Isolated plantar dislocation of the 1st metatarsophalangeal joint.

Plantar dislocation of the 1st metatarsophalangeal joint is an extremely rare injury. To the best of our knowledge, there are no previous reports in the literature of an isolated dislocation of this type requiring open reduction and surgical repair. In this case report, we describe the clinical and operative findings and discuss in detail our surgical technique for the successful management of this unusual injury.

Mid-infrared optical parametric amplifier based on a LGSe crystal and pumped at 1.6 µm.

We demonstrate the generation of 22.6 µJ of combined energy at 3 µm for sub-300fs pulses at a repetition rate of 1 kHz using a LGSe optical parametric amplifier (OPA). The LGSe OPA is pumped by the 140-fs 1.6 µm pulses from a 300-mW KTA optical parametric chirped pulse amplifier (OPCPA) based on an all-optical synchronization scheme. By using a highly-nonlinear fiber, the output of an erbium-doped fiber laser operating at 1560 nm is shifted to 1050 nm in order to coherently seed a Nd:YLF regenerative amplifier. The LGSe OPA is seeded using the MIR coming from the amplification of the 1.6 µm in the OPCPA.

Serial analysis of gene expression in the southern cattle tick following acaricide treatment of larvae from organophosphate resistant and susceptible strains.

Organophosphate resistant and susceptible tick larvae from laboratory strains of the southern cattle tick, Rhipicephalus (Boophilus) microplus were exposed to low doses of the organophosphate (OP) acaricide, coumaphos. Serial analysis of gene expression (SAGE) was used to analyse differential gene expression in response to OP treatment and to compare the responses of OP-treated and -untreated resistant and susceptible tick larvae. An R. microplus Gene Index was used as an EST database to identify genes which corresponded to SAGE tags whose abundance changed in response to acaricide exposure. Relative quantitative RT-PCR was used to confirm the differential expression results from the SAGE experiments. Of particular interest is a SAGE tag which corresponds to a cytochrome P450-like EST in the Gene Index which was more abundant in untreated OP resistant larvae compared to untreated OP susceptible larvae. This SAGE tag was also more abundant in OP resistant larvae treated with OP compared to OP susceptible larvae treated with OP.

The C terminus of the Ca channel alpha1B subunit mediates selective inhibition by G-protein-coupled receptors.

Inhibition of calcium channels by G-protein-coupled receptors depends on the nature of the Galpha subunit, although the Gbetagamma complex is thought to be responsible for channel inhibition. Ca currents in hypothalamic neurons and N-type calcium channels expressed in HEK-293 cells showed robust inhibition by G(i)/G(o)-coupled galanin receptors (GalR1), but not by Gq-coupled galanin receptors (GalR2). However, deletions in the C terminus of alpha(1B-1) produced Ca channels that were inhibited after activation of both GalR1 and GalR2. Inhibition of protein kinase C (PKC) also revealed Ca current modulation by GalR2. Imaging studies using green fluorescent protein fusions of the C terminus of alpha(1B) demonstrated that activation of the GalR2 receptor caused translocation of the C terminus of alpha(1B-1) to the membrane and co-localization with Galphaq and PKC. Similar translocation was not seen with a C-terminal truncated splice variant, alpha(1B-2). Immunoprecipitation experiments demonstrated that Galphaq interacts directly with the C terminus of the alpha(1B) subunit. These results are consistent with a model in which local activation of PKC by channel-associated Galphaq blocks modulation of the channel by Gbetagamma released by Gq-coupled receptors.

More mysteries of opium reveal'd: 300 years of opiates.

This year is the 300th anniversary of the publication of one of the first books written about opiates and their subjective effects. Since that time the influence of opiates in Western society has grown enormously, as has our knowledge of the mechanisms by which these drugs produce their effects. Wars have been fought over the use of opiates and the economies of several countries depend on their production. In this article, some aspects of the history and effects of opiates on the arts in particular are explored.

Ca2+ and reactive oxygen species in staurosporine-induced neuronal apoptosis.

