Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes.

Acute mu and kappa opioids activate the ERK/MAPK phosphorylation cascade that represents an integral part of the signaling pathway of growth factors in astrocytes. By this cross-talk, opioids may impact neural development and plasticity among other basic neurobiological processes in vivo. The mu agonist, [D-ala2,mephe4,glyol5]enkephalin (DAMGO), induces a transient stimulation of ERK phosphorylation, whereas kappa agonist, U69,593, engenders sustained ERK activation.

Measuring quality of care nationwide.

This brief summarizes a study conducted by researchers at the RAND Corporation that measured the quality of health care for randomly selected adults from 12 communities across the United States. Because the researchers used 439 quality indicators to evaluate health care performance in 30 clinical areas, including diabetes mellitus, hypertension, heart disease, and related preventive care, the size and comprehensiveness of this study is particularly noteworthy. The findings reveal comparable deficits in adherence to standard care processes by both inpatient and outpatient providers within the 12 chosen communities.

Improving the delivery of care for diabetes patients with a collaborative model.

A diverse group of home care agencies participated in a national Home Health Diabetes Learning Collaborative focused on developing the skills of practitioners to implement process-of-care changes among their diabetes populations. Through face-to-face meetings, conference calls, and "listserv" communications, these agencies worked together to plan, test, and spread best practice change concepts. Early evaluation results suggest the collaborative was an effective mechanism for achieving rapid quality improvements in the home care setting.

Charting the course for home health care quality: action steps for achieving sustainable improvement: conference proceedings.

On June 30 and July 1, 2003, the first national meeting Charting the Course for Home Health Care Quality: Action Steps for Achieving Sustainable Improvement convened in New York City. The Center for Home Care Policy & Research of the Visiting Nurse Service of New York (VNSNY) hosted the meeting with support from the Robert Wood Johnson Foundation. Fifty-seven attendees from throughout the United States participated.

Walking for wellness: a collaborative program to maintain mobility in hospitalized older adults.

To prevent the functional decline in older patients that often results from restricted activity during hospitalization, the Walking for Wellness program was designed to educate patients about remaining mobile during their stay and to provide daily walking assistance from cross-trained transportation staff. Screening procedures often identified patients who could benefit from physical therapy, and the medical and therapy staff used the program to maintain gains accomplished for patients who remained hospitalized after being discharged from therapy.

Differential effects of gestational buprenorphine, naloxone, and methadone on mesolimbic mu opioid and ORL1 receptor G protein coupling.

In addition to its use for heroin addiction pharmacotherapy in general, buprenorphine has advantages in treating maternal heroin abuse. To examine the gestational effects of buprenorphine on opioid receptor signaling, the [(35)S]-GTP gamma S in situ binding induced by the mu agonist [D-Ala(2),MePhe(4),Gly(5)-ol] enkephalin (DAMGO) or the nociceptin/orphanin FQ (N/OFQ) agonist was measured in mesolimbic structures of pup brains from pregnant rats administered with buprenorphine +/- naloxone, naloxone, or methadone by osmotic minipump. Drug- and gender-based changes in DAMGO- and N/OFQ-induced GTP gamma S binding were discovered in mesolimbic regions of dam, P2, and P7 brains.

Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model.

Objective: To determine whether ascorbic acid might be of benefit for the treatment of spontaneous osteoarthritis (OA) when administered over a long period of time.

Methods: We investigated the effects of 8 months' exposure to low, medium, and high doses of ascorbic acid on the in vivo development of histologic knee OA in the male Hartley guinea pig. The low dose represented the minimum amount needed to prevent scurvy.

Kappa editing rescues autoreactive B cells destined for deletion in mice transgenic for a dual specific anti-laminin Ig.

We explored mechanisms involved in B cell self-tolerance in a double- and triple-transgenic mouse model bearing the LamH-C mu Ig H chain conventional transgene and a gene-targeted replacement for a functional V kappa 8J kappa 5 L chain gene. Whereas the H chain is known to generate anti-laminin Ig in combination with multiple L chains, the H + L Ig binds ssDNA in addition to laminin. Immune phenotyping indicates that H + L transgenic B cells are regulated by clonal deletion, receptor editing via secondary rearrangements at the nontargeted kappa allele, and anergy.

The effectiveness of a nurse-led transitional care model for patients with congestive heart failure.

This research brief reports on a study that evaluated the effectiveness of a transitional care model for patients with congestive heart failure (CHF). The model focused on improving the transition from hospital to home care by upgrading traditional discharge practices and implementing an evidence-based educational program. It used usual care nurses, rather than specialist nurses, to carry out the intervention.

Mu opioid transactivation and down-regulation of the epidermal growth factor receptor in astrocytes: implications for mitogen-activated protein kinase signaling.

Astroglia are a principal target of long-term mu antiproliferative actions. The mitogen-activated protein (MAP) kinase known as extracellular signal-regulated kinase (ERK), is a key mediator of cell proliferation. In studies on the mechanism of short- and long-term mu opioid regulation of the ERK signaling pathway, we show that the mu opioid agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), acting via the endogenous mu opioid receptor (MOR), induced sequential epidermal growth factor receptor (EGF) receptor (EGFR) Tyr phosphorylation, Ser phosphorylation, and down-regulation in immortalized rat cortical astrocytes.

Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKCdelta promotes cellular survival and chemotherapeutic resistance.

Drugs that target protein kinase C (PKC) are now being evaluated in patients with non-small cell lung cancer (NSCLC), but the role of PKC in NSCLC cells remains unclear. We report here that NSCLC cell lines show enhanced phosphorylation and altered expression of specific PKC isoforms compared with normal lung epithelial cells. PKC inhibition variably increased apoptosis, with rottlerin, a PKCdelta inhibitor, being most effective and potentiating chemotherapy-induced apoptosis, especially with trastuzumab.

Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells.

Tobacco-related diseases such as lung cancer cause over 4.2 million deaths annually, with approximately 400,000 deaths per year occurring in the US. Genotoxic effects of tobacco components have been described, but effects on signaling pathways in normal cells have not been described.

Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells.

To evaluate the role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in breast cancer cell survival and therapeutic resistance, we analyzed a panel of six breast cancer cell lines that varied in erbB2 and estrogen receptor status. Akt activity was constitutive in four cell lines and was associated with either PTEN mutations or erbB2 overexpression. Akt promoted breast cancer cell survival because a PI3K inhibitor, LY294002, or transient transfection of a dominant-negative Akt mutant inhibited Akt activity and increased apoptosis.

The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants.

Ascorbic acid has been associated with the slowing of osteoarthritis progression in guinea pig and man. The goal of this study was to evaluate transcriptional and translational regulation of cartilage matrix components by ascorbic acid. Guinea pig articular cartilage explants were grown in the presence of L-ascorbic acid (L-Asc), D-isoascorbic acid (D-Asc), sodium L-ascorbate (Na L-Asc), sodium D-isoascorbate (Na D-Asc), or ascorbyl-2-phosphate (A2P) to isolate and analyze the acidic and nutrient effects of ascorbic acid.