Adreno-Muscarinic Synergy of Contractile Responses From Human Hyperplastic Prostate.

PURPOSE: Adreno-muscarinic synergy, a supra-additional contractile response to simultaneous application of α-adrenoreceptor and muscarinic receptor agonists, is a feature of several lower urinary tract regions that have dual sympathetic and parasympathetic innervation. We tested the hypothesis that synergy is also a feature of prostate tissue obtained from men with benign prostatic enlargement. METHODS: Isolated tissue strips were dissected from prostate 'chips', collected after transurethral prostate resection procedures for in vitro experiments, to measure isometric tension at 36°C. RESULTS: Added separately to the superfusate, phenylephrine and carbachol generated contractions with mean pEC50 (-log10EC50) values of 5.36 and 5.58, respectively, although phenylephrine maximal responses were about six-fold greater. In the presence of carbachol, the mean phenylephrine pEC50 was significantly increased to 5.84 and maximal response increased by 28%; overall, a significant synergistic response was demonstrated. The synergistic response was reduced by muscarinic receptor antagonists, most potently by the M3-selective agent 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide), and less so by M2 and M1-selective inhibitors gallamine and pirenzepine, but with an overall profile indicating M3/M2 mediation of the synergistic response. The magnitude of the synergistic response was variable between prostate chips that provided isolated preparations suggesting regional heterogenicity, although their zonal origin could not be determined. CONCLUSION: These experiments show that adreno-muscarinic contractile synergy is a feature of human hyperplastic prostate tissue. This has implications for the use of a combination therapy of α-blockers and anti-muscarinic agent to relieve secondary symptoms associated with benign prostatic hyperplasia, at least in men who can tolerate antimuscarinics without a risk of retention.

Discovery of 5-Azaquinoxaline Derivatives as Potent and Orally Bioavailable Allosteric SHP2 Inhibitors.

SHP2 has emerged as an important target for oncology small-molecule drug discovery. As a nonreceptor tyrosine phosphatase within the MAPK pathway, it has been shown to control cell growth, differentiation, and oncogenic transformation. We used structure-based design to find a novel class of potent and orally bioavailable SHP2 inhibitors. Our efforts led to the discovery of the 5-azaquinoxaline as a new core for developing this class of compounds. Optimization of the potency and properties of this scaffold generated compound 30, that exhibited potent in vitro SHP2 inhibition and showed excellent in vivo efficacy and pharmacokinetic profile.

Mapping Teacher Informal Advice Networks as a Tool for District Administrators: A Case Study.

With few resources and little time for professional development, science education leaders need ways to efficiently disseminate effective pedagogical practices, improve instruction, and support science teachers (Shaked and Schecter, 2016). Efficient leader strategies are especially important as teachers and districts face reforms to existing standards. One potential avenue for dissemination is leveraging the informal social networks of teachers. Therefore, it is necessary to map and interpret informal teacher networks. We describe a case study involving a partnership of university researchers and a district science curriculum specialist who collected survey data to map district teacher informal advice-seeking networks. We also describe the kinds of network analysis information that science education leaders can use to make strategic decisions about the costs and benefits of efforts directed at all teachers (e.g. workshops, annual professional development time) and those directed at highly connected teachers who can become or already are informal leaders in their communities.

Narrative Review of Topiramate: Clinical Uses and Pharmacological Considerations.

