A practical guide to the management of phobias.

When a patient reports symptoms suggestive of phobia, ask questions designed to clarify thoughts and behaviors. A 4-step exposure therapy plan can also help.

A proteomic analysis of liver mitochondria during acute endotoxemia.

OBJECTIVE: Accumulating evidence indicates that mitochondrial function is impaired in vital organs during sepsis. In addition to oxidative phosphorylation, mitochondria participate in diverse cellular functions ranging from protein and lipid metabolism to programmed cell death. We analyzed liver mitochondrial protein expression patterns (i.e., proteomics) during acute endotoxemia to discover novel insights into mitochondrial responses to acute systemic inflammation. DESIGN: A normotensive endotoxemia model was employed in which altered mitochondrial morphology occurs under conditions minimizing the potentially confounding effects of tissue hypoxia and acidosis. SETTING: University medical research laboratory. SUBJECTS: Random-source, adult, male cats. INTERVENTIONS: Hemodynamic resuscitation and maintenance of acid-base balance and tissue oxygen availability were provided to preserve baseline homeostatic conditions. Treatment groups received isotonic saline vehicle (control; n = 5) or endotoxin (lipopolysaccharide, LPS, at 3.0 mg/kg intravenously; n = 5]. Liver samples were obtained 4 h posttreatment, and mitochondrial proteins were isolated and quantitatively compared using two-dimensional gel electrophoresis. Differentially expressed proteins (> 1.5-fold change relative to controls) were identified using mass spectrometry. MEASUREMENTS AND RESULTS: Among over 500 protein spots that were separated 14 were differentially expressed in mitochondria of LPS-treated animals relative to matching controls. Spectrometric analyses demonstrated increased expression of urea cycle enzymes, heat shock protein (HSP) 60 and manganese superoxide dismutase, whereas expression of HSP70, F(1)-ATPase and key enzymes regulating lipid metabolism was reduced. CONCLUSIONS: Considering the known functions of each of the proteins exhibiting altered expression, it is likely that the observed changes in liver mitochondrial protein expression are reflective of significant changes in mitochondrial function in response to endotoxemia.

Calmodulin interactions with IQ peptides from voltage-dependent calcium channels.

Calmodulin (CaM) functions as a Ca(2+) sensor for inactivation and, in some cases, facilitation of a variety of voltage-dependent Ca(2+) channels. A crucial determinant for CaM binding to these channels is the IQ motif in the COOH-terminal tail of the channel-forming subunit. The binding of CaM to IQ peptides from Lc-, P/Q-, and R-type, but not N-type, voltage-dependent Ca(2+) channels increases the Ca(2+) affinity of both lobes of CaM, producing similar N- and C-lobe Ca(2+) affinities. Ca(2+) associates with and dissociates from the N-lobe much more rapidly than the C-lobe when CaM is bound to the IQ peptides. Compared with the other IQ peptides, CaM-bound Lc-IQ has the highest Ca(2+) affinity and the most rapid rates of Ca(2+) association at both lobes, which is likely to make Ca(2+) binding to CaM, bound to this channel, less sensitive than other channels to intracellular Ca(2+) buffers. These kinetic differences in Ca(2+) binding to the lobes of CaM when bound to the different IQ motifs may explain both the ability of CaM to perform multiple functions in these channels and the differences in CaM regulation of the different voltage-dependent Ca(2+) channels.