine and lipid mediator production using bone marrow derived mast cells (BMMCs) and the transformed rat basophilic leukemia mast cell line RBL-2H3. Methods included enzymatic assays, fluorimetry, ELISAs, and microscopy. A root extract of E. purpurea, and low and high alkylamide-containing fractions prepared from this extract, were also tested for effects on mast cell function. Finally, we tested A15 for effects on calcium responses in RAW 264.7 macrophage and Jurkat T cell lines. RESULTS: A15 inhibited ß-hexosaminidase release from BMMCs and RBL-2H3 cells after treatment with the calcium ionophore A23187 by 83.5% and 48.4% at 100µM, respectively. Inhibition also occurred following stimulation with IgE anti-DNP/DNP-HSA. In addition, A15 inhibited 47% of histamine release from A23187-treated RBL-2H3 cells. A15 prevented the rapid rise in intracellular calcium following FcεRI crosslinking and A23187 treatment suggesting it acts on the signals controlling granule release. An E. purpurea root extract and a fraction with high alkylamide content derived from this extract also displayed these activities while fractions with little to no detectable amounts of alkylamide did not. A15 mediated inhibition of calcium influx was not limited to mast cells as A23187-stimulated calcium influx was blocked in both RAW 264.7 and Jurkat cell lines with 60.2% and 43.6% inhibition at 1min post-stimulation, respectively. A15 also inhibited the release of TNF-α, and PGE2 to a lesser degree, following A23187 stimulation indicating its broad activity on mast cell mediator production. CONCLUSIONS: These findings suggest that Echinacea extracts and alkylamides may be useful for treating allergic and inflammatory responses mediated by mast cells. More broadly, since calcium is a critical second messenger, the inhibitory effects of alkylamides on calcium uptake would be predicted to dampen a variety of pathological responses, suggesting new uses for this plant and its constituents.

Equine herpesvirus type 1 modulates inflammatory host immune response genes in equine endothelial cells.

Equine herpesvirus myeloencephalopathy (EHM), a disease caused by equine herpesvirus type 1 (EHV-1), is characterized by severe inflammation, thrombosis, and hypoxia in central nervous system (CNS) endothelial cells, which can result in a spectrum of clinical signs including urinary incontinence, ataxia, and paralysis. Strains of EHV-1 that contain a single point mutation within the viral DNA polymerase (nucleotide A2254>G2254: amino acid N752→D752) are isolated from EHM afflicted horses at higher frequencies than EHV-1 strains that do not harbor this mutation. Due to the correlation between the DNA Pol mutation and EHM disease, EHV-1 strains that contain the mutation have been designated as neurologic. In this study, we measured virus replication, cell to cell spread efficacy, and host inflammatory responses in equine endothelial cells infected with 12 different strains of EHV-1. Two strains, T953 (Ohio 2003) (neurologic) and Kentucky A (KyA) (non-neurologic), have well described disease phenotypes while the remaining strains used in this study are classified as neurologic or non-neurologic based solely on the presence or absence of the DNA pol mutation, respectively. Results show that the neurologic strains do not replicate better or spread more efficiently in endothelial cells. Also, the majority of the host inflammatory genes were modulated similarly regardless of EHV-1 genotype. Analyses of host gene expression showed that a subset of pro-inflammatory cytokines, including the CXCR3 ligands CXCL9, CXCL10, and CXCL11, as well as CCL5, IL-6 and TNF-α were consistently up-regulated in endothelial cells infected with each EHV-1 strain. The identification of specific pro-inflammatory cytokines in endothelial cells that are modulated by EHV-1 provides further insight into the factors that contribute to the immunopathology observed after infection and may also reveal new targets for disease intervention.

Trends in Social Work. Nephrology social work meets integrated care: A partnership for the road ahead.

Integrated care has brought changes to the field of nephrology social work. In turn, nephrology social work has brought innovative contributions to the field of integrated care. The new social work service delivery systems described in this article are sure to help the industry reach its goals to keep care patient-centered while maintaining quality and reducing the costs of treating end stage renal disease. Social workers are called to serve the needs of the client, the family, the community and the society at large. Nephrology social workers are right where they belong in the ESRD integrated care environment. They feel right at home.

