Action of sisal (Agave sisalana, Perrine) extract in the in vitro development of sheep and goat gastrointestinal nematodes

Active compounds from Agave sisalana with antiparasitic action against gastrointestinal nematodes (GINs) could be an alternative to diversify the range of parasite management methods in the livestock sector. The objective of this study was to evaluate the in vitro action of A. sisalana extract on the development of sheep and goat GINs. The extract, obtained from shredded sisal leaves, was utilized at various concentrations in the egg hatch test (EHT), larval development test (LDT), larval feeding inhibition test (LFIT) and adult motility test (AMT). The LC(50) and LC(95) in the EHT were 6.90 and 24.79 mg/mL, in the LDT were 0.041 and 0.067 mg/mL and in the LFIT were 0.053 and 0.24 mg/mL, respectively, showing a dose-dependent relationship. The development and feeding inhibition on L(1) were both 100% at a dose of 0.12 mg/mL. In the AMT there was 100% inhibition at 75 mg/mL after 24h of exposure. The extract of A. sisalana therefore demonstrated significant action on L(1) at 0.12 mg/mL. So, if part of the A. sisalana extract passes through the animal's gastrointestinal system, this material can have a significant effect on the parasites in the feces. This is an interesting approach because it can drastically reduce the pasture contamination as well as the infection of herds.     

The benzomorphan-based LP1 ligand is a suitable MOR/DOR agonist for chronic pain treatment

AimsPowerful analgesics relieve pain primarily through activating mu opioid receptor (MOR), but the long-term use of MOR agonists, such as morphine, is limited by the rapid development of tolerance. Recently, it has been observed that simultaneous stimulation of the delta opioid receptor (DOR) and MOR limits the incidence of tolerance induced by MOR agonists. 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-phenylpropanamide (LP1) is a centrally acting agent with antinociceptive activity comparable to morphine and is able to bind and activate MOR and DOR. The aim of this work was to evaluate and compare the induction of tolerance to antinociceptive effects from treatment with LP1 and morphine.Main methodsHere, we evaluated the pharmacological effects of LP1 administered at a dose of 4 mg/kg subcutaneously (s.c.) twice per day for 9 days to male Sprague–Dawley rats. In addition, the LP1 mechanism of action was assessed by measurement of LP1-induced [³⁵S]GTPγS binding to the MOR and DOR.Key findingsData obtained from the radiant heat tail flick test showed that LP1 maintained its antinociceptive profile until the ninth day, while tolerance to morphine (10 mg/kg s.c. twice per day) was observed on day 3. Moreover, LP1 significantly enhanced [³⁵S]GTPγS binding in the membranes of HEK293 cells expressing either the MOR or the DOR.SignificanceLP1 is a novel analgesic agent for chronic pain treatment, and its low tolerance-inducing capability may be correlated with its ability to bind both the MOR and DOR.     

A novel xylan degrading β-d-xylosidase: purification and biochemical characterization

Aspergillus ochraceus, a thermotolerant fungus isolated in Brazil from decomposing materials, produced an extracellular ??-xylosidase that was purified using DEAE-cellulose ion exchange chromatography, Sephadex G-100 and Biogel P-60 gel filtration. ??-xylosidase is a glycoprotein (39?% carbohydrate content) and has a molecular mass of 137?kDa by SDS-PAGE, with optimal temperature and pH at 70?°C and 3.0?C5.5, respectively. ??-xylosidase was stable in acidic pH (3.0?C6.0) and 70?°C for 1?h. The enzyme was activated by 5?mM MnCl₂ (28?%) and MgCl₂ (20?%) salts. The ??-xylosidase produced by A. ochraceus preferentially hydrolyzed p-nitrophenyl-??-d-xylopyranoside, exhibiting apparent K_m and V_max values of 0.66?mM and 39?U (mg protein)^?1 respectively, and to a lesser extent p-nitrophenyl-??-d-glucopyranoside. The enzyme was able to hydrolyze xylan from different sources, suggesting a novel ??-d-xylosidase that degrades xylan. HPLC analysis revealed xylans of different compositions which allowed explaining the differences in specificity observed by ??-xylosidase. TLC confirmed the capacity of the enzyme in hydrolyzing xylan and larger xylo-oligosaccharides, as xylopentaose.     

Quinolylhydrazones as novel inhibitors of Plasmodium falciparum serine protease PfSUB1

Plasmodium falciparum subtilisin-like protease 1 (PfSUB1) is a serine protease that plays key roles in the egress of the parasite from red blood cells and in preparing the released merozoites for the subsequent invasion of new erythrocytes. The development of potent and selective PfSUB1 inhibitors could pave the way to the discovery of potential antimalarial drugs endowed with an innovative mode of action and consequently able to overcome the current problems of resistance to established chemotherapies. Through the screening of a proprietary library of compounds against PfSUB1, we identified hydrazone 2 as a hit compound. Here we report a preliminary investigation of the structure-activity relationships for a class of PfSUB1 inhibitors related to our identified hit.     

1,3-Azoles from ortho-naphthoquinones: Synthesis of aryl substituted imidazoles and oxazoles and their potent activity against Mycobacterium tuberculosis

Twenty-three naphthoimidazoles and six naphthoxazoles were synthesised and evaluated against susceptible and rifampicin- and isoniazid-resistant strains of Mycobacterium tuberculosis. Among all the compounds evaluated, fourteen presented MIC values in the range of 0.78 to 6.25 μg/mL against susceptible and resistant strains of M. tuberculosis. Five structures were solved by X-ray crystallographic analysis. These substances are promising antimycobacterial prototypes.     

Selective consequences of catastrophes for growth rates in a stream-dwelling salmonid

Optimal life histories in a fluctuating environment are likely to differ from those that are optimal in a constant environment, but we have little understanding of the consequences of bounded fluctuations versus episodic massive mortality events. Catastrophic disturbances, such as floods, droughts, landslides and fires, substantially alter the population dynamics of affected populations, but little has been done to investigate how catastrophes may act as a selective agent for life-history traits. We use an individual-based model of population dynamics of the stream-dwelling salmonid marble trout (Salmo marmoratus) to investigate how trade-offs between the growth and mortality of individuals and density-dependent body growth can lead to the maintenance of a wide or narrow range of individual variation in body growth rates in environments that are constant (i.e., only demographic stochasticity), variable (i.e., environmental stochasticity), or variable with catastrophic events that cause massive mortalities (e.g., flash floods). We find that occasional episodes of massive mortality can substantially reduce persistent variability in individual growth rates. Lowering the population density reduces density dependence and allows for higher fitness of more opportunistic strategies (rapid growth and early maturation) during the recovery period.