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G A Conder L W Jen K S Marbury S S Johnson P M Guimond E M Thomas B L Lee 《The Journal of parasitology》1990,76(2):168-170
Currently, no in vivo laboratory model is available for evaluating anthelmintics against the important ruminant helminth Haemonchus contortus. This report outlines a novel anthelmintic assay utilizing immunosuppressed (0.02% hydrocortisone in feed) jirds, Meriones unguiculatus, infected with H. contortus. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of H. contortus, treated per os on day 10 postinoculation (PI), and necropsied on day 13 PI. Each stomach was removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Stomach contents were examined using a stereomicroscope (15-45x). A variety of standard anthelmintics has been evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses (mg/kg) comparable to those required for efficacy against H. contortus in ruminants. This model provides an important new tool to assess preliminarily the activity of experimental drugs against H. contortus in vivo prior to studies in ruminants and also may provide a useful tool for studying host-parasite interactions for H. contortus. 相似文献
3.
In the anesthetized closed-chest canine model of Gram-negative endotoxemia (n = 10), we tested the hypothesis that the effect of cardiac cycle-specific intrathoracic pressure pulses delivered by a heart rate-(HR) synchronized high-frequency jet ventilator (sync HFJV) on systolic ventricular performance is dependent on the level of preload. To control for HFJV frequency, hemodynamic responses were also measured at fixed frequency within 15% of HR (async HFJV). Biventricular stroke volumes (SV) were measured by electromagnetic flow probes. Measurements were made before (baseline) and 30 min after infusion of 1 mg/kg Escherichia coli endotoxin (serotype 055:B5) and then after 2 mg/kg propranolol at both low (less than 10 mmHg) left ventricular filling pressure (LVFP) and high (greater than 10 mmHg) LVFP. Ventricular function curves, aortic pressure-flow (P-Q) relationships, and venous return (VR) curves were analyzed. We found that endotoxin did not alter VR curves but shifted the aortic P-Q curves to the left with pressure on the x-axis (P less than 0.05). Volume loading increased SV (P less than 0.01) because of a rightward shift of the VR curve. No specific differences occurred with either sync or async HFJV during endotoxin, presumably because of preserved VR and shifted aortic P-Q. The lack of cardiac cycle-specific effects of ITP appears to be due to the selective endotoxin-induced changes in peripheral vasomotor tone that counterbalance any depressed myocardial contractility. 相似文献
4.
Anonymous nuclear DNA markers in the American oyster and their implications for the heterozygote deficiency phenomenon in marine bivalves 总被引:4,自引:0,他引:4
A puzzling population-genetic phenomenon widely reported in allozyme
surveys of marine bivalves is the occurrence of heterozygote deficits
relative to Hardy-Weinberg expectations. Possible explanations for this
pattern are categorized with respect to whether the effects should be
confined to protein-level assays or are genomically pervasive and expected
to be registered in both protein- and DNA-level assays. Anonymous nuclear
DNA markers from the American oyster were employed to reexamine the
phenomenon. In assays based on the polymerase chain reaction (PCR), two
DNA-level processes were encountered that can lead to artifactual genotypic
scorings: (a) differential amplification of alleles at a target locus and
(b) amplification from multiple paralogous loci. We describe symptoms of
these complications and prescribe methods that should generally help to
ameliorate them. When artifactual scorings at two anonymous DNA loci in the
American oyster were corrected, Hardy-Weinberg deviations registered in
preliminary population assays decreased to nonsignificant values.
Implications of these findings for the heterozygote-deficit phenomenon in
marine bivalves, and for the general development and use of PCR-based
assays, are discussed.
相似文献
5.
Marta Clariano Vanda Marques João Vaz Salma Awam Marta B. Afonso Maria Jesus Perry Cecília MP Rodrigues 《化学与生物多样性》2023,20(3):e202300222
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile. 相似文献
6.
François Binet Gaëlle Mawambo Nicholas Sitaras Nicolas Tetreault Eric Lapalme Sandra Favret Agustin Cerani Dominique Leboeuf Sophie Tremblay Flavio Rezende Aimee M. Juan Andreas Stahl Jean-Sebastien Joyal Éric Milot Randal J. Kaufman Martin Guimond Timothy E. Kennedy Przemyslaw Sapieha 《Cell metabolism》2013,17(3):353-371
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7.
