Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. ...Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-β-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 μg) and dexamethasone (25 μg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 μg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.
•Zebrafish is an important model to study inflammation.•The peltatoside isolated from Annona crassiflora Mart is a potential anti-inflammatory agent.•Researching new medicaments from natural sources is a promising field.
The recently described Mexican parasitic wasp Eurytoma sivinskii Gates and Grissell (Hymenoptera: Eurytomidae), attacks Anastrepha obliqua (Diptera: Tephritidae) pupae in the soil. The life cycle ...(egg to adult) is completed in 23.1 (± 2.1) d (mean ± S.E.) at 27 ± 2°C. Females were capable of superparasitism and laid 1-8 eggs per host (2.59 ± 1.56, mean ± S.E.), but invariably only 1 adult parasitoid emerged. Oviposition occurred primarily in the medial and posterior portions of the host. Eurytoma sivinskii is ectoparasitic since 100% of the eggs are laid within the internal cavity of the puparium and on the surface of the pupa of the host fly. In no case were first and second instars parasitized. However, 1 third-instar out of 625 fly pupae exposed, yielded a single parasitoid per host. Eight-day-old pupae yielded the most parasitoids although females laid eggs in 1-d- to 14-d-old pupae. There were no significant differences in rates of parasitism among female E. sivinskii of different ages. Adults derived from eggs laid in the posterior region developed more rapidly, but adult sex ratio and percent of emergence were the same in both posterior and medially laid eggs. Regardless of oviposition location, adults were more likely to emerge through the middle of the puparium.
We describe and illustrate for the first time the egg, larva, and pupa of Eurytoma sivinskii Gates and Grissell (Hymenoptera: Eurytomidae), a parasitoid that attacks Anastrepha obliqua (Macquart) ...pupae in Veracruz, Mexico. We obtained the immature stages of E. sivinskii using lab-reared A. ludens (Loew) pupae as hosts.
Display omitted
•Charge-neutral PAMAM-G4 dendrimer has the most favorable binding free energies for CRO, MTX, and FUS, which is result of counterbalance of electrostatics and van der Waals ...interactions.•The Rg value of PAMAM-G4 dendrimer at a neutral pH is slightly higher than the G4-PAMAM-drug complexes, except PAMAM-G4-MTX, demonstrating a mild expansion upon complexation that is in line with an encapsulation process.•MTX has good encapsulation properties at neutral and acid pH, whereas CRO and FUS exhibit better encapsulation properties at acid pH than at neutral or basic pH.•Dendrimer-drug complexes are more stable at neutral than basic and acid pH conditions, confirming the ability of G4-PAMAM to carry drugs at neutral pH and release them at acid or basic pH conditions.
Dendrimers are synthetic macromolecules with a highly-branched structure and high concentration of surface groups. Among dendrimers, Poly(amidoamine) (PAMAM) has received substantial attention as a novel drug carrier and delivery system. Depending on the generation and type of terminal groups, dendrimer toxicity could change and include cytotoxicity. Although PAMAM is water soluble, molecular modeling of the dendrimer-drug complex is considered challenging for exploring the conformational mobility of dendrimers and atomic specific interactions during the dendrimer-drug association. However, conventional protocols for predicting binding affinities have been designed for small protein molecules or protein-protein complexes that can be applied to study the dendrimer-drug association. In this work, we performed docking calculations for a set of 94 previously reported compounds on PAMAM of fourth generation (G4-PAMAM) to select six compounds, cromoglicic acid (CRO) − a mast cell stabilizer, Fusidic acid (FUS) − a bacteriostatic antibiotic, and Methotrexate (MTX) − a chemotherapy agent and immune system suppressant, which have the highest affinities for G4-PAMAM, and Lidocaine (LDC) − used to numb tissue in a specific area and for ventricular tachycardia treatment, Metoprolol (MET) − a β1 receptor blocker, and Pindolol (PIN) − a β blocker, which have the lowest affinities for the G4-PAMAM dendrimer, to perform MD simulations combined with the molecular mechanics generalized/Poisson-Boltzmann surface area MMGBSA/MMPBSA approach to investigate the interactions of generating 4 charge-neutral, charge-basic and charge-acid G4-PAMAM dendrimers. In addition, to validate these theoretical G4-PAMAM-drug complexes, the complexes were experimentally conjugated to determine their stability in aqueous solubility studies immediately and over one year. Our results show that among the different commercial drugs, both charged and neutral PAMAM have the most favorable binding free energies for CRO, MTX, and FUS, which appears to be due to a complex counterbalance of electrostatics and van der Waals interactions. These theoretical and aqueous solubility studies supported the high affinity of methotrexate for the G4-PAMAM-drug due to its carboxyl and aryl moieties that favor its accommodation by noncovalent interactions.
