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991.
Testosterone, administered in the form of an inclusion complex with 2-hydroxypropyl--cyclodextrin by subcutaneous injection, enters the circulation in a manner markedly similar to the natural episodic release by the testes. The effects of a regimen of once-a-day administration of complexed testosterone to adult (castrated or intact) rats and to senescent (intact) rats were investigated. Although this procedure left the castrated animals with concentrations of circulatory hormone far below physiological levels for much of the day, a significant improvement in androgen-sensitive behavior and physiology was obtained. Furthermore, the testosterone effects were more pronounced when high doses were used periodically rather than when the same total amount of testosterone was equally divided among doses. The same supplementation to intact rats intensified androgen-sensitive behavior and physiology over normal levels. In senescent rats uniform pulses of the testosterone complex also improved behavior and physiology. Specifically, spermatogenesis was stimulated and, notably, the treatment increased muscle weight without substantial enlargement of the prostate. Since the testosterone–cyclodextrin complex also can be effectively administered as a sublingual tablet, the data suggest that similar regimens may be recommended for elderly men suffering from decreases in muscle mass. 相似文献
992.
Biochemical characterisation of para-aminophenol-induced nephrotoxic lesions in the F344 rat 总被引:5,自引:0,他引:5
Kevin P. R. Gartland Frank W. Bonner John A. Timbrell Jeremy K. Nicholson 《Archives of toxicology》1989,63(2):97-106
The acute biochemical effects of the nephrotoxin p-aminophenol (PAP) were studied in detail using a combination of conventional bioanalytical and 1H-NMR spectroscopic methods. Dosing PAP (25–100 mg/kg) to male F344 rats resulted in a dose-related proximal nephropathy with consequent elevations in urinary enzymes, glucose, and urine total protein as shown by conventional methodology. 1H-NMR spectroscopy at 400 MHz of urine from PAP-treated rats also revealed a characteristic glycosuria, with concomitant amino aciduria. The increased excretion of these compounds indicates functional defects in the proximal tubule and reduced solute reabsorption efficiency. In addition, 1H-NMR urinalysis and conventional enzymatic analysis showed a dose-related lactic aciduria. Other changes detected by 1H-NMR included a dose-related reduction in the excretion of citrate (confirmed by a conventional biochemical method) and an increase in the excretion of acetate. The degree of abnormalities shown by 1H-NMR urinalysis agreed well with histopathological observations and conventional biochemical indices of nephrotoxicity. 1H-NMR urinalysis therefore serves to highlight changes in the excretion of low MW urine components not routinely studied by conventional biochemical analysis.Abbreviations ALP
alkaline phosphatase
- APAP
paracetamol
- BUN
blood urea nitrogen
- GFR
glomerular filtration rate
- GOT
glutamate oxaloacetate transaminase
- LAP
leucine aminopeptidase
- LDH
lactate dehydrogenase
- MW
molecular weight
- NAG
N-acetyl--D-glucosaminidase
- PAP
p-aminophenol
- ppm
parts per million
- TMAO
trimethylamine N-oxide
- UFR
urine flow rate 相似文献
993.
P. C. Moser 《Psychopharmacology》1989,99(1):48-53
Previous work suggests that the elevated plusmaze test of anxiety is insensitive to the anxiolytic effects of the novel anxiolytic buspirone, which shows an anxiogenic-like profile in this test. This paper examines some of the possible reasons for this and the role that buspirone's agonist activity at 5-HT1A receptors plays in this effect. A variety of 5-HT1A receptor agonists (p-aminophenylethylm-trifluromethylphenyl piperazine, (+)- and (-)-MDL 72832) showed similar activity to buspirone, as did the related compound ipsapirone. (-)-MDL 72832 was more potent than (+)-MDL 72832, in keeping with its stereoselective action at 5-HT1A receptors. The 2-adrenoceptor antagonist properties of 1-pyrimidinyl piperazine, a metabolite of buspirone, did not appear to be relevant to this action of buspirone as neither it nor idazoxan showed an anxiogenic-like profile. Neither chronic treatment with buspirone (1 mg/kg SC twice a day for 16 days) nor depletion of 5-HT withp-chlorophenylalanine changed the anxiogenic-like activity of buspirone in the elevated plus-maze test. These results suggest that an agonist action at postsynaptic 5-HT1A receptors mediates the anxiogenic-like effects of buspirone in the elevated plus-maze test and that this test may either be insensitive to certain classes of anxiolytics or is measuring something unrelated to human anxiety states. 相似文献
994.
