Search PubMed⌕ Search

Biomedical subjects

M Sulkowska

Publications and source records attributed to M Sulkowska.

At least 73 records · Page 4Linked to original sources

Effect of human recombinant tumour necrosis factor-alpha and pentoxifylline on the ultrastructure of type II alveolar epithelial cells in pregnant and non-pregnant rabbits.

An ultrastructural study was made of the morphological changes in type II alveolar epithelial cells (epII) of pregnant and non-pregnant rabbits, given human recombinant tumour necrosis factor-alpha (TNF-alpha) to induce experimental shock. TNF-alpha (biological activity 2-4 x 10(7) U/mg of protein) was injected once intraperitoneally, at a dose of 100 micrograms/kg body weight. The moderating effects of pentoxifylline (PTXF), given as four intraperitoneal doses (20 mg/kg) at 12-h intervals before injection of TNF-alpha, were also assessed. In animals treated with PTXF + TNF-alpha and with TNF-alpha only, damage to lung tissue, particularly to epII, was observed. Many epII had empty lamellar bodies. These changes were particularly distinct in the rabbits given TNF-alpha only. PTXF limited the degree of damage to epII, particularly that shown by the lamellar bodies. There were no significant differences in degree of damage to alveolar epithelial cells between pregnant and non-pregnant rabbits. Thus, the increased risk of severe complications due to shock observed in pregnancy may not be associated with changes in the surfactant system. However, further studies, particularly biochemical analysis of the surfactant, are necessary to confirm this.

Animals↗

The contribution of type II pneumocytes and alveolar macrophages to fibroplasia processes in the course of enzymatic lung injury.

The aim of the paper was to evaluate mutual relations in the system of alveolar macrophage (AM) - type II pneumocyte (PII) - interstitium of alveolar septa, in the course of experimental lung emphysema in rats subjected to BCG vaccine effect. Administration of BCG vaccine resulted in the cumulation of AM within pulmonary alveoli. These cells exhibited morphological features of increased activity. Intratracheal papain injection induced intralobular emphysema changes, partly generalized, in the animal lungs. The emphysematous changes, with domination of interalveolar septum atrophy, were accompanied by focal accumulation of collagen and elastin. Fibroplasia processes were strongly pronounced in BCG- and papain-treated animals. The areas of connective tissue fibres cumulation revealed indistinctness of the boundary line between PII and the interstitium in some places. Anchorage of collagen fibres and microfibrillary structures were observed in the cytoplasm of PII. The morphological examinations of AM - fibroblasts co-cultures as well as the evaluation of the uptake of 3H-thymidine did not show any significant differences between respective co-cultures of fibroblasts and AM isolated both from the lungs of control and experimental animals (treated with BCG or papain, and BCG+papain). However, a significant growth was noted in 3H-thymidine uptake between fibroblast cultures realized with or without cells isolated from the lungs. The results obtained suggest the possibility of active participation of PII and AM in fibroplasia processes in the course of lung rebuilding after papain administration and in pathological states of the pulmonary tissue, particularly when they are accompanied by increased activity of alveolar macrophages. They also support the inflammatory-repair hypothesis in the development of emphysematous changes.

Animals↗

Contribution of capillary endothelium to cor pulmonale development in experimental lung emphysema.

The aim of this study was the ultrastructural analysis of the changes in the endothelium of myocardial capillaries and the processes observed in their vicinity in consecutive stages of experimental lung emphysema. Emphysematous changes in the lungs of Wistar rats were induced with a single intraperitoneal infusion of proteolytic enzyme solution, papain, in a dose of 20 mg/kg b.w./0.5 ml PBS. Ultrastructural analysis of the changes within the right ventricle and the subendocardial part of the left ventricle of the heart was made by a transmission electron microscope after 1, 3 and 6 months following papain administration. Special attention was paid to the analysis of changes found in the vicinity of newly formed myocardial capillaries. Animals killed after 1 and 3 months following papain infusion showed blurred borderline between the endothelium of the newly formed myocardial capillaries and perivascular connective matrix. The new vessels had poorly developed basement membrane. Fibrillary structures and/or collagen fibrils were found instead. The latter frequently demonstrated features of disorders in the structure and spatial distribution. Neither fibroblasts nor their processes were observed in the vicinity of the new collagen fibrils. Pericytes were occasionally present. In the later period (6 months from intratracheal papain infusion) well formed collagen fibres dominated in the vicinity of myocardial capillaries. The results of the ultrastructural analysis suggest the possibility of active contribution of endothelial cells to the processes of perivascular fibrosis within the myocardium in the course of experimental lung emphysema.

Animals↗

Ultrastructural study of endogenous lipid pneumonia and pulmonary alveolar proteinosis coexistent with lung cancer.

