Endoglin, a homodimeric transmembrane glycoprotein, is a part of the transforming growth factor-beta (TGF-beta) receptor cascade. It has been demonstrated that endoglin can affect TGF-beta signaling and eNOS expression by affecting SMAD proteins in vitro. We planned to go one step forward and evaluate whether endoglin is co-expressed with SMAD2, phosphorylated SMAD2/3 protein and eNOS in endothelium of normocholesterolemic C57BL/6J mice, and in advanced atherosclerotic lesions in hypercholesterolemic apoE/LDLr-deficient mice by means of fluorescence immunohistochemistry. Female C57BL/6J mice were fed with a chow diet (standard laboratory diet) for 12 weeks after weaning (at the age of 4 weeks). Two-month-old female apoE/LDLr-deficient mice were fed the western type diet (atherogenic diet) containing 21% fat (11% saturated fat) and 0.15% cholesterol for 2 months. Immunohistochemical analysis of endoglin, SMAD2, phosphorylated SMAD2/3 and eNOS expression was performed in mice aortic sinus. Immunohistochemical analysis showed the expression of endoglin in intact endothelium in both C57BL/6J and apoE/LDLr-deficient mice and in endothelium covering the atherosclerotic lesion in apoE/LDLr-deficient mice. Fluorescence immunohistochemistry revealed co-expression of endoglin with SMAD2, phosphorylated SMAD2/3 and eNOS in intact aortic endothelium in C57BL/6J mice. Moreover, strong co-localization of endoglin, SMAD2, phosphorylated SMAD2/3 and eNOS was also detected in endothelium covering atherosclerotic lesions in apoE/LDLr-deficient mice. In conclusion, we suggest that endoglin, SMAD2, phosphorylated SMAD2/3 and eNOS may be important in vessel endothelium homeostasis underlying their role in atherogenesis.

• MeSH
• aorta cytologie   MeSH
• apolipoproteiny E nedostatek   genetika   MeSH
• cévní endotel metabolismus   MeSH
• dieta aterogenní MeSH
• endoglin MeSH
• fluorescenční protilátková technika přímá MeSH
• fosforylace MeSH
• hypercholesterolemie metabolismus   MeSH
• imunohistochemie MeSH
• intracelulární signální peptidy a proteiny genetika   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• protein Smad2 genetika   metabolismus   MeSH
• protein Smad3 genetika   metabolismus   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoproteiny E MeSH
• endoglin MeSH
• Eng protein, mouse MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• protein Smad2 MeSH
• protein Smad3 MeSH
• synthasa oxidu dusnatého, typ III MeSH

Adhesion between Sertoli cells and germ cells is important for spermatogenesis. Cadherins are Ca(2+)-dependent transmembrane proteins that mediate cell-cell adhesion. The aim of this study was to compare the expression of P-cadherin in unilaterally cryptorchid and busulphan-treated rat testes using immunohistochemistry. The pattern of expression of P-cadherin in the seminiferous epithelium changed with the stage of the seminiferous epithelium. The membranes of round spermatids and membranes and cytoplasm of spermatocytes were strongly positive. Our experiments revealed that busulphan treatment (2 doses - 10 mg/kg of body weight - 21 days apart) and cryptorchism led to destructive changes in the structure of seminiferous tubules, together with the decrease in P-cadherin expression. The expression of P-cadherin disappeared in the spermatids segregated from the epithelium while segregated spermatocytes remained still positive for P-cadherin during the 3- to 11-day cryptorchid period. In busulphan-treated animals, the expression of P-cadherin was dependent on the presence or absence of the spermatocytes and spermatids in the tubules. Strong positivity for P-cadherin was observed in the spermatocytes that re-appeared in the regenerating seminiferous epithelium. We suggest that P-cadherin participates in the architecture of adherens junctions in testis, plays an important role in maintaining normal spermatogenesis and that cryptorchism and busulphan treatment lead to adherens junction disintegration.

