Thermodynamic temperature assignment to the point of inflection of the melting curve of high-temperature fixed points.

The thermodynamic temperature of the point of inflection of the melting transition of Re-C, Pt-C and Co-C eutectics has been determined to be 2747.84 ± 0.35 K, 2011.43 ± 0.18 K and 1597.39 ± 0.13 K, respectively, and the thermodynamic temperature of the freezing transition of Cu has been determined to be 1357.80 ± 0.08 K, where the ± symbol represents 95% coverage. These results are the best consensus estimates obtained from measurements made using various spectroradiometric primary thermometry techniques by nine different national metrology institutes. The good agreement between the institutes suggests that spectroradiometric thermometry techniques are sufficiently mature (at least in those institutes) to allow the direct realization of thermodynamic temperature above 1234 K (rather than the use of a temperature scale) and that metal-carbon eutectics can be used as high-temperature fixed points for thermodynamic temperature dissemination. The results directly support the developing mise en pratique for the definition of the kelvin to include direct measurement of thermodynamic temperature.

Transcriptome analysis of the synganglion from the brown dog tick, Rhipicephalus sanguineus.

Tick control strategies rely heavily on chemicals (acaricides), most of which target the central nervous system. With increasing resistance, new acaricides are urgently needed but knowledge of tick neurobiology is surprisingly limited, notably the number of neural-specific gene sequences. One thousand and eight expressed sequence tags (ESTs) were obtained from a normalized cDNA library from Rhipicephalus sanguineus synganglia. Putative functional identities were assigned to 44% whereas 34% were unknown/novel sequences. Of particular interest were ESTs encoding a chitinase-like enzyme, an acetylcholinesterase and four transmembrane receptors including two glutamate-gated chloride channel receptors, a leucokinin-like receptor and a nicotinic acetylcholine receptor alpha-subunit. This study highlights the benefits of using both neural tissues and normalized libraries in an EST-approach for identifying potential acaricide targets expressed as rare transcripts.

Implications of efavirenz for neuropsychiatry: a review.

Antiretroviral therapy has revolutionized the treatment of the human immunodeficiency virus because it has improved the clinical outcomes of patients. It is essential that these drugs cross the blood-brain barrier, since the virus is present in the central nervous system (CNS). Efavirenz passes through this barrier satisfactorily and can reduce the deleterious central effects of the human immunodeficiency virus. However, patients treated with efavirenz have been observed to experience psychiatric symptoms such as mania, depression, suicidal thoughts, psychosis, and hallucinations. The aim of this review is to describe the pharmacokinetic and pharmacodynamic properties of efavirenz and its major neuropsychiatric symptoms and the neurochemical pathways associated with these changes in the CNS. The databases Medline and Lilacs were used to search for review articles and preclinical and clinical research articles published from January 1996 to 2010. The search terms used were efavirenz, central nervous system, neuropsychiatry, neurotransmitters, adverse effects, and neurochemistry. Subject categories considered included effects on viral replication, pharmacokinetic and pharmacodynamic properties of efavirenz, and neuropsychiatric adverse effects including time course, duration, and probable mechanisms involved. The mechanisms involved in these changes include interference with cytochrome P450 enzymes, cytokines, tryptophan-2-3-dioxygenase, and brain creatine kinase.

Characterization of the vasopressin receptor on WRK-1 cells.

Specific vasopressin binding to WRK-1 rat mammary tumor cells was assessed and compared with vasopressin-induced alterations in phosphatidylinositol metabolism. Scatchard analysis revealed the presence of two binding sites: a saturable, high affinity site with a dissociation constant of 1 X 10(-9) M and an n of 2700 sites per cell, and a nonsaturable, apparent lower affinity site. The higher affinity site appeared to have V1a specificity and to correlate with vasopressin's ability to stimulate phosphatidylinositol turnover in the cells.

H(+)-dependent ATPase and K+ channel activities in the rat thyroid cell strain FRTL-5.

Using the fluorescent indicators 2',7'-bis(2-carboxyethyl)-5'-(6')-carboxyfluorescein and Oxonol V to monitor intracellular pH (pHi) and cell membrane potential respectively, we have investigated the involvement of H(+)-dependent ATPase and H(+)-dependent K+ channels in the recovery of the rat thyroid cell strain FRTL-5 from experimentally induced cytosolic acidification and membrane hyperpolarization events. Following exposure of cells to the weak acid sodium butyrate (24 mmol/l) under bicarbonate-free incubation conditions, cytoplasmic acidification was maximal after 3 min, attaining a pHi of 6.42. The subsequent recovery of pHi was unimpaired by the absence of extracellular K+, but was reduced in the presence of the Na+ antagonist amiloride (1 mmol/l), recovering by 0.11 +/- 0.003 units, compared with 0.27 +/- 0.02 units under amiloride-free conditions. In the presence of the H(+)-dependent ATPase antagonist N,N'-dicyclohexylcarbodiimide (DCC), the pHi recovery observed in amiloride-containing, K(+)-free buffer was abolished. The recovery of pHi in Na(+)- and K(+)-containing buffer was accompanied by hyperpolarization of the cell membrane, the later stage of which was reduced after blockade of K+ channels with BaCl2, implying a major contribution of transmembrane K+ movement to such events. In contrast to its attenuating effect on pHi recovery, DCC was ineffective in reducing butyrate-dependent membrane hyperpolarization, suggesting that H(+)-dependent ATPase may not be a major contributory factor to this event. However, when K+ channels were blocked by addition of BaCl2, addition of DCC abolished the butyrate-induced membrane depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Transmembrane Na+/H+ exchange in the rat thyroid cell strain FRTL-5: a possible role in insulin-like growth factor-I-mediated proliferation.