Water hyacinth Eichhornia crassipes is considered the most damaging aquatic weed in the world. However, few studies have quantified the impact of this weed economically and ecologically, and even fewer studies have quantified the benefits of its control. This paper focuses on water loss saving as the benefit derived from biological control of this plant between 1990 and 2013 at New Year’s Dam, Alicedale, Eastern Cape, South Africa. Estimates of water loss due to evapotranspiration from water hyacinth vary significantly; therefore, the study used three different rates, high, medium and low. A conservative raw agriculture value of R 0.26 per m3 was used to calculate the benefits derived by the water saved. The present benefit and cost values were determined using 10% and 5% discount rates. The benefit/cost ratio at the low evapotranspiration rate was less than one, implying that biological control was not economically viable but, at the higher evapotranspiration rates, the return justified the costs of biological control. However, at the marginal value product of water, the inclusion of the costs of damage to infrastructure, or the adverse effects of water hyacinth on biodiversity, would justify the use of biological control, even at the low transpiration rate. 相似文献
8.
Variant heparan sulfates synthesized in developing mouse brain differentially regulate FGF signaling
Ford-Perriss M Guimond SE Greferath U Kita M Grobe K Habuchi H Kimata K Esko JD Murphy M Turnbull JE 《Glycobiology》2002,12(11):721-727
Heparan sulfates (HSs) exert critical regulatory actions on many proteins, including growth factors, and are essential for normal development. Variations in their specific sulfation patterns are known to regulate binding and signaling of fibroblast growth factors (FGFs) via tyrosine kinase receptors (FGFRs). We previously reported differences in sulfation patterns between HS species expressed by embryonic day 10 (E10) and E12 mouse neural precursor cells. We have examined the abilities of the different HS species to support signaling of the relevant FGF-FGFR combinations expressed early during brain development. For FGF8, which only functions early (E8-E11), E10 HS showed preferential activation. The most potent signaling for FGF8 was via FGFR3c, for which E10 HS was strongly active and E12 HS had no activity. For FGF2, which functions from E10 to E13, HS from both stages showed similar activity and were more potent at activating FGFR1c than the other receptors. Thus, we find a stage-specific correlation with activation. To explore the potential mechanisms for the generation of these stage-specific HS species, we investigated the expression of the HS sulfotransferase (HSST) isozymes responsible for creating diverse sulfation motifs in HS chains. We find that there are stage-specific combinations of HSST isozymes that could underlie the synthesis of different HS species at E10 and E12. Collectively, these data lead us to propose a model in which differential expression of HSSTs results in the synthesis of variant HS species that form functional signaling complexes with FGFs and FGFRs and orchestrate proliferation and differentiation in the developing brain. 相似文献
9.
Wai Kit Chan Katherine Howe James M. Clegg Scott E. Guimond David J. Price Jeremy E. Turnbull Thomas Pratt 《PloS one》2015,10(6)
Heparan sulfate (HS) is a linear carbohydrate composed of polymerized uronate-glucosamine disaccharide units that decorates cell surface and secreted glycoproteins in the extracellular matrix. In mammals HS is subjected to differential sulfation by fifteen different heparan sulfotransferase (HST) enzymes of which Hs2st uniquely catalyzes the sulfation of the 2-O position of the uronate in HS. HS sulfation is postulated to be important for regulation of signaling pathways by facilitating the interaction of HS with signaling proteins including those of the Fibroblast Growth Factor (Fgf) family which signal through phosphorylation of extracellular signal-regulated kinases Erk1/2. In the developing mouse telencephalon Fgf2 signaling regulates proliferation and neurogenesis. Loss of Hs2st function phenocopies the thinned cerebral cortex of mutant mice in which Fgf2 or Erk1/2 function are abrogated, suggesting the hypothesis that 2-O-sulfated HS structures play a specific role in Fgf2/Erk signaling pathway in this context in vivo. This study investigated the molecular role of 2-O sulfation in Fgf2/Erk signaling in the developing telencephalic midline midway through mouse embryogenesis at E12.5. We examined the expression of Hs2st, Fgf2, and Erk1/2 activity in wild-type and Hs2st-/- mice. We found that Hs2st is expressed at high levels at the midline correlating with high levels of Erk1/2 activation and Erk1/2 activation was drastically reduced in the Hs2st-/- mutant at the rostral telencephalic midline. We also found that 2-O sulfation is specifically required for the binding of Fgf2 protein to Fgfr1, its major cell-surface receptor at the rostral telencephalic midline. We conclude that 2-O sulfated HS structures generated by Hs2st are needed to form productive signaling complexes between HS, Fgf2 and Fgfr1 that activate Erk1/2 at the midline. Overall, our data suggest the interesting possibility that differential expression of Hs2st targets the rostral telencephalic midline for high levels of Erk signaling by increasing the sensitivity of cells to an Fgf2 signal that is rather more widespread. 相似文献
10.
Jennifer MP Woo Zhuofeng Lin Mohamad Navab Casey Van Dyck Yvette Trejo-Lopez Krystal MT Woo Hongyun Li Lawrence W Castellani Xuping Wang Noriko Iikuni Ornella J Rullo Hui Wu Antonio La Cava Alan M Fogelman Aldons J Lusis Betty P Tsao 《Arthritis research & therapy》2010,12(3):R93