The aim of the study was the ultrastructural analysis of endogenous lipid pneumonia (ELP)-type changes localized in the vicinity of primary neoplasms of the lungs. The analysis was carried out on the material obtained from 30 patients with non-small cell lung carcinoma (NSCLC). Routine histopathological examination was performed in light microscope, focusing mainly on the presence or lack of ELP-type changes. Ultrastructural examinations in transmission electron microscope used 12 cases classified among early (4 cases) or advanced (8 cases) ELP forms. Results of the study reveal a likely coexistence of ELP- and PAP (pulmonary alveolar proteinosis)-type changes in the vicinity of NSCLC and suggest a correlation between the processes leading to the development of ELP or/and PAP. Ethiopathogenesis of the changes observed and the role of granulocytes, macrophages and type II alveolar epithelial cells are discussed.

Carcinoma, Non-Small-Cell Lung↗

Role of endothelins in lung pathology.

The endothelins are a group of peptides present in a number of tissues and organs. They are powerfully vasoactive, causing both contraction and relaxation of blood vessels. They are also active in the lung causing long lasting bronchoconstriction. Endothelins binding sites are widely distributed and are localized to airway and pulmonary vascular smooth muscle, fibroblasts, submucosal glands, and airway nerves, indicating that endothelins may have widespread effects. The current study presents a potential contribution of endothelins to pathogenesis of a number of lung diseases.

Animals↗

Fine needle aspiration biopsy cytology of pulmonary tumors.

Transthoracic fine needle aspiration specimens of the pulmonary tumors were obtained from 144 patients. Fine needle aspiration biopsy were performed using local anaesthesia and ultrasonographic or scopie control. The 20-gauge needles were used to obtain the specimens. 93 of patients have been diagnosed as squamous cell carcinomas, 28 as adenoid carcinomas, 18 as anaplastic carcinomas and 5 as a non neoplastic lesions (tuberculoma and abscessus). The tumors were typed according to the second WHO histological classification. Analysis of the date indicated that malignant neoplasms were identified correctly with an accuracy of 92.0%. There were not false positive diagnoses. There were two false negative diagnoses (squamous cell carcinoma) and in three cases the diagnosis were as suspected for malignancy. The results confirmed the value of fine needle aspiration cytopathology for the diagnosis of pulmonary tumors.

Adenocarcinoma↗

Protective effect of human recombinant tumour necrosis factor-alpha against lung metastases of the Morris hepatoma in rats.

The effect of intratumour (i.t.) administration of human recombinant tumour necrosis factor-alpha (hrecTNF-alpha) on Morris 5123 hepatoma spontaneous lung metastases was studied. Tumour was implanted in the skeletal muscles of the right hind limb of Buffalo rats. Two weeks after the implantation treatment with cytokine started. The cytokine was injected i.t. in a single dose of 10 micrograms in 4- and 8-day cycles. In control animals PBS was administered, respectively. Then all rats were necropsied and the extent of lung metastases was determined. Data were expressed as volume of lung metastases. In this study we observed significant antimetastatic effects of hrecTNF-alpha (p < 0.05) determined by reduced volume of lung metastases in treated animals.

Animals↗

Alveolar epithelial cells after intratumour administration of HREC TNF-alpha mutein VI.

The aim of this study was to explore the effect of intratumour mutein VI-Hrec TNF-alpha administration upon the ultrastructural changes within the pulmonary tissue, with special attention paid to type II alveolar epithelial cells. The experiment was carried out on Buffalo rats with implantable Morris hepatoma series 5123 in the skeletal muscles of the limb. Mutein VI-Hrec TNF-alpha was administered in a dose of 10 micrograms once a day in a cycle of eight days. Control animals were given saline (PBS). Ultrastructural changes within the pulmonary tissue were evaluated in the electron transmission microscope (TEM), with special attention paid to alveolar epithelial cells. In the animals receiving hrec TNF-alpha mutein VI, damage to the alveolar epithelial cells was found. In the later period (14 days after the mutein treatment), repairing processes were observed, accompanied by intensified fibrotic processes in the interalveolar septal interstitium, with the subsequent pulmonary tissue rebuilding. The study confirmed the possibility of a peripheral action of hrec TNF-alpha mutein VI after its administration to the experimental Morris hepatoma and found the alveolar epithelial cells to be a key element of the pulmonary tissue subjected to the cytokine effect.

Animals↗

Comparative studies on the effect of TNF-alpha and endotoxin on the ultrastructural picture of pulmonary capillaries in pregnant rabbits.