Using the fluorescent pH indicator 2'7'-bis(2-carboxyethyl)-5'-(6')-carboxyfluorescein to monitor intracellular pH (pHi), we have investigated whether transmembrane Na+/H+ exchange, as measured by experimental changes in pHi under bicarbonate-free incubation conditions, may be involved in the early growth-promoting actions of insulin-like growth factor-I (IGF-I) on the rat thyroid cell stain FRTL-5. In initial studies to characterize Na+/H+ exchange in FRTL-5 cell suspensions, the recovery of a resting pHi in acid-loaded cells was shown to be dependent upon the presence of extracellular Na+, was enhanced by the presence of the sodium ionophore monensin and was abolished by amiloride, an antagonist of Na+/H+ antiport activity. Unlike TSH, which was without effect on the pHi of FRTL-5 cells for up to 15 min after addition, IGF-I (1000 micrograms/l) caused a rapid and sustained increase within 3 min, which was abolished in medium in which Na+ had been replaced with an iso-osmotic level of choline chloride. The change in pHi in response to IGF-I was mimicked by phorbol 12-myristate 13-acetate (PMA; 100 nmol/l), an activator of thyroid cell proliferation. In the presence of TSH, exposure of cells to IGF-I or PMA had no additional effect on the cytoplasmic alkalinization induced by either of these two agonists alone. However, blockade of transmembrane Na+/H+ exchange with amiloride inhibited both the individual actions of IGF-I and PMA on [methyl-3H]thymidine incorporation, and the synergistic interaction between TSH and IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

High-affinity ivermectin binding to recombinant subunits of the Haemonchus contortus glutamate-gated chloride channel.

Glutamate-gated chloride channels (GluCls) are targets for the avermectin anthelmintics. A family of five GluCl subunit genes encoding seven subunits has been identified in Caenorhabditis elegans. We have previously shown that two orthologous genes in the parasite, Haemonchus contortus, encode three GluCl subunits (HcGluClbeta, Hcgbr-2A and Hcgbr-2B) with high amino-acid identity (>80%) to their C. elegans counterparts. We amplified and cloned a further subunit cDNA, HcGluClalpha, from H. contortus eggs. Sequence comparisons suggested that this subunit was closely related to, but not orthologous with, the C. elegans GluClalpha1, alpha2 or alpha3/GBR-2 subunits ( approximately 55% amino-acid identity). The HcGluClalpha cDNA from an ivermectin-resistant isolate contained no coding changes from the wild-type. All of the known H. contortus GluCl cDNA clones were subcloned into the expression vector pcDNA3.1 and transiently expressed in COS-7 cells. As predicted by functional data from the C. elegans orthologues, the Hcgbr-2A and HcGluClbeta subunits failed to bind [3H]ivermectin. The Hcgbr-2B and HcGluClalpha subunits bound [3H]ivermectin with high affinity; the K(d) values were 70+/-16 and 26+/-12 pM, respectively. This binding was inhibited by a variety of avermectins, though cold ivermectin was the most potent inhibitor of [3H] ivermectin binding. Picrotoxin, fipronil, glutamate and GABA all failed to compete for ivermectin binding to either subunit. The affinity of [3H]ivermectin binding to H. contortus L3 P2 larval membrane preparations was re-examined and found to be 70+/-7 pM. The properties of orthologous GluCl subunits are likely to be conserved across species, but the repertoire and relative importance of those subunits may vary.

Proinflammatory chemokine induction in keratocytes and inflammatory cell infiltration into the cornea.