Due to the diverse mechanisms of action of antiseizure drugs, there has been a rise in prescriptions of these drugs for non-epileptic pathologies. One drug that is now being used for a variety of conditions is topiramate. This is a narrative review that used PubMed, Google Scholar, MEDLINE, and ScienceDirect to review literature on the clinical and pharmacologic properties of topiramate. Topiramate is a commonly prescribed second-generation antiseizure drug. The drug works through multiple pathways to prevent seizures. In this regard, topiramate blocks sodium and calcium voltage-gated channels, inhibits glutamate receptors, enhances gamma-aminobutyric acid (GABA) receptors, and inhibits carbonic anhydrase. Topiramate is approved by the Food and Drug Administration (FDA) for epilepsy treatment and migraine prophylaxis. Topiramate in combination with phentermine is also FDA-approved for weight loss in patients with a body mass index (BMI) > 30. The current target dosing for topiramate monotherapy is 400 mg/day and 100 mg/day to treat epilepsy and migraines, respectively. Commonly reported side effects include paresthesia, confusion, fatigue, dizziness, and change in taste. More uncommon and serious adverse effects can include acute glaucoma, metabolic acidosis, nephrolithiasis, hepatotoxicity, and teratogenicity. Related to a broad side effect profile, physicians prescribing this drug should routinely monitor for side effects and/or toxicity. The present investigation reviews various anti-seizure medications before summarizing indications of topiramate, off-label uses, pharmacodynamics, pharmacokinetics, adverse effects, and drug-drug interactions.

New species and records of Heterospio (Annelida, Longosomatidae) from continental shelf, slope and abyssal depths of the Atlantic Ocean, Pacific Ocean, Indian Ocean and adjacent seas.

Nineteen species of the rare polychaete genus Heterospio are reported, 15 of which are new to science. The status of H. longissima Ehlers, 1874, the type-species, is reviewed. The specimens examined are from several locations in the North Atlantic Ocean, Gulf of Mexico, Caribbean Sea, off Br azil, the Indian Ocean, the Pacific Ocean off California, New Zealand, Australia, and the South China Sea. Deep-water samples from the western North Atlantic Ocean collected by the late Drs. H.L. Sanders and R.R. Hessler that were reported by Hartman as H. longissima were re-examined and referred to two new species, H. hartmanae n. sp. (abyssal depths, New England to Bermuda transect) and H. guiana n. sp. (bathyal depths off Suriname). Other materials from the Sanders/Hessler North Atlantic collections were also examined and referred to two additional species, H. canariensis n. sp. (deep water off Canary Islands) and H. southwardorum n. sp. (Bay of Biscay) as well as H. cf. reducta from off SW Ireland in bathyal depths. New collections from the North Atlantic region include additional materials of H. hartmanae n. sp. (deep water off the Mid-Atlantic and SE USA), H. aruba n. sp. (Caribbean Sea), H. bathyala n. sp. (deep water off SE USA), and H. dibranchiata n. sp. (deep water, Gulf of Mexico). Heterospio paulolanai n. sp. is from shelf depths off southeastern Brazil. Heterospio knoxi n. sp. is from the North Island of New Zealand, H. ehlersi n. sp. is from the Gulf of Thailand, in the South China Sea, H. bidentata n. sp. is described from deep water in the Coral Sea off eastern Australia, and H. alata n. sp. and H. brunei n. sp. are described from deep water off the Island of Borneo in the South China Sea. Heterospio africana n. sp. and H. antonbruunae n. sp. are described from off east Africa in the Mozambique Channel. New records and descriptions of H. catalinensis, H. indica, and H. peruana are presented. The 15 new species reported here nearly triple the number of previously known species of Heterospio, with 23 species now recognized. All known species are tabulated and compared.

New species and records of Caulleriella, Chaetocirratulus and Chaetozone (Annelida, Cirratulidae) from continental shelf and slope depths of the Western North Atlantic Ocean.

Seventeen species of cirratulid polychaetes, 13 new to science, are reported from continental shelf and slope depths of the western North Atlantic Ocean. The samples were collected as part of deep-water offshore reconnaissance surveys from New England to the Carolinas and long-term monitoring programs in Boston Harbor, Massachusetts Bay, and Georges Bank off Massachusetts. The new species are included in the genera Caulleriella (C. cryptica n. sp.), Chaetocirratulus (C. hessleri n. sp., C. sandersi n. sp., and C. tomaculus n. sp.), and Chaetozone (C. adunca n. sp., C. artaspinosa n. sp., C. brychiata n. sp., C. castouria n. sp., C. donerae n. sp., C. lophia n. sp., C. novagracilis, n. sp., C. paucispinosa n. sp. and C. profunda n. sp. In addition, Chaetozone gayheadia Hartman, 1965 is redescribed based on type-material and additional collections and transferred to the genus Chaetocirratulus. Chaetozone benthaliana McIntosh, 1985 is designated a species inquirendum because it was described from a posterior fragment that cannot be confirmed as belonging to any known cirratulid genus or species. Updated descriptions and new records are provided for Chaetozone anasima, C. diodonta, and C. hystricosa all originally described by Doner Blake (2006).

