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Biomedical subjects

M Zabel

Publications and source records attributed to M Zabel.

At least 37 records · Page 2Linked to original sources

Is bisacodyl absorbed at all from suppositories in man?

A HPLC procedure was developed to determine free BHPM in human plasma and urine after prior deconjugation of its glucuronides with glucuronidase. A single dose administration of a 10 mg bisacodyl suppository from Glaxo Wellcome, Poznań (Poland) to 16 volunteers each resulted in its low active metabolite (BHPM) plasma levels (10-55 microgram l(-1)) according to general assumptions. Its prompt laxative effect appeared within 56.6+/-10.8 min. The calculated serum half-life time of BHPM glucuronide excretion in urine was approximately 7.32+/-0.99 h. BHPM was excreted in urine in only 3. 36+/-0.52% if compared with the above bisacodyl rectal dose administered. Any relationship between BHPM plasma and/or urine levels and its laxative action does not occur. These results confirm the thesis that the laxative action of bisacodyl suppositories is initiated through a direct interaction of the drug in the rectum.

Adolescent↗

Metal telluride clusters composed of niobocene carbonyl, telluride, and cobalt carbonyl units: syntheses, structures, and reactivity

Abstract: The reaction of [Cp#2NbTe2H] (1#; Cp# = Cp* (C5Me5) or Cp(x) (C5Me4Et)) with two equivalents of [Co2(CO)8] gives a series of cobalt carbonyl telluride clusters that contain different types of niobocene carbonyl fragments. At 0 degrees C, [Cp#2NbTe2CO3(CO)7] (2#) and [Co4Te2(CO)10] (3) are formed which disappear at higher temperatures: in boiling toluene a mixture of [cat2][Co9Te6(CO)8] (5#) (cat= [Cp#2Nb(CO)2]+) and [cat2][Co11Te7(CO)10] (6#) is formed along with [cat][Co(CO)4] (4#). Complexes 6# transform into [cat][Co11Te7(CO)10] (7#) upon interaction with HPF6 or wet SiO2. The molecular structures of 2(Cp(x)), 4(Cp(x)), 5(Cp*), 6(Cp*) and 7(Cp*) have been determined by X-ray crystallography. The structure of the neutral 2(Cp(x)) consists of a [Co3(CO)6Te2] bipyramid which is connected to a [(C5Me4Et)2Nb(CO)] fragment through a mu4-Te bridge. The ionic structures of 4(Cp(x)), 5(Cp*), 6(Cp*) and 7(Cp*) each contain one (4, 7) or two (5, 6) [Cp#2Nb(CO)2]+ cations. Apart from 4, the anionic counterparts each contain an interstitial Co atom and are hexacapped cubic cluster anions [Co9Te6(CO)8]2- (5) or heptacapped pentagonal prismatic cluster anions [Co11Te7(CO)10]n- (n=2: [6]2- , n=1: [7]-), respectively. Electrochemical studies established a reversible electron transfer between the anionic clusters [Co11,Te7(CO)10]- and [Co11Te7(CO)10]2in 6# and 7# and provided evidence for the existence of species containing [Co11Te7(CO),0] and [Co11Te7(CO)0]3-. The electronic structures of the new clusters and their relative stabilities are examined by means of DFT calculations.

Journal Article↗

[Mechanism of induction and termination of ventricular fibrillation--significance of dispersion of ventricular repolarization].

