ABSTRACT
We have previously found that in vitro traumatic injury uncouples IP3-mediated intracellular free calcium ([Ca2+]i) signaling in astrocytes (Rzigalinski et al., 1998; Floyd et al., 2001). Since Group I metabotropic glutamate receptors (mGluRs) are coupled to IP3-mediated Ca2+ signaling, we investigated their role in the in vitro strain injury of cultured astrocytes. Astrocytes grown on Silastic membranes were labeled with 3H-myo-inositol and strain (stretch)-injured. Cells injured in the presence of LiCl to prevent inositol phosphate metabolism were acid extracted and inositol phosphates (IPx) isolated using anion exchange columns. Reactive gliosis was assessed as increased glial fibrillary acidic protein immunoreactivity (GFAP-IR). Pre- but not post-injury administration of (RS)-1-aminoindan-15-decarboxylic acid (AIDA) or (S)-4-carboxy-3-hydroxyphenylglycine (S4CH3HPG), both group I mGluR antagonists, attenuated injury-induced increases in IPx. Injury increased GFAP-IR in astrocytes at 24 and 48 h post injury, which was reduced or blocked by AIDA or inhibition of phospholipase C (PLC) with U73122. These findings suggest that strain injury activates Group I mGluRs, causing aberrant IPx production and uncoupling of the PLC signaling pathway. Changes in this signaling pathway may be related to induction of reactive gliosis. Additionally, our results suggest a complex physical coupling between G protein receptor, PLC, and IP3 receptor, in support of the conformational coupling model.
Subject(s)
Astrocytes/drug effects , Astrocytes/metabolism , Gliosis/metabolism , Glycine/analogs & derivatives , Inositol Phosphates/metabolism , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Type C Phospholipases/antagonists & inhibitors , Animals , Astrocytes/cytology , Calcium/metabolism , Cells, Cultured , Excitatory Amino Acid Antagonists/pharmacology , Glial Fibrillary Acidic Protein/metabolism , Gliosis/drug therapy , Glycine/pharmacology , Indans/pharmacology , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Stress, MechanicalABSTRACT
INTRODUCTION: Spouse/partner violence is a major public health problem that affects 3 to 6 million women per year. Many studies show that the majority of health care practitioners do not detect or respond to cases of spouse/partner violence in their practice. Research suggests that there are potential barriers to reporting or detecting this problem. A barrier often cited is lack of proper education or training regarding spouse/partner violence. The objective of this study was to determine if physicians who received spouse/partner violence education at various stages of their careers were more likely to screen patients for spouse/partner violence. METHODS: A survey was developed and administered to family physicians and obstetricians/gynecologists in Virginia. The data were analyzed to determine screening practice and spouse/partner violence education among respondents. Four different educational opportunities were analyzed to determine potential determinants of screening. RESULTS: All respondents who had spouse/partner violence education were more likely to screen every patient than those who were lacking this education. Receiving lectures during residency training was found to be a significant predictor of screening every patient for spouse/partner violence among respondents. DISCUSSION: Screening every patient for exposure to spouse/partner violence is the ideal situation. This study indicates that education about spouse/partner violence has a significant impact on screening tendencies if provided during a physician's residency program.
Subject(s)
Clinical Competence , Education, Medical, Continuing , Physician's Role , Physicians/standards , Spouse Abuse/diagnosis , Spouse Abuse/prevention & control , Adult , Education, Medical, Continuing/standards , Family Practice/education , Family Practice/standards , Female , Gynecology/education , Gynecology/standards , Humans , Male , Middle Aged , Obstetrics/education , Obstetrics/standards , Quality Assurance, Health Care , Surveys and Questionnaires , United States , VirginiaABSTRACT
In our previous studies, we have shown that in vitro biaxial strain (stretch) injury of neurons in neuronal plus glial cultures increases intracellular free calcium ([Ca(2+)](i)) and decreases mitochondrial membrane potential (deltapsi(m)). The goal of this study was to determine whether strain injury, without the addition of exogenous agents, causes glutamate release, and whether NMDA receptor antagonists affect the post-strain injury rise in [Ca(2+)](i) and decrease in deltapsi(m). [Ca(2+)](i) and deltapsi(m) were measured using the fluorescent indicators fura-2 AM and rhodamine-1,2,3 (rh123). Strain injury of neuronal plus glial cultures caused an immediate 100-200 nM elevation in neuronal [Ca(2+)]i and a decline in neuronal deltapsi(m) by 15 min post-injury. Pretreatment with the NMDA receptor antagonist MK-801 (10 microM) attenuated the [Ca(2+)](i) elevation after mild, but not moderate and severe injury. MK-801 pretreatment reduced the decline in deltapsi(m) after mild and moderate, but not after severe injury. The NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid (APV; 100 microM) had effects similar to MK-801. Simultaneous measurement of [Ca(2+)](i) and deltapsi(m) demonstrated a significant correlation and a temporal relationship between [Ca(2+)](i) elevation and depression of deltapsi(m). We conclude that NMDA receptor stimulation contributes to some of the changes in [Ca(2+)](i) and deltapsi(m) after less severe strain injury. However, after more pronounced injury other mechanisms appear to be more involved.
