Linker for Activation of T-cell Family Member2 (LAT2) a Lipid Raft Adaptor Protein for AKT Signaling, Is an Early Mediator of Alkylphospholipid Anti-leukemic Activity

Lipid rafts are highly ordered membrane domains rich in cholesterol and sphingolipids that provide a scaffold for signal transduction proteins; altered raft structure has also been implicated in cancer progression. We have shown that 25 mu M 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC), an alkylphospholipid, targets high cholesterol domains in model membranes and induces apoptosis in leukemia cells but spares normal hematopoietic and epithelial cells under the same conditions. We performed a quantitative (SILAC) proteomic screening of ODPC targets in a lipid-raft-enriched fraction of leukemic cells to identify early events prior to the initiation of apoptosis. Six proteins, three with demonstrated palmitoylation sites, were reduced in abundance. One, the linker for activation of T-cell family member 2 (LAT2), is an adaptor protein associated with lipid rafts in its palmitoylated form and is specifically expressed in B lymphocytes and myeloid cells. Interestingly, LAT2 is not expressed in K562, a cell line more resistant to ODPC-induced apoptosis. There was an early loss of LAT2 in the lipid-raft-enriched fraction of NB4 cells within 3 h following treatment with 25 mu M ODPC. Subsequent degradation of LAT2 by proteasomes was observed. Twenty-five mu M ODPC inhibited AKT activation via myeloid growth factors, and LAT2 knockdown in NB4 cells by shRNA reproduced this effect. LAT2 knockdown in NB4 cells also decreased cell proliferation and increased cell sensitivity to ODPC (7.5X), perifosine (3X), and arsenic trioxide (8.5X). Taken together, these data indicate that LAT2 is an early mediator of the anti-leukemic activity of alkylphospholipids and arsenic trioxide. Thus, LAT2 may be used as a target for the design of drugs for cancer therapy. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.019661, 1898-1912, 2012.

Limitations in activities of people affected by leprosy after completing multidrug therapy: application of the SALSA scale

Objectives: To identify people affected by leprosy with impairments after completing multidrug therapy for leprosy, and to assess their limitations in conducting daily activities by applying the Screening of Activity Limitation and Safety Awareness (SALSA) scale. Methods: A cross-sectional study was performed of all residents of a medium-sized city who were treated for leprosy from 1998 to 2006. A specific questionnaire was applied to obtain general and clinical data and the SALSA scale was used to assess limitations in activities. Impairments were assessed using the 'World Health Organization leprosy disability grading system' (WHO-DG). Findings: Of the 335 people affected by leprosy treated in the period, 223 (62.1%) were located and interviewed. A total of 51.6% were female with a mean age of 54 years (SD +/- 15.72) and 67.9% had up to 6 years formal education. The borderline form predominated among interviewees (39.9%) and 54.3% suffer from associated diseases with hypertension (29.1%) and diabetes (10.3%) being the most common. Pain was reported by 54.7% of interviewees. By multiple logistic regression analysis, associations were found between limitations in activities and being female (P < 0.025), family income <= 3 minimum wages (P-value < 0.003), reports of major lesions (P-value < 0.004), pain (P-value < 0.001), associated diseases (P-value < 0.023) and the WHO-DG (P-value < 0.001). Disabilities, as identified using the WHO-DG, were less common (32%) than limitations in activities as evaluated by the SALSA scale (57.8%). Conclusion: Limitations in activities proved to be common in people affected by leprosy and were. associated with low income, being female, reported major lesions, disability, disease and pain.

Providing health care to women with tuberculosis: the family focus perspective

To analyze the relationship between the practice of family health team workers and women with tuberculosis, according to the family focus dimension. The participants were eight family health team workers from a city in the Joao Pessoa metropolitan area (Paraiba -PB). Data were collected through semi-structured interviews, and then subjected to thematic content analysis. The workers recognize the critical social condition that women with tuberculosis live in, as well as the prejudice they face. They suggest that these women require care based on the concept of comprehensiveness in health. They also highlight the importance of Directly Observed Therapy -Short Course, the existence of incentives, and the women's poor adherence to educational activities and groups. Few workers recognize the inclusion of relatives in the care of women with tuberculosis, which implies the need for discussion regarding this fact with the purpose of improving tuberculosis treatment effectiveness.

Spiritist Psychiatric Hospitals in Brazil: Integration of Conventional Psychiatric Treatment and Spiritual Complementary Therapy

In Brazil, during the XX century, dozens of Spiritist psychiatric hospitals emerged seeking to integrate conventional medical treatment with complementary spiritual therapy. This combined inpatient treatment is largely found in Brazil, where many psychiatric hospitals stem from the Spiritist movement. The present report describes the use of these spiritual practices, their operating structure, health professionals involved, modalities of care, and institutional difficulties in integrating spiritual practices with conventional treatment in six leading Brazilian Spiritist psychiatric hospitals. These hospitals combine conventional psychiatric treatment with voluntary-based spiritual approaches such as laying on of hands ("fluidotherapy"), lectures regarding spiritual and ethical issues, intercessory prayer, spirit release therapy ("disobsession") and "fraternal dialogue". The non-indoctrination and optional nature of these spiritual complementary therapies seem to increase acceptance among patients and their family members. In conclusion, the Spiritist psychiatric hospitals in Brazil have, for more than half a century, provided an integrative approach in the treatment of psychiatric disorders, associating conventional and spiritual treatments, more specifically Spiritist therapy. The lack of standardized treatment protocols and scientific studies remain a barrier to assessing the impact of this integrative approach on patients' mental health, quality of life, adherence, and perceived quality of treatment.