The aim of the present study was the comparative analysis of morphological changes found in the pulmonary microcirculation of pregnant rabbits in the course of experimental septic shock induced by endotoxin or human recombinant TNF-alpha administration. The experiments used 30 female rabbits, white Dutch, c.3 kg mean body weight. The endotoxin Escherichia coli, serotype S.0127: 138 (Sigma) was applied in a single dose of 100 micrograms/kg b.w. intraperitoneally. The human recombinant TNF-alpha (biological activity 2-4 x 10(7) U/mg of protein) was injected intraperitoneally, also once, in a dose of 100 micrograms/kg b.w. Morphological examinations were based on the ultrastructural analysis in the transmission electron microscope. The ultrastructural analysis revealed no morphological differences between pregnant and non-pregnant rabbits which received TNF-alpha. However, significant differences were observed between animals given TNF-alpha and those given the endotoxin. These differences referred to endothelium damage degree and to the cellular composition of inflammatory infiltrations. More severe damage to endothelial cells (necrosis inclusive) was observed in the endotoxin-treated rabbits. Blood vascular lumen in these animals showed cellular aggregation, of neutrophils and platelets in particular as well as microthrombi. An increased tendency towards the development of these changes was noted in pregnant rabbits. The lumen of pulmonary capillaries in TNF-alpha treated animals showed domination of monocytic cells. Features of endothelial cell stimulation were observed, although without a tendency to form microthrombi.

Animals↗

Quantitative and morphological changes in BAL-isolated cells after the administration of TNF-alpha into Morris hepatoma.

The aim of this study was to explore the effect of intratumor TNF-alpha administration upon the composition and adherence degree of cells isolated from the lungs through multiple bronchoalveolar lavages (BAL). Ultrastructural evaluation of BAL-isolated cells was performed in the scanning electron microscope (SEM). The experiment used Buffalo rats. A suspension of 3 x 10(6) cells of Morris hepatoma (5123 series) was injected to the right hind leg of the animals. After fourteen days, TNF-alpha was administered into the tumor in a dose of 1.5 x 10(4) U in 0.5 ml PBS solution. The animals of group I were given 4 doses of TNF-alpha and group II-8 doses of TNF-alpha every 24 hours. Control groups consisted of rats with injected Morris hepatoma which were given PBS solution instead of TNF-alpha (group III A, B) and animals without the hepatoma, given intramuscullary 4 or 8 TNF-alpha, respectively (groups IV A, B). No statistically significant differences were noticed between groups I and II with regard to the number of macrophages and neutrophils isolated from the rat lungs compared with control group IV. However, such differences were observed compared with group III. In group II and IV B, an increase in the adherence of isolated cells was found compared with group III, as well as arise in the number of macrophages with the largest diameters. We found a correlation between the increase in cell adherence and ultrastructural changes (in SEM) suggesting an increased activity of BAL-isolated cells.

Animals↗

Contribution of capillary endothelium to the processes of pulmonary tissue rebuilding in the course of acute enzymatic lung injury.

Ultrastructural analysis was made of the pulmonary capillary endothelial cells, with special regard paid to their possible contribution to the processes of pulmonary tissue rebuilding initiated by intratracheal infusion of a proteolytic enzyme-papain. Experimental animals (male Wistar rats) were additionally given BCG vaccine in doses activating the alveolar macrophage system. The study was performed after 1 day, and 1, 4 and 12 weeks following papain administration. In the animals given BCG vaccine, ultrastructural exponents of endothelial cell activation were found. Cumulation of inflammatory cells, mainly monocytes, was observed in vascular lumen. Application of papain solution to animals caused a number of damaging and exudative changes, being most pronounced within vascular endothelium in animals simultaneously given BCG vaccine. In later periods, rebuilding and productive processes, accompanied by collagen cumulation in the interstitium of interalveolar septa, dominated. In the animals receiving BCG vaccine and papain, ultrastructural pictures indicated active contribution of endothelial cells to the processes of pulmonary tissue rebuilding initiated by intratracheal infusion of the proteolytic enzyme.

Animals↗

Ultrastructural analysis of the pneumocyte-interstitium boundary line in the course of enzymatic lung injury.

The studies were performed basing on the experimental model of acute pulmonary tissue injury. Papain in a dose of 2 mg/ml PBS/100 g b.w. was administered once, intratracheally, on the 21st day of the experiment. Besides, female Wistar rats were injected twice with BCG vaccine in a dose of 4 x 10(8) microorganisms. BCG vaccine was administered intraperitoneally on the 1st and 14th day of the experiment to activate the system of mononuclear phagocytes. Control rats were intratracheally or/and intraperitoneally given PBS solution. All the animals were killed on the 28th, 35th and 42nd day of the experiment. A single intratracheal papain injection induced emphysematous changes in the animal lungs. The changes were accompanied by basement membrane rebuilding and focal collagen and elastin cumulation. An increase in the number of type II alveolar epithelial cells was observed. Anchorage of collagen fibres and microfibrillary structures in the cytoplasm of type II pneumocytes was observed in the BCG- and papain-treated animals. There, the cytoplasmic membrane of type II cells was completely indistinct and the cytoplasm formed processes to penetrate into the connective tissue fibres. The results obtained indicate possible contribution of type II pneumocytes to fibroplasia processes during lung parenchyma rebuilding and suggest the necessity to include fibroplasia elements in the existing definition of emphysema.