It has been known for many years that ventricular fibrillation may be induced and terminated by electrical field stimuli. Recent experimental studies have shown that both fibrillation and defibrillation have a common electrophysiologic mechanism that is based on the interaction between the electrical field stimulus and ventricular repolarization. Ventricular fibrillation will be induced if the field stimulus is applied with the area of vulnerability, this area of vulnerability is defined two dimensionally by the shock coupling interval and shock strength, and is modified by the configuration of the shock. A field shock that is applied within the area of vulnerability causes heterogeneity of ventricular repolarization immediately after the shock (postshock dispersion), thereby enabling the development of circuit movements and reentry, and resulting in ventricular fibrillation. High energy shocks, however, that are applied above the area of vulnerability (i.e., above the upper limit of vulnerability) will not induce ventricular fibrillation due to homogeneous prolongation of repolarization and a resulting small postshock dispersion. In analogy, ventricular fibrillation will continue after unsuccessful low-energy defibrillation shocks due to high postshock dispersion, whereas a high-energy shock will synchronize ventricular repolarization, thereby causing small postshock dispersion and termination of ventricular fibrillation. This paper describes the relation between fibrillation, defibrillation and ventricular repolarization based on experimental findings. A possible clinical application of these findings is that the upper limit of vulnerability may be used as a surrogate for the defibrillation threshold. Thus, defibrillation threshold testing may not be necessary during future implantations of automatic cardioverter defibrillators.

Defibrillators, Implantable↗

Subtypes of thymic epithelial cells defined by neuroendocrine markers.

The study attempted to define characteristics of thymic epithelial cells within rat thymus based on the expression of neuroendocrine markers. Using an immunohistochemical approach, the following markers were localised: protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE) and chromogranin A (ChA). It was shown that cells displaying immunostaining typical for individual markers reside in distinct regions of the thymus and represent subtypes within various populations of thymic epithelial cells. An immunoreactivity for PGP 9.5 was found exclusively in a subtype of cortical epithelial cells, located mostly within the inner zone of the cortex. On the other hand, NSE represented a marker of most epithelial cells located in the medulla. Few such cells which were negative for NSE proved positive for ChA. Among the cells with a strong reaction for NSE some cells also manifested a positive reaction for ChA. While the pattern of neuroendocrine marker distribution may reflect functional properties of thymic epithelial cells which might be different within distinct areas of the thymus, the differential expression of individual markers seems to reflect biological activity of the cells and/or distinct stages of their differentiation.

Animals↗

Detection of DNA, mRNA and early antigen of the human cytomegalovirus using the immunomax technique in autopsy material of children with intrauterine infection.

The present study focuses on the immunomax technique in association with the avidin-biotin-peroxidase complex (ABC) technique and a non-isotopic variation of in situ hybridisation (ISH) for optimal microscopical detection of human cytomegalovirus (HCMV). The studies were performed on an archival paraffin material originating from five children deceased due to intrauterine infection. The results of immunocytochemical and hybridocytochemical studies, with or without amplification using biotinylated tyramine, were compared with the routine histopathological results and results obtained using the polymerase chain reaction (PCR). Early antigen (EA)-HCMV was demonstrated in approximately twice as many cells as detected in the routine staining and also in cells that seemed morphologically intact. The hybridocytochemical studies confirmed the presence of HCMV DNA in cells that were positive in the immunocytochemical tests and, in addition (using the ISH-immunomax technique), in cell nuclei of intact myocardial myocytes. In general, fewer cells manifested the presence of HMCV mRNA than the presence of HCMV DNA. The immunomax technique was found to be more sensitive than the techniques of classical immunocytochemistry or of ISH. The former technique permitted the documentation of a higher number of HCMV replication sites than could be detected using the latter techniques. However, the clinical course of HCMV infection or the cause of death of the children was not directly related to the intensity of HCMV expression in tissues.

Antigens, Viral↗

[The analysis of estrogen and pregesterone receptors in leiomyomas cell in different phases of menstrual cycle].

The aim of a study was immunocytochemical analysis of estrogen (ER) and progesterone (PgR) receptors in uterine leiomyomas cells derived from patients who underwent an operation in three different phases: in the follicular phase of the menstrual cycle (12 cases), in the luteal phase (20 cases) and in the postmenopausal age (18 cases). The examined receptors reflect the tissue sensibility to activity of sex steroid hormones and play an important role in the pathogenesis of uterine leiomyomas. Performed studies showed that expression of ER and PgR does not depend on the phase of the menstrual cycle and that it seems to be similar like in the postmenopausal stage. In all groups PgR expression was significantly higher then the expression of ER. In the group of patients in which the surgery was performed during the luteal phase of the menstrual cycle was demonstrated negatively correlation (-0.4846) between the expression of ER in relation to the expression of PgR.

