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Biomedical subjects

M Dittrich

Publications and source records attributed to M Dittrich.

At least 19 recordsLinked to original sources

Hypoxia influences generation and propagation of electrical activity in embryonic cardiomyocyte clusters.

The influence of tissue hypoxia on the generation and propagation of excitation was studied in spontaneously beating embryonic cardiomyocyte clusters grown in eight 9-12 days old embryoid bodies. Within the embryoid bodies one to three separately active clusters of cardiomyocytes were found, each having its own pacemaker cell. Lowering of tissue PO(2) caused bradycardia as well as arrhythmia in all embryoid bodies investigated. The mean frequency of the extracellularly recorded action potentials decreased under conditions of pronounced hypoxia from a mean of 1.4-1.8 Hz to below 0.8 Hz. In three embryoid bodies hypoxia-sensitive as well as hypoxia-tolerant cardiomyocyte clusters were found. The hypoxia-insensitive cardiomyocytes showed a low frequency of spontaneous activity. In addition to the observed changes in the generation of excitation, tissue hypoxia caused an approximately 60% reduction in the velocity of conduction within the cardiomyocyte clusters. Moreover, in at least one of the eight experiments propagation failure with an incomplete block in spread of excitation was observed. All hypoxia-induced effects on generation and propagation of embryonic cardiomyocyte excitation were completely reversible after reoxygenation.

Animals↗

Local response of L-type Ca(2+) current to nitric oxide in frog ventricular myocytes.

1. The regulation of L-type Ca(2+) current (I(Ca)) by the two nitric oxide (NO) donors sodium nitroprusside (SNP, 1 microM to 1 mM) and (+/-)-S-nitroso-N-acetylpenicillamine (SNAP, 3 or 10 microM) was investigated in frog ventricular myocytes using double voltage clamp and double-barrelled microperfusion techniques. 2. SNP and SNAP depressed the isoprenaline (ISO, 10-100 nM)- or forskolin (FSK, 1 microM)-mediated stimulation of I(Ca) via cGMP activation of the cGMP-stimulated phosphodiesterase (PDE2). Complete inhibition of the ISO (100 nM) response was observed at 1 mM SNP. 3. When SNP was applied locally, i.e. to one-half of the cell, and ISO to the whole cell, the response of I(Ca) to ISO was strongly antagonized in the cell half exposed to SNP (up to 100 % inhibition at 1 mM SNP) but a relatively small depression was observed in the other half of the cell (only 20 % inhibition at 1 mM SNP). 4. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO, 1 mM) reversed the local effect of SNAP (3 microM) on FSK-stimulated I(Ca) when applied to the same side as the NO donor, but had no effect when applied to the other side of the cell. 5. A local application of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, 30 microM), a selective inhibitor of PDE2, fully reversed the local effect of SNP (100 microM) or SNAP (10 microM) on I(Ca) but had no effect on the distant response. 6. When EHNA was applied on the distant side, with SNP (1 mM) and ISO (100 nM) applied locally, the distant effect of SNP was fully reversed. 7. Our results demonstrate that in frog ventricular myocytes stimulation of guanylyl cyclase by NO leads to a strong local depletion of cAMP near the L-type Ca(2+) channels due to activation of PDE2, but only to a modest reduction of cAMP in the rest of the cell. This may be explained by the existence of a tight microdomain between L-type Ca(2+) channels and PDE2.

Adenine↗

Ischemia increases detectable endothelial nitric oxide synthase in rat and human myocardium.

The aims of the present study were to establish if myocardial ischemia/reperfusion is associated with altered eNOS activity and if myocardial eNOS detection depends on its activity. We determined detectable eNOS in (1) myocardium of isolated perfused rat hearts subjected to either global or regional ischemia and (2) in left ventricular biopsies from patients undergoing two different methods of myocardial protection (i.e., intermittent cold blood cardioplegia and continuous coronary perfusion with warm, beta-blocker-enriched blood) during coronary artery surgery. NOS detection was performed by NADPH-d staining and three eNOS-antibodies against different eNOS epitopes. In addition, activity dependent alteration of detectable eNOS was proofed by bradykinin treatment for 2 to 10 min. Ischemic and receptor mediated eNOS activation increased NADPH-d reactivity and eNOS immunoreaction as measured by antibodies against either amino acids of a central bovine eNOS domain or the human eNOS N-terminal end. In contrast, the antibody against the human eNOS C-terminal end exhibited no alteration of eNOS immunoreaction. The transient eNOS activation was associated with increased cGMP content. In human myocardium subjected to ischemia during cardiac surgery we found that early reperfusion increases eNOS activity. These data demonstrate a strong association between myocardial ischemia/reperfusion and increased eNOS activity as measured by immunocytochemical staining against specific eNOS epitopes. It appears that eNOS activation and subsequent NO release may act as a regulatory system to counter balance the potentially deleterious effects of myocardial ischemia/reperfusion.