PURPOSE: To determine the effect of interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha on cytokine, chemokine, and receptor expression in corneal stromal cells; the effect of corneal scrape injury on monocyte chemotactic and activating factor (MCAF) expression and monocyte-macrophage influx into the stroma; and the effect of MCAF and granulocyte colony-stimulating factor (G-CSF) microinjection on inflammatory cell infiltration into the stroma. METHODS: Gene array technology was used to evaluate changes in cytokine, chemokine, and receptor gene expression in stromal fibroblasts in response to IL-1alpha and TNFalpha. Expression of MCAF mRNA and protein was monitored with an RNase protection assay and Western blot analysis, respectively. Keratocyte MCAF protein expression in the rabbit cornea was detected with immunocytochemistry. After epithelial scrape injury, monocytes-macrophages were detected in rabbit corneas, by immunocytochemistry for monocyte-macrophage antigen. Inflammatory cell infiltration after MCAF and G-CSF microinjection into the stroma of mouse corneas was monitored with hematoxylin and eosin staining. RESULTS: IL-1alpha or TNFalpha upregulated the expression of several proinflammatory chemokines in stromal fibroblasts in culture. These included G-CSF, MCAF, neutrophil-activating peptide (ENA-78), and monocyte-derived neutrophil chemotactic factor (MDNCF). MCAF mRNA upregulation was confirmed by RNase protection assay, and MCAF protein was detected by Western blot analysis. MCAF protein was detected in keratocytes at 4 hours and 24 hours after epithelial injury, but not in keratocytes in the unwounded cornea. Corneal epithelial injury triggered the influx of monocytes-macrophages into the corneal stroma in the rabbit. Microinjection of MCAF and G-CSF into mouse cornea resulted in the influx of monocytes-macrophages and granulocytes, respectively, into the stroma. CONCLUSIONS: Proinflammatory chemokine induction in keratocytes is mediated by IL-1alpha and TNFalpha. The proinflammatory chemokines produced by the keratocytes probably trigger the influx of inflammatory cells into the stroma after epithelial injury associated with corneal surgery, contact lenses, or trauma.

Left hemispheric overactivation in schizophrenia: relationship to clockwise circling.

Schizophrenic patients, nonschizophrenic patients, and nonpsychiatric controls were compared in their demonstration of clockwise circling (CC), and in lateral eye movement responses to verbal and spatial questions. Only schizophrenic subjects who did not evidence CC showed inappropriate left hemisphere arousal to spatial stimuli. A tendency was noted for CC to occur more frequently among paranoid than nonparanoid schizophrenics. The results, taken together with other recent findings, suggest that the absence of CC may correlate with a more severe form of schizophrenia, and one more likely to be characterized by overarousal of the left cerebral hemisphere.

Stability of an extemporaneously compounded levothyroxine sodium oral liquid.

The stability of levothyroxine sodium in oral liquid dosage forms compounded from commercially available tablets was studied. Levothyroxine sodium oral liquids (25 micrograms/mL) were prepared from tablets and from powder with and without methylparaben preservative and transferred to amber, high-density polyethylene bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90, samples were taken from each bottle and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. There was significant degradation of levothyroxine sodium in all the formulations. However, the tablet-based formulation without preservative stored at 4 degrees C retained at least 90% of its initial concentration for eight days after compounding. Degradation occurred faster in the tablet-based formulation with preservative. None of the formulations retained > or = 90% initial potency by day 14. An extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL compounded from crushed tablets was stable for eight days when stored in amber bottles at 4 degrees C.

Adverse reactions associated with nefopam.

AIM: To review postmarketing experience of adverse reactions associated with nefopam. METHODS: Spontaneous reports of adverse reactions associated with nefopam over a 12 year period received by the New Zealand Centre for Adverse Reactions Monitoring were reviewed. RESULTS: There were 70 reports of adverse reactions thought to be causally related to nefopam, most of which appear to be predictable extensions of the pharmacological effect of nefopam, and included confusion, hallucinations, convulsions, dizziness, headache, sweating, urinary retention, nausea, vomiting, tachycardia and palpitations. The first report of angina is described. Convulsions occurred in a stable epileptic in whom nefopam was contraindicated, and in another where the seizure threshold may have been lowered by a concomitant tricyclic antidepressant. CONCLUSIONS: Nefopam can cause unpleasant adverse effects and there are important cautions and contraindications with this analgesic. A clearer presentation of its basic pharmacology in the datasheet should help to ensure appropriate use.

A survey of allopurinol dosage prescribing.

AIM: To evaluate the appropriateness of allopurinol dosage according to renal function in patients at Dunedin and Wakari hospitals. METHOD: A prospective survey of all patients receiving allopurinol therapy at Dunedin and Wakari hospitals during a four week period in January/February 1994 was performed. Data were collected from medication charts, patient notes and laboratory records. Dosage prescribed was compared with established guidelines. RESULTS: Of 46 patients on allopurinol treatment 18 were prescribed at least 100 mg more than the recommended daily dose. Twenty-nine out of the 46 surveyed patients (median age 77 years) had mild to moderate renal impairment. CONCLUSIONS: A significant proportion of patients were receiving excessive doses. Although information regarding the allopurinol hypersensitivity syndrome and individualised allopurinol dosage is available, it is evident that many practitioners remain unaware of the recommendations.