Development and Validation of an Analytical Method for Quantitation of Alpha-Pinene Oxide in Rodent Blood and Mammary Glands by GC-MS.

Alpha-pinene is a monoterpene found in the oil of coniferous trees and has a wide variety of applications. Alpha-pinene oxide (APO) is a potential reactive metabolite of alpha-pinene in rodents. The objective of this work is to validate a gas chromatography-mass spectrometry method to quantitate APO in rat and mouse blood and mammary glands in support of studies investigating the toxicity and toxicokinetic behavior of alpha-pinene. The method was validated in male Sprague Dawley rat blood over the concentration range of 5-250 ng/mL. Matrix standard curves were linear (r ≥ 0.99), and accuracy (percent relative error, %RE) was ≤±15% for standards at all levels. Intra- and interday precision (percent relative standard deviation, %RSD) and accuracy (%RE) were evaluated at three concentration levels (10, 50 and 200 ng/mL) and were ≤6.3% and ≤±5.4%, respectively. The limit of detection, determined from the SD of the limit of quantitation (5 ng/mL), was 1.06 ng/mL. Standards as high as 25,000 ng/mL could be accurately quantified after diluting to the validated range (%RE ≤ ±7.1%; %RSD ≤ 5.8%). APO was stable in rat blood for at least 70 days in frozen storage (-80°C). APO could accurately be quantified in male and female Hsd:Sprague Dawley® SD® rat and B6C3F1 mouse blood (mean %RE ≤ ±5.3%; %RSD ≤ 7.8%) and female B6C3F1 and Sprague Dawley rat mammary glands (mean %RE ≤ ±14.6%; %RSD ≤ 8.1%) using a primary matrix standard curve. These results demonstrate that the method is suitable for the analysis of APO in rodent blood and mammary glands generated from toxicokinetic and toxicology studies.

Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor.

KRASG12D, the most common oncogenic KRAS mutation, is a promising target for the treatment of solid tumors. However, when compared to KRASG12C, selective inhibition of KRASG12D presents a significant challenge due to the requirement of inhibitors to bind KRASG12D with high enough affinity to obviate the need for covalent interactions with the mutant KRAS protein. Here, we report the discovery and characterization of the first noncovalent, potent, and selective KRASG12D inhibitor, MRTX1133, which was discovered through an extensive structure-based activity improvement and shown to be efficacious in a KRASG12D mutant xenograft mouse tumor model.

New species and records of Caulleriella (Annelida, Cirratulidae) from shelf and slope depths of the Western North Atlantic Ocean.

Six species of Caulleriella (Cirratulidae), four new to science, are reported from continental shelf and slope depths of the western North Atlantic. The majority of new material was collected as part of deep-water reconnaissance and monitoring surveys along the U.S. Atlantic coast from New England to the Carolinas that were intended to understand the potential impacts of oil and gas exploration in poorly known offshore environments. Additional materials from shallow water and shelf habitats off New England and New York as part of other projects are also included. New species include: Caulleriella filiformia n. sp., C. nobska n. sp., C. pintada n. sp., and C. rodmani n. sp. In addition, new records and comments are provided for C. venefica Doner Blake, 2016 a widespread shelf species and C. sp., a potential new species represented by a few specimens from rocky nearshore New England habitats. The latter may be related to the enigmatic C. fragilis (Leidy, 1855). A review of known deep-water species of Caulleriella is provided.

New species and records of Orbiniidae (Annelida, Polychaeta) from continental shelf and slope depths of the Western North Atlantic Ocean.