Adrenergic beta-Antagonists↗

[Head circumference in relation to sonographic morphometry of the cerebral ventricles in neonates and infants].

AIM: To determine normal values of sonographic measurements of the brain in neonates and infants. METHOD: Cerebral ultrasonographic examinations were performed in 143 healthy newborns and infants. The size of the ventricles was determined by ascertaining distances as well as performing planimetric measurements of the ventricular area and circumference in standardized planes. RESULTS: Throughout the course of the study we observed a continous increase in size and a strong correlation with head circumference. The middle coronary plane used for the measurements allows the accurate representation of the ventricles and a more objective assessment of size. CONCLUSION: Based on the morphometric data, charts for the determination of ventricular size were developed.

Body Height↗

[Use of synthetic biodegradable polymers in medicine].

Synthetic biodegradable polymers, such as polyesters, polyanhydrides, polyorthoesters, polycarbonates, polyphosphoesters, polyphosphazenes, polyesteramides, polyalkylenoxalates, polyalkylcyanoacrylates, etc., are represented as materials which are being tested for use, or which have been already used in surgery, orthopaedics, and pharmacy. A particular attention is devoted to their use in the preparation of systems with prolonged release or with targeted biodistribution of active ingredients.

Biodegradation, Environmental↗

20-Hydroxyecdysone release from biodegradable devices: the effect of size and shape.

20-Hydroxyecdysone (20-OH) is a natural compound with many demonstrated effects on the physiological functions of vertebrates, particularly increased protein synthesis. Our study sought a suitable dosage form with continuous release of the drug lasting several weeks for implantation into agricultural animals. Biodegradable microparticles and implants of poly(L-lactic) and poly(DL-lactic) acids were prepared. Oligomers of these materials were synthesized, and a method of melting the binary mixture of the oligomer and 20-OH was employed. The particles were prepared simply by grinding the solidified block of the melt and sieving. Implants were prepared by extruding the melt into silicone tubes, removing the solidified content, and cutting into cylinders of 2 mm diameter and various lengths. A new method of preparation of hollow cylinders by aspirating air into silicone tubes filled with the melt was developed. The experiments demonstrated stability of 20-OH during heat treatment. Release of the active ingredient was tested in static in vitro conditions, analogous to those at the site of implantation, and prolonged drug release was obtained with both types of implant. The hollow implants gave release rates nearest to ideal zero-order kinetics and would appear most appropriate for testing in vivo.

Absorbable Implants↗

Voltage-dependent K(+) current in capillary endothelial cells isolated from guinea pig heart.

Capillary fragments were isolated from guinea pig hearts, and their electrical properties were studied using the perforated-patch and cell-attached mode of the patch-clamp technique. A voltage-dependent K(+) current was discovered that was activated at potentials positive to -20 mV and showed a sigmoid rising phase. For depolarizing voltage steps from -128 to +52 mV, the time to peak was 71 +/- 5 ms (mean +/- SE) and the amplitude of the current was 3.7 +/- 0.5 pA/pF in the presence of 5 mM external K(+). The time course of inactivation was exponential with a time constant of 7.2 +/- 0.5 s at +52 mV. The current was blocked by tetraethylammonium (inhibitory constant approximately 3 mM) but was not affected by charybdotoxin (1 microM) or apamin (1 microM). In the cell-attached mode, depolarization-activated single-channel currents were found that inactivated completely within 30 s; the single-channel conductance was 12.3 +/- 2.4 pS. The depolarization-activated K(+) current described here may play a role in membrane potential oscillations of the endothelium.

Action Potentials↗

Role of ATP-dependent K(+) channels in the electrical excitability of early embryonic stem cell-derived cardiomyocytes.