Animals↗

Evaluation of the effect of macrophage system activation on the intensity degree of early destructive changes in acute enzymatic lung injury.

The effect of macrophage system activation on the intensity degree of early destructive changes induced with intratracheal infusion of a proteolytic enzyme-papain was evaluated in the paper. The study was carried out on male Wistar rats. BCG vaccine was used as a macrophage system activating substance. Damage degree of the pulmonary tissue was evaluated after 2 hours following papain administration by determining W/D index (wet lungs/dry lungs). Spectrophometric analysis of bronchoalveolar lavages (BAL) was made in order to evaluate the advancement of haemorrhagic alterations in the lungs. Damage to the pulmonary tissue was greater in the animals given BCG vaccine and papain, compared with controls and papain treated animals. Differences in the intensity degree of destructive changes assessed using both the W/D index and haemoglobin content in BAL were statistically significant. The results obtained indicate a particular role of activation of the macrophage system in the development of early destructive changes due to intratracheal administration of proteolytic enzymes and point to the significance of these changes in the morphogenesis of experimental lung emphysema.

Animals↗

Surfactant system in lung cancer. Endogenous lipid pneumonia.

The aim of the study was the evaluation of endogenous lipid pneumonia-type changes developing in the vicinity of primary tumors of the lungs. The postoperative material collected from 56 patients operated for non-small cell lung cancer was examined. The coexistence of endogenous lipid pneumonia-type changes with squamous cell carcinoma and large cell carcinoma of the lung was most common. Patients with these histopathological types of carcinoma had lower percentage of metastases to the lymph nodes. Endogenous lipid pneumonia was found to accompany most frequently the tumors 3 < or = 6 cm in diameter and it was slightly more common in the vicinity of peripheral tumors.

Carcinoma, Non-Small-Cell Lung↗

The effect of pentoxifylline on ultrastructural picture of type II alveolar epithelial cells and generation of reactive oxygen species during cyclophosphamide-induced lung injury.

The aim of the study was to evaluate the effect of pentoxifylline (PTXF) on the production of reactive oxygen species in the rat lungs after intraperitoneal (i.p.) cyclophosphamide (CP) administration (150 mg/kg b.w.) and to draw a correlation between the morphological changes and biochemical findings. Morphological examinations were based on ultrastructural analysis in the transmission electron microscope. It was found that single i.p. CP administration caused destructive changes, particularly within mitochondria and lamellar bodies of type II alveolar epithelial cells (EP II), and within blood vessels of interalveolar septa. The changes were accompanied by an increase in the MDA (malondialdehyde) homogenates. The animals receiving PTXF + CP showed normalization of MDA level and minor damage to EP II confined to alterations in lamellar bodies of EP II. The vascular changes observed after i.p. CP administration were manifested in endothelial swelling and accumulation of neutrophilic granulocytes, monocytes and in the later period blood platelets within the capillaries of interalveolar septa. The cells were tightly attached to endothelium. The changes in the vascular system were accompanied by a significant decrease in the activity of antioxidant enzymes (Cu,Zn-SOD and GSSG-R) in the blood serum collected from the left ventricle of the heart. In the animals given PTXF + CP, a higher decrease was revealed in the activity of these enzymes. Ultrastructural examinations found morphological signs of a facilitated flow, mainly of cellular elements, through the vessels of the interalveolar septa of the lungs.

Animals↗

Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type II alveolar epithelial cells.

The effect of repeated doses of TNF-alpha on the histological picture of the pulmonary tissue was analyzed in the present study. Special attention was paid to the lung rebuilding processes. TNF-alpha was applied intraperitoneally for two weeks in a dose of 10 micrograms/0.5 ml PBS/24h. Morphological analysis of the pulmonary tissue was performed after 1 and 28 days following the last TNF-alpha dose. The study revealed focal pulmonary tissue rebuilding with emphysema-like changes twenty eight days following termination of TNF-alpha administration. The rebuilding processes included interalveolar septal atrophy, collagen accumulation and damage-repair changes in type II alveolar epithelial cells. It has been demonstrated that apart from the protease-antiprotease hypothesis of the lung emphysema, the inflammatory-repair hypothesis should be considered. Both hypotheses are complementary to each other and interpret the emphysema-like changes as complications of various pathological conditions of the pulmonary tissue.

Animals↗