Twenty-four species of Orbiniidae, 12 new to science, are reported from continental shelf and slope (deep-sea) habitats of the western North Atlantic. The majority of new material was collected during reconnaissance and monitoring surveys along the entire U.S. Atlantic coast from New England to the Carolinas that were intended to understand the potential impacts of oil and gas exploration in poorly known offshore environments. Additional materials from shallow water and shelf habitats off New England and New York as part of other projects are also included. New collections of Califia schmitti (Pettibone, 1957), Leitoscoloplos acutus (Verrill, 1873), L. fragilis (Verrill, 1873), L. obovatus Mackie, 1987, L. robustus (Verrill, 1873), Scoloplos intermedius (Hartman, 1965), Orbinia swani (Pettibone, 1957), Phylo felix (Kinberg, 1866), P. norvegicus (Sars, 1872), P. ornatus (Verrill, 1873), and Questa trifurcata (Hobson, 1970) provide additional morphological details, variability, and extended geographic and bathymetric distributions of previously known species. New species include Leitoscoloplos pustulus n. sp., Scoloplos papillatus n. sp., S. pettiboneae n. sp., S. pseudoarmiger n. sp., S. verrilli n. sp., Leodamas cuneatus n. sp., L. mucronatus n. sp., L. notoaciculatus n. sp., Phylo paraornatus n. sp., Orbiniella acsara n. sp., O. armata n. sp., and O. mimica n. sp. Juveniles of some species of Leitoscoloplos and Scoloplos were found to resemble known species of the meiofaunal orbiniid genus Schroederella Laubier, 1962. As such, S. berkeleyi Laubier, 1971 is referred to synonymy with Leitoscoloplos acutus. More importantly, the genus Schroederella was found to be pre-occupied by Schroederella Enderlein, 1921 in the Insecta, Diptera, family Helomyzidae. Gesaschroederella nomen nov. is therefore proposed as a replacement name for the polychaete homonym.

Annelids of the eastern Australian abyss collected by the 2017 RV 'Investigator' voyage.

In Australia, the deep-water (bathyal and abyssal) benthic invertebrate fauna is poorly known in comparison with that of shallow (subtidal and shelf) habitats. Benthic fauna from the deep eastern Australian margin was sampled systematically for the first time during 2017 RV 'Investigator' voyage 'Sampling the Abyss'. Box core, Brenke sledge, and beam trawl samples were collected at one-degree intervals from Tasmania, 42°S, to southern Queensland, 24°S, from 900 to 4800 m depth. Annelids collected were identified by taxonomic experts on individual families around the world. A complete list of all identified species is presented, accompanied with brief morphological diagnoses, taxonomic remarks, and colour images. A total of more than 6000 annelid specimens consisting of 50 families (47 Polychaeta, one Echiura, two Sipuncula) and 214 species were recovered. Twenty-seven species were given valid names, 45 were assigned the qualifier cf., 87 the qualifier sp., and 55 species were considered new to science. Geographical ranges of 16 morphospecies extended along the eastern Australian margin to the Great Australian Bight, South Australia; however, these ranges need to be confirmed with genetic data. This work providing critical baseline biodiversity data on an important group of benthic invertebrates from a virtually unknown region of the world's ocean will act as a springboard for future taxonomic and biogeographic studies in the area.

Trends in the Detection, Management and 30-Day Outcomes of Spontaneous Coronary Artery Dissection: A Six-Year, New Zealand Centre Experience.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important but under-recognised cause of acute coronary syndrome (ACS), particularly in younger women. We assessed trends in the detection, management and outcomes of all patients with SCAD over 6 consecutive years. METHODS: All patients with first diagnosis of SCAD at Christchurch Public Hospital, New Zealand, between January 2014 and January 2020 were included. Patient management and outcomes were determined by retrospective review of medical records. SCAD presentations were compared to total ACS presentations, obtained from a national ACS (ANZACS-QI) database. RESULTS: We identified 113 patients with angiographic diagnosis of SCAD. Median age was 54 years (88% female). The detection of SCAD increased over the period, both as a total number (Kendall's τ 0.87, p=0.015) and as a proportion of all ACS (p value for trend <0.0001). In 2019, SCAD represented 2.4% of all ACS and 18% of ACS in females aged less than 60 years. The most common presentation was non-ST elevation myocardial infarction (NSTEMI) in 72%; and, there was an increase in NSTEMI compared with STEMI over the period (p=0.023). Initial strategy of percutaneous coronary intervention (PCI) was undertaken in 12% of patients, with a significant trend towards a more conservative approach over the study period (p=0.019). The rate of 30-day major adverse cardiovascular events (MACE) was 8.8% overall, and significantly reduced over the study period to 3% in 2019 (p value for trend, 0.006). CONCLUSIONS: The detection of SCAD has increased and is a particularly important cause of ACS in younger women. This increase has been largely driven by an increasing number of NSTEMI patients diagnosed with SCAD, associated with a significant improvement in 30-day MACE.