Single, murine embryonic stem cell-derived early stage cardiomyocytes dissociated from embryoid bodies expressed two inward rectifier K(+) channels, I(K1) and the ATP dependent K(+) current. I(K1) exhibited low density in early stage cardiomyocytes, but increased significantly in late stage cells. In contrast, the ATP dependent K(+) current was expressed at similar densities in early and late stage cardiomyocytes. This current was found to be involved in the determination of the membrane potential, since glibenclamide depolarized early cardiomyocytes and exerted a positive chronotropic effect. Some cardiomyocytes displayed a bursting behavior of action potentials, characterized by alternating periods with and without action potentials. During the phases without action potentials, the membrane potential was hyperpolarized, indicating the involvement of K(+) channels in the generation of this bursting behavior. Extracellular recording techniques were applied to spontaneously contracting areas of whole embryoid bodies. In 20% of these bursting behavior similar to that seen in the single cells was observed. In regularly beating embryoid bodies, bursting could be induced by reduction of substrates from the extracellular medium as well as by superfusion with the positive chronotropic agents Bay K 8644 or isoproterenol. Perfusion with substrate-reduced medium induced bursting behavior after a short latency, isoproterenol and Bay K 8644 resulted in a positive chronotropic response followed by bursting behavior with longer latencies. The spontaneous bursting was blocked by glibenclamide. These experimental results suggest that intermittent activation of ATP dependent K(+) channels underlies the bursting behavior observed in single cardiomyocytes and in the whole embryoid body. Conditions of metabolic stress lead to the rhythmic suppression of action potential generation. Our data indicate that ATP dependent K(+) channels play a prominent role in the cellular excitability of early cardiomyocytes.

2,4-Dinitrophenol↗

Evaluation of ultrasonographic staging systems for the assessment of Schistosoma mansoni induced hepatic involvement.

For the sonographic assessment and grading of hepatosplenic morbidity induced by Schistosoma mansoni infection, several quantitative and qualitative classification systems have been used. In an attempt to evaluate two staging systems, a study was performed as part of a schistosomiasis research and control programme in Richard Toll, Senegal. A total of 700 residents of the township N'diangué were parasitologically, clinically and sonographically examined in July 1993. Two ultrasound observers (M.D. and E.D.) applied the Cairo and the Managil classification (E.D. only) for the grading of periportal thickening of the liver. In spite of high prevalence and intensity of infection, severe hepatic morbidity was rare. According to the Cairo classification, there was a high percentage of subjects with grade I periportal thickening, with considerable inter-observer variability. In the Cairo classification, which is based on the diameter of peripheral portal vein branches, firm cut-offs are used, independent of body height. We show the relationship between body height and portal vein diameters and recommend the use of body height-dependent reference values to avoid falsely high percentages of periportal thickening, especially in children. To minimize inter-observer variability, a clarification of existing instructions for taking measurements for grading is suggested. These suggestions have been considered during the follow-up expert meeting on the Cairo classification in Niamey under the auspices of the World Health Organization in October 1996.

Adolescent↗

[Phytotherapeutic aspects of diseases of the circulatory system. 6. Leuzea carthamoides (WILLD.) DC: the status of research and possible use of the taxon].

Leuzea carthamoides (WILLD.) DC., Asteraceae, has become an important taxon usable in human practice and animal production in recent years. Originally an endemic plant of southern Siberia, now it is widely grown not only in the Union of Independent States, once the original region of introduction, but also in central and eastern Europe. The principal constituents of the whole plant are ecdysteroids (5 beta-cholest-6-on-7-ene derivatives) and flavonoids. In addition, the aerial part contains sesquiterpenic lactones of the guajanolide type, and the roots contain polyines (on the thiophene base). The present paper comprehensively discusses the occurrence, content and biological activity of these substances, the preparations manufactured from the plant, their use in therapeutic practice, food manufacture and animal production in the world and the Czech Republic. The plant has certainly become a taxon with prospects in the Czech Republic, particularly as the source of 20-hydroxyecdysone, which is getting into the limelight in the world.

Animals↗

Inwardly rectifying K+ channels in freshly dissociated coronary endothelial cells from guinea-pig heart.

1. Inwardly rectifying K+ (IK(IR)) currents of freshly dissociated coronary endothelial cells from guinea-pig heart were investigated with the perforated-patch technique. 2. The whole-cell current-voltage relationship of endothelial cells showed strong inward rectification. Increasing the extracellular K+ resulted in an increase of inward currents. The slope conductance of the cells in the potential range negative to the calculated potassium equilibrium potential (EK) with 5, 60 and 150 mM external potassium was 0.18 +/- 0.14, 0.55 +/- 0.50 and 0.63 +/- 0.29 nS (mean +/- S.D.), respectively. 3. To quantify the steepness of inward rectification, the voltage dependence of the chord conductance of the cells was fitted with a Boltzmann function. The slope factor k describing the steepness of the relationship was 6.8 +/- 1.5 mV. 4. Extracellular barium induced a potential- and time-dependent block of inward currents through endothelial KIR channels. Half-maximum inhibition of IK(IR) currents was achieved with < or = 1 microM barium at a membrane potential of -70 mV in a solution containing 60 mM K+. 5. Whole-cell inward currents revealed the opening and closing of single KIR channels. The single-channel conductance was 26 +/- 3 pS with 60 mM external K+ and 33 +/- 6 pS with 150 mM external K+. 6. Our results suggest that the electrical properties of freshly dissociated endothelial cells are to a large extent determined by five to sixty active strong inwardly rectifying K+ (KIR) channels.