Staurosporine (0.03-0.5 microM) induced a dose-dependent, apoptotic degeneration in cultured rat hippocampal neurons that was sensitive to 24-h pretreatments with the protein synthesis inhibitor cycloheximide (1 microM) or the cell cycle inhibitor mimosine (100 microM). To investigate the role of Ca2+ and reactive oxygen species in staurosporine-induced neuronal apoptosis, we overexpressed calbindin D28K, a Ca2+ binding protein, and Cu/ Zn superoxide dismutase, an antioxidative enzyme, in the hippocampal neurons using adenovirus-mediated gene transfer. Infection of the cultures with the recombinant adenoviruses (100 multiplicity of infection) resulted in a stable expression of the respective proteins assessed 48 h later. Overexpression of both calbindin D28K and Cu/Zn superoxide dismutase significantly reduced staurosporine neurotoxicity compared with control cultures infected with a beta-galactosidase overexpressing adenovirus. Staurosporine-induced neuronal apoptosis was also significantly reduced when the culture medium was supplemented with 10 or 30 mM K+, suggesting that Ca2+ influx via voltage-sensitive Ca2+ channels reduces this apoptotic cell death. In contrast, neither the glutamate receptor agonist NMDA (1-10 microM) nor the NMDA receptor antagonist dizocilpine (MK-801; 1 microM) was able to reduce staurosporine neurotoxicity. Cultures treated with the antioxidants U-74500A (1-10 microM) and N-acetylcysteine (100 microM) also demonstrated reduced staurosporine neurotoxicity. These results suggest a fundamental role for both Ca2+ and reactive oxygen species in staurosprine-induced neuronal apoptosis.

kappa-Opioid receptor activates an inwardly rectifying K+ channel by a G protein-linked mechanism: coexpression in Xenopus oocytes.

cRNAs encoding the kappa-opioid receptor and an inwardly rectifying, G protein-coupled, K+ channel were coinjected into Xenopus oocytes. The effects of kappa-opioid receptor agonists and antagonists on the membrane currents in these oocytes were studied using the two-electrode voltage-clamp technique. The kappa-opioid receptor agonists U69593 and dynorphin A induced a concentration-dependent inward current (EC50 of approximately 0.3 microM and approximately 30 nM, respectively) after coinjection of both cRNAs, whereas the mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (10 microM) and the delta-opioid receptor agonist [D-Pen2,5]enkephalin (1 microM) had no effect. The agonist-induced inward current was reversible upon washing out of the agonists and was inhibited in the presence of the K+ channel blocker Ba2+ (0.1 mM). The specific kappa-opioid receptor antagonist norbinaltorphimine (0.1 microM) and the nonspecific opioid receptor antagonist naloxone (1 microM) abolished the agonist-induced currents. Furthermore, the agonist-induced currents exhibited rapid desensitization in the continuous presence of the agonists or after repeated application. Preincubation of the coinjected oocytes with pertussis toxin (400 ng/ml for 3 days of 1.5 microgram/ml for 24 hr) abolished most of the agonist-induced activation of the inwardly rectifying K+ current. We therefore conclude that specific stimulation of the kappa-opioid receptor can activate the inwardly rectifying K+ channel through a pertussis toxin-sensitive G protein.

Structure and functional characterization of neuronal alpha 1E calcium channel subtypes.

We have cloned overlapping cDNAs encoding alpha 1E Ca2+ channel subunits from mouse and human brain. We observed that these alpha 1E transcripts were widely distributed in the central nervous system. We also demonstrated the existence of two variants of the human alpha 1E subunit. Comparison of the sequence of these alpha 1E subunits to those from other species suggests that at least four alternatively spliced variants of alpha 1E exist. Expression of human alpha 1E in HEK293 cells and Xenopus oocytes produced high voltage-activated Ca2+ currents that inactivated rapidly (tau approximately 20 ms at 0 mV). The size of the currents obtained were enhanced approximately 40-fold by co-expression with human neuronal alpha 2 and beta Ca2+ channel subunits. alpha 1E currents were insensitive to the drugs and toxins previously used to define other classes of voltage-activated Ca2+ channels. Thus, alpha 1E-mediated Ca2+ channels appear to be a pharmacologically distinct class of voltage-activated Ca2+ channels.

Interwoven threads: occupational therapy, feminism, and holistic health.

