Measuring Ucrit and endurance: equipment choice influences estimates of fish swimming performance.

This study compared the critical swimming speed (Ucrit ) and endurance performance of three Australian freshwater fish species in different swim-test apparatus. Estimates of Ucrit measured in a large recirculating flume were greater for all species compared with estimates from a smaller model of the same recirculating flume. Large differences were also observed for estimates of endurance swimming performance between these recirculating flumes and a free-surface swim tunnel. Differences in estimates of performance may be attributable to variation in flow conditions within different types of swim chambers. Variation in estimates of swimming performance between different types of flumes complicates the application of laboratory-based measures to the design of fish passage infrastructure.

The dual impact of ecology and management on social incentives in marine common-pool resource systems.

Understanding how and when cooperative human behaviour forms in common-pool resource systems is critical to illuminating social-ecological systems and designing governance institutions that promote sustainable resource use. Before assessing the full complexity of social dynamics, it is essential to understand, concretely and mechanistically, how resource dynamics and human actions interact to create incentives and pay-offs for social behaviours. Here, we investigated how such incentives for information sharing are affected by spatial dynamics and management in a common-pool resource system. Using interviews with fishermen to inform an agent-based model, we reveal generic mechanisms through which, for a given ecological setting characterized by the spatial dynamics of the resource, the two 'human factors' of information sharing and management may heterogeneously impact various members of a group for whom theory would otherwise predict the same strategy. When users can deplete the resource, these interactions are further affected by the management approach. Finally, we discuss the implications of alternative motivations, such as equity among fishermen and consistency of the fleet's output. Our results indicate that resource spatial dynamics, form of management and level of depletion can interact to alter the sociality of people in common-pool resource systems, providing necessary insight for future study of strategic decision processes.

Currents connecting communities: nearshore community similarity and ocean circulation.

Understanding the mechanisms that create spatial heterogeneity in species distributions is fundamental to ecology. For nearshore marine systems, most species have a pelagic larval stage where dispersal is strongly influenced by patterns of ocean circulation. Concomitantly, nearshore habitats and the local environment are also influenced by ocean circulation. Because of the shared dependence on the seascape, distinguishing the relative importance of the local environment from regional patterns of dispersal for community structure remains a challenge. Here, we quantify the "oceanographic distance" and "oceanographic asymmetry" between nearshore sites using ocean circulation modeling results. These novel metrics quantify spatial separation based on realistic patterns of ocean circulation, and we explore their explanatory power for intertidal and subtidal community similarity in the Southern California Bight. We find that these metrics show significant correspondence with patterns of community similarity and that their combined explanatory power exceeds that of the thermal structure of the domain. Our approach identifies the unique influence of ocean circulation on community structure and provides evidence for oceanographically mediated dispersal limitation in nearshore marine communities.

A differential role for ceramide kinase in antigen/FcɛRI-mediated mast cell activation and function.

BACKGROUND: Mast cells are specialized secretory cells releasing multiple inflammatory mediators when activated. Activation requires antigen/IgE cross-linking of FcɛRI receptors, initiating a complex intracellular signalling cascade. Ceramide kinase (CERK) is a novel lipid kinase implicated in several inflammatory cellular signalling processes. OBJECTIVE: We sought to investigate a role for CERK in FCɛRI/IgE-mediated mast-cell activation. METHODS: The rat and human mast cell-lines RBL-2H3 and LAD-2, respectively, were stimulated via FcɛRI or with the active product of CERK [ceramide-1-phosphate (C-1P)]. Multiple end-points were measured by enzyme-linked immunosorbent assay; histamine (pre-formed early-phase mediator), prostaglandin D2 (PGD2 - rapidly metabolized early-phase mediator) and interleukin (IL) -13 (de novo transcribed late-phase mediator). RESULTS: We demonstrated that C-1P alone induced release of histamine and PGD2 and was additive to antigen-mediated activation. C-1P did not stimulate IL-13 by a statistically significant amount. Using a specific inhibitor of CERK, antigen-mediated release of histamine and PGD2 was significantly inhibited. Finally, we identified that, for histamine, CERK was downstream of spleen tyrosine kinase, phosphoinositol-3 kinases and phospholipase C, but upstream of c-jun N-terminal kinase (JNK); while for PGD2 CERK was positioned upstream of JNK, mitogen-activated protein kinase kinase and cyclooxygense. CONCLUSIONS AND CLINICAL RELEVANCE: We have identified a differential role for CERK in mast-cell activation and begun to elucidate its position in the mast cell-signalling cascade, thereby suggesting a model by which CERK may be mediating its effects. This type of study is essential for complete understanding of activation pathways that may eventually be used to identify new targets for drug discovery in inflammatory diseases.