Animals↗

Influence of processing conditions on the release of sodium fluoride from oligomeric L-lactic acid matrices.

Matrices were prepared in the shape of rods with a diameter of 4 mm and a length of 10 mm. They were composed of oligomers of L-lactic acid (Mw 2550-11730 Daltons) and micronized sodium fluoride particles. Sodium fluoride concentration was kept in the range 5-60%. Matrices were prepared by melting the mixture of L-lactic acid oligomer and sodium fluoride. Two types of products according to the applied cooling rate were prepared and evaluated for release characteristics in vitro. Sink conditions of isotonic phosphate buffer solution pH = 7.4 at 37 degrees C were maintained throughout the experiment. The concentration of dissolved sodium fluoride was determined by ion-selective electrode. It was documented that the release rate of sodium fluoride is strongly dependent on the molecular weight of oligomer. The effects of sodium fluoride concentration and cooling rate of melted mixture were evaluated by ANOVA, separately for each oligomer. The effect of sodium fluoride concentration was significant at each oligomer studied, while the influence of cooling rate was significant with higher molecular weight oligomers. Moreover, this effect is ambiguous and dependent on the capability of oligomers to form crystalline phases and on the form and geometric arrangement of this phase.

Biocompatible Materials↗

[Representation and transfer of labeled reference structures in X-ray, CT and MR imaging].

PURPOSE: Image information obtained with different methods should be exactly transferable to profit fully from the single advantage the different imaging method has in localisation and for further treatment planning. Prominent anatomical points serve as reference structures (landmarks) for the transference of imaging information and details of situation. Aim of this study is the improvement of reproductability by comparing topographic relations, measurements and positioning in different imaging-procedures with supporting marking aids/surface markers. MATERIAL AND METHODS: By using pharmacological capsules and plastic tubes filled with oily contrast medium containing iodine (Lipiodol; Byk Gulden), marking aids were developed which can be seen in similar definite limits within the framework of MRI-, CT- and conventional X-ray-Imaging. RESULTS: A method to view these new, artificial markers in combination with individual, anatomical landmarks is introduced. The marking aid/surface marker, fixed on anatomical reference structures on the skin, does not result in an additional burden for the patient. CONCLUSIONS: The new, artificial markers are also useful for making other structures recognizable, such as anatomical relation lines, center of the portal and edges in planning imaging for radiotherapy treatments and are used as leading and reference structures to compare localisation and extent of lesions in X-ray-, CT- and MRI. Marking aids/surface markers do not have to be changed in different imaging methods.

Magnetic Resonance Imaging↗

Ultrasonography as a diagnostic aid for a district hospital in the tropics.

To improve diagnostic capabilities, an ultrasound unit was installed at a major hospital in Wad Medani, Sudan. During the implementation period (October 1986 to March 1987) of ultrasound service, 863 patients were examined cooperatively by Sudanese and German physicians. The service covered internal medicine (47.5%), obstetrics and gynecology (31.6%), surgery (12.5%), and pediatrics (8.4%). Pathologic findings were seen in 75% of the patients. In obstetrics, the rate of pathologic findings was 40%. Five hundred eighty-three pathologic findings were detected in organ systems that constituted the primary indication for ultrasonography (of a total of 1,009 indications). The clinical benefit of ultrasonography was evaluated in 289 randomly selected patients in a standardized questionnaire completed by the attending physicians. The final clinical diagnosis was established or substantially revised in 21.5% of the patients, based on the ultrasonographic report. The previously reported diagnosis was supported in 69.5% of the patients. Medical management was directly influenced in 26% of the patients. We conclude that the clinical benefit of ultrasonography at a district hospital in the tropics is substantial, providing cost-effective, immediate therapeutic benefits in 25% of the patients examined. The technique thereby contributes to better and more rational patient management in institutions with limited resources.

Adolescent↗

Renal growth in patients nephrectomized for Wilms tumour as compared to renal agenesis.

Compensatory growth in 27 undiseased congenital solitary kidneys and in 31 solitary kidneys in patients with Wilms tumour was monitored in long-term follow-up studies by ultrasound volume biometry. In congenital solitary kidneys hypertrophy was not detectable at the time of birth. Parenchymal mass increase achieved 188% of the volume of a healthy kidney within at least 4 years of life and afterwards paralleled the physiological growth documented in healthy kidney pairs. Disease-free kidneys in Wilms tumour patients all developed a similar 180% volume augmentation within 2-4 years after nephrectomy, irrespective of the chosen mode of radiation and single or triple chemotherapy. The age of the patient at onset of surgical and concomitant conservative therapy determined slight differences in kinetics but not in degree of compensatory growth.

Adolescent↗