Development and Validation of an Analytical Method for Quantitation of Alpha-pinene in Rodent Blood and Mammary Gland by Headspace GC-MS.

Alpha-pinene (AP), produced by pine trees and other plants, is the main component of turpentine and is used as a fragrance and flavor ingredient. Exposure occurs via use of personal care and household cleaning products and in the lumber industry. Despite widespread exposure, toxicity data for AP are limited. The objective of this work was to develop and validate a method to quantitate AP in rodent blood and mammary glands, in support of toxicokinetic and toxicology studies of AP. The method uses 100 µL of blood or ~100 mg of mammary gland with analysis by headspace gas chromatography-mass spectrometry. The samples are diluted with internal standard (2H3-AP, IS) and sealed in headspace vials; mammary glands are homogenized within the vial. The vials are equilibrated briefly at 60°C before a headspace sample is analyzed. The method was validated in Sprague Dawley rat blood over the range 5-500 ng/mL and mammary gland over the range 100-5000 ng/g. The method was linear (r ≥0.99), accurate (mean relative error (RE) ≤±13.4%) and precise (relative standard deviation (RSD) ≤7.1%) in both matrices. Recoveries incorporating IS were ≥88.7% at all concentrations in both tissues. Standards as high as 1500 ng/mL in blood and 20,000 ng/g in mammary gland could be analyzed using lower injection volume or extrapolating the calibration curve beyond the upper limit of quantitation (mean %RE ≤±18.7; %RSD ≤2.2). Loss of AP occurred during overnight autosampler storage as well as frozen storage in as few as 15 days, but incorporation of IS prior to storage corrected for the loss such that calculated concentrations were within 84.7-117% of day 0 concentrations following frozen storage up to ≥32 days in both matrices. Matrix evaluation was performed in Hsd:Sprague Dawley®SD® rat and B6C3F1 mouse blood and mammary glands (mean %RE ≤±9.2; %RSD ≤4.3). These data demonstrate that the method is suitable for determination of AP in rodent blood and mammary glands.

Analysis of Nicotine and Non-nicotine Tobacco Constituents in Aqueous Smoke/Aerosol Extracts by UHPLC and Ultraperformance Convergence Chromatography-Tandem Mass Spectrometry.

The non-nicotine constituents of tobacco may alter the reinforcing effects of nicotine, but the quantitative and qualitative profiles of these chemicals in tobacco products such as electronic cigarettes (e-cigarettes), cigars, and waterpipe tobacco are not well characterized. The objective of this work was to develop and validate analytical methods to utilize saline both as an extraction solvent for smoke condensates from cigarettes, little cigars, and waterpipe tobacco and aerosols from e-cigarettes and as a delivery vehicle of nicotine and non-nicotine constitents for nonclinical pharmacological studies. Ultrahigh-performance liquid chromatography was used to analyze nicotine and acetaldehyde, and a novel ultraperformance convergence chromatography-tandem mass spectrometry method was developed to analyze anabasine, anatabine, cotinine, myosmine, nornicotine, harmane, and norharmane. Linearity was confirmed for each standard curve with correlation coefficients (r) ≥ 0.99, and relative errors (RE) for the standards were ≤±10% over the calibration ranges. Method validation was performed by preparing triplicate samples in saline to mimic the composition and concentration of each analyte in the smoke or aerosol condensate and were used to determine method accuracy and precision. Relative standard deviation values were ≤15% and mean RE ≤15% for each analyte at each concentration level. Selectivity of the methods was demonstrated by the absence of peaks in blank vehicle or diluent samples. Storage stability was assessed over ∼45 days. Precision (%RSD ≤ 13) and recovery (percent of day 0 ≥ 80%) indicated that the saline formulations of all four products could be considered stable for up to ∼45 days at 4-8 °C. Therefore, the use of saline both as an extraction solvent and as a delivery vehicle adds versatility and improved performance in the study of the pharmacological effects of constituents from mainstream smoke and aerosols generated from cigarettes, little cigars, waterpipes, and e-cigarettes.