Abstract
Considering that their distribution is limited to altitudinal gradients along mountains that are likely to become warmer and drier, climate change poses an increased threat to temperate ...forest species from tropical regions. We studied whether the understorey shrub
L
upinus elegans
, endemic to temperate forests of west‐central
M
exico, will be able to withstand the projected temperature increase under seven climate change scenarios. Seeds were collected along an altitudinal gradient and grown in a shade‐house over 7 months before determining their temperature tolerance as electrolyte leakage. The plants from colder sites tolerated lower temperatures,
i.e
. the temperature at which half of the maximum electrolyte leakage occurred (
LT
50
), ranged from −6.4 ± 0.7 to −2.4 ± 0.3 °C. In contrast, no pattern was found for tolerance to high temperature (
LT
50
average 42.8 ± 0.3 °C). The climate change scenarios considered here consistently estimated an increase in air temperature during the present century that was higher for the maximum air temperature than for the mean or minimum. In particular, the anomaly from the normal maximum air temperature at the study region ranged from 2.8 °C by 2030 to 5.8 °C by 2090. In this respect, the inability of
L
. elegans
to adapt to increasingly higher temperatures found here, in addition to a possible inhibition of reproduction caused by warmer winters, may limit its future distribution.
Considering that their distribution is limited to altitudinal gradients along mountains that are likely to become warmer and drier, climate change poses an increased threat to temperate forest ...species from tropical regions. We studied whether the understorey shrub Lupinus elegans, endemic to temperate forests of west-central Mexico, will be able to withstand the projected temperature increase under seven climate change scenarios. Seeds were collected along an altitudinal gradient and grown in a shade-house over 7 months before determining their temperature tolerance as electrolyte leakage. The plants from colder sites tolerated lower temperatures, i.e. the temperature at which half of the maximum electrolyte leakage occurred (LT50), ranged from −6.4 ± 0.7 to −2.4 ± 0.3 °C. In contrast, no pattern was found for tolerance to high temperature (LT50 average 42.8 ± 0.3 °C). The climate change scenarios considered here consistently estimated an increase in air temperature during the present century that was higher for the maximum air temperature than for the mean or minimum. In particular, the anomaly from the normal maximum air temperature at the study region ranged from 2.8 °C by 2030 to 5.8 °C by 2090. In this respect, the inability of L. elegans to adapt to increasingly higher temperatures found here, in addition to a possible inhibition of reproduction caused by warmer winters, may limit its future distribution.
Nine known alkaloids (+)-isodomesticine (1), (+)-norisodomesticine (2), (+)-nantenine ( 3), (+)-neolitsine (4), (+)-lirioferine (5), (+)-N-methyllaurotetanine (6), (+)-norlirioferine (7), ...(+)-isoboldine (8) and (+)-reticuline (9) were isolated from young leaves of Guatteria dumetorum. Their structures were confirmed by NMR, mass and UV spectral analysis and by comparison to literature data. The growth inhibitory activity of each alkaloid was determined against the parasite Leishmania mexicana. Compounds 1-4 all showed significant activity whereby potency increased when a methylenedioxy functionality was present, especially at the 1,2-positions.
The recently described Mexican parasitic wasp Eurytoma sivinskii Gates and Grissell (Hymenoptera: Eurytomidae), attacks Anastrepha obliqua (Diptera: Tephritidae) pupae in the soil. The life cycle ...(egg to adult) is completed in 23.1(± 2.1) d (mean ± S.E.) at 27 ± 2°C. Females were capable of superparasitism and laid 1-8 eggs per host (2.59. ± 1.56, meant S.E.), but invariably only 1 adult parasitoid emerged. Oviposition occurred primarily in the medial and posterior portions of the host. Eurytoma sivinskii is ectoparasitic since 100% of the eggs are laid within the internal cavity of the puparium and on the surface of the pupa of the host fly. In no case were first and second instars parasitized. However, 1 third-instar out of 625 fly pupae exposed, yielded a single parasitoid per host. Eight-day-old pupae yielded the most parasitoids although females laid eggs in 1-d- to 14-d-old pupae. There were no significant differences in rates of parasitism among female E. sivinskii of different ages. Adults derived from eggs laid in the posterior region developed more rapidly, but adult sex ratio and percent of emergence were the same in both posterior and medially laid eggs. Regardless of oviposition location, adults were more likely to emerge through the middle of the puparium.
PDF