Occupational therapy is a predominantly female profession; 93% to 95% of occupational therapists are women. The implications and ramifications of this reality have seldom been directly addressed. In this article, beliefs about balance, activity, environment, and autonomy are explored from the perspectives of occupational therapy, feminism, holistic health, and medicine. The assertion that occupational therapy has more in common philosophically with feminism and holistic health than it does with medicine is supported. This awareness provides a new framework for examining current issues of concern to the profession, such as support for purposeful activity, existence outside the mainstream of power holders, and problems and powers inherent in being seen as a women's profession. Recommendations are made that occupational therapists commit more money and energy to encourage, facilitate, and support female leadership; develop innovative strategies for keeping members who take time out to raise families informed; support more holistic and feminist reorganization of work settings; instill awareness of these issues in our students; and address our strengths as a women's profession. All occupational therapists must also confront their own anti-women prejudice.

Potassium channel activators abolish excitotoxicity in cultured hippocampal pyramidal neurons.

When hippocampal pyramidal neurons are grown in culture they develop excitatory synaptic contacts. If these cultures are perfused with Mg2(+)-free, glycine supplemented medium the neurons exhibit fluctuations in [Ca2+]i and associated cell death ('excitotoxicity'). These phenomena involve the activation of NMDA receptors. When cultures are treated with the K(+)-channel activators cromakalim and diazoxide both the [Ca2+]i fluctuations and the neuronal death are abolished. These effects are reversed by the sulfonylurea glyburide. It thus appears that K(+)-channel activators may be a novel therapeutic intervention in epilepsy and associated disorders.

Purification and characterization of Go alpha and three types of Gi alpha after expression in Escherichia coli.

Complementary DNAs for the G protein alpha subunits Gi alpha 1, Gi alpha 2, Gi alpha 3, and Go alpha were expressed in Escherichia coli, and the four proteins were purified to homogeneity. The recombinant proteins exchange and hydrolyze guanine nucleotide, are ADP-ribosylated by pertussis toxin, and interact with beta gamma subunits. The rates of dissociation of GDP from Gi alpha 1 and Gi alpha 3 (0.03 min-1) are an order of magnitude slower than that from rGo alpha; release of GDP from Gi alpha 2 is also relatively slow (0.07 min-1). However, the values of kcat for the hydrolysis of GTP by rGo alpha and the three rGi alpha proteins are approximately the same, about 2 min-1 at 20 degrees C. The recombinant proteins restore inhibition of Ca2+ currents in pertussis toxin-treated dorsal root ganglion neurons in response to neuropeptide Y and bradykinin, indicating that the proteins can interact functionally with all necessary components of at least one signal transduction system. The two different receptors function with different arrays of G proteins to mediate their responses, since all four G proteins restored responses to bradykinin, while Gi alpha 2 was inactive with neuropeptide Y. Despite these results, high concentrations of activated Gi alpha proteins are without effect on adenylyl cyclase activity, either in the presence or absence of forskolin or Gs alpha, the G protein that activates adenylyl cyclase. These results are consistent with the hypothesis that G protein beta gamma subunits are primarily responsible for inhibition of adenylyl cyclase activity.

Excitotoxicity induced by enhanced excitatory neurotransmission in cultured hippocampal pyramidal neurons.

Cultures of rat hippocampal pyramidal neurons were used to examine the roles of excitatory synaptic transmission, NMDA receptors, and elevated [Ca2+]i in the production of excitotoxicity. In integral of 70% of the cells observed, perfusion with Mg2(+)-free, glycine-supplemented medium induced large spontaneous fluctuations or maintained plateaus of [Ca2+]i. [Ca2+]i fluctuations could be blocked by tetrodotoxin, NMDA receptor antagonists, dihydropyridines, or compounds that inhibit synaptic transmission in the hippocampus, but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. When cells were treated with Mg2(+)-free, glycine-supplemented medium and examined 24 hr later, integral of 30% of the neurons were found to have died. Cell death could be inhibited by the same agents that reduced [Ca2+]i fluctuations. These results support a role for direct excitatory synaptic transmission, as opposed to the general release of glutamate, in excitotoxicity. A major role for synaptically activated NMDA receptors, rather than kainate/quisqualate receptors, is also indicated. Neuronal death may be produced by abnormal changes in neuronal [Ca2+]i.

Modifying hypnotic suggestibility with the Carleton Skills Training program.

