Status epilepticus evokes prolonged increase in the expression of CCL3 and CCL4 mRNA and protein in the rat brain.
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):193-207.Status epilepticus evokes prolonged increase in the expression of CCL3 and CCL4 mRNA and protein in the rat brain.1, , , .1The Nencki Institute of Experimental Biology, Warsaw, Poland.AbstractCCL3 and CCL4 are proinflammatory chemokines belonging to the CC family. Increase in expression of mRNA coding for various chemokines including CCL3 and CCL4 has been often detected with global transcriptome profiling of brain tissue following epileptogenic stimuli as well as in epilepsy in experimental models and in human patients. Despite this, little is known about the expression of these proteins in epileptogenesis or epilepsy. In the present work CCL3 and CCL4 mRNA and protein expression were studied in the amygdala stimulation model of temporal lobe epilepsy using quantitiative PCR and immunohistochemistry. Expression of CCL3 and CCL4 mRNA in the block of tissue containing enthorinal and piriform cortices, amygdala and piriform nucleus was markedly up-regulated at 1, 4, 14 and 30 days following stimulation and in hippocampal CA1 was significantly increased at 1 and 4 days following stimulation. Expression of CCL3 and CCL4 proteins was elevated in astrocytes in the enthorinal and piriform cortices, amygdala, and hippocampus showing the largest increase at 4D after status epilepticus. Increase in mRNA and protein levels of CCL3 and CCL4 in the animal model of temporal lobe epilepsy suggests their role in disease development or recovery form epileptogenic insult. Existence of multiple targets for these chemokines in the damaged brain allows several possibilities of influencing neuronal and glial functions.PMID:
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External link. Please review our .Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatm...
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):1993-8.Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer: potential for rapid monitoring of treatment responses.1, , , , , , , , .1Department of Urology, Lund University, Sk?ne University Hospital, Malm?, Sweden.AbstractBACKGROUND: The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration. Therefore, we assessed elimination rates of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon((R))), a novel GnRH antagonist.METHODS: This study included 24 patients treated with degarelix. Blood was taken at 1, 3, 7, 14, 21 and 28 days after injection of degarelix. Free and total PSA were measured with a commercial dual-label assay, and with inhouse research assays of intact PSA and hK2.RESULTS: Median (interquartile range, IQR) tPSA at baseline was 23.4 (15.8, 59.8). Twenty-two patients (92 % ) reached castrate levels of testosterone within 24 h of degarelix initiation, and all patients did so within 72 h. All kallikrein forms declined in an exponential fashion after degarelix administration. The median time to 50 % reduction in biomarker level was 8 – 9 days for tPSA or complexed PSA vs. 2-4 days for hK2, iPSA and fPSA. The percentage eliminated at day 3 and day 7 was significantly higher for hK2, iPSA and fPSA than for tPSA (all p & 0.02), while tPSA and complexed PSA were similar.CONCLUSIONS: The rapid decline of fPSA, iPSA and hK2 after fast induction of castration with degarelix is similar to that reported after prostatectomy and offers a novel, informative method to monitor rapid onset of therapeutic action targeting signaling of the androgen receptor.PMID:
[PubMed - indexed for MEDLINE] Median percent change in biomarkers over time. Black line: tPSA; red line: cPSA (calculated); green line: fPSA; orange line: iPSA; gray line: hK2. The dark blue line shows median testosterone levels pre-treatment (day 0) and post-treatment at days 1, 3, 7, 14, 21, and 28; the light blue line represents the castration cut-off of 0.5 ng/ml. Confidence intervals are not shown in order to facilitate readability of the figure. There is an apparent rebound in free PSA levels at 21 days, while testosterone levels remained below the castration cut-off. Given the variability associated with these estimates due to the small sample size, we interpret these findings as consistent with these levels continuing to decline or levelling off past 14 days.Clin Chem Lab Med. ;50(11):.Publication TypesMeSH TermsSubstancesGrant SupportFull Text SourcesMedicalMiscellaneous
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