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Biomedical subjects

J Madej

Publications and source records attributed to J Madej.

At least 19 recordsLinked to original sources
PubMed2004

Changes in gene expression in the lungs of Mg-deficient mice are related to an inflammatory process.

It has been well documented that experimental hypomagnesemia in rodents evokes, as an early consequence, an inflammatory response. This also leads to the activation of cells producing reactive species of oxygen and, as a result, to the oxidative damage of tissues. Several studies have shown that lungs might be a specific target of Mg deficiency. Here, we report that 3 weeks of Mg deficiency in mice resulted in inflammatory processes in the lungs, including interstitial and perivascular pneumonia, manifested by the infiltration of leukocytes, plasmocytes and histiocytes, as well as the phenomenon of disseminated intravascular coagulation (DIC). These phenomena were accompanied by changes in gene expression assessed by cDNA array. In this study we identified 26 genes significantly changed by Mg deficiency, mostly involved in the anti-oxidative response, regulation of cell cycle and growth, apoptosis as well as cell-cell and cell-matrix interactions. We conclude that these changes are related to the phenomena of inflammatory and oxidative processes and consecutive remodeling occurring in the tissues as a result of Mg deficiency. This may have implications for at least several lung pathologies, including allergies, asthma, SIDS (Sudden Infant Death Syndrome) or facilitate formation of lung metastases.

Animals↗
PubMed2003

Ultrastructural studies on malignant lymphoma in dogs, with the use of computer imaging.

Malignant lymphoma is one among the most often diagnosed malignant tumors in dogs. In the course of the disease lymphatic glands become enlarged and infiltrations form in internal organs or skin. Studies on the ultrastructure of neoplastic lymphocytes were carried out on a formalin-fixed and parafin-embedded material with a Hulquist and Karlsson's method. Numerous aplastic cells with large nuclei, abundan eu- or heterochromatin and unstabilised nucleolus were observed on TEM slides. The cells differed clearly from normal lymphocytes with highly condesed heterochromatin and stabilised nucleoli.

Animals↗
PubMed2003

Secretory dysfunction of vascular endothelium limits the effect of angiotensin converting enzyme inhibitor quinapril on aggregation of erythrocytes in experimental hypertension.

Using automatic erythrocyte aggregometer type MA-1 (Myrenne gmbh, Germany), we investigated the hypothesis that therapeutic effectiveness of quinapril--angiotensin converting enzyme inhibitor (ACEI)--in the treatment of hypertension would correlate with improvement of red blood cell (RBC) aggregability. Experiments were performed on commercially available inbred strain of spontaneously hypertensive male rats (SHR) aged 19-21 weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats genetically related to SHR were used as a control. Aggregability of RBC in hypertensive rats was significantly higher than in control WKY animals. Quinapril (100 microg/kg) administered i.p. for 8 days improved RBC aggregability in normotensive rats but surprisingly not in SHR animals. Beneficial effect of quinapril on RBC aggregation observed in normotensive animals did not occur when this drug was injected in combination with aspirin (1 or 50 mg/kg) or with indomethacin (20 mg/kg) or with L-NAME (10 mg/kg). However, much the same damaging effects on RBC aggregability were observed when aspirin, indomethacin or L-NAME were each administered into normotensive animals without quinapril. In contrast with normotensive rats, aggregability of RBC in SHR was not affected either by quinapril or by indomethacin and by L-NAME, given separately or in combination. The only compound significantly worsening RBC aggregability in SHR was aspirin but this effect was not dose-dependent. Quinapril-induced improvement of RBC aggregability in normotensive rats (but not in SHR) was completely abolished by simultaneous administration of B2 receptor antagonist icatibant and successfully mimicked by 8 days of treatment with bradykinin. In vitro aggregability of RBC isolated from WKY was not affected by previous incubation (30 min at 37 degrees C) with quinapril, indomethacin or L-NAME. Only aspirin (3 mM) significantly increased RBC aggregability as compared to placebo. It is concluded that under physiological conditions quinapril efficiently inhibits RBC aggregability and this effect is modulated by secretion of endothelial mediators, mainly prostacyclin and nitric oxide. In hypertension quinapril, in spite of lowering of arterial blood pressure, is unable to display its beneficial effects on RBC aggregability possibly due to the hypertension-induced/accompanied dysfunction of vascular endothelium. Aspirin revealed unique erythrocyte damaging properties, presumably independent of inhibition of cyclooxygenase but related to a direct membrane protein acetylation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Mesoionic oxatriazoles (MOTA): NO-donating characteristics and pharmacology.

Biological role of nitric oxide (NO), functioning of isoforms of NO synthetases (NOS) and pharmacology of principle NO-donors were reviewed. NO donating characteristics and pharmacology of 23 mesoionic oxatriazoles (MOTA) were compared with those of 5-morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (NaNP) and glyceryl trinitrate (GTN). It is concluded that in vitro NO donating profile of MOTA hardly can be used as a predicting measure for their pharmacological activities either in vitro or in vivo. If anything, fast NO releasers seem to be stronger vasorelaxants than MOTA with slow NO releasing properties. Still, among representatives of this last category of MOTA one may find efficient antithrombotic and thrombolytic agents. For instance, MOTA 5-oxides were more potent thrombolytics than SIN-1, SNAP or NaNP. Also MOTA with potent anti-platelet action in vitro seem to be potent relaxants of tracheal strips. In summary, by manipulating the chemical structures of MOTA one may obtain relative selectivity towards vasorelaxant, anti-platelet, thrombolytic or tracheorelaxant properties. Thus different categories of MOTA might be designed with a hope of achieving hypotensive, antithrombotic, thrombolytic or anti-asthmatic drugs.

Animals↗
PubMed2002

Endothelial secretogogues and deformability of erythrocytes.

Many diseases of the heart and circulatory system have been linked with both dysfunction of vascular endothelium and insufficient deformability of erythrocytes. Using shear stress laser diffractometry we investigated whether deformability of erythrocytes would be regulated endogenously by generation of two endothelial secretogogues: prostacyclin and nitric oxide. Experiments were performed in rats ex vivo and with whole blood or isolated erythrocytes in vitro. Iloprost--a stable analogue of prostacyclin (10 microg/kg i.v.) and SIN-1 (NO-donor) at a dose of 2 mg/kg/min i.v induced a significant improvement of deformability of erythrocytes ex vivo. Improvements of deformability by these two compounds were also evident in vitro when they were applied at a range of concentrations of 1 microM and 3 microM, respectively. Cyclooxygenase (indomethacin 20 mg.kg i.v.) and nitric oxide synthase (L-NAME 10 mg/kg i.v.) inhibitors while worsening deformability ex vivo, they did not affect (3 mM and 10 microM, respectively) rheological functions of erythrocytes in vitro. Aggravating effects of these inhibitors on erythrocyte deformability ex vivo were reversed by prostacyclin and nitric oxide supplemented exogenously. Aspirin at a low (1 mg/kg i.v.) and high dose (50 mg/kg i.v.), contrary to indomethacin and L-NAME, aggravated erythrocyte deformability either ex vivo or in vitro. It is concluded that autocrine function of vascular endothelium plays an important role in regulation of rheology of red blood cells in flowing blood. The mechanism of this phenomenon is unclear but some possible explanations are discussed. In addition, in our experiments aspirin revealed unique erythrocyte damaging properties, possibly independent of inhibition of cyclooxygenase, but related to a direct protein acetylation.

Animals↗
PubMed2001

Bioastrophysical aspects of low energy ion irradiation of frozen anthracene containing water.

The origin of life on Earth remains a fascinating mystery in spite of many theories existing on this subject. However, it seems that simple prebiotic molecules could play an essential role in the formation of more complex organisms. In our experiment, we synthesized a class of these molecules (quinones) bombarding frozen anthracene containing water with low energy hydrogen ions. This experiment roughly simulated the astrophysical conditions which one can find in the solar system. Thus, we can hypothesize that prebiotic molecules could be created by interaction of the solar wind with interplanetary dust grains. The delivery of these molecules to early Earth may have contributed to the generation of life on our planet.

Anthracenes↗
PubMed2001

Comparison of endothelial pleiotropic actions of angiotensin converting enzyme inhibitors and statins.