• MeSH
• busulfan farmakologie   MeSH
• imunohistochemie MeSH
• kadheriny metabolismus   MeSH
• kryptorchismus metabolismus   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• testis účinky léků   metabolismus   MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• busulfan MeSH
• kadheriny MeSH

The mycophenolate mofetil, a prodrug of mycophenolic acid, is a new immunosuppressive drug with a specific mechanism of action consisting in the inhibition of T- and B-lymphocytes proliferation. A series of animal experiments showed efficiency of the mycophenolate mofetil administered in monotherapy or in combination with other immunosuppressants to prolong the survival of different allo- and xenotransplanted grafts. In clinical trials, the mycophenolate mofetil, cyclosporine, and steroids demonstrated high efficacy in the prevention of acute rejection in the solid allotransplanted organs. The mycophenolate mofetil seems to be a suitable candidate for the treatment of many other, e.g., autoimmune and inflammatory diseases.

• MeSH
• imunosupresiva * škodlivé účinky   farmakologie   terapeutické užití   MeSH
• kyselina mykofenolová * škodlivé účinky   analogy a deriváty   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• rejekce štěpu imunologie   prevence a kontrola   MeSH
• transplantační imunologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• imunosupresiva * MeSH
• kyselina mykofenolová * MeSH

Histological changes which appear as a result of reperfusion injury of cold-preserved rat liver were studied at intervals of 0 hr, 3 hr, 24 hr and 48 hr of cold storage. The isolated livers were stored in a UW solution (University of Wisconsin), which is used in human liver transplantations. Computer image analysis of light microscopic sections (methyl green-pyronin stained) was used for the study and quantification of injured cells. The method of TUNEL was performed to prove possible apoptosis of sinusoidal endothelial cells and heptocytes. Bile production during reperfusion and ALT, AST, LDH and ACP were measured in the reperfusion medium at the end of the 90 min reperfusion. It has been confirmed that prolongation of the cold storage of liver results in extensive changes in the liver structure and increased injury of liver cells. Sinusoidal endothelial cells were damaged more and earlier than hepatocytes. It has been shown that methyl green-pyronin stained sections are advantageous for the study of these morphological changes, allowing the strongest view of these changes. The appearance of TUNEL positive cells and an increase in the levels of biochemical parameters, e.g. AST or ALT, indicate earlier cell injury. The methodology described in this article can be used for the study of reperfusion injury of the liver and for the study of this phenomenon in other experiments.

• MeSH
• játra enzymologie   patologie   MeSH
• koncové značení zlomů DNA in situ MeSH
• krysa rodu Rattus MeSH
• nízká teplota * MeSH
• potkani Wistar MeSH
• reperfuzní poškození metabolismus   patologie   MeSH
• techniky in vitro MeSH
• uchovávání orgánů * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

The present review has focused on the cell adhesion molecules from the cadherin superfamily, in particular on E- and VE-cadherin. In general, cadherins are a large group of cell adhesion molecules located at intercellular junctions called adherent junctions. They play an important role in embryogenesis and morphogenesis in animals and humans due to their adhesive and cell-signalling functions. Disturbances of the expression or function of cadherins and their associated proteins called catenins are crucial for the initiation and development of many pathological states. E-cadherin is an epithelium-specific cadherin that is required for the development and maintenance of the normal function of all epithelial cells in tissues. The loss or down-regulation of E-cadherin is a key event in the process of tumour invasion and metastasis. The assessment of E-cadherin immunoreactivity may be a useful prognostic marker in some cancers, complementary to the established prognostic factors. VE-cadherin is an endothelium-specific cadherin, which plays a relevant role in vascular homeostasis. It has been demonstrated that VE-cadherin is required for normal vasculogenesis, angiogenesis, and for the maintenance of vascular integrity. Disruption of VE-cadherin-catenin complexes by some inflammatory agents such as thrombin, by inflammatory cells, or shear stress is accompanied by an increase in vascular permeability in vivo and in vitro.