The Carleton Skills Training (CST) program was used to investigate (a) whether increases in hypnotic responsiveness obtained at Carleton University could be replicated at a different laboratory, (b) the influence of demand characteristics on suggestibility gains, and (c) whether initial gains are maintained over time. After two screening sessions, a replication and experimental group received the CST program, while a control group was allowed to practice hypnotic responding. All groups were then tested twice. Whereas the replication group was told that training and testing were part of the same experiment, the experimental group was told that training and testing were unrelated. Trained subjects returned after 4 months for a final session. Results indicated that (a) the CST program does increase hypnotic responsiveness, (b) suggestibility gains found in this study were relatively modest, (c) demand characteristics may influence suggestibility gains, and (d) suggestibility gains were not maintained at follow-up.

Effects of relaxation and aversive visual stimulation on dark focus accommodation.

There is evidence that sympathetic innervation induces decreases in accommodation or accommodation amplitude. If so, emotional stress that produces sympathetic activation should induce similar changes in accommodation. In two experiments, dark focus accommodation was assessed following deep relaxation and after subjects looked at gruesome slides. Results showed that stress exposure led to lower dark focus values than did relaxation. Further, the degree to which dark focus was affected depended on subjects' levels of perceived arousal, and on the degree of stressfulness represented by the slides. It was concluded that psychological stress can produce predictable changes in accommodation, changes most parsimoniously understood in terms of autonomic innervation of the ciliary body.

Prenatal ontogeny of neurons with enkephalin-like immunoreactivity in the rat central nervous system: an immunohistochemical mapping investigation.

Immunohistochemical techniques were used to describe the presence of endogenous levels of enkephalin-like immunoreactivity (ELI) in the developing central nervous system of the rat up until birth. The appearance and prenatal ontogeny of nerve cell bodies, nerve fiber pathways and varicose terminal plexuses expressing ELI were thus mapped using the indirect fluorescence immunohistochemical technique and fluorescein- and rhodamine-conjugated second antisera. ELI was first observed in beaded fibers along the midline from ventral pons to cervical spinal cord by prenatal day 15. Fluorescence could not be observed in the brains of 14 day old fetuses, although the adrenal medulla did show ELI at this stage. ELI-positive cell bodies at prenatal day 18 were found in most areas in which they have previously been described in adult rats. Many of the cells observed at prenatal day 18 were, however, not seen in untreated full term fetuses with the techniques used here. ELI-positive fibers and terminal fields begin to approach adult distributions at prenatal day 21--22. Several ELI-positive axon pathways which have not been previously reported from adult or developing brain, such as e.g. pathways in medial neocortex, in fasciculus retroflexus, in tractus mammillothalamicus, between ventral hypothalamus and globus pallidus and between ventromedial pons and the locus coeruleus area, are described. Semischematic maps are presented which outline all ELI-positive material as seen in sagittal projections of the central nervous system of 15 day, 18 day and full term fetuses. Maps of representative transverse sections of the full term brain are also included.

Development of tolerance to the prolactin-releasing action of morphine and its modulation by hypothalamic dopamine.

Exogenous and endogenous opioids are known to stimulate PRL release by the anterior pituitary. Morphine and the opioid peptides [D-Ala2, D-Leu5]enkephalin and beta-endorphin have also been shown to decrease dopamine (DA) release by nerve terminals in the median eminence. The present study examined the ability of morphine sulfate (MS) to decrease DA turnover in the median eminence and increase plasma PRL concentrations in rats made tolerant to opioids by chronic treatment with MS. In naive rats, MS (10 mg/kg, sc) caused a mean increase in serum PRL of 79 ng/ml. After treatment with increasing doses of MS for 4 days, the same dose of MS caused an increase of only 18 ng/ml, indicating that tolerance to the PRL-releasing action of MS occurred. In the same animals, tolerance to the ability of MS to slow DA turnover in the median eminence also occurred, as demonstrated by an attenuation of the action of MS to decrease median eminence DA turnover. These results are consistent with the idea that MS and endogenous opioids increase the rate of release of PRL from the adenohypophysis by slowing the release of DA from the median eminence. This, in turn, results in a decrease in the inhibitory tone exerted on pituitary lactotropic cells and, consequently, a greater rate of PRL release.