Female↗

Immunocytochemical evaluation of reorganisation of keratinocyte cytoskeleton induced by change in Ca2+ concentration in culture medium.

Ca2+ level-induced changes in the arrangement of cytoskeleton of cultured keratinocytes were estimated immunocytochemically, by evaluating expression of specific cytokeratins, desmoplakin and tubulin. Keratinocytes were isolated from fragments of skin of dead human foetuses. Culture of epidermal cells was performed in two phases: phase I yielded cells of high proliferation abilities in serum-free Keratinocyte SFM of low Ca2+ level (0.03 mM); in phase II differentiated cells were obtained in Dulbecco medium of a high Ca2+ concentration (1.2 mM). Immunocytochemical evaluation of phase I and II cells revealed an array of differences which involved mainly expression and distribution of specific cytokeratins, distribution of tubulin, testifying to a different microtubule arrangement and distribution of desmoplakin and indicating a tendency to form desmosomes. The changes were induced by the changes in Ca2+ level in the culture medium.

Calcium↗

S-100 protein immunoreactivity in mammalian testis and epididymis.

The present study deals with immunohistochemical localization of S-100 protein in mouse, bank vole and pine vole testis and epididymis. S-100 protein immunoreactivity was observed in the endothelia of capillaries and lymphatic sinusoids of pine vole testis. A reaction to S-100 protein of the same intensity as that noted in the endothelia of testicular capillaries was found in myoid cells of pine vole and bank vole seminiferous tubules. Moreover, a positive reaction to S-100 protein was observed in bank vole and mouse Leydig cells. In the epididymis, a weaker reaction to S-100 occurred in smooth muscles of pine vole and mouse epididymal duct. Despite difficult interpretation of physiological role of S-100 protein we suggest that it may be a part of the blood-testis barrier. It may also participate in the processes of transcytosis and contractility; its cellular expression is regulated by local factors. However, location of S-100 is not specific to the representatives of the same order.

Animals↗

[Cardiac autonomic tone in risk stratification after myocardial infarct: results of a prospective long-term study of 411 consecutive patients].

Prognosis of patients surviving acute myocardial infarction has substantially improved over the last two decades. However, stratification of patients at risk for death due to arrhythmic events remains a clinical challenge. Due to the important role of the autonomic nervous system in the genesis of sudden death, autonomic markers such as heart rate variability and baroreflex sensitivity have recently gained attention as risk stratification parameters. The present study reports the results of noninvasive risk stratification in 411 consecutive postinfarction patients treated due to contemporary therapeutical guidelines with a high proportion of patients discharged with a patent infarct related artery. The diagnostic arsenal of risk parameters comprised heart rate variability, baroreflex sensitivity, and more traditional markers such as non-sustained ventricular tachycardia, left ventricular ejection fraction, and ventricular late potentials. Patients were followed for a mean of 33 +/- 21 months. Stepwise logistic regression analysis revealed that left ventricular function, both autonomic markers, and the patency of the infarct related artery were independent predictors of the prospectively defined primary study endpoint, i.e., all-cause mortality plus ventricular tachyarrhythmic events. With respect to the secondary endpoint (ventricular tachyarrhythmic events), left ventricular function, heart rate variability, and infarct vessel patency were independent predictors. Ventricular late potentials and nonsustained ventricular tachycardia had no predictive value with respect to ventricular tachyarrhythmic events. These findings from a large prospective long-term study demonstrate the value of markers of cardiac autonomic tone in identifying infarct survivors at risk for malignant ventricular tachyarrhythmias and sudden death.

Adult↗

[T-wave alternans in microwave frequency as a new indicator of disordered ventricular repolarization: pathophysiology, methodology, clinical results].