• MeSH
• CD antigeny MeSH
• cévní endotel metabolismus   MeSH
• embryo savčí fyziologie   MeSH
• epitel metabolismus   MeSH
• kadheriny fyziologie   MeSH
• lidé MeSH
• nádory metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cadherin 5 MeSH Prohlížeč
• CD antigeny MeSH
• kadheriny MeSH

The transfer kinetics of cyclosporine across the dually perfused rat placenta in the maternal to fetal direction and a possible involvement of P-glycoprotein were investigated. The transplacental clearance of cyclosporine in the materno-fetal direction was found to be dependent on the maternal inflow concentration of cyclosporine. Coadministration of cyclosporine with an excess of quinidine or chlorpromazine into the maternal compartment revealed 1.7- and 1.9-fold increase in cyclosporine concentration in the fetal compartment. In the experiments where quinidine was present both in the maternal and fetal compartments, cyclosporine appeared in the fetal compartment significantly faster, and its amount was three times higher when compared with controls. Conversely, quinidine or chlorpromazine did not affect the transplacental passage of L-[(3)H]-glucose. The interference of quinidine with the metabolism of cyclosporine in the placenta was excluded because only traces of M-1 and M-17 metabolites were found in the fetal solutions. Sodium azide, a mitochondrial respiratory inhibitor, was found to double the rate of cyclosporine, but not L-[(3)H]-glucose, passage across the placenta. Our findings indicate that P-glycoprotein pumps cyclosporine out of the trophoblast cells of the rat placenta in the ATP-dependent manner and restricts the passage of cyclosporine across the placental barrier.

• MeSH
• azid sodný farmakologie   MeSH
• časové faktory MeSH
• chinidin farmakologie   MeSH
• chlorpromazin farmakologie   MeSH
• cyklosporiny farmakokinetika   MeSH
• glukosa farmakokinetika   MeSH
• kinetika MeSH
• krysa rodu Rattus MeSH
• maternofetální výměna látek * MeSH
• P-glykoprotein fyziologie   MeSH
• perfuze MeSH
• placenta metabolismus   MeSH
• potkani Wistar MeSH
• techniky in vitro MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• azid sodný MeSH
• chinidin MeSH
• chlorpromazin MeSH
• cyklosporiny MeSH
• glukosa MeSH
• P-glykoprotein MeSH

An incidence of bilateral gonadoblastoma in a 23-month old, mentally retarded boy with congenital sporadic aniridia, undescended dysgenetic testes, deletion of a chromosome (11) (p1302p14.2) and a later occurring unilateral Wilms' tumor is reported. The patient was treated by bilateral gonadectomy, nephrectomy, and chemotherapy, and is alive and well five years later. Another three aniridia/gonablastoma observations from the literature are discussed, two of them without and one in combination with Wilms' tumor. Diagnosis of gonadoblastoma remained unsuspected in two cases until autopsy and in another two cases it was done at surgery. A comparison of four cases reveals common finding--aniridia, dysgenetic gonads, genital abnormalities, mental retardation, deletion of 11p13, early occurrence and bilaterality of gonadoblastoma.

• MeSH
• aniridie genetika   MeSH
• chromozomální delece * MeSH
• gonadoblastom genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 11 * MeSH
• mentální retardace MeSH
• mnohočetné abnormality genetika   MeSH
• mnohočetné primární nádory genetika   MeSH
• nádory ledvin genetika   MeSH
• předškolní dítě MeSH
• syndrom MeSH
• testikulární nádory genetika   MeSH
• Wilmsův nádor genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1 mg/kg, i.v.), which produced up to 12-fold increases in the number of excreted epithelial cells, was examined. Repeated administration of cyclosporin A (45 and 56 mg/kg, p.o.) produced up to 23-fold increases in the number of excreted epithelial cells. The degree of excretion of epithelial cells after administration of both drugs was compared with the urinary excretion of alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, which indicated nephrotoxicity in amphotericin B and cyclosporin A with a lower sensitivity than the increase in the excretion of epithelial cells. In the experiment with cyclosporin A, urinary excretion of epithelial cells was further correlated with renal functional tests (clearance of polyfructosan and hippurate.

