Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala

The mu-opioid receptor (mu-OR), like most G-protein-coupled receptors, is rapidly internalized after agonist binding. Although opioid peptides induce internalization in vivo, there are no studies that demonstrate mu-OR internalization in response to natural stimuli. In this study, we used laser-scanning microscopy to demonstrate that estrogen treatment induces the translocation of mu-OR immunoreactivity (mu-ORi) from the membrane to an internal location in steroid-sensitive cell groups of the limbic system and hypothalamus. Estrogen-induced internalization was prevented by the opioid antagonist naltrexone, suggesting that translocation was largely dependent on release of endogenous agonists. Estrogen treatment also altered the pattern of mu-ORi at the bright-field light microscopic level. In the absence of stimulation, the majority of immunoreactivity is diffuse, with few definable mu-OR+ cell bodies or processes. After stimulation, the density of distinct processes filled with mu-ORi was significantly increased. We interpreted the increase in the number of mu-OR+ processes as indicating increased levels of internalization. Using this increase in the density of mu-OR+ fibers, we showed that treatment of ovariectomized rats with estradiol benzoate induced a rapid and reversible increase in the number of fibers. Significant internalization was noted within 30 min and lasted for >24 hr after estrogen treatment in the medial preoptic nucleus, the principal part of the bed nucleus, and the posterodorsal medial amygdala. Naltrexone prevented the increase of mu-OR+ processes. These data imply that estrogen treatment stimulates the release of endogenous opioids that activate mu-OR in the limbic system and hypothalamus providing a "neurochemical signature" of steroid activation of these circuits.     

External review for promotion and tenure in schools of nursing

A literature review conducted for a 1989 article on assessing the quality of life in surgical studies revealed that quality of life was more often mentioned than measured. Few authors reported the use of known, standardized scales. The objective of this study was to determine if and to what extent this situation has changed. A MEDLINE search of surgical studies published between 1989 and 1995 produced over 277 abstracts of surgical studies containing the words "quality of life." The abstracts were studied in three time periods: 1989-1990, 1991-1992 and 1993-1995. Findings indicated that the use of the term "quality of life" increased markedly over the study period, and studies using standardized measures escalated from 27.4% in 1989-1990 to 48.3% in 1993-1995. Those abstracts not stating how quality of life was assessed decreased from 48.4% in the early period to 21.7% in the last period. Of the abstracts reporting studies that used quality of life measures, 33% came from cancer studies, 21.7% from cardiovascular or respiratory studies, 14.8% from gastroenterology studies, 13.4% from nephrology studies and 6.1% from orthopedic studies. Surgical investigators selected a variety of global measures of quality of life as well as disease-specific instruments. The abstracts also revealed that surgeons are using quality-of-life assessment to monitor patients over time, to help select patients for surgery, to determine the effect of surgical treatment and for making policy decisions. Notwithstanding the limitations of this project, there is evidence in the literature that surgeons are increasingly willing to assess the impact of the surgical interventions by quality-of-life measures and are becoming more familiar with the diverse measures used to assess quality of life.     

Healing of adult male survivors of childhood sexual abuse

1. Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication. 2. This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively. 3. Thirty-one children aged 6 months to 5 years were included and received a 2 mg kg-1 single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half-lives (mean +/- s.d.) were: 7.7 +/- 1.8 h, 21.9 +/- 6.8 h, 44.7 +/- 10.2 h in the "inducer', "other' and "inhibitor' groups respectively. 4. Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3 mg l-1. The mean minimum plasma concentration for the three groups was 2.54 +/- 1.28 mg l-1 at steady state. 5. Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.     

Signal transduction in vertebrate growth cones navigating in vivo

Navigating growth cones need signal transduction machinery to amplify and transmit the effects of extracellular signals throughout the growth cone. In culture, many drugs that affect second messengers are known to modulate neurite extension (with different effects on different neurons), and gradients of calcium influx and cyclic nucleotide analogs can cause growth cones to turn. However, it is not clear which of these responses are physiologically relevant, as axons grow through much more complex environments in vivo. The "exposed brain" preparation in Xenopus embryos provides an experimentally tractable system in which it is possible to study growth, pathfinding, and target recognition of retinal growth cones in vivo, while pharmacologically manipulating their signal transduction systems. These growth cones can also be easily studied in explant culture. We describe preliminary results of parallel in vivo and in vitro experiments using an array of drugs that perturb transduction molecules. Surprisingly, calcium ionophores and cyclic nucleotide analogs have no significant effect on retinal axon growth or pathfinding. Several agents including herbimycin A, ML-7, mastoparan, and RHC80267 inhibit retinal axon growth, both in vivo and in vitro, suggesting that tyrosine kinases, myosin, heterotrimeric G-proteins, and diacylglycerol lipase are important for retinal growth cones navigating in the optic pathway.     

