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Biomedical subjects

M Grigorov

Publications and source records attributed to M Grigorov.

At least 19 recordsLinked to original sources

A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.

Ochratoxin A (OTA) is a mycotoxin occurring naturally in a wide range of food commodities. In animals, it has been shown to cause a variety of adverse effects, nephrocarcinogenicity being the most prominent. Because of its high toxic potency and the continuous exposure of the human population, OTA has raised public health concerns. There is significant debate on how to use the rat carcinogenicity data to assess the potential risk to humans. In this context, the question of the mechanism of action of OTA appears of key importance and was studied through the application of a toxicogenomics approach. Male Fischer rats were fed OTA for up to 2 years. Renal tumors were discovered during the last 6 months of the study. The total tumor incidence reached 25% at the end of the study. Gene expression profile was analyzed in groups of animals taken in intervals from 7 days to 12 months. Tissue-specific responses were observed in kidney versus liver. For selected genes, microarray data were confirmed at both mRNA and protein levels. In kidney, several genes known as markers of kidney injury and cell regeneration were significantly modulated by OTA. The expression of genes known to be involved in DNA synthesis and repair, or genes induced as a result of DNA damage, was only marginally modulated. Very little or no effect was found amongst genes associated with apoptosis. Alterations of gene expression indicating effects on calcium homeostasis and a disruption of pathways regulated by the transcription factors hepatocyte nuclear factor 4 alpha (HNF4alpha) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were observed in the kidney but not in the liver. Previous data have suggested that a reduction in HNF4alpha may be associated with nephrocarcinogenicity. Many Nrf2-regulated genes are involved in chemical detoxication and antioxidant defense. The depletion of these genes is likely to impair the defense potential of the cells, resulting in chronic elevation of oxidative stress in the kidney. The inhibition of defense mechanism appears as a highly plausible new mechanism, which could contribute to OTA carcinogenicity.

Administration, Oral↗

Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project.

OBJECTIVE: To assess cognitive functions and their correlates for a dementia-free cohort of old patients with isolated systolic hypertension. DESIGN: Cross-sectional data from the randomization period of the European Trial in Elderly with Systolic Hypertension (Syst-Eur Vascular Dementia Project). SETTING: Sixteen European countries and Israel. PARTICIPANTS: We studied 2252 patients aged 60-100 years (mean 70). MAIN OUTCOME MEASURES: Mini Mental State Examination (MMSE) and Spearman correlation of MMSE scores to demographic data or blood pressure. RESULTS: The MMSE was successfully completed for 1474 women and 751 men. The baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg (means +/- SD). Median age at which education of patients at school had stopped was 15 years. Men and women who consumed alcohol (28%) had median intakes of 8 and 3 g/day, respectively. The median MMSE score was 29 (range 15-30). The maximum score of 30 was attained by 609 (30%) subjects. Fifty-nine (3%) patients had a MMSE score of 23 or less. The MMSE score decreased with advancing age (r = -0.21, P < 0.001). Both for men and for women, it was positively correlated to the level of education (r = 0.30 and r = 0.32, P < 0.001). For women after adjustment for age and the level of education, the score was correlated negatively to systolic blood pressure (r = -0.07, P < 0.05) but positively to intake of alcohol (r = 0.06, P < 0.05). CONCLUSION: In a cohort of elderly patients with isolated systolic hypertension, baseline cognitive function measured in terms of the MMSE score was high, probably due to selective recruitment of patients who were not clinically demented. Blood pressure was a weak contributor to cognitive status compared with age and level of education. Baseline cognitive function of women was negatively and independently correlated to systolic blood pressure.

Aged↗

[The effect of myosin from the human myocardium on quantitative T-lymphocyte values--active rosettes in patients with myocardial infarct and stenocardia].

The aim of the investigation is to study the influence of human myocardium myosin on the quantitative values of T-lymphocytes examined as active rosettes [correction of rosellae] in patients with ischemic heart disease. The study included 99 patients with ischemic heart disease, 49 of them with myocardial infarction and 50--with stenocardia. The controls were 61 clinically healthy donors. It was established that the active rosettes [correction of rosellae] in the patients with myocardial infarction were significantly less than in the controls (p less than 0.05). A significant inhibiting action of the human myocardium myosin on the active rosettes [correction of rosellae] was manifested (p less than 0.002). This action in the patients with stenocardia was less expressed (p less than 0.05). Myosin from a striated muscle did not exert an inhibiting action (p greater than 0.1). The results prove the participation of human myocardium myosin in the pathogenetic mechanism of T-lymphocytes suppression in patients with ischemic heart disease.

Adult↗

[The cellular immunity indices of patients with a rheumatic heart defect].

In 29 patients with clinical diagnosis of rheumatic valvular disease the quantitative values of active rosettes and the specific sensitization to human heart myosin were examined. The specific sensitization to human heart myosin was examined by two methods concurrently: method of inhibiting leucocyte migration in agarose and method for direct specific lymphocytolysis with myosin. The results were compared with those of 44 clinically healthy controls. In the patients with rheumatic valvular disease (RVD) the values of the active rosettes are significantly lower (p less than 0.01) than in the healthy controls. With the method of direct specific lymphocytolysis with myosin statistically significant sensibilization of the lymphocytes to myosin was found in the patients with RVD (p less than 0.001). In 5 patients examined before and after operation it was established that 2-4 weeks after a successful correction of the hemodynamics the specific sensibilization of the lymphocytes to myosin was no more present.

B-Lymphocytes↗

The effect of Haversian remodeling on the tensile properties of human cortical bone.

The purpose of this study was to determine the effect of Haversian remodeling on the tensile properties of human cortical bone by testing specimens containing, as far a possible, a single type of bone tissue. Fifty-one specimens were prepared from sixteen fresh tibias, removed at autopsy. Age range was 19-35. Regions were selected so that the specimens would consist almost exclusively of either primary bone or Haversian bone. The ultimate tensile strength, ultimate strain and Young's modulus of elasticity were determined at a loading rate of 0.05 mm s-1. The primary bone specimens were found to have a significantly higher ultimate tensile strength and modulus of elasticity than those formed of Haversian bone.

Adult↗

[Reliability of an echocardiographic evaluation of the left ventricular pumping function in ischemic heart disease].

Almost simultaneous angiographic and echocardiographic determination of the pump indices of left ventricle was performed to 38 male patients, aged 34 to 58. A special computer was used for the processing of the data. The echocardiographic indices were calculated by three formulae: cube, Forteen and Teiholz . Coefficients of correlation were derived between the two methods, confirming a relatively high reliability of echocardiography in the evaluation of left ventricular pump function, particularly if the calculations were selectively performed according to one of the three formulae, depending on the value of diastolic measure of left ventricle.

Adult↗

[Diagnosis and functional assessment of pulmonary thromboembolism].

The authors discuss the problems of diagnostics and functional assessment of pulmonary thrombo-embolia. The potentialities of the clinical indices, electrocardiography, X-ray, blood-gas analysis, capnography, right cardiac catheterization and angiopulmography in the diagnostics and assessment of the form of thrombo-embolia of pulmonary artery were revealed in 54 patients with cardiac and pulmonary form of thrombo-embolia. The stage potentialities in that respect of the various health institutions are outlined and the necessity of evacuation of the patients where they would be best attended is stressed upon.

Adult↗

[Comparative evaluation between the impedance method and the Fick method for determining cardiac minute volume].

The authors determined the minute heart volume, according to Fick method with right cardiac catheterization of 20 healthy youths. With the comparison of the results obtained, the differences were within the limits of +/- 10, and in almost half of the examined-- +/- 5%. The relatively small discrepancies in the values obtained, suggest that the impedence-method proves to be a reliable method for bloodless determination of minute heart volume.

Adolescent↗

[Hemodynamic and phase characteristics of the impedance cardiogram].

The authors realized synchronous records of impedance--cardiogram with PCG, ECG and the curves of the pressure within the separate cardio-vascular segments. That enables them to make a phase characteristic of the separate parts of impedance-cardiographic curve, thus establishing that the latter is synchronized with the mechanics of the left ventricle.

Adolescent↗

[Abdominal manifestations of chronic pyelonephritis].

The most frequent abdominal complaints in chronic pyelonephritis are analyzed and one patient is described, who with the exacerbation of the disease manifested the clinical picture of acute abdomen. The involvement of visceral-dermal reflexes with hyperalgesia, muscular defense, vomiting, meteroism and disturbances in intestinal motility imitated the picture of acute abdominal drama, forcing the surgical intervention. The varied abdominal symptomatics in about 20 per cent of the cases with chronic exacerbated pyelonephritis, should be critically assessed by the therapeutists.

Abdomen, Acute↗

[Possibilities of intracardiac phonocardiography in congenital defects with left-right shunt].

The author shares his experience from intracardial phonocardiography of 48 patients with congenital heart defects with leftright shunt. The importance of the method is stressed upon, particularly in cases with interauricular and interventricular defect, not only for the diagnosis of the disease but for the differential diagnosis in difficult cases as well. The characteristic murmurs are presented, recorded intracardially in the three of the basic congenital heart defect with left-right shunt--interauricular defect, interventricular defect, and open Botal's duct.

Adolescent↗

[Functional assessment of respiration and blood circulation in pectus excavatum].

Functional investigation was carried out on respiration and cardiovascular system of 57 adolescents with pectus excavatum. Right cardiac catheterization was performed to 10 of them. Two thirds of the cases with right bundle branch block and 7 out of the tenth with catheterizatium were established to have elevated telediastolic pressure in right ventricle and diminished cardiac index, supplying grounds to the authors to presume a difficulty in the filling of the right ventricle resulting from the mechanic pressure due to the deformity. Respiratory deviations proved to be negligible. The indications for operation are determined by the results from the complex functional examinations.

Adolescent↗