[A closet for the storage of histologic preparations].
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Biomedical subjects
Publications and source records attributed to C H Becker.
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In order to find out whether after repeated intermittent treatment with angiotensin-II (A-II) the hypertrophically and hyperplastically altered vascular walls show the same adaptation as with normotensive rats (NR), investigations were performed on 44 male 16-week-old spontaneously hypertensive rats (SHR) (Okamoto-Aoki). In three repeated series daily doses of 0.15 mg depot A-II, the lowest blood pressure effective dose attended by vascular and organic reactions, were applied for 5 days. We found that the functional reactivity of the arterial vascular system in SHR was retained after repeated intermittent administration of A-II despite the hypertrophically hyperplastic processes. This was equally true for the structural reactivity as shown by the occurrence of equal vascular alterations following each new injection series as those which appeared after the first administration of A-II. Thereafter, no structural adaptation of the arterial vascular system occurred in the SHR. The extensive A-II induced vascular alterations did not lead in SHR to additional sustained increase in blood pressure. On discontinuation of A-II treatment the A-II-induced vascular alterations reconverted within a month, even after repeated intermittent A-II treatment, despite the existence of high blood pressure. They are thus reversible. A similar remission is observed also with the A-II-induced myocardial alterations. It thus becomes obvious that, with maintained reactivity of the vascular walls against A-II and with an existing hypertension, R-A-S stimulating factors obviously are able to induce structural alterations at the arterial vessels.
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The pectin-gelatin complex coacervate system was evaluated and characterized. The effects of final pH, mixing pH, colloid ratio, and solution concentration were investigated. A recovery procedure yielding microglobules of a controlled and uniform size in dry powder form which were readily revertible in water to a polydispersed suspension was developed. The effect of various conditions and additives on the recovery morphology and size of the microglobules was evaluated.
The non-cleared influences of the sympathetic nervous system [sN] on structural reactions of SHR and on the direct cardiac effects of AII and the structural vascular behavior were investigated. In 67 spontaneously hypertensive rats (Okamoto-Aoki) and 55 normotonic Wistar rats (NR) the blood pressure behaviour, the structural vascular and organ reactions and the noradrenaline (NA) content of the myocardium were examined with an intact sympathetic nervous system as well as after its almost complete elimination by chemical sympathectomy with 6-hydroxy-dopamine (6-OH-DA). Moreover, the functional and structural responsiveness of the arterial vessels of sympathectomized animals to angiotensin II administrations was investigated. 6-OH-DA in the dosage applied, induces during its time of action in NR a smaller, in SHR a larger decrease of blood pressure and, presumably induced by intense NA-depletion of the myocardium, myocardial alterations. Despite extensive AII-induced alterations of the already early hypertrophically-hyperplastically changed vascular wall, the structural and functional responsiveness of the arterial vascular system was maintained even after sympathectomy, and the sensitivity of the SHR to AII remained. For maintaining hypertension, the cooperation of structural and functional influences is necessary, as is indicated by the reduction of blood pressure in sympathectomized SHR and its regular return to the daily initial values of normotonic animals under additional AII administration. Besides the vascular alterations contributing to the exacerbation of the hypertension, here the sNS is of essential importance. For obtaining a total pressure effect of AII the sNS obviously has not necessarily to be intact, though its activity state can influence the responsiveness of the arterial vascular system to AII. The reduction of the sympathicotonus by sympathectomy seems to have a protective effect on the development of AII-induced structural vascular alterations; in contrast to the myocardium in SHR, in which it induces an exacerbation and an increase in the AII-induced myocardial alteration. These findings obtained from rats are supposed to be important also for the essential hypertension in man. By maintaining the functional responsiveness of the arterial vascular system, antihypertensives which react with the different parts of the sNS cab become effective while structural alterations of the vascular wall can be influenced, too. The possibility of the simultaneous development of myocardial alterations should be taken into special consideration.
In 55 spontaneously hypertensive rats (SHR) (Okamoto/Aoki) and 63 normotensive Wistar rats (NR) receiving Angiotensin-II, hypertrophically-hyperplastically altered vessels of SHR were tested for their functional and structural reactivity and compared with the behaviour of the arterial vascular system at essential hypertension of man. After 5 days of treatment with 0.15 and 0.02 mg depot-Angiotensin II (A-II) SHR showed an increase in systolic and, with 0.15 mg A-II, even in diastolic blood pressure and bradycardia. At either A-II dosage, plasmatic vasculoses were found at the arterioles and small arteries both in SHR and similarly treated NR, though in higher frequency and in a larger quantity in SHR, as it was the case also with myocardial alterations. Although in the arterial vessels in SHR there developed already primary hypertrophically-hyperplastic wall alterations, A-II application led to functional and structural reactions. Consequently, an additional vasoconstrictor stimulus does not lead in SHR to a process comparable with essential hypertension in man, but merely to reversible, acute vasculopathies.
Autoradiographic, light and electron microscopic investigations on the effect of depot angiotensin on the hearts of rats suggested that the myocardium and the intramural vessels reacted with an activation of the mesenchymal and DNA metabolism already 3 hrs, after the injection of depot angiotensin. The reactions in the capillaries and small arterioles were dominating. Degenerative alterations could be found in the cardiac muscle cells only 9 hrs. after injection and culminated in infarction-like necroses and intensive mesenchymal proliferation after the 4th A II injection. Despite further daily applications of A II the degenerative and necrotic myocardial alterations will extensively diminish until the 14th day of experiment, while the mesenchymal activation and the enhanced DNA synthesis in the vessels remained unchanged. Thus an initial stage with the development of disseminated muscle fibre necroses and infarction-like alterations and a stage of compensatory adaptation may be distinguished in the heart after depot angiotensin injections.
In X-ray microanalysis of biological tissues, high Cl-peaks are constantly observable. Higher Cl-peaks in the tissue than in the epon environment suggest that most Cl originates from the tissue. Therefore rough regional estimations of the Cl level could be possible.
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Medicated and unmedicated microglobules prepared from complex coacervates of Type A gelatin and acacia were recovered as water-insoluble powders consisting of discrete units, which were spontaneously revertible to highly disperse systems when suspended in water or physiological electrolyte solutions. Spherical microglobules containing up to 15% (w/w) sulfamerazine had a nominal diameter of 30 micron in aqueous suspension. Larger but irregularly shaped products containing up to 45% (w/w) sulfamerazine were also recovered. The relationships of the weight of sulfamerazine added per coacervate batch to weight yield and percent (w/w) included sulfamerazine of the microglobules were both linear.
X-ray microanalysis was performed on ultrathin sections of tissues from six rats, four of which having been exposed to experimental metabolic disorder by overdoses of NaCl and Ca-Vit. D2, respectively. It was demonstrated that the elements Cl, Si, P, S, Ca and traces of Fe are identifiable quantitatively in arteriolar walls of colon, heart and kidney even after conventional electron microscopic preparation (fixation, dehydration and Epon embedding). Depending on the pretreatment considerable differences in elemental quantities between animal groups were observed. The reliability of these findings must be confirmed by further tests on a greater number of individuals.
A 14-days' training of rats designed to adapt the animals to the procedure of blood-pressure measurement caused in the myocardium a decrease, in serum an increase in noradrenaline ( NA) content. The latter remained unchanged following 3 days of treatment with 2.5 mg depot angiotensin II (AII) but decreased by more than one-half in the myocardium of untreated animals, and increased in serum. Despite the considