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Biomedical subjects

R Zorc-Pleskovic

Publications and source records attributed to R Zorc-Pleskovic.

11 recordsLinked to original sources

Apoptosis of cardiomyocytes in myocarditis.

Apoptosis of cardiomyocytes has been reported to be involved in the pathogenesis of heart failure of different aetiologies. The purpose of this study is to assess the role and extent of apoptosis of cardiomyocytes in active myocarditis. Endomyocardial samples from the right ventricle of 22 patients with active myocarditis were compared with 25 traffic accident victims without a history of cardiovascular disease. Twenty-two patients fulfilled the histopathologic Dallas criteria for myocarditis. The TUNEL method and immunostaining for active caspase 3 were used for the detection of apoptosis. Immunohistochemical methods were used for the evaluation of regulators of apoptosis (p53, Bcl-2) and evaluation of interstitial cells (macrophages, T and B lymphocytes). Apoptosis of cardiomyocytes (TUNEL-positive and anti-caspase 3-positive cardiomyocytes), which was not p53-dependent, was present in 0.3 to 0.4% (0.3% by TUNEL method and 0.4% by immunostaining for active caspase 3) of cardiomyocytes in active myocarditis, whereas only few apoptotic cardiomyocytes (0.0006 +/- 0.002% TUNEL-positive cardiomyocytes and 0.001 +/- 0.002% active caspase 3-positive cardiomyocytes) were found in the control group (P = 0.001). Apoptotic (TUNEL-positive and active caspase 3-positive) cardiomyocytes were found in small clusters. An increased expression of Bcl-2 was found in active myocarditis compared to the controls (P < 0.01), yet Bcl-2 failed to protect myocytes from apoptosis. We provide evidence of apoptosis of cardiomyocytes in active myocarditis, which may be involved in the development of heart failure.

Apoptosis↗

Microcystin-LR induces alterations in heart muscle.

MC-LR belongs to a family of cyanobacterial toxins. MC-LR acts as serine-threonine phosphatase-1 and -2A inhibitor. Chronic intoxication with low doses of this toxin promotes liver tumour formation and induces kidney injury. The aim of the study was to evaluate whether chronic exposure to relatively low doses of MC-LR has toxic effects on hearts of treated animals. Male adult Wistar rats were treated every second day for 8 months with MC-LR (10microg/kg i. p., N = 5). Control groups were treated either with a vehicle (ethanol and methanol 4 : 1 v/v; N = 5) or with physiologic saline (N = 4). We found that MC-LR could induce enlargement of cardiomyocytes (MC-LR = 20.984microm+/-1.351, vehicle=17.454microm +/-0.518, saline = 15.996microm+/-1.430), loss of cell cross-striations, lower myofibril volume fraction (MC-LR = 0.3657mm(3)/mm(3) +/- 0.0337, vehicle=0.4716mm(3)/mm(3) +/-0.0086, saline = 0.4793 mm(3)/mm(3)+/-0.0101), fibrosis (MC-LR = 0.0747mm(3)/mm(3)+/-0.01288, vehicle = 0.0275 mm(3)/mm(3) +/- 0.0076, saline = 0.0309mm(3)/mm(3) +/-0.0074) and mononuclear infiltration in the interstitial tissue. The TUNEL staining of the heart sections of rats in all groups showed no apoptotic cells. We may conclude that long-term exposure to relatively low doses of MC-LR represents a considerable risk of injury of the heart.

Animals↗

Colon mucosal cells after combined radiotherapy and chemotherapy.

The aim of this study was to investigate early histological and stereological changes in enterocytes, lymphocytes, mast cells, serotonin- and somatostatin-secreting cells in colon mucosa the first day after the end of combined radiotherapy and chemotherapy. For experimental model 20 Beagle dogs were used. Ten dogs were given platinol every 5 days over 20 days and they were irradiated 20 days with 32 Gy (every second day with a fractional dose of 3.2 Gy) onto the whole pelvis and tail. Another 10 dogs represented a control group. For detection of apoptosis the TUNEL technique was used, whereas immunohistochemical methods were performed for detection of somatostatin- and serotonin-secreting cells, and for proliferating cell nuclear antigen in epithelial cells. The volume density of enterocytes in apoptosis was increased, and Vv of paracrine cells (mast cells, somatostatin and serotonin positive cells) was significantly increased in the treated group compared to the control group. In the treated group a significantly lower Vv of lymphocytes and PCNA-positive enterocytes was shown compared to the control group. The results of our experiments showed that combined radiotherapy and chemotherapy caused loss of enterocytes and lymphocytes early after the therapy. It was associated with an increased volume density of paracrine cells. These morphological changes in the colon mucosa might be the earliest changes leading to disruption of the mucosal barrier, malabsoption syndrome, stenosis, inflammation and other complications resulting from the radiotherapy and chemotherapy.

Animals↗

An unusual complication after percutaneous drainage of a pancreatic pseudocyst into the stomach.

In the period between September 1995 and June 1999, we performed percutaneous drainage into the stomach in 12 patients. There were no complications or pseudocyst recurrences on insertion or after endoscopic removal of the catheter, which was left in site for 1 year on average. After endoscopic removal of the drainage catheter, one of the patients presented with a cystic formation in the stomach wall, which caused stomach emptying disorder. Therefore, the patient had to be reoperated. The cyst wall was incised and a part of the cystic wall sampled for histological examination. The cyst was then drained into the isolated Roux loop of the jejunum. Histological findings of the cystic wall specimen showed the presence of granulation tissue and smooth muscle layers with ganglia cells of myenteric nerve plexus. Despite this complication, we believe that percutaneous endoscopically and ultrasonographically guided drainage of pancreatic pseudocyst into the stomach by means of a double pigtail catheter is a good method that yields encouraging results in sonographically selected cases. The position of the drainage catheter needs to be checked endoscopically, and the catheter should be removed only after 1 year.

Adult↗

Colon mucosal cells after high-dose fractional irradiation.

The aim of this study was to investigate histological and stereological changes in cryptal enterocytes, mucosal lymphocytes and mast cells 10 days after irradiation. For experimental model, 24 Beagle dogs 1-2 years old were used. Twelve dogs were irradiated 20 days with 32 Gy over the whole pelvis and tail. Another 12 dogs represented a control group. For the detection of apoptosis, the TUNEL technique was used. Histological and stereological analyses were performed using a Wild sampling microscope M 1000. In the irradiated group, volume density (P < 0.01), numerical density (P < 0.05) and average volume of lymphocytes (P < 0.001) were significantly lower than in the nonirradiated group. Numerical areal density of mast cells in the irradiated group was also significantly lower (P < 0.05). Volume density (P < 0.001) and average volume of mast cells (P < 0.001) were significantly higher in the irradiated group. The results of our experiments show that irradiation causes injury and loss of lymphocytes and mast cells in the colon mucosa. Apoptosis was detected in enterocytes and lymphocytes in the irradiated group and in nonirradiated group in equal numbers (2.5+/-0.3 vs. 2.3+/-0.3; ns.), suggesting that 10 days after high-dose irradiation, the cell loss is not due to apoptosis.

Animals↗

Local pulmonary malformation caused by bilateral coronary artery and bronchial artery fistulae to the left pulmonary artery in a patient with coronary artery disease.

At 10 years of age and again at 25, our patient had been treated for pulmonary tuberculosis due to the presence of a localized pulmonary shadow. Coronary angiography at age 59 revealed 3 fistulous communications: from the right and circumflex coronary arteries and from the left bronchial artery. All 3 emptied into the same recipient artery, the distal part of a left pulmonary artery branch, which produced substantial left-to-right shunt. On computed tomography, cystic formations could be seen in the pulmonic area. The pulmonary tuberculosis for which this patient had been treated in his youth was in the same part of the lung where the shunt was discovered. Our conclusion is that the initial diagnosis was in error.

Arterio-Arterial Fistula↗

Morphometrical and stereological analysis of myocardial mast cells in myocarditis and dilated cardiomyopathy.

Mast cells play a certain role in inflammation and immunological reactions. Cardiac mast cells, shown by sodium sulfate-alcian blue staining, were evaluated in endomyocardial biopsy specimens in patients with unexplained congestive heart failure. The results of histopathological analysis were consistent with active myocarditis according to the Dallas criteria in 10 patients (15%), borderline myocarditis in 9 (13.8%), and dilated cardiomyopathy in 25 patients (38.5%); these results were compared with a control group of 10 traffic accident victims. The highest numerical areal density of mast cells was found in active myocarditis (3.92 counts/mm2, SD = 1.84), followed by borderline myocarditis (2.76 counts/mm2, SD = 1.66), dilated cardiomyopathy (1.56 counts/mm2, SD = 0.45) and control group (0.77 counts/mm2, SD = 0.19). Degranulation involved 27% (SD = 3.6) of mast cells in active myocarditis, 18% (SD = 4.5) of mast cells in borderline myocarditis, 10.8% (SD = 3.12) of mast cells in dilated cardiomyopathy and 4% (SD = 2.0) of mast cells from autopsy tissue. The differences among the four groups were statistically significant (P <0.001). The increased number of mast cells and the higher degree of their degranulation in myocarditis compared to dilated cardiomyopathy and to control group indicate that they were activated. The mast cells could be involved in modulation of fibrous response, since they tended to be associated with areas of fibrosis. Likewise, numerical areal density and degree of degranulation of mast cells could also be used as additional diagnostic criteria for acute myocarditis, since a higher numerical areal density and degree of degranulation were present in myocarditis vs. dilated cardiomyopathy and control group.

Adolescent↗

The effect of chronic hypercalcemia or hypocalcemia on the follicular and parafollicular cells in rat thyroid gland.

In three experiments of 30 weeks' duration, 93 adult female Wistar rats received controlled amounts of calcium with food and water, to produce a state of either hypercalcemia or hypocalcemia. A systematic stereological analysis of the thyroid glands and a radioimmunological analysis of thyroxine, triiodothyronine, and thyrotropine were performed. In the hypercalcemic rats, a reactive hyperplasia of the parafollicular cells was established; this was accompanied by morphological and biochemical signs of hyperfunction of the follicular cells, despite a reduced central stimulation by thyrotropin. In the hypocalcemic animals, no quantitative morphological changes in the parafollicular cells were observed; however, morphological and biochemical signs of hypofunction of the follicular cells were obvious, despite stronger central stimulation by thyrotropin. It is concluded that the extrinsic regulation of follicular cells by the blood calcium level is stronger than the intrinsic regulation by hypothalamo-hypophyseal hormones.

Animals↗

The interdependence of the follicular, parafollicular, and mast cells in the mammalian thyroid gland: a review and a synthesis.

The aim of this paper is to summarize some of our quantitative descriptive and experimental studies, to discuss them in view of the literature data, and to present a synthesis of the topic. The results of stereological analysis of some tissue components of the rat thyroid gland have been compared with the results of topological studies on the parafollicular cells of various mammalian species. Localization of the parafollicular cells in the central regions of the thyroid gland lobes, where the follicular cell activity seems to be greater than in the periphery of the lobes, has led to the hypothesis that the parafollicular cells regulate (stimulate and/or suppress) the activity of the follicular cells. Long-term application and antithyroid drugs to mice and rats has shown that excessive concentrations of thyrotropin provoke hyperplasia of both the follicular cells and the intrathyroid mast cells and, transiently, of the parafollicular cells. This and some of the literature data are congruent with the hypothesis that the parafollicular and mast cells also stimulate the follicular cells by their paracrine secretions. Long-term application of antithyroid drugs to mice and rats has shown that excessive concentrations of cular cells but also probably stimulation of the follicular cells, as judged by the stereological measurements. The biological meaning of the spatial integration of follicular and parafollicular cells seems to be a functional coordination of both epithelial cell lines, supported by intrathyroid mast cells.

Acid Phosphatase↗

Carcinogenesis after sublethal ionizing irradiation and regular avoidance irritation.

160 mice of the BALB/C strain of both sexes, aged 3 months, were divided into four equal groups out of which two were regularly irritated by a combination of an optical signal and electrical stroke. After one month of irritation one nonirritated and one irritated group were whole body irradiated with a single dose of 6.65 Gy (1.83 Gy/min), the other two groups were sham irradiated. The mice lived until their spontaneous death or one year after irradiation, respectively, when the rest of the animals were sacrificed. The appearance of malignant tumors was noted. Irradiation shortened the survival time while the irritation had an appeasing, compensatory effect, more expressed in the males than in the females. After irradiation the number and assortment of the tumors increased and the latent period essentially shortened. In the irritated animals the number and assortment of the malignant tumors were reduced and a tendency for lengthening of the latent time period was seen; these differences, however, were not statistically significant. In spite of some differences the response in both sexes to irradiation and irritation or their combination was similar.

Animals↗

Apoptosis and proliferation of cardiomyocytes in heart failure of different etiologies.

Apoptosis and proliferation of myocytes were studied in human heart failure (HF). Endomyocardial samples from the right ventricle of 38 patients with terminal HF were compared with 10 traffic accident victims without a history of cardiovascular disease. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of p53, bcl-2, proliferation cell nuclear antigen (PCNA), and proliferation marker MIB-1. Apoptosis of cardiomyocytes, which was not p53-dependent, was present in 0.07 % of myocytes in HF, whereas no apoptotic myocytes were found in the control group (p < 0.01). An increased expression of bcl-2 was found in HF compared to controls (p < 0.01), yet bcl-2 failed to protect myocytes from apoptosis. Increased expression of proliferation markers was found in myocytes in HF compared to controls (PCNA labeling: 3.7% vs. 1.2%, p < 0.01; MIB-1 labeling: 0.1% vs. 0%, p< 0.01). Nevertheless, no mitotic figures in cardiomyocytes were found in our specimens. The volume density of interstitium was 22% in HF vs. 10% in the control group (p < 0.01). In conclusion, apoptosis of cardiomyocytes and fibrosis play an important role in HF, whereas clinical importance and the rate of myocyte proliferation remain to be determined.

Adult↗