Two in vitro and one in vivo assay were performed to study the endothelial pleiotropic actions of "tissue type" angiotensin converting enzyme inhibitors (ACE-Is) such as perindopril and quinapril, their active forms, that is, quinaprilat and peridoprilat, or of statins belonging to natural (lovastatin), semisynthetic (simvastatin), and synthetic enantiomeric (atorvastatin, cerivastatin) classes. Cytoplasmic [Ca2+]i levels in cultured bovine aortic endothelial cells and endothelium-dependent nitric oxide-mediated coronary vasodilatation in the Langendorff preparation of guinea pig heart constituted our in vitro assays. The in vivo assay consisted of study of PGI2-mediated thrombolytic response in arterial blood of rats after intravenous administration of drugs. In this last assay, perindopril and quinapril proved to be, by two orders of magnitude, more potent PGI2-dependent thrombolytics than the most potent statin (atorvastatin). However, in both in vitro assays we found a higher endothelial efficacy of statins as compared to ACE-Is. In particular, those statins that contain the lactone ring in their molecules (lovastatin, simvastatin) were the most potent coronary vasodilators. In summary, the in vivo profile of action of ACE-Is and statins contrasted with their reversed order of potency in vitro. We hypothesize that the endocrine-like function of the pulmonary circulation [28-31] may be responsible for the in vivo bradykinin-triggered, PGI2-mediated thrombolysis by ACE-Is, whereas the pleiotropic action of statins, possibly involving inhibition of prenylation [14-19], is diffused throughout many vascular beds.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

[Postero-medial release in surgical treatment of congenital clubfeet: a comment to Turco's method based on personal experience].

Complete correction of congenital clubfeet by conservative treatment is often impossible. Surgical treatment plays a major role in treatment of this deformity. At the Department of Pediatric Orthopedics in Lublin between 1970 and 1999 1041 children (1253 feet) were treated surgically with Turco's method, in the authors' own modification. The paper presents the technically optimal procedure, the range of tendon elongation. The way the wound is closed is particularly stressed, as well as the need to achieve muscle balance, along with a description of proper post-op care. The material was analysed as a whole, although particular attention was given to three periods: 1970-1975, 1980-1985, 1990-1995. The results were assessed according to the Turco classification, the Magone classification in accordance with the injunctions of the Scientific Committee Meeting of the Pediatric Section of the Polish Orthopedic Society held in Poznan. Good and very good results were achieved in 65-67% of the cases, while satisfactory and bad results were found in 23-30% of the cases.

Adolescent↗
PubMed2001

Activity of glycogen depolymerizing enzymes in extracts from brain tumor tissue (anaplastic astrocytoma and glioblastoma multiforme).

An approximately threefold increase in glycogenolytic activity of the neutral alpha-1,4-glucosidase and a twofold increase in the same activity of the acid isoform have been found in extracts of anaplastic astrocytoma and glioblastoma multiforme tumors of brain tissue. "Maltase activity" of the respective enzymes increased by 60-80% in both kinds of tumor extracts. However a significant decrease in a-amylase and almost complete disappearance of phosphorylase activities have also been found in both kinds of tumors.

Astrocytoma↗
PubMed2000

Thrombolysis by thienopyridines and their congeners.

We propose that anti-platelet thienopyridines, such as ticlopidine or clopidogrel, are thrombolytic owing to endothelial release of prostacyclin (PGI2) and tissue plasminogen activator (t-PA). In this study we used anaesthetised Wistar rats with extracorporal circulation in which arterial blood superfused thrombi which adhered to a strip of collagen. Weight of thrombi was continuously monitored. When administered intravenously, clopidogrel or its R enantiomer deprived of anti-platelet action, both at doses of 3 mg x kg(-1), produced lost in weight of thrombi by 14.1 +/- 1.3% or 16.0 +/- 1.4% (n = 9), and at doses 10 mg x kg(-1) by 28.3 +/- 2.3% or 30.4 +/- 1.9% (n = 8), respectively. Maximum of thrombolysis occurred 30-45 min following the drug administration. Ticlopidine at a dose of 30 mg x kg(-1) reduced weight of thrombi by 33.7 +/- 1.7% (n = 32). Thrombolytic action of ticlopidine was accompanied by a rise in 6!keto-PGF1alpha blood levels from 0.42 +/- 0.10 to 1.58 +/- 0.29 ng x ml(-1) and t-PA antigen plasma levels from 4.70 +/- 1.00 to 12.90 +/- 1.15 ng x ml(-1) (n = 7). Five out of eleven tested thienopyridine congeners with pyrimidine or pyrimidinone instead of pyridine rings had thrombolytic potencies similar to that of clopidogrel (ED30s at a range of 6.2-11.4 mg x kg(-1)). A substantial increase in thrombolytic potency (ED30s at a range of 0.3-2.1 mg x kg(-1)) was observed for congeners in which thienyl ring was condensed with an additional cyclopentyl, cyclohexyl or cycloheptyl structures or in which thienopyridine complex was replaced for a pyridopyrimidine one. We claim that thienopyridines, independently of their delayed anti-platelet action, do produce immediate thrombolysis in vivo. This new activity emulates capacity of their native, non-metabolised molecules to release prostacyclin and tissue plasminogen activator. We have also shown that structural changes in molecules of thienopyridines may intensify their thrombolytic potency.

Animals↗
PubMed2000

The antitumor effect of postoperative treatment with genistein alone or combined with cyclophosphamide in mice bearing transplantable tumors.

Genistein has been shown to be an inhibitor of tumor growth as well in vitro as in vivo. In addition to its antitumor effect, genistein reveals the antimetastatic and antiangiogenic properties. In this paper we described the results of our studies on the antimetastatic activity of genistein alone or combined with cyclophosphamide (CY) in mice which before this treatment were exposed to surgical excision of the primary tumor. Three transplantable subcutaneously growing mouse tumors were applied: Lewis lung cancer (LL2), B16F-10 melanoma and 16/C mammary cancer. The antitumor and antimetastatic effect was evaluated by the estimation of a number of lung colonies and a number of primary tumor recurrence as compared to the control mice exposed to the s.c. tumor extirpation only. Twenty days after the surgery, an average of 52 lung tumor colonies per mouse were detected in control mice bearing LL2 cancer. The treatment with genistein resulted in the reduction of the lung colonies to 24 per mouse. The treatment with CY reduced the number of lung colonies to 12 (p < 0.05) and combined treatment with both agents to 4 (p < 0.05). The percentage of primary tumor recurrence was 25, 86, 67 and 80% in the control, genistein treated, CY treated, and genistein + CY treated mice, respectively. Twenty days after the surgery, no lung metastases in the control mice bearing B16F-10 melanoma were observed. The percentage of primary tumor recurrence in the control, genistein treated, CY treated and genistein + CY treated mice was: 86, 29, 57 and 67% respectively. Two different protocols of the treatment with genistein were applied in 16/C mammary cancer model. In the first one genistein was injected before and in the other after surgical excision of tumor. The histological examination revealed the presence of lung metastases in all, untreated and treated, according to both protocols groups of mice. The percentage of primary tumor recurrence in the control mice, genistein treated according to the protocol I, and II was: 100, 40, and 40%, respectively.

Animals↗
PubMed1999

[Contemporary model for treatment of erythroplakia].

In literature worldwide is still commonly used the term erosion to describe red areas within cervix around the external orifice. In such cases with negative cytology result, for cervical cancer prevention, the electrocoagulation or electro-conisation or other destructive operations are routinely used. Without colposcopy verification such management is inappropriate. The physician treats but does not know what he treats. It may be both common ectopy or regeneration zone so physiologic cervical states but it may be also CIN or even early cervical cancer, however cytologically negative. The first group of lesions is effectively diagnosed with colposcopy without additional diagnostic procedures and the CIN lesions are diagnosed in high percentage of accuracy. Not all of these lesions should be treated. In the group of colposcopically and cytologically unsuspected lesions just very extensive lesions with active mucous glands should be treated. Such lesions cause recurrent cervical inflammation. All other erythroplakia type lesions demand no treatment. The presence of ectopy around the external cervical orifice is just profitable for diagnosis of epithelial changes and cervical physiologic processes observation. All cases of abnormal colposcopy or cytology results, suspected of CIN should be treated as prevention of cervical cancer. In lower CIN grades electroresection (LEEP) is recommended, while in higher grades the cervical conisation is the appropriate mode of treatment.

Colposcopy↗
PubMed1998

Metastatic potential of human CX-1 colon adenocarcinoma cells is dependent on the expression of sialosyl Le(a) antigen.

Several lines of evidence indicate that sialosyl Le(a), tumor-associated carbohydrate antigen present on human colon carcinoma cells, is involved in formation of metastases. To study the role of this carbohydrate structure in development of metastases, we have used the clone of human colon carcinoma CX-1 cells transfected with antisense expression vector containing fragment of cDNA for alpha1,3/4-fucosyltransferase (FT III), which is involved in synthesis of sialosyl Le(a) tetrasaccharide. It has been reported previously that, in contrast to the parental cells, the antisense-transfected CX-1.1AS5 cells do not express sialosyl Le(a) and do not adhere to E-selectin-expressing CHO cells. In the present work we have studied the formation of liver metastases by CX-1.1AS5 cells after their orthotopic or intrasplenic implantation into athymic nu/nu mice. After orthotopic implantation of sialosyl Le(a)-negative colon carcinoma CX-1.1AS5 cells, the number of mice with liver metastases was markedly lower (21% of mice) in comparison with their number after implantation of the parental CX-1.1 cells (86% of mice). However, no differences in ability to form colonies in liver were observed between parental CX-1.1 cells and antisense-transfected CX-1.1AS5 cells after intrasplenic inoculation. The liver metastases were formed in 89% and 84% of mice, respectively. Our data support the thesis on the importance of sialosyl Le(a) antigen expression in the development of liver metastases by colon cancer cells, and indicate the role of transplantation route and primary tumor localization in formation of metastases.

Adenocarcinoma↗
PubMed1992

Colposcopy staging and treatment of papillomavirus infection of the cervix.

The specificity of colposcopy findings in HPV infections allows the colposcopic differentiation of these lesions. In all of these colposcopically selected cases, additional tests included cytology with immunoperoxidase reaction (IPR), and, recently, virus typing with the use of ViraPap HPV DNA Detection test and ViraType HPV DNA Typing test became also available. When needed, histological examination of the specimen was carried out. In 202 detected and treated cases of HPV infections in females, and in 5 in males, four groups of lesions have been colposcopically distinguished. Group I contains early and fully developed, unsuspected typical papillomas; Group II--atypical papillomas which are usually colposcopically suspected of CIN and/or cancer; Group III--the so-called subclinical forms, i.e. cases with secondary diminution of epithelial transparency, i.e. acetic acid white epithelium, secondary simple punctuation and/or mosaic (flat condylomas) that are visible only in colposcopic magnification and usually suspected of CIN; and Group IV--the so-called latent lesions without any colposcopic findings and only with positive IPR. CIN 3 (including CIS) was determined histologically in five cases of Group II, and CIN 1-2 in ten cases of Group III. HPV virus type 16/18 was found only in cases of CIN 3. The cases of atypical papilloma (Group II) and recently those containing HPV virus type 16/18 were treated by means of surgical conisation or cryosurgery. The remaining cases (Groups I, II, IV) were treated with orally administered Tetracycline and Vitamin A. The effectiveness of this antibiotic/vitamin therapy in the group of typical papilloma and subclinical HPV lesions amounted to 75%.(ABSTRACT TRUNCATED AT 250 WORDS)

Colposcopy↗
PubMed1990

Colposcopy as a method of management strategy in CIN and microinvasive cancer.

During nearly 40 years of using colposcopy, an original management strategy in CIN and early cervical cancer was developed and confirmed in 2 study groups of cervical lesions containing respectively 1228 and 6001 cases. This approach is based on colposcopy as the main method in early detection of CIN and cancer, with supplementary cytology in necessary cases, and on a coloposcopic-histological staging of these lesions for treatment qualification. Colposcopy alone is a fairly adequate method for diagnosis of 60% of examined cases, and coloscopy with directed biopsy in the next 20% of colposcopically highly suspect findings. Only in the remaining 20% of colposcopically less suspect findings and in the cases of "unsatisfactory colposcopy", supplementary was cytology required. In this study colposcopy findings connected with histological evaluation of the specimens provided a basic way for determining the advancement of processes and the selection method for the appropriate type and extent of treatment. CIN 1 and 2 and small focuses of CIN 3 including CIS entirely visible on the ectocervix, in childless young women were treated by cryosurgery. In all remaining cases of CIN 3, the basic therapeutic method was cold-knife conization. In exceptional cases simple hysterectomy can be a more adequate treatment. Depending on our colposcopic-histological staging, in Stage IA1--conization, whereas in Stage IA2--a moderately extended hysterectomy should be optionally performed. The management strategy introduced is an economical, fully effective and quick way of detection and selection of the method for the treatment of CIN and early cervical cancer.

Biopsy↗