Primary prevention of sudden cardiac death is hampered by the inability to accurately identify high risk patients. Various noninvasive methods such as determination of left ventricular function or heart rate variability as well as invasive electrophysiologic testing are currently used for risk stratification. Noninvasive measurement of microvolt T wave alternans (TWA) is a promising new method to assess repolarization abnormalities; in experimental studies, TWA was associated with an increased incidence of ventricular tachyarrhythmias. Since the occurrence of TWA is heart rate-dependent, it is measured either during atrial pacing or during exercise stress testing. The first clinical validation of the method was performed in patients undergoing invasive EP testing to assess prediction of inducibility of ventricular tachyarrhythmias. A first prospective validation of the noninvasive method was performed in patients surviving out-of-hospital cardiac arrest fitted with an ICD. Further studies have shown a good concordance between invasive and noninvasive TWA determination. The occurrence of TWA in this population was of predictive value with respect to arrhythmia recurrence. Recently published data confirm the value of TWA assessment with respect to identification of patients with congestive heart failure at high risk of malignant ventricular tachyarrhythmias. The use of this method in post myocardial infarction risk stratification is currently under prospective evaluation.

Cardiac Pacing, Artificial↗

Polyhormonal aspect of the endocrine cells of the human fetal pancreas.

Histological studies were performed on 30 pancreases obtained from normal human fetuses aged between the 9th and 38th week. For immunocytochemistry, the avidin-biotin-peroxidase method was used to identify and colocalise insulin, glucagon, somatostatin, pancreatic polypeptide and proliferating cell nuclear antigen. In the 9th week, cells containing all investigated peptides were present. During the fetal period, two populations of endocrine cells have been distinguished, Langerhans islets and freely dispersed cells. The free cells were polyhormonal, containing insulin, glucagon, somatostatin and pancreatic polypeptide, and were localised in the walls of pancreatic ducts throughout the whole gland. During the development of the islets we have observed four stages: (1) the scattered polyhormonal cell stage (9th-10th week), (2) the immature polyhormonal islet stage (11th-15th week), (3) the insulin monohormonal core islet stage (16th-29th week), in which zonular and mantle islets are observed, and (4) the polymorphic islet stage (from the 30th week onwards), which is characterised by the presence of monohormonal cells expressing glucagon or somatostatin. Bigeminal and polar islets also appeared during this last stage. The islets consisted of an insulin core surrounded by a thick (in the part developing from the dorsal primordium) or thin rim (part of the pancreas concerned with the ventral primordium) of intermingled mono- or dihormonal glucagon-positive or somatostatin-positive cells. The most externally located polyhormonal cells exhibited a reaction for glucagon, somatostatin and pancreatic polypeptide. Apart from the above-mentioned types of islets, all arrangements observed in earlier stages were present. Proliferating cell nuclear antigen-positive cells (single in the large islets and more numerous in the smaller ones) were predominantly observed in the outermost layer. Taken together our data indicate that, during the human prenatal development of the islet, endocrine cells are able to synthesise several different hormones. Maturation of these cells involved or depended on a change from a polyhormonal to a monohormonal state and is concerned with decreasing proliferative capacity. This supports the concept of a common precursor stem cell for the hormone-producing cells of the fetal human pancreas.

Animals↗

Prevalence, characteristics and prognostic value during long-term follow-up of nonsustained ventricular tachycardia after myocardial infarction in the thrombolytic era.

