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.

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.

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.

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.

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.

Formulation and stability of naltrexone oral liquid for rapid withdrawal from methadone.

OBJECTIVE: To assess the stability of naltrexone oral liquid prepared from tablets and powder, and to evaluate its use in precipitating rapid withdrawal from methadone. DESIGN: Naltrexone 1 mg/mL oral liquids were prepared from tablets and powder and stored in the dark at 4, 25, and 70 degrees C. Similar formulations containing 5 mg/mL were stored at 70 degrees C. The 1-mg/mL formulation prepared from tablets was clinically evaluated in inducing rapid withdrawal in two drug-dependent individuals receiving methadone maintenance treatment using a naltrexone dose titration protocol. SETTING: A university pharmacy school and affiliated urban teaching hospital. MAIN OUTCOME MEASURES: Samples removed at six time points were analyzed for naltrexone concentration to assess decomposition over 90 days. An opioid withdrawal symptom checklist was used to assess the severity of the withdrawal symptoms prior to, and 30 minutes after, each dose of naltrexone. RESULTS: Decomposition of naltrexone in all formulations stored at 4 and 25 degrees C was not significant over 90 days. Both patients tolerated naltrexone 1 mg/mL oral liquid, but found it bitter and gritty. Withdrawal symptoms were experienced immediately after the first dose, but were resolving by the end of day 3 of naltrexone treatment, at which stage both patients were able to tolerate a 50-mg tablet of naltrexone as maintenance. CONCLUSIONS: Naltrexone 1 mg/mL oral liquids prepared from tablets or powder are stable when stored in the dark for 60 days at 4 degrees C and for 30 days at 25 degrees C. The formulation prepared from tablets provides flexible dosing in patients undergoing rapid withdrawal from methadone.

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.

Fluconazole infused via a nephrostomy tube: a novel and effective route of delivery.

Fluconazole is an effective oral or intravenous anti-fungal agent. It undergoes little or no metabolism with 70-80% of the drug excreted unchanged in the urine. There is no readily available information on its effectiveness in treating fungal urinary tract infections in the presence of chronic renal failure. We report a case of chronic renal failure with ureteric obstruction complicated by infection with Candida albicans that was successfully treated by the infusion of fluconazole via a nephrostomy tube. There were no complications related to the use of fluconazole.

Stability of hydrocortisone oral suspensions prepared from tablets and powder.

OBJECTIVE: To assess the stability, dosage uniformity, and clinical acceptability of hydrocortisone oral suspensions prepared from tablets and powder. DESIGN: Hydrocortisone 2.5 mg/mL oral suspensions were stored in the dark for 91 days at 5, 25, and 40 degrees C. Dosage uniformity was assessed by repeated sampling of the formulation prepared from tablets at 5 and 25 degrees C. The formulation was clinically evaluated in 2 pediatric patients. SETTING: A university pharmacy school and affiliated urban teaching hospital. PARTICIPANTS: A brother (4 y old) and sister (1 y old) with congenital adrenal hyperplasia maintained on a commercially available hydrocortisone cypionate suspension. MAIN OUTCOME MEASURES: Samples removed at 5 time points were analyzed for hydrocortisone to assess decomposition over 90 days. Dosage uniformity was evaluated by intra- and interday variability. Palatability was examined in the 2 children and urinary cortisol concentrations were measured in the boy before and 5 days after commencing the formulation prepared from tablets. RESULTS: Decomposition of hydrocortisone was not significant except in the formulation that was prepared from tablets and stored at 40 degrees C. Dosage uniformity gave coefficients of variation less than 4.5%. The formulation was well-tolerated and resulted in satisfactory urinary cortisol concentrations in the boy. CONCLUSIONS: The hydrocortisone oral suspensions supply a uniform dose and are chemically stable when stored in the dark at 5 and 25 degrees C for at least 30 days. They provide flexible and convenient dosage forms for pediatric patients.

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.

Evidence for the polymorphic oxidation of debrisoquine and proguanil in a Khmer (Cambodian) population.

The frequency distributions of the urinary metabolic ratios of debrisoquine and proguanil were measured in a population of unrelated Khmers. Out of 98 Khmer subjects studied, two were identified as poor metabolisers of debrisoquine when a metabolic ratio of 12.6 was used as the cut off point. This represents a prevalence of debrisoquine poor metabolisers of 2.1% (95% confidence interval 0.25-7.3%) which is similar to other Asian populations. Based on the distribution of the ratio of proguanil to cycloguanil excreted in urine, and using an antimode value of 10, the prevalence of poor metabolisers of proguanil in a Khmer population was estimated to be 18.4% (95% confidence interval 10.9-28.1%). The frequency of poor metabolisers of proguanil in Khmers was higher than that described for Caucasian populations, but similar to most reported results in Asian populations.

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.

Social interaction effects on restrained eating.

The eating behavior of college women scoring within either the above-average or middle ranges on the Restraint Scale was compared following brief social encounters with male students or other female students, or a no-encounter control situation. The eating of average restraint women was significantly depressed following interaction with a partner whom the subjects considered attractive. For high restraint women a nonsignificant tendency towards disinhibition of eating following interaction with an attractive other occurred. Personality ratings by partners indicated that high restraint women presented a distinct social persona to male, but not female, strangers in the brief experimental interaction.

Stability of dantrolene oral suspension prepared from capsules.

The chemical stability of an extemporaneously compounded dantrolene oral suspension (5 mg/ml dantrolene sodium) in Syrup BP containing citric acid with and without methyl hydroxybenzoate preservative was studied on storage at 5, 25 and 40 degrees C for 150 days in high density polyethylene dispensing bottles. The amount of dantrolene free acid in suspension was monitored by a stability indicating HPLC assay. There was no significant decomposition of dantrolene under all storage conditions irrespective of the presence of preservative. The results show that the formulation of dantrolene oral suspension provides a convenient and stable dosage form for use in pediatric patients and in those unable to swallow capsules. It is recommended that the formulation be stored at room temperature and in the absence of microbiological testing a shelf-life of 30 days is proposed for the product prepared with preserved syrup.