• MeSH
• acetylglukosaminidasa moč   MeSH
• amfotericin B toxicita   MeSH
• antibakteriální látky toxicita   MeSH
• antigeny CD13 moč   MeSH
• cyklosporin toxicita   MeSH
• epitel účinky léků   enzymologie   MeSH
• epitelové buňky MeSH
• hippuráty moč   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• imunosupresiva toxicita   MeSH
• krysa rodu Rattus MeSH
• ledvinové kanálky cytologie   účinky léků   enzymologie   MeSH
• moč cytologie   MeSH
• nemoci ledvin chemicky indukované   MeSH
• potkani Wistar MeSH
• radioizotopy jodu MeSH
• toxikologie metody   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• xenobiotika toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylglukosaminidasa MeSH
• amfotericin B MeSH
• antibakteriální látky MeSH
• antigeny CD13 MeSH
• cyklosporin MeSH
• hippuráty MeSH
• hippuric acid MeSH Prohlížeč
• imunosupresiva MeSH
• radioizotopy jodu MeSH
• xenobiotika MeSH

The synthesis of epsilon-aminocaproic acid esters is described. Two representative members from a group of five of the 1-alkyl homologues synthetized as flexible analogues of 1-alkylazacyclohepatanone derivatives were evaluated in vitro for their effectiveness on the transport of theophylline through the excised human cadaver skin in comparison with Azone. The 1-octyl- and 1-dodecyl-epsilon-aminocaproic acid esters (OCEAC and DDEAC) show excellent penetration enhancement. Donor samples contained 2.5% theophylline and 1% enhancers tested in three different vehicles. Fluxes of theophylline were increased with OCEAC about 19 times from olive oil, 45 times from water, and about 38 times from water-propylene glycol (3:2) vehicle toward controls (with DDEAC about 17, 39, and 35 times, respectively) and they were markedly higher than Azone under the given conditions. Acute LD50's (i.p. in mice) of OCEAC (DDEAC) were 245 mg/kg (352 mg/kg), with a slightly lower toxicity than Azone. OCEAC and DDEAC did not exhibit acute dermal irritation in vivo on rabbits at a 5% concentration in white petrolatum.

• MeSH
• aminokapronáty * MeSH
• aplikace kožní MeSH
• azepiny farmakologie   MeSH
• chemická stimulace MeSH
• činčila MeSH
• dráždivé látky toxicita   MeSH
• indikátory a reagencie MeSH
• kožní absorpce účinky léků   MeSH
• králíci MeSH
• kyselina 6-aminokapronová chemická syntéza   farmakologie   toxicita   MeSH
• LD50 MeSH
• lidé MeSH
• myši MeSH
• rozpustnost MeSH
• techniky in vitro MeSH
• theofylin farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• aminokapronáty * MeSH
• azepiny MeSH
• dodecyl 6-aminocaproate MeSH Prohlížeč
• dráždivé látky MeSH
• indikátory a reagencie MeSH
• kyselina 6-aminokapronová MeSH
• laurocapram MeSH Prohlížeč
• octyl 6-aminocaproate MeSH Prohlížeč
• theofylin MeSH

The influence of the anti-inflammatory drug ibuprofen on the activity of ornithine decarboxylase (ODC, EC 4.1.1.17), the key enzyme of polyamine synthesis, was studied using a 20,000 g supernatant of rat testis and regenerating liver homogenates as sources of the enzyme. Ibuprofen, in all concentrations studied (10(-6) to 2 x 10(-3) M), did not influence either testicular or hepatic ODC activity in vitro. The role of ODC in inflammatory processes and the lack of ODC inhibition by ibuprofen are discussed in view of the controversial findings of other authors.

• MeSH
• eflornithin farmakologie   MeSH
• ibuprofen farmakologie   MeSH
• inhibitory ornithindekarboxylasy * MeSH
• játra enzymologie   MeSH
• krysa rodu Rattus MeSH
• ornithindekarboxylasa metabolismus   MeSH
• potkani Wistar MeSH
• testis enzymologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• eflornithin MeSH
• ibuprofen MeSH
• inhibitory ornithindekarboxylasy * MeSH
• ornithindekarboxylasa MeSH