New species and records of deep-water Orbiniidae (Annelida, Polychaeta) from the Eastern Pacific continental slope, abyssal Pacific Ocean, and the South China Sea.

Eighteen species of Orbiniidae, 15 new to science, are reported from deep-sea habitats in the Pacific Ocean and the South China Sea. The collection includes specimens from continental slope and abyssal soft sediments as well as hydrothermal vent and methane seep sites. New collections of Califia calida Hartman, 1957, Naineris uncinata Hartman, 1957, and Phylo nudus (Moore, 1911) allow redescription and new distributional records of these species to be documented. Five species of Leitoscoloplos: L., cliffordi n. sp., L. gordaensis n sp., L. lunulus n. sp., L. sahlingi n. sp., and L. williamsae n. sp. are described together with a new species of Berkeleyia, B. lelievre n. sp., two new species of Scoloplos: S. californiensis n. sp. and S. sparsaciculus n. sp., and a new species of Leodamas, L. bathyalis n. sp. In addition, six new species of Orbiniella are described: O. abyssalis n. sp., O. eugeneruffi n. sp., O. grasslei n. sp., O. longilobata n. sp., O. rugosa n. sp., and O. tumida n. sp.

Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer.

Capping off an era marred by drug development failures and punctuated by waning interest and presumed intractability toward direct targeting of KRAS, new technologies and strategies are aiding in the target's resurgence. As previously reported, the tetrahydropyridopyrimidines were identified as irreversible covalent inhibitors of KRASG12C that bind in the switch-II pocket of KRAS and make a covalent bond to cysteine 12. Using structure-based drug design in conjunction with a focused in vitro absorption, distribution, metabolism and excretion screening approach, analogues were synthesized to increase the potency and reduce metabolic liabilities of this series. The discovery of the clinical development candidate MRTX849 as a potent, selective covalent inhibitor of KRASG12C is described.

RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies.

INTRODUCTION: Novel rearranged in transfection (RET)-specific tyrosine kinase inhibitors (TKIs) such as selpercatinib (LOXO-292) have shown unprecedented efficacy in tumors positive for RET fusions or mutations, notably RET fusion-positive NSCLC and RET-mutated medullary thyroid cancer (MTC). However, the mechanisms of resistance to these agents have not yet been described. METHODS: Analysis was performed of circulating tumor DNA and tissue in patients with RET fusion-positive NSCLC and RET-mutation positive MTC who developed disease progression after an initial response to selpercatinib. Acquired resistance was modeled preclinically using a CCDC6-RET fusion-positive NSCLC patient-derived xenograft. The inhibitory activity of anti-RET multikinase inhibitors and selective RET TKIs was evaluated in enzyme and cell-based assays. RESULTS: After a dramatic initial response to selpercatinib in a patient with KIF5B-RET NSCLC, analysis of circulating tumor DNA revealed emergence of RET G810R, G810S, and G810C mutations in the RET solvent front before the emergence of clinical resistance. Postmortem biopsy studies reported intratumor and intertumor heterogeneity with distinct disease subclones containing G810S, G810R, and G810C mutations in multiple disease sites indicative of convergent evolution on the G810 residue resulting in a common mechanism of resistance. Acquired mutations in RET G810 were identified in tumor tissue from a second patient with CCDC6-RET fusion-positive NSCLC and in plasma from patients with additional RET fusion-positive NSCLC and RET-mutant MTC progressing on an ongoing phase 1 and 2 trial of selpercatinib. Preclinical studies reported the presence of RET G810R mutations in a CCDC6-RET patient-derived xenograft (from a patient with NSCLC) model of acquired resistance to selpercatinib. Structural modeling predicted that these mutations sterically hinder the binding of selpercatinib, and in vitro assays confirmed loss of activity for both anti-RET multikinase inhibitors and selective RET TKIs. CONCLUSIONS: RET G810 solvent front mutations represent the first described recurrent mechanism of resistance to selective RET inhibition with selpercatinib. Development of potent inhibitor of these mutations and maintaining activity against RET gatekeeper mutations could be an effective strategy to target resistance to selective RET inhibitors.

