Protracted release of the LHRH agonist avorelin (MF 6001) from two depot formulations in dogs and men

Avorelin is a new superagonist of naturalluteinizing-hormone-releasing-hormone. Avorelin hasbeen formulated in high molecular weight polylactic glycolic acid to afford protracted andcontinuous release of the peptide from subcutaneousimplants. Two different formulations (10 and 15 mg)were tested first in dogs and then in men during aclinical phase II trial. Chemical castration wasmaintained for at least 6 months in dogs withboth formulations. A similar duration of activity(approximately 6 months) was observed in men.     

The application of robotics and mass spectrometry to the characterisation of the Drosophila melanogaster indirect flight muscle proteome

The rapid accumulation of sequence data generated by the various genome sequencingprojects and the generation of expressed sequence tag databases has resulted in the need forthe development of fast and sensitive methods for the identification and characterisation oflarge numbers of gel electrophoretically separated proteins to translate the sequence data intobiological function. To achieve this goal it has been necessary to devise new approaches toprotein analysis: matrix-assisted laser desorption and electrospray mass spectrometry havebecome important protein analytical tools which are both fast and sensitive. When combinedwith a robotic system for the in-gel digestion of electrophoretically separated proteins, itbecomes possible to rapidly identify many proteins by searching databases with MS data. Thepower of this combination of techniques is demonstrated by an analysis of the proteins presentin the myofibrillar lattice of the indirect flight muscle of Drosophila melanogaster. Theproteins were separated by SDS-PAGE and in-gel proteolysis was performed bothautomatically and manually. All 16 major proteins could quickly be identified by massspectrometry. Although most of the protein components were known to be present in theflight muscle, two new components were also identified. The combination of methodsdescribed offers a means for the rapid identification of large numbers of gel separatedproteins.     

Thalassomermis megamphis n. gen., n. sp. (Mermithidae: Nemata) from the Bathyal South Atlantic Ocean

Thalassomermis megamphis n. gen., n. sp. (Mermithidae: Nemata) was extracted from sediment collected off the coast of Brazil at a depth of approximately 1,000 m. Although the food of this new nematode is unknown, the reduction of the stoma and esophagus and presence of a trophosome indicate that it is parasitic in its juvenile stages. Thalassomermis megaraphis n. gen., n. sp. is assigned to Mermithidae because of its similarity to that family in the appearance of the cephalic sensory receptors, the long and tubular vagina, and copulatory muscles of the male extending posteriorly throughout most of the length of the tail. Thalassomermis megamphis n. gen., n. sp. differs from all other members of Mermithidae by the large, lenticular, intracuticular amphidial fovea with coiled, emergent terminal filaments as well as the small amphidial aperture situated over the center of the fovea.     

Posttetanic potentiation of human dorsiflexors

O'Leary, Deborah D., Karen Hope, and Digby G. Sale.Posttetanic potentiation of human dorsiflexors.J. Appl. Physiol. 83(6):2131-2138, 1997.Twitch contractions of the ankle dorsiflexors were evoked before and after applied 7-s tetanic stimulation at 100 Hzin 20 young adults. Torque decreased 15% during the tetanus. At 5 safter tetanus, twitch peak torque had potentiated 45%. Potentiationdeclined to 28% after 1 min, rose slightly to 33% at 2 min, anddeclined slowly with potentiation still 25% after 5 min. There waslarge intersubject variation in the amount of potentiation(5-140%) and its persistence (5 to 20 min). The muscle compoundaction potential (M wave) did not change significantly (from pretetanicvalue) at 5 s after tetanus but increased sharply (26%) at 2 min andthen subsided. Twitch half relaxation time (23%) decreasedsignificantly more than twitch rise time (13%) 5 s after tetanus andrecovered more slowly. Twitch rates of torque development (75%) andrelaxation (71%) increased similarly 5 s after tetanus and were stillelevated (~25%) at 5 min. The extent of twitch torque potentiationwas significantly inversely correlated with pretetanic twitch rise time(r = 0.69), half relaxation time (r = 0.61), andtwitch-to-tetanus ratio (r = 0.66). The data indicate that posttetanic potentiation has agreater effect on twitch half relaxation time than on time to peaktorque and is more prominent in muscles with a short twitch time courseand small twitch-to-tetanus ratio.

