Wellenastrilde(Estrilda asrild) in Portugal

Ohne Zusammenfassung     

Histopathological effects of cisplatin,doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats

Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs.     

Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen

Background  

Bet v 1 is an important cause of hay fever in northern Europe. Bet v 1 isoforms from the European white birch (Betula pendula) have been investigated extensively, but the allergenic potency of other birch species is unknown. The presence of Bet v 1 and closely related PR-10 genes in the genome was established by amplification and sequencing of alleles from eight birch species that represent the four subgenera within the genus Betula. Q-TOF LC-MS^E was applied to identify which PR-10/Bet v 1 genes are actually expressed in pollen and to determine the relative abundances of individual isoforms in the pollen proteome.     

Tumor necrosis factors alpha and beta differ in their capacities to generate interleukin 1 release from human endothelial cells

The capacity of the tumor necrosis factors, TNF-alpha and TNF-beta, products of activated macrophages and lymphocytes, respectively, to stimulate interleukin 1 (IL-1) release from endothelial cells derived from human umbilical veins was examined in vitro. Recombinant TNF-alpha caused IL-1 release by 4 hr with maximal levels of 17 U/ml by 24 hr; half-maximal stimulation occurred at approximately 80 pM. In contrast, recombinant TNF-beta was a relatively poor stimulus for IL-1 release. Even at concentrations as high as 600 pM, only 3 U of IL-1/ml were recovered; maximal IL-1 release (10 to 12 U/ml) required up to 5 nM TNF-beta. Natural, glycosated human TNF-beta was comparable in activity to recombinant TNF-beta. TNF-beta did not directly inhibit the IL-1 comitogenesis assay, nor was there evidence that TNF-beta induced the release of an IL-1 inhibitor, in that supernatants generated in the presence of TNF-beta did not inhibit thymocyte proliferation to a recombinant IL-1 standard. Binding of the recombinant TNF to endothelial monolayers was assessed by using [125I]TNF-alpha in competition studies with cold TNF-alpha and TNF-beta. Binding of TNF-alpha was half-maximal at 80 pM with an average of 664 receptors/cell and Kd = 0.043 nM. Although TNF-beta was capable of fully competing for [125I]TNF-alpha binding, half-maximal binding occurred at 800 pM TNF-beta. These data suggest that the TNF receptors on human endothelial cells may reflect the structural differences between these two homologous cytokines.     

The role of IFN-gamma in the pathology of experimental endotoxemia

Proinflammatory cytokines provoked by circulating bacterial LPS mediate many of the destructive host responses characteristic of septic shock. To determine if the lymphokine IFN-gamma has a similar pathogenic role during endotoxic shock, mice were pretreated with murine rIFN-gamma (rMuIFN-gamma) at various times relative to challenge with Salmonella enteritidis LPS. Subsequent mortality was increased when rMuIFN-gamma was administered before or up to 4 h after endotoxin challenge. Pretreatment with rMuIFN-gamma resulted in nearly fivefold increases in serum TNF during endotoxemia, but TNF levels were unaffected by IFN administered after endotoxin. The increased levels of serum TNF probably reflected enhanced translation of this factor, as tissue expression of TNF mRNA did not increase correspondingly in IFN-pretreated mice. To examine the role of IFN-gamma produced endogenously during endotoxemia, mice were pretreated with 0.5 mg of anti-IFN-gamma mAb before endotoxin injection. This treatment significantly reduced mortality from endotoxic shock but caused only minor decreases in serum TNF. Anti-IFN-gamma administered 2 h after endotoxin was similarly protective. These results demonstrate a significant role for IFN-gamma in the pathology of septic shock, both indirectly as an activator of monokines known to promote lethality and possibly by other, late-acting mechanisms.     

Different receptors mediate the hepatic catabolism of tissue-type plasminogen activator and urokinase.

Tissue-type plasminogen activator (t-PA) and urokinase (u-PA) are proteins with partial structural similarity and which are of importance in the therapy of thrombotic diseases. Both are known to be cleared from the circulation in vivo by uptake in the liver. The present study investigated whether the hepatic catabolism of u-PA and t-PA is mediated by a common receptor system. Four experimental protocols of increasing complexity were used: hepatocyte plasma membranes, isolated primary hepatocytes, liver perfusion and whole animals. For t-PA, a specific high-affinity binding site to hepatocytes and plasma membranes could be defined with a mean Kd of 4 +/- 3 nM, whereas the Kd for u-PA was less than 300 nM. Binding of t-PA could not be competed for by u-PA, and vice versa. Furthermore, clearance of t-PA in isolated perfused rat livers and in rabbits in vivo was 3-fold higher than that of u-PA, and a 50-100-fold molar excess of u-PA failed to inhibit clearance of t-PA in either system, and vice versa. Taken together, the results imply that hepatic elimination of t-PA and u-PA is mediated by distinct receptor systems of differing affinity.     

Brain nitric oxide synthase is a biopterin- and flavin-containing multi-functional oxido-reductase.

Brain nitric oxide synthase is a Ca2+/calmodulin-regulated enzyme which converts L-arginine into NO. Enzymatic activity of this enzyme essentially depends on NADPH and is stimulated by tetrahydrobiopterin (H4biopterin). We found that purified NO synthase contains enzyme-bound H4biopterin, explaining the enzymatic activity observed in the absence of added cofactor. Together with the finding that H4biopterin was effective at substoichiometrical concentrations, these results indicate that NO synthase essentially depends on H4biopterin as a cofactor which is recycled during enzymatic NO formation. We found that the purified enzyme also contains FAD, FMN and non-heme iron in equimolar amounts and exhibits striking activities, including a Ca2+/calmodulin-dependent NADPH oxidase activity, leading to the formation of hydrogen peroxide at suboptimal concentrations of L-arginine or H4biopterin.