Otagiri Masaki Yamamichi Ryuji Marayama Toru Imai Teruko Suenaga Ayaka Imamura Yorishige Kimachi Kazuhiko 《Pharmaceutical research》1989,6(2):156-159
The interactions of acidic and basic drugs with 1-acid glycoprotein (1-AGP) were investigated using circular dichroism (CD) measurements. Extrinsic Cotton effects were generated by the binding of drugs to 1-AGP. The CD data suggested the presence of a single binding site on the 1-AGP molecule. The induced ellipticities of the acidic drug–1-AGP system decreased with increasing pH, while the ellipticities for the basic drugs increased with pH. The ellipticities for all drugs were reduced by the addition of fatty acids. Furthermore, the induced ellipticities decreased in the presence of cesium chloride for basic drugs bound to 1-AGP. The extrinsic Cotton effects therefore appear to result from hydrophobic interaction with 1-AGP for the acidic drugs and from hydrophobic and electrostatic interactions for the basic drugs. 相似文献
995.
Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2 总被引:4,自引:0,他引:4
Hu YW Rocheleau L Larke B Chui L Lee B Ma M Liu S Omlin T Pelchat M Brown EG 《Virology》2005,332(2):538-549
Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns. 相似文献
996.
We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes. 相似文献
997.
Recent studies have demonstrated that α-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of α-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger’s Disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to α-SM actin. Our data showed that α-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy. 相似文献
998.
Kretschmer U Bonhagen K Debes GF Mittrücker HW Erb KJ Liesenfeld O Zaiss D Kamradt T Syrbe U Hamann A 《European journal of immunology》2004,34(11):3070-3081
Endothelial selectins are crucial for the recruitment of leukocytes into sites of inflammation. On T cells, ligands for selectins become induced upon differentiation into the effector/memory stage. Initial in vitro studies suggested a correlation between the Th1 phenotype and ligand expression, but whether this also holds true in vivo remained uncertain. We here analyzed selectin ligands on CD4+ T cells producing IFN-gamma, IL-4 or IL-10, prototypic cytokines of the Th1, Th2 and Tr1 subset, respectively. We analyzed mice infected with influenza virus, the bacterium Listeria, and the parasites Toxoplasma (all Th1 models) or Nippostrongylus (Th2 model). A link between the Th1 phenotype and ligand expression was not found in vivo. Surprisingly, the potentially regulatory IL-10-producing T cells displayed the highest frequency of ligand-positive cells in general. Within the inflamed tissues, the frequencies of P-selectin-binding cells increased in the dominant subset, either Th1 or Th2. Up-regulation was also found for E-selectin ligands during influenza, but not Nippostrongylus infection. In conclusion, conditions driving T cell polarization into either Th1 or Th2 in vivo do not affect the expression of selectin ligands, but acquisition of P-selectin binding and hence migration into inflamed tissues is boosted by an inflammatory milieu. 相似文献
999.
Koyanagi M Imanishi K Arimura Y Kato H Yagi J Uchiyama T 《International immunology》2004,16(2):315-326
To determine the levels of maturation and differentiation ofmurine CD4 single-positive (SP) T cells, we compared the secondaryresponses of staphylococcal enterotoxin A (SEA)-induced neonatalthymic, adult thymic and adult splenic CD4 SP T cell blastsprepared from whole or heat-stable antigenlow CD4 SP T cells.Proliferative responses upon re-stimulation with SEA were strongin adult splenic CD4 SP T cell blasts, but quite weak in neonatalthymic and adult thymic CD4 SP T cell blasts. SEA-induced IL-2production was weaker in neonatal thymic blasts than in theadult splenic CD4 SP T cell blasts. In contrast, SEA-inducedIL-4 production was high in neonatal thymic CD4 SP T cell blasts,and low in adult splenic and thymic CD4 SP T cell blasts. Expressionof GATA-3, that directs production of IL-4 in T cells, examinedat protein and mRNA levels, was higher in neonatal thymic cellsthan in adult thymic and splenic cells. These results suggestthat neonatal and adult thymic CD4 SP T cells in the final stageof maturation are relatively immature compared with adult splenicCD4 SP T cells. The cytokine production profile of neonatalthymic CD4 SP T cells suggests that they are inclined towardsa Th2 response. 相似文献
1000.
活动性类风湿关节炎患者sICAM-1、sVCAM-1的变化及意义 总被引:2,自引:0,他引:2
目的 :测定活动性类风湿关节炎 (RA)患者血清中sICAM 1、sVCAM 1水平 ,探讨sICAM 1、sVCAM 1与IL 1、TNF、IFN γ及病情的关系。方法 :用酶联免疫分析法 (ELISA)检测 30例活动性RA患者与 30例健康对照者sICAM 1、sVCAM 1、IL 1、TNF、IFN γ水平。结果 :RA患者血清sICAM 1、sVCAM 1、IL 1、TNF、IFN γ水平明显高于正常对照组 (P<0 0 0 1) ,sICAM 1与IL 1、IFN γ正相关 ,与RF亦呈正相关 ,sVCAM 1与IL 1、TNF、IFN γ正相关 ,与ESR、CRP、Stock指数正相关。结论 :RA患者血清sI CAM 1、sVCAM 1水平显著升高 ,sICAM 1、sVCAM 1可能参与RA发病过程 ,sICAM 1可作为判断病情严重性的指标 ,sVCAM 1可作为观察病情活动性的指标。 相似文献