Definition of the Linear Region of X-Ray -Induced Cable Response

Cable response to X-rays is linear with incident fluence, provided the deposited charge in cable dielectrics is directly proportional to the X-ray flux. To estimate the level at which the linear region ends, we discuss three nonlinear processes that modify the deposited charge profile in a hypothetical cable model: field-limiting in vacuum gaps, ionization effects in air-filled gaps, and radiation-induced dielectric conductivity. The exact level at which limiting of the Norton driver in an elemental length of cable begins depends on the cable geometry and the X-ray source. Estimates of the onset of nonlinearities caused by field-limiting and by dielectric conductivity are found in terms of cable and source parameters. With air-filled gaps, the Norton driver is always nonlinear. In addition to limiting of the Norton drivers, the load response of a long cable may be limited because propagating currents are attenuated by the induced conductivity of the bulk of the dielectric.     

Spontaneous output of acetylcholine from rat diaphragm preparations declines after treatment with botulinum toxin

A gas chromatographic spectrometric assay was used to measure tissue and released acetylcholine and choline in diaphragm preparations of rats previously injected with botulinum toxin type A. Botulinum intoxication was found not to alter the acetylcholine content of rat diaphragms in vivo or in fully paralyzed muscles in vitro. This result provides direct support for the hypothesis that botulinum toxin blocks transmitter release without affecting acetylcholine synthesis. However, in diaphragm preparations in vitro, this toxin was found to inhibit not only the evoked release of acetylcholine but also the spontaneous "leakage" of acetylcholine that is measured at rest. Additional experiments were performed to characterize this action of the toxin. The magnitude of the decline in resting acetylcholine output appears to be too large to be accounted for solely by the known effect of botulinum toxin to reduce the frequency of miniature endplate potentials. The mechanism of this action of botulinum toxin remains an enigma.     

Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA

Aspirin (ASA) triggers the formation of 15-epi-lipoxins (15-epi-LXs or ATL [ASA-triggered LX]), which are potent bioactive eicosanoids that may contribute to the therapeutic impact of ASA. To elucidate the role of these new compounds in vivo, it is essential to establish quick and sensitive detection methods. To this end, we prepared an enzyme-linked immunosorbent assay specific for 15-epi-LXA4 that proved to be highly sensitive (IC50 approximately 50 pg, minimum detection approximately 3.5 pg) and stereoselective. The amounts of 15-epi-LXA4 generated by human neutrophils from peripheral blood of healthy volunteers using this enzyme-linked immunosorbent assay were in agreement with those values obtained by liquid chromatography. Formation of 15-epi-LXA4 was cell ratio-dependent during THP-1 (a monocytic leukemia cell line)-neutrophil interactions with ASA-treated cells, and 15-epi-LXA4 was not detected with either cell type alone. Generation of 15-epi-LXA4 was also examined in murine peritonitis with ASA administration. Exudates from ASA-treated mice showed increased production of 15-epi-LXA4 that was diminished by indomethacin, a blocker of ASA-dependent acetylation of prostaglandin G/H synthase. A cytochrome P450 inhibitor administered in the presence of ASA did not prevent 15-epi-LXA4 formation, which suggests that P450 does not significantly contribute to formation of 15-epi-LXA4 in this murine model. These results indicate that the new enzyme-linked immunosorbent assay is both sensitive and selective for 15-epi-LXA4 and that 15-epi-LXA4 is produced by human leukocyte-leukocyte interactions. In addition, 15-epi-LXA4 is generated by inflammatory exudates when ASA is administered during murine peritonitis and when prostaglandin G/H synthase is upregulated and acetylated. This assay should provide rapid means to investigate 15-epi-LXA4 generation in both cellular and animal models.     

A controlled trial of venlafaxine in trichotillomania: interim phase I results

Vibrio vulnificus, a particularly virulent halophilic vibrio, has been isolated from the blood and skin necrotic lesion of a hemodialyzed patient with sepsis. The patient has had exposure of the skin to seawater. Various chronic conditions including renal failure have a great risk for developing septicemia due to V vulnificus. It is necessary to inform persons with liver diseases or immunocompromising conditions of hazards associated with the consumption of undercooked seafood and seawater exposure.     

Comparative studies on mammalian Hoxc8 early enhancer sequence reveal a baleen whale-specific deletion of a cis-acting element

Variations in regulatory regions of developmental control genes have been implicated in the divergence of axial morphologies. To find potentially significant changes in cis-regulatory regions, we compared nucleotide sequences and activities of mammalian Hoxc8 early enhancers. The nucleotide sequence of the early enhancer region is extremely conserved among mammalian clades, with five previously described cis-acting elements, A-E, being invariant. However, a 4-bp deletion within element C of the Hoxc8 early enhancer sequence is observed in baleen whales. When assayed in transgenic mouse embryos, a baleen whale enhancer (unlike other mammalian enhancers) directs expression of the reporter gene to more posterior regions of the neural tube but fails to direct expression to posterior mesoderm. We suggest that regulation of Hoxc8 in baleen whales differs from other mammalian species and may be associated with variation in axial morphology.