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61.
Dolle RE Michaut M Martinez-Teipel B Belanger S Graczyk TM DeHaven RN 《Bioorganic & medicinal chemistry letters》2007,17(9):2656-2660
A series of opioid peptide ligands containing modified N-terminal tyrosine (Tyr) residues was prepared and evaluated against cloned human mu, delta, and kappa opioid receptors. This work extends the recent discovery that (S)-4-carboxamidophenylalanine (Cpa) is an effective tyrosine bioisostere. Amino acids containing negatively charged functional groups in place of tyrosine's phenolic hydroxyl lacked receptor affinity, while exchange of Tyr for (S)-4-aminophenylalanine was modestly successful. Peptides containing the new amino acids, (S)-4-carboxamido-2,6-dimethylphenylalanine (Cdp) and (S)-beta-(2-aminobenzo[d]thiazol-6-yl)alanine (Aba), displayed binding (K(i)) and functional (EC(50)) profiles comparable to the parent ligands at the three receptors. Cdp represents the best performing Tyr surrogate in terms of overall activity, while Cpa and Aba show a subtle proclivity toward the delta receptor. 相似文献
62.
Giardia sp. Cysts and Infectious Cryptosporidium parvum Oocysts in the Feces of Migratory Canada Geese (Branta canadensis) 下载免费PDF全文
Thaddeus K. Graczyk Ronald Fayer James M. Trout Earl J. Lewis C. Austin Farley Irshad Sulaiman Altaf A. Lal 《Applied microbiology》1998,64(7):2736-2738
Fecal droppings of migratory Canada geese, Branta canadensis, collected from nine sites near the Chesapeake Bay (Maryland), were examined for the presence of Cryptosporidium parvum and Giardia spp. Cryptosporidium sp. oocysts were found in feces at seven of nine sites, and Giardia cysts were found at all nine sites. The oocysts from three sites were infectious for mice and molecularly identified as the zoonotic genotype of Cryptosporidium parvum. Waterfowl can disseminate infectious C. parvum oocysts in the environment. 相似文献
63.
Graczyk TK McOliver C Silbergeld EK Tamang L Roberts JD 《Applied and environmental microbiology》2007,73(12):4069-4070
Commercial Atlantic blue crabs (Callinectes sapidus) were exposed to 2.0x10(4) infectious waterborne oocysts of Cryptosporidium parvum. The study demonstrated that blue crabs can transfer C. parvum oocysts to persons involved in handling or preparing crabs and that they may contaminate other surfaces or products during storage. 相似文献
64.
Jakub Gbalski Filip Graczyk Daniel Zauski 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1120
Human has used plants to treat many civilisation diseases for thousands of years. Examples include reserpine (hypertension therapy), digoxin (myocardial diseases), vinblastine and vincristine (cancers), and opioids (palliative treatment). Plants are a rich source of natural metabolites with multiple biological activities, and the use of modern approaches and tools allowed finally for more effective bioprospecting. The new phytochemicals are hyaluronidase (Hyal) inhibitors, which could serve as anti-cancer drugs, male contraceptives, and an antidote against venoms. In turn, tyrosinase inhibitors can be used in cosmetics/pharmaceuticals as whitening agents and to treat skin pigmentation disorders. However, the activity of these inhibitors is stricte dependent on their structure and the presence of the chemical groups, e.g. carbonyl or hydroxyl. This review aims to provide comprehensive and in-depth evidence related to the anti-tyrosinase and anti-Hyal activity of phytochemicals as well as confirming their efficiency and future perspectives. 相似文献
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Alfreda Stadlin Heung Ling Choi Karl Wah Keung Tsim David Tsang 《Molecular neurobiology》1995,11(1-3):67-76
It has been reported from this laboratory that prenatal cocaine exposure results in the postnatal transient alterations of
rat striatal dopamine uptake sites examined from postnatal 0–32 wk. The present study aims to examine whether this will result
in a direct/indirect stimulation of dopamine D2 receptors. Pregnant rats were dosed orally with cocaine hydrochloride (60 mg/kg/d) from gestational day (GD) 7–21. Control
animals received an equivalent volume of water. The striatum from the offspring at postnatal 0–32 wk was examined. The radioligand
[3H]sulpiride was used for the Scatchard analysis of the D2 receptors, and the changes in the levels of mRNA for the D2 receptor were studied using Northern blot analysis. Results from the present study revealed that in the control group, there
was an age-dependent increase in the number of D2 receptor sites (B
max:44.00±2.12 to 178.00±45.10 fmol/mg protein) and in the levels of D2 mRNA from PN0–32 wk with the most rapid increase occurring during the first 4 wk of postnatal development. Prenatal cocaine
exposure resulted in only a significant decrease (p<0.001) in the number of D2 receptor sites at PN0 wk and in a 10% increase in mRNA levels at PN3, 4, and 12 wk. It was concluded from this study that
prenatal cocaine exposure resulted in minimal postnatal changes in the dopamine D2 receptor. 相似文献
68.
Costea I Mack DR Israel D Morgan K Krupoves A Seidman E Deslandres C Lambrette P Grimard G Levy E Amre DK 《PloS one》2010,5(12):e15672
Background and Objectives
Epidemiological evidence for the role of polyunsaturated fatty-acids (PUFA) in Crohn''s disease (CD) is unclear, although the key metabolite leucotriene B4 (LTB4) is closely linked to the inflammatory process. We hypothesized that inherited variation in key PUFA metabolic enzymes may modify susceptibility for CD.Methods and Principal Results
A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children ≤20 yrs diagnosed with CD and controls were recruited. 19 single nucleotide polymorphisms (SNPs) across the ALOX5 (4) CYP4F3 (5) and CYP4F2 (10) genes, were genotyped. Associations between SNPs/haplotypes and CD were examined. A total of 431 cases and 507 controls were studied. The mean (±SD) age of the cases was 12.4 (±3.3) years. Most cases were male (56.4%), had ileo-colonic disease (L3±L4, 52.7%) and inflammatory behavior (B1±p, 87%) at diagnosis. One genotyped CYP4F3 SNP (rs2683037) not in Hardy-Weinberg Equilibrium was excluded. No associations with the remaining 4 CYP4F3 SNPs with CD were evident. However haplotype analysis revealed associations with a two-marker haplotype (TG) (rs3794987 & rs1290617) (p = 0.02; permuted p = 0.08). CYP4F2 SNPs, rs3093158 (OR (recessive) = 0.56, 95% CI = 0.35–0.89; p = 0.01), rs2074902 (OR (trend) = 1.26, 95% CI = 1.00–1.60; p = 0.05), and rs2108622 (OR (recessive) = 1.6, 95% CI = 1.00–2.57; p = 0.05) were significantly associated whereas rs1272 (OR (recessive) = 0.58, 95% CI = 0.30–1.13; p = 0.10) showed suggestions for associations with CD. A haplotype comprising these 4 SNPs was significantly associated (p = 0.007, permuted p = 0.02) with CD. Associations with SNP rs3780901 in the ALOX5 gene were borderline non-significant (OR (dominant) = 1.29, 95% CI = 0.99–1.67; p = 0.056). A haplotype comprising the 4 ALOX5 SNPs (TCAA, p = 0.036) was associated with CD, but did not withstand corrections for multiple comparisons (permuted p = 0.14).Conclusions
Inherited variation in enzymes involved in the synthesis/metabolism of LTB4 may be associated with CD. These findings implicate PUFA metabolism as a important pathway in the CD pathogenesis. 相似文献69.
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