Fluconazole therapy in a rhesus monkey (Macaca mulatta) with epidural Trichosporon beigelii in a cephalic recording cylinder.

An adult female rhesus monkey with a cephalic recording cylinder surgically implanted over a craniotomy site developed cloudy cylinder fluid and a white gelatinous plaque on the epidural capsule surface. Results of baseline hematologic, serum biochemical, and cerebrospinal fluid analysis and simian retrovirus panel were unremarkable. Aerobic culture of the cylinder fluid yielded a pure culture of Trichosporon beigelii. This organism is a ubiquitous saprophytic fungus that is a potential pathogen, especially in the immunocompromised host. Factors that could have contributed to the infection included a microenvironment in the cylinder that was favorable to fungal growth, and presence of a dural pseudocapsule of collagen and granulation tissue in the implant which could have inhibited cellular defense mechanisms. An intravenous formulation of fluconazole was selected for direct application into the recording cylinder on the basis of safety and efficacy. Fluconazole is a highly water-soluble, metabolically stable bis-triazole antifungal with excellent cerebrospinal fluid penetration and low toxicity. A 4-week course of treatment eliminated Trichosporon organisms from the cylinder. Change to oral administration of fluconazole was made at that time to allow use of cephalic cylinder antibiotics that are incompatible with fluconazole. Further treatment with fluconazole was continued orally for 3 more months to prevent fungal recrudescence. Culture of cylinder fluid was performed periodically for 6 months after resolution, and results remained negative for T. beigelii. This case is believed to be the first reported T. beigelii infection in a non-human primate. Fluconazole was effective in eliminating the infection from the cylinder and preventing its recurrence.

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration.

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.

Gas chromatographic method for solvent residues in drug raw materials.

A gas chromatographic (GC) method for screening drug raw materials, soluble in aqueous media, for volatile solvent residues has been developed. After dissolution, separate portions of the drug are each separately extracted with n-octane, toluene, and ether and injected into a chromatograph equipped with a porous polymer column and a flame ionization detector. The range of extractant polarities provides chromatograms which, taken together, are free of interfering peaks from 0 to approximately 20 min. Peaks due to solvent residues in the drug are identified by retention time with confirmation of identity by GC-MS.

Determination of azobenzene and hydrazobenzene in phenylbutazone and sulfinpyrazone products by high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of azobenzene and hydrazobenzene in phenylbutazone and sulfinpyrazone raw materials and formulations. The drug raw material or formulation is shaken with 1N NaOH and n-hexane and centrifuged. The n-hexane layer is injected into a chromatograph equipped with a 10-micron cyano-amino bonded phase column. Azobenzene and hydrazobenzene are detected at 313 and 254 nm, respectively; the sensitivities are approximately 1 and 2 ppm, respectively, in the raw materials and formulations.

Drug quality assessment methods. I. Gas-liquid chromatographic assay and identification of seven barbiturates.

A gas-liquid chromatographic (GLC) procedure has been developed for the assay and identification of amobarbital, butabarbital, heptabarbital, mephobarbital, pentobarbital, phenobarbital, and secobarbital in single component capsule, elixir, injectable, suppository, and tablet formulations. After extraction into chloroform from an acidified aqueous mixture of the product, the drug is eluted isothermally from a methylphenylsilicone GLC column at 210 or 240 degrees C and quantitated relative to thiamylal internal standard. Results were in good agreement with those obtained using pharmacopeial assay methods. The method is suitable for the rapid assessment of commercial formulations.

Routine quality evaluation of benzodiazepine drugs to USP-NF specifications.