OBJECTIVES: The purpose of this study was to determine the prevalence, characteristics and the predictive value of nonsustained ventricular tachycardia (VT) for subsequent death and arrhythmic events after acute myocardial infarction (AMI). BACKGROUND: Nonsustained VT has been linked to an increased risk for sudden death in coronary patients. It is unknown whether this parameter can be used for selection of high-risk patients to receive an implantable defibrillator for primary prevention of sudden death in patients shortly after AMI. METHODS: In 325 consecutive infarct survivors, 24-h Holter monitoring was performed 10+/-6 days after AMI. All patients underwent coronary angiography, determination of left ventricular function and assessment of heart rate variability (HRV). Mean follow-up was 30+/-22 months. RESULTS: There was a low prevalence (9%) of nonsustained VT shortly after AMI. Nonsustained VT together with depressed left ventricular ejection fraction (LVEF) was found in only 2.4% of patients. During follow-up, 25 patients reached one of the prospectively defined end points (primary composite end point of cardiac death, sustained VT or resuscitated ventricular fibrillation; secondary end point: arrhythmic events). Kaplan Meier event probability analyses revealed that only HRV, LVEF and status of the infarct-related artery were univariate predictors of death or arrhythmic events. The presence of nonsustained VT carried a relative risk of 2.6 for the primary study end point but was not a significant predictor if only arrhythmic events were considered. On multivariate analysis, only HRV, LVEF and the status of the infarct artery were found to be independently related to the primary study end point. CONCLUSIONS: There is a low prevalence of nonsustained VT shortly after AMI. Only 2% to 3% of all infarct survivors treated according to contemporary guidelines demonstrate both depressed LVEF and nonsustained VT. The predictive value of nonsustained VT for subsequent mortality and arrhythmic events is inferior to that of impaired autonomic tone, LVEF or infarct-related artery patency. Accordingly, the use of nonsustained VT to select patients for primary implantable cardioverter/defibrillator prevention trials shortly after AMI appears to be limited.

Adult↗

Immunocytochemical study of parafollicular (C) cells of the thyroid in some wild rodents.

Studies were done on 3 wild species of rodents: field voles (Microtus agrestis, Linnaeus 1761), bank voles (Clethrionomys glareolus, Schreber 1780), and forest mice (Apodemus flavicollis, Melchior 1834). Immunocytochemical reactions were used to detect calcitonin (CT), calcitonin gene-related peptide (CGRP), neuron-specific enolase (NSE), chromogranin A (CgA) in the thyroid parafollicular (C) cells in all species examined. Antisera to human CT, rat CGRP, bovine CgA, rat NSE and human NSE give probably a positive reaction in all C cells in the rodents examined. However, in the NSE determining reaction, much feebler positive C cells were observed. Individual variation in respect of shape and distribution of C cells was observed in all species. In forest mice the C cells resembled in shape the C cells previously described in mouse and rat. In field voles and bank voles the C cells were assembled into small groups more often than in forest mice. Antibodies (anti-human CT, anti-rat CGRP, anti-bovine CgA, anti-rat NSE and anti-human NSE) used by us were good markers of C cells in the thyroids of the 3 species of free-living rodents examined.

Animals↗

Effect of follicular cells on calcitonin gene expression in thyroid parafollicular cells in cell culture.

Expression of calcitonin (CT) gene in thyroid parafollicular cells involves alternate formation of CT mRNA or CGRP mRNA. High amounts of CT mRNA are formed only in thyroid gland and formation of CGRP mRNA dominates in the remaining organs. Apart from paracrine and endocrine factors, mRNA formation on the CT gene seems to be affected also by direct contacts with other cells present in the thyroid gland, in which parafollicular cells are located next to follicular cells. The present study aimed at examining whether thyroid follicular cells affect formation of mRNAs for CT and CGRP in parafollicular cells. The studies were performed in cell cultures. A parafollicular cell line (TT cells) and a follicular cell line (F6BTY cells) served as the experimental model. For comparison, co-cultures with fibroblasts, 3T3 cells, and malignant melanoma, MM cells, were also examined. CT gene expression was examined at the level of mRNAs (in situ hybridization and morphometric studies) and at the level of hormones (immunocytochemistry, morphometric studies and radioimmunological estimation of hormone levels in the medium). The immunocytochemical and hybridocytochemical studies, in line with morphometry studies, demonstrated that F6BTY and 3T3 cells were capable of affecting mRNA production for CT and CGRP and that they changed the ratio of CGRP/CT secretion by TT cells, as a sequel of contact between the two cell types and due to mediation of secreted substances. On the other hand, the malignant melanoma MM cells showed no effect on the secretion ratio. Our study seems to indicate that control of mRNA formation from CT gene may involve not only humoral factors but also direct contacts with other cells, which may explain differences in expression of the gene between cells localized in different organs.

Calcitonin↗