Part 2. The promise of symptom-targeted intervention to manage depression in dialysis patients: improving mood and quality of life outcomes.

The Practice Outcome Evaluation of using Symptom Targeted Intervention (STI) to manage depressed mood in dialysis patients reviewed social worker experiences and observations using STI. The evaluation was guided by the following questions: 1. What is the feasibility of STI in nephrology social work? 2. What is nephrology social worker comfort level with clinical assessment, intervention, and tracking? 3. What is the potential efficacy of STI on reducing depression? Initial results suggest that STI enhances existing nephrology social work skills in identifying, treating, and tracking outcomes of patient issues requiring clinical intervention. Most social workers spent 1.5 hours over a six-week period using STI techniques to address symptoms of depression with a patient. This rather short period of intervention led to a reported improvement in PCS and MCS scores of 51.6% and 61.3% of patients, respectively, and improvement in CES-D scores in 72.1% of patients. While this practice outcome evaluation is limited by how social workers were selected and the small number of patients, it demonstrates options for further study of the efficacy of STI in reducing depression. The brief time invested in training holds promise for impacting nephrology social work and improving patient and dialysis clinics' outcomes.

The promise of symptom-targeted intervention to manage depression in dialysis patients.

Research with tens of thousands of dialysis patients has established a link between depression, health-related quality of life scores, survival, and hospitalizations. In fact, physical and mental functioning scores are as predictive of death and hospitalization as Kt/V and albumin. Some models for managing depression in the dialysis clinic have been developed. These models address barriers to accessing community mental health services. They also promote collaboration between the nephrology social worker and nephrologist to assurethat patients receive counseling and/or antidepressant medications when they need them. Part 1 of this article will introduce a promising new method designed for nephrology social workers to help patients manage depression. This method, known as symptom-targeted intervention (STI), can be used in brief intervals with patients while they are receiving dialysis treatments to help reduce depressive symptoms and improve quality of life. The second part of this article, which will appear in the June issue of Nephrology News & Issues, will report the outcomes of a 17-state pilot study in which more than 45 nephrology social workers used brief, focused STI methods with more than 75 patients in the dialysis clinic setting. The impact of STI on depression and quality of life in this sample will be explored as well as how those outcomes may impact hospitalizations, improve patient survival, and contain costs in a bundled reimbursement environment.

Improving psychosocial health in hemodialysis patients after a disaster.

Twenty-two social workers implemented a cognitive-behavioral intervention with 69 patients in 22 dialysis units in Louisiana to improve psychosocial health following Hurricanes Katrina and Rita. Pre- and post-intervention questionnaires measured psychosocial status domains (general health status, social functioning, burden of kidney disease, depressed mood, anxiety, and mastery). Participants rated their general health status (p < .05) and social functioning (p < .05) significantly higher after the intervention. Participants who listened to the class Managing stress through communication and problem solving and discussed it with their social worker, had significant improvement in depressed mood score (p < .05) after completing the program, compared to participants who did not discuss this material with their social worker. Sixty-five percent had scores indicating depressed mood before the program, compared with 56% following. The more positive participants' program evaluation, the higher their quality of life (lower perceived burden of kidney disease [p = .05]).

Overcoming early learning barriers in hemodialysis patients: the use of screening and educational reinforcement to improve treatment outcomes.

A dialysis team project to improve patient knowledge resulted in a significant improvement in patient understanding of health-risk behavior related to blood pressure and albumin management in a large hemodialysis clinic. This project demonstrates that brief intervention combined with a well-coordinated renal team can successfully steer the team's time and resources toward improving treatment outcomes, despite the busy feel of the day-to-day dialysis clinic. Analysis of the barriers to successfully educating the ESRD patient is performed and the full intervention is described. The nephrology social worker, the RN and an area manager of 5 outpatient dialysis clinics speak of their experience with the project. A participant (ESRD patient) describes his sense of satisfaction with care.