New Species of Cirratulidae (Annelida, Polychaeta) from the Caribbean Sea.

Fifteen species in seven genera of Cirratulidae are reported from shallow-water collections in the Caribbean Sea primarily as part of the Caribbean I expedition of the research vessel Alpha Helix in 1977 and smaller separate collections from Panama and Venezuela. Thirteen species, all bitentaculates, are new to science. New species include Aphelochaeta caribbeanensis n. sp.; six species of Caulleriella: C. angusticrista n. sp., C. convexacapa n. sp., C. microbidentata n. sp., C. parapicula n. sp., C. parvinasa n. sp., and C. quadrata n. sp.; Chaetozone dossena n. sp.; three species of Kirkegaardia: K. filiformis n. sp., K. panamaensis n. sp., and K. playita n. sp.; and two species of Dodecaceria: D. alphahelixae n. sp. and D. dibranchiata n. sp. Additionally, two multitentaculate cirratulids, Cirriformia sp. from Panama and Timarete punctata (Grube, 1859) from Nicaragua are reported.

New species of Cirratulidae (Annelida, Polychaeta) from abyssal depths of the Clarion-Clipperton Fracture Zone, North Equatorial Pacific Ocean.

Abyssal polychaetes of the family Cirratulidae were collected as part of reconnaissance and benthic impact experimental surveys at Clarion-Clipperton Fracture Zone manganese nodule sites in 1984 and 1993-1994. All specimens were collected from the 4500-4900 m depth range. Twelve species of Cirratulidae were identified, of which 11 are new to science. Aphelochaeta abyssalis n. sp., A. clarionensis n. sp., A. clippertonensis n. sp., A. spargosis n. sp., A. tanyperistomia n. sp., A. wilsoni n. sp., Caulleriella bathytata n. sp., Chaetozone akaina n. sp., C. grasslei n. sp., C. truebloodi n. sp. and Tharyx hessleri n. sp. Most of these species are small deposit-feeding threadlike worms that reside in the upper 5 cm of the sediment and represent a unique assemblage of abyssal taxa.

Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison.

Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single oral administration of 10, 30, or 100 mg/kg. Sulfolane was rapidly absorbed in rats with the maximum plasma concentration, Cmax, reached at ≤1.47 h. Although Cmax increased proportionally to the dose, the half-life of elimination increased with the dose and the area under the concentration versus time curve (AUC) increased more than proportionally to the dose. In male and female rats, plasma elimination half-life increased with the dose from 1.97 to 6.33 h. Absorption of sulfolane in mice following oral administration was more rapid than in rats with Cmax reached at ≤0.55 h. In addition, mice had a shorter half-life (≤ 1.25 h) and a lower AUC than rats. In male and female mice, both Cmax and AUC increased more than proportionally to the dose. Bioavailability of sulfolane was higher in rats (81-83%) than mice (59-63%) at 10 mg/kg; at 30 and 100 mg/kg, bioavailability >100% in both species and sexes suggesting that the saturation of metabolism and clearance processes of sulfolane may begin at a single oral dose of ~30 mg/kg. There was no apparent sex difference in toxicokinetic parameters of sulfolane in rats and mice. These data demonstrate that sulfolane was well-absorbed following oral administration with high bioavailability in rats and mice with some species differences, but no sex difference.