Is the effect of calcium diet or parathyroidectomy on the development of hypertension in spontaneously hypertensive rats mediated by atrial natriuretic peptide?
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Biomedical subjects
Publications and source records attributed to H Geiger.
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Intravenous injection of prostacyclin (100 micrograms/kg) in rats resulted in a decrease of systolic blood pressure within 2 minutes. Concentrations of cAMP in 15 brain regions and nuclei were determined by radioimmunoassay. In lower brain stem nuclei, such as the nucleus of the solitary tract and the lateral reticular nucleus (A1 and C1 catecholaminergic cell groups) cAMP levels were depleted significantly, while in others, including the locus coeruleus and the periaqueductal central gray, cAMP levels did not show any alterations. Levels of cAMP were also depleted in some of the hypothalamic nuclei (periventricular, anterior hypothalamic, ventromedial), and in cerebral cortical areas. Lowered cAMP levels in brain areas might indicate lower cellular activity in cells participating in baroreceptor control mechanisms.
The quantitatively most important noradrenergic cell group of the brain is the locus coeruleus. Significantly increased cAMP concentration could be measured in spontaneously hypertensive rats in comparison to normotensive Wistar-Kyoto control rats at every stage investigated. Furthermore, both the basal activity and maximal stimulation of Ca++- and GTP-dependent adenylate cyclase as well as phosphodiesterase activity were significantly decreased in the spontaneously hypertensive rats at 14 weeks of age. The possible role of the locus coeruleus in spontaneous hypertension is presumed in counterregulatory mechanisms against rising blood pressure.
This paper describes a neural network model whose structure is designed to closely fit neuroanatomical and -physiological data, and not to be most suitable for rigorous mathematical analysis. It is shown by computer simulation that a process of self-organization that departs from a fixed retinotopic order at peripheral layers and includes Hebbian modifications of synaptic connectivity at higher processing levels leads to a system that is capable of mimicking various functions of visual systems: In the initial state the overall structure of the network is preset, individual connections at higher levels are randomly selected and their strength is initialized with random numbers. For this model the outcome of the self-organization process is determined by the stimulation during the developmental phase. Depending on the type of stimuli used the model can either develop towards a feature-selective "preprocessor" stage in a complex vision system or towards a subsystem for associative recall of abstract patterns. This flexibility supports the hypothesis that the principles embodied are rather universal and can account for the development of various nervous system structures.
The manufacturing procedures used for the preparation of human plasma proteins that were established before AIDS was first described may reasonably be expected to provide AIDS safe products. Such manufacturing procedures are heat treatment at 60 degrees C in solution for ten hours, described as pasteurization, preparation of human immunoglobulins by ethanol precipitation, pepsin treatment, and sulfonation. To test whether these methods effectively inactivated and/or eliminated the AIDS causing human immunodeficiency virus (HIV), nine volumes or more of plasma or a plasma fraction taken from a production lot were spiked with HIV using one volume of a HIV concentrate and were then subjected to exactly the same procedure as that specified for the manufacturing process. HIV infectivity titres of the initial HIV/plasma protein mixtures and of the resulting products after treatment were determined by the H9 cell assay. In all cases studied complete inactivation/elimination of the added HIV was achieved. We therefore conclude that pasteurization of human plasma proteins or the manufacturing procedure used for the isolation of immunoglobulins from plasma pools result in final products which do not contain any infectious HIV and which are thus safe in that they cannot be vehicles for the transmission of AIDS.
1. The influence of two angiotensin-converting enzyme inhibitors, captopril and enalapril, on the cAMP content of microdissected brain areas was examined in spontaneously hypertensive rats. Both drugs depleted systolic arterial blood pressure significantly. 2. Captopril and enalapril increased the level of cAMP in catecholaminergic cell groups in the lower brain-stem. Captopril was more effective in the substantia nigra, while enalapril treatment resulted in high cAMP levels in the ventrolateral medulla oblongata (A1 catecholaminergic cell group). 3. Both drugs, especially captopril, depleted cAMP content in the cingulate cortex. 4. No changes in cAMP levels were measured in the primary baroreceptor centre (nucleus of the solitary tract) following either captopril or enalapril treatment.
Variations in calcium alimentation influence the development of high blood pressure in genetic hypertensive rats. Different calcium feeding and changes in parathyroid hormone status cause altered cAMP-content in specific brain areas. All animals with high calcium diet show significant elevated cAMP-content in the locus coeruleus, irrespective of parathyroid status. These findings support the hypothesis that elevated cAMP-concentrations reflect an increased depressor activity of the locus coeruleus.
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In a modern therapy concept coagulation factor concentrates are widely used for prophylaxis of bleeding events and in intensive care medicine. In the past their use was limited by the risk of transmitting virus diseases to the patient. Therefore, it was a challenge to modern plasma fractionation to develop purification processes which are able to eliminate and inactivate viruses. At present several methods for virus inactivation are used; their efficiency is not finally proven. Practical experience exists with a method in which viruses are inactivated by heat treatment in solution. A similar process is used since more than 40 years to produce albumin and was proven to be safe. Today, all coagulation factor preparations can be treated by this inactivation method and produced in large scale. Together with a high degree of viruses elimination during the purification process the therapy with coagulation factors has become much safer.
The Timm and selenium staining techniques, based on silver amplification of endogenous zinc, produce an electron-dense precipitate in boutons. The staining characteristics of the two methods were compared by examining two allocortical regions, prepiriform cortex and entorhinal cortex, in the brain of the European hedgehog. In the 3 layers of prepiriform cortex and the 6 layers of entorhinal cortex the methods revealed sublayers, which allows a precise delimitation of areas 28M, 28L, a short transition zone, and the prepiriform cortex. The lamination of the entorhinal cortex of the hedgehog is similar to that found in the rat, but appears less distinct. This may point to a lower degree of afferent organization. For light microscopical investigations, the selenium technique appears superior to Timm's method because it produces a more distinct zonation pattern.
The question has been raised as to whether there exists any transfer of information between neighboring retinal areas following presentation of spatially limited optical stimuli. Our experiments were aimed at mechanisms by which spatial frequency information could be transferred from one part of the visual field to another. Within a 0.9 degree X 2.5 degree section of the 3.6 degree X 2.5 degree testfield the observers adapt to a number of moving sinusoidally-modulated brightness or hue gratings of different spatial frequencies. As known by many publications the sensitivity to spatial frequencies changes in the adapted area. We find that this influence on the contrast threshold decreases as the distance to the adaptation section increases. Hence our results suggest mechanisms within the visual system mathematically best described by a local spectrum analysis.
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The freeze-drying of biological material, which is to be quantitatively analyzed (micro-amount level) for compounds of low or intermediate molecular weight, should be either omitted or handled under strict control. This is because compounds such as amino acids, sugars, flavonoids, glycosides, coenzymes, peptides, etc., might be removed from concentrates and (or) the ground biological material by the high vacuum.
Results are given on tolerability and bioavailability of an intramuscular immunoglobulin (Ig) preparation (BI 2.011) with high titer against cytomegalo-virus (CMV). For rapid and long-lasting protection a dosage of 0.2 ml/kg body weight anti-CMV-Ig with a titer of 1:50 000 (Enzyme-Linked Immunosorbent Assay) is recommended. Prophylaxis should be taken into account in seronegative patients suffering from immune defects, that experience transplantation surgery and/or multiple injections of blood products.
Recently the question has been raised whether the presence of prekallikrein activator (PKA) in human blood products for i.v. application could possibly cause adverse reactions in the recipient as observed now and then. Up to now a correlation between both properties is far from being established, even though in the U.S. there has been extensive discussion over some PPL batches containing elevated amounts of PKA, presumed to be causally related to an increased frequency of side reactions. As has been demonstrated in the past through wide clinical experience, human albumin is an exceptionally safe blood product. If at all, side effects sometimes seem to occur related to certain individual lots, the reason for which is still unrevealed. In the pursuit of eventually finding some association between PKA levels in and side reactions with albumin, we performed PKA measurements on a panel of commercial human albumin batches, a few of which had been reported occasionally to cause adverse reactions. The assay procedure was essentially that published (3). BOB PKA reference No 1 was included as a standard. PKA was detected in moderate amounts in huge series of albumin batches without any reported side reactions. We conclude, therefore, that PKA levels in the range of trace amounts cannot be related to side reactions with human albumin preparations.
In a prospective study, 44 children receiving Adriamycin (ADR) for various neoplastic diseases underwent serial estimations of the systolic time intervals (STI) for the noninvasive assessment of left ventricular myocardial performance. Five of the 44 children developed clinical signs of ADR-related congestive heart failure at a cumulative dose of less than 550 mg/m2 body surface area. Clinical symptoms, changes in the electrocardiogram and in the chest X-ray were preceded in every case by changes of the STI, mainly a prolongation of the left ventricular pre-ejection period (PEP), or a decrease of the ejection time (ET)/pre-ejection period (PEP) ratio (ET/PEP). A continous increase of the PEP and a decrease of the ET/PEP-ratio also gave an indication of myocardial dysfunction during ADR treatment in the other children without clinical signs of congestive heart failure. This subclinical cardiotoxic effect of ADR below the critical cumulative dose of 550 mg/m2 was observed in children with pre-existent myocardial damage, with preceding thoracic irradiation, or during concurrent chemotherapy, of which cyclophosphamide seemed to be most important. Thus, the estimation of the STI proved helpful and reliable in the early detection of incipient heart failure and in the selection of high risk patients in children receiving ADR treatment.
A collaborative assay was conducted by 9 laboratories on 31 samples of human albumin which were in clinical use. It was the object of the study to establish test systems which would differentiate between albumins of venous or placental origin. The properties examined for this purpose were: appearance, total protein, haem, polymers, alkaline phosphatase and blood group substances. Additional tests such as for beta-thromboglobulin and citrate were included; pyrogenicity, however, was excluded because this was under study for all plasma proteins at that time. Results obtained were in satisfactory agreement both between laboratories and between samples. They, therefore, enabled the verification of a number of correlations in the test systems. The evaluation did not allow, however, the differentiation of the samples in relation to their origin. The results were, therefore, regarded as a tool to define the upper limits of acceptance for human albumins corresponding to the quality prescribed by the European Pharmacopoeia.