     

Characterization of midgut proteinase activities of white grubs: Lepidiota noxia,Lepidiota negatoria,and Antitrogus consanguineus (scarabaeidae,melolonthini)

The proteinases in the midguts of three scarab white grub species, Lepidiota noxia, L. negatoria, and Antitrogus consanguineus, were investigated to classify the proteinases present and to determine the most effective proteinase inhibitor for potential use as an insect control agent. pH activity profiles indicated the presence of serine proteinases and the absence of cysteine proteinases. This was confirmed by the lack of inhibition by specific cysteine proteinase inhibitors. Trypsin, chymotrypsin, elastase, and leucine aminopeptidase activities were detected by using specific synthetic substrates. A screen of 32 proteinase inhibitors produced 9 inhibitors of trypsin, chymotrypsin, and elastase which reduced proteolytic activity by greater than 75%. © 1995 Wiley-Liss, Inc.     

Cryptic dehalogenase and chloroamidase genes in Pseudomonas putida and the influence of environmental conditions on their expression

Mutants of two strains of Pseudomonas putida expressed two cryptic chloroamidases (C-amidase and Hamidase) and one cryptic dehalogenase (DehII). The mutants were selected on either 2-chloropropionamide (2CPA) or 2-monochloropropionate (2MCPA), developing as papillae in parental colonies growing on a metabolisable support substrate. Mutants expressing C-amidase were selected if 2CPA was utilised as either a carbon or a nitrogen source. H-amidase mutants were selected only if 2CPA was used as a nitrogen source. Growth temperature and pH affected the frequency of papillae production, although different temperatures and pHs did not affect the overall growth characteristics of the parental colonies. Decreasing growth temperature increased the frequency of 2cpa⁺ papillae formation, but decreased the frequency of 2mcpa⁺ papillae formation. Low pH (6.0) prevented the formation of 2mcpa⁺ and 2cpa⁺ papillae. However, in the case of the 2cpa⁺ papillae, decreasing the growth temperature also allowed papillae formation at pH 6.0.Abbreviations CAA Chloroacetamide - 2CPA 2-Chloropropionamide - DCA Dichloroacetic acid - HAA Halogenated alkanoic acid - 2MCPA 2-Monochloropropionic acid     

Crystallization and X-ray analysis of a single fab binding domain from protein L of Peptostreptococcus magnus

Protein L is a multi domain cell wall constituent of certain strains of Peptostreptococcus magnus which binds to the variable domain of immunoglobulin κ-light chains. A single immunoglobulin-binding domain of M_r = 9000 from this protein has been isolated and crystallized. The crystals are of space group P4₂2₁2, with cell dimensions a = b = 66.9 Å, c = 68.3 Å, and diffract to at least 2.2 Å resolution. The asymmetric unit of the crystal contains two molecules of the protein L domain, related by a noncrystallographic 2-fold axis, as revealed by a self-rotation function calculated with native diffraction data. © 1995 Wiley-Liss, Inc.     

Analogs of arachidonic acid methylated at C-7 and C-10 as inhibitors of leukotriene biosynthesis

The syntheses and biological activity of (all )-7,7-dimethyl-5-8,- 11,14-eicosatetraenoic acid, (all )-7,7,-dimethyl-5,8,11-eicosatrienoic acid, ( , -7,7-dimethyl-5,8-eicosadienoic acid, (all )-10,10-dimetyl- 5,8,11,14-eicosatetraenoic acid, (all -10,10-dimethyl-5,8,11-eicosatrienoic acid, and .-( , -15-hydroxy-7,7-dimethyl-5,8-eicosadienoic acid are described. These arachidonic acid analogs are all inhibitors of ionophore-induced SRS-A biosynthesis in rat peritoneal cells. Their mode of action may involve inhibition of phospholipase A₂ rather than Δ⁵-lipoxygenase. These compounds failed to exhibit significant activity in an model designed to detect inhibitors of antigen-induced, leukotriene-mediated bronchoconstriction is sensitized guinea pigs.