A GLC procedure was developed for the evaluation of diazepam, chlordiazepoxide, and flurazepam formulations to USP-NF specifications for drug content, content uniformity, impurities, and identity by retention times and peak areas. The polyimide column, instrument zone temperatures, gas flows, internal standard solution, extraction solvent, and auxiliary equipment were the same for each drug. No derivatization of the samples was required. The GLC assay values (mean of 10 individual dosage units) for diazepam and flurazepam products were in good agreement with the results obtained by the pharmacopeial composite assays. With chlordiazepoxide capsules, when the levels of the two pharmacopeial impurities determined by GLC were added to the GLC assay results (mean of 10), athe aggregate values were consistent wit the drug content results found by the nonspecific USP method. The procedure can be made sensitive to impurity levels of approximately 0.01% for 2-amino-5-chlorobenzophenone and to approximately 0.2% for 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide. With the equipment used, the estimated potential outputs in lots per working day for a complete quality profile (drug content, content uniformity, purity, and identity) were seven for chlordiazepoxide if no impurity test was required, five if such a test was required, eight for diazepam, and seven for flurazepam.

Impurities in drugs V: Meprobamate.

One lot of meprobamate raw material and 28 lots of tablets were examined for impurities by TLC. All lots contained di-(2-methyl-2-propyl-3-carbamoyloxypropyl) carbonate (V) at levels that ranged between 0.1 and 1.0% of the total drug content. Nine lots also contained low levels of a second impurity (approximately 0.1%), and one of these lots contained a third impurity (approximately 0.1%), neither of which was identified. Estimates of the unidentified impurities were based on the assumption of a TLC response with furfural-hydrochloric acid spray equivalent to that of meprobamate. Compound V was identified by mass spectrometry and PMR and IR spectroscopy and by comparison of the TLC Rf value to that of a synthesized sample of V.

Impurities in drugs IV: Indomethacin.

One lot of indomethacin raw material, five lots of capsule preparations, and three lots of supporitory formulations were screened for impurities by TLC. Only the suppository products exhibited impurities above trace levels. The two main impurities were present at levels estimated at approximately 0.5 and 2%. After isolation from preparative TLC plates, they were identified by NMR, IR, and mass spectroscopy as the alpha-substituted monoglyceryl esters of 4-chlorobenzoic acid and indomethacin, respectively.

Simple GLC analysis of anticonvulsant drugs in commercial dosage forms.

A simple, specific GLC procedure is described for the analysis of one sedative and six anticonvulsant drugs in pharmaceutical dosage forms. Sample aliquots of ethotoin, glutethimide, mephenytoin, methsuximide, and phensuximide were shaken with or extracted into ethyl acetate, diluted with the internal standard (diphenyl phthalate) solution, injected into a gas chromatograph, and eluted from a methylsilicon column. Primidone and phenytoin samples (extracted as the free acid) required derivatization with N,O-bis(trimethylsilyl)acetamide prior to chromatography. The same temperature programming conditions and flow rate settings were used for all seven drugs. The GLC results agreed well with those obtained using the pharmacopeial methods.

Selective GLC determination of epinephrine, isoproterenol, and phenylephrine in pharmaceutical dosage forms.

A simple, specific GLC analytical procedure for the quantitation of epinephrine, isoproterenol, and phenylephrine in commercial tablets, powders, inhalation solutions, ophthalmic and nasal drops, and injectable preparations is presented. Samples are taken to dryness where required, the dried residue is reacted with an appropriate trimethylsilylating reagent, and the derivatives are eluted from a methyl silicone column using temperature programming. Quantitation of the flame-ionization detector signal is achieved relative to the dibenzyl succinate internal standard by an electric integrator. The results obtained by applying the method to the analysis of each of the three drugs in several simulated decomposed mixtures were in good agreement with theoretical values, even at impurity levels of up to 80% by weight. When applied to commercial formulations, the procedure was feasible for tablets, powders, and solutions at drug concentrations of 0.2% or greater. The commonly incorporated buffering and antioxidant excipients did not interfere.

The Shiers arthroplasty of the knee.

Thirty-one patients with rheumatoid arthritis were reviewed after Shiers arthroplasty of the knee joint for which the main indication was intractable pain. Seven patients had the operation done to both knees. This review was done to assess the long-term results two to seven years later. All patients were clinically and radiologically assessed, and our results showed that pain and instability recurred within eighteen months. Thus it is likely that a prosthesis which allows rotation, and in which the bearing surfaces are metal on plastic, will replace the Shiers prosthesis.