Biomedical subjects

M Zorc

Publications and source records attributed to M Zorc.

At least 19 recordsLinked to original sources

PubMed2006

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↗

PubMed2006

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↗

PubMed2004

Haemochromatosis-causing mutations C282Y and H63D are not risk factors for coronary artery disease in Caucasians with type 2 diabetes.

Iron metabolism might be involved in the pathogenesis of CAD, and C282Y and H63D mutations in the HFE gene are associated with increased serum iron levels and net iron accumulation. The aim of this study was to look for a relationship between the C282Y and H63D gene mutations of the HFE gene and coronary artery disease (CAD) in a group of patients with type 2 diabetes lasting more than 10 years. The C282Y and H63D gene mutations were tested in 338 Caucasians with type 2 diabetes: 156 cases with CAD and 182 subjects with no history of CAD. The C282Y and the H63D HFE gene distributions in patients with CAD (C282Y: YY 0.6%, CY 9.0%, CC 90.4%; H63D: DD 3.8%, HD 21.8%, HH 74.4%) were not significantly different from those of diabetic subjects without CAD (C282Y: YY 0%, CY 8.2%, CC 91.8%; H63D: DD 2.2%, HD 20.3%, HH 77.5%). In conclusion, we failed to demonstrate that the C282Y and H63D HFE gene mutations were risk factors for CAD in Caucasians with type 2 diabetes lasting longer than 10 years.

Coronary Artery Disease↗

PubMed2001

Myocytes' apoptosis and proliferation in endomyocardial biopsy as prognostic factors in terminal heart failure.

The aim of the preliminary study was to evaluate the role of apoptosis and proliferation of myocytes in order to predict the prognosis and optimal treatment of patients with end-stage dilated cardiomyopathy. Endomyocardial biopsy was performed during open-heart surgery (reductive annuloplasty of double orifice) in 19 patients with end-stage dilated cardiomyopathy. The terminal deoxynucleotidyl transferase d-UTP-biotin nick-end labelling (TUNEL) method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of inhibitor of apoptosis such as proto-oncogene Bcl-2 (B-cell lymphoma gene), and proliferative markers such as proliferation cell nuclear antigen (PCNA) and Ki-67 proliferative antigen. The increased percentage of apoptotic myocytes and decreased expression of bcl-2 is associated with earlier death after surgery. Increased expression of proliferation markers of myocytes in patients who survived seven years after surgery compared to those who died within three years suggest that adult cardiomyocytes are not terminally differentiated and this might represent potential growth reserve of the diseased heart. Based on our preliminary study we may conclude that myocytes' apoptosis and proliferative activity might help us to predict the prognosis and optimal treatment of patients with end-stage dilated cardiomyopathy.

Adult↗

PubMed2001

Interaction between gene polymorphisms of renin-angiotensin system and metabolic risk factors in premature myocardial infarction.

The renin-angiotensin system is involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The authors investigated the association of genetic variability in the renin-angiotensin system (RAS) with premature MI and interactive effects between gene polymorphisms and metabolic risk factors on MI risk. Their study compared 142 patients with MI younger than 55 years with 142 healthy subjects. Polymorphisms of angiotensin-I converting enzyme (ACE) gene (insertion/deletion), angiotensinogen gene (M235T), and angiotensin-II type-1 receptor (AGT1R) gene (A1166C) were tested. The ACE-DD (deletion/deletion) genotype conferred a twofold independent risk for MI (confidence interval [CI] = 1.1-3.7; p = 0.01) after adjustment for cardiovascular risk factors, whereas angiotensinogen-TT genotype and AGT1R-AA genotype were not independent risk factors for MI. An interactive effect on MI risk was found between ACE-DD and AGT1R-AA genotypes (odds ratio [OR]=2, 95% CI= 1-3.9), between ACE-DD and angiotensinogen-TT genotypes (OR = 2.7, 95% CI = 1-7.3), as well as among ACE-DD, angiotensinogen-TT, and AGT1R-AA genotypes (OR=4.8, 95% CI = 1-22.8). Similarly, metabolic risk factors interacted with angiotensinogen-TT genotype (OR= 2, 95% CI = 1.1-3.9) on MI risk. The ACE-DD genotype is an independent risk factor for MI in patients younger than 55 years. Additionally, the authors provide evidence of an interactive effect on MI risk between risk genotypes of RAS, as well as between the angiotensinogen-TT genotype and metabolic risk factors.

Angiotensinogen↗

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

Effect of apolipoprotein E polymorphism and apolipoprotein A-1 gene promoter polymorphism on lipid parameters and premature coronary artery disease.

Genetic and environmental factors regulate lipid metabolism and phenotypic expression of CAD. In this study we assessed the effects of apoE gene polymorphism and apoA1 gene promoter polymorphism on lipid metabolism and risk for CAD. In a case-control study, 166 patients with CAD were compared with 130 healthy subjects. The apoE allele frequencies of patients vs. control group were 6.3% vs. 7.7% for e2, 84.3% vs. 84.6% for e3, and 9.4% vs. 7.7% for e4. Individuals with e3e4 and e4e4 genotypes had higher total (P = 0.023) and LDL cholesterol levels (P = 0.04) than individuals with other genotypes. There were no differences in lipid parameters between the subjects with the apoA1-GG genotype and subjects with AG or AA genotypes. However, univariate analysis revealed no association between risk genotypes (e3e4 and e4e4 genotypes) of apoE and CAD risk (OR = 1.1; 95% CI = 0.6-2.1, P = 0.8) as well as no association between the GG genotype and CAD risk (OR 0.7; 95% CI = 0.5-1.2, P = 0.19). No evidence for a synergistic interaction between e3e4 plus e4e4 genotypes and apoA1-GG genotype on CAD risk was found (OR = 1.3, 95% CI = 0.6-2.9; P = 0.5). One individual with familial defective apolipoprotein B-100 (Arg3500Gln) was found in each group. In conclusion, the apoE gene polymorphism affected the total and LDL cholesterol levels, whereas neither the apoE gene polymorphism nor the apoA-1 gene promoter polymorphism were shown to be independent risk factors for CAD in Slovenia.

Age of Onset↗

PubMed2000

Deletion/insertion polymorphism in the angiotension-converting enzyme gene as a risk factor in the Slovenian patients with coronary heart disease.

The angiotensin-converting enzyme (ACE) plays by degradation of angiotensin I and bradykinin, an important role in modulations of smooth muscle proliferation and vascular tone. Typical plasma levels of ACE accompany the I/D polymorphism; however, a controversy exists as to whether the DD genotype of the ACE polymorphism affects the risk for the development of coronary heart disease (CHD). We compared the I/D polymorphism in 171 Slovenian CHD patients that were younger than 55 years with 134 healthy control individuals. The DD genotype is associated with a 2.3-fold increase in the risk for CHD.

Coronary Disease↗

PubMed2000

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↗

PubMed1999

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↗

PubMed1996

I/D polymorphism at the locus for ACE and apo A-I gene promoter polymorphism as risk factors for coronary artery disease in patients with familial hypercholesterolemia.

In our study we searched for an association between the insertion/deletion (I/D) polymorphism at the ACE locus as well as apo A-I promoter polymorphism and coronary artery disease (CAD) in patients with familial hypercholesterolemia (FH). 34 FH patients over 40 years were ascertained; 16 patients with CAD were compared with 18 patients without CAD. There was an excess of DD or ID genotype in FH patients with CAD (OR = 4.9, CI = 1.17-22.17; Fisher exact p = 0.012), however, no association between G to A substitution in the promoter region of the apo A-I gene and CAD was found. Our results suggest that the DD/ID genotype at the ACE gene locus might be an important genetic risk factor for CAD in FH patients.

Adult↗

PubMed1982

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↗

PubMed1979

Stress and Ehrlich ascites tumor in mouse.

The aim of the study was to investigate the interaction of the psychosomatic stress and the Ehrlich ascites tumor (EAT) growth in mice. The stressor consisted of combination of a light signal followed by a mild electric shock. The first experiment was performed on CBA mice irritated for 0, 2 and 4 weeks respectively, prior to intraperitoneal transplantation of the EAT. In the second study, mice of BALBc strain were used. Stress was applied 4 weeks before the tumor transplantation and continued throught the experiment. Both the irritated and the nonirritated animals were subjected to either intraperitoneal or subcutaneous inoculation of the EAT. In both experiments, mice were left to live until their spontaneous death. In the first experiment, after a 2-week irritation the experimental animals showed a significantly longer survival time as compared to the controls. Longer or shorter duration of the irritation had no significant effect on the results obtained. Results yielded by the second experiment showed no significant difference in the time of survival of the irritated and nonirritated animals after the i. p. transplantation, whereas after the s. c. inoculation of the EAT, the irritation significantly increased the survival period. The EAT in irritated mice was observed to have invaded the vitals later and less frequently than in the nonirritated animals. Quantitative histological analysis of some endocrine and lymphatic organs revealed signs of stress in the experimental animals. The EAT transplant, per se, had a stressogenic effect too.

Animals↗

PubMed1975

"Genital dyscrinism" as a cause of subfertility in mice of the CBA strain.

Following four generations of inbred mating (brother-sister) in three direct lineages of CBA strain mice, sterility appeared which from that generation forward became more frequent. The genital organs in animals of both sexes were altered. There was a noticeable occurrence of cysts in the ovaries of female animals already following the third month; in mice approximately one year of age this condition was followed by cystic glandular hyperplasia of the endometrium, sometimes complicated by disturbances in blood circulation, inflammation or even malignancy. In some female animals, manifesting, due to cysts, completely degenerated ovaries, the rest of the genital system was severely atrophic. Male animals frequently showed severe atrophy of the seminiferous epithelium along with preserved interstitial cells and hypertrophic seminal vesicles. These pathological changes represent an independent nosologic unit, for which the label "genital dyscrinism" has been proposed. The authors have considered an endocrine mechanism as the possible cause of these pathological changes which are presumed to be genetically conditioned.

Animals↗

PubMedDate not supplied

Joint effect of G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism on the risk of premature coronary artery disease.

The study sought an association between the G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism and premature coronary artery disease (CAD), and the interactive effect on CAD risk between the G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism as well as between tested polymorphisms and traditional risk factors. 167 patients with CAD younger than 55 years were compared with 132 healthy subjects. The frequency of factor V point mutation was 7.8 % among Slovene patients with premature CAD, and 4.5 % among controls. No association was found between either the factor V point mutation (AG genotype) or M1M1 genotype of factor VII Arg/Gln(353) gene polymorphism and the risk of CAD in Slovenia using univariate analysis (factor V point mutation: OR = 1.8, 95% CI = 0.7-4.9; p = 0.25; factor VII Arg/Gln(353) gene polymorphism: OR = 1, 95 % CI = 0.6-1.7; p = 0.9). However, a joint effect on the risk of CAD was found between factor V point mutation (AG genotype) and M1M1 genotype (OR = 3.6, 95 % CI = 1-12.9; p = 0.03). Additionally, an interactive effect on CAD risk was found between AG genotype and metabolic risk factors (OR = 3.8, 95% CI = 1.1-13.6; p = 0.03). In conclusion, we provide evidence for a joint effect on CAD risk between G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism as well as between factor V point mutation and metabolic risk factors.

Age of Onset↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Changes in left ventricular morphology and function in end-stage dilated cardiomyopathy after reductive annuloplasty of double mitral and tricuspid orifices.

BACKGROUND AND AIM: The aim of this study is to show the changes in left ventricular morphology and function after reductive annuloplasty of double mitral and tricuspid orifices (RADO) in ischemic dilated cardiomyopathy (IDCM) and primary dilated cardiomyopathy (PDCM) analyzed by intraoperative transesophageal echocardiography (TEE). METHODS: There were 274 patients, mean age 50.1 years, 188 operated due to IDCM with ejection fraction under 30%, and 86 patients due to PDCM. Mitral annuloplasty according to A. Carpentier and our own procedure was done in 49 and 225 patients, respectively. In 265 cases (97%) our modified De Vega's tricuspid annuloplasty was performed. RESULTS CONCLUSION: RADO significantly changes left ventricular morphology, reverses remodeling of the heart, decreases sphericity of the left heart, improves hemodynamic function of both ventricles, and slows down progression of cardiac failure. We recommend RADO in the early stage of PDCM, immediately after the first decompensation, and as an important associated procedure in IDCM.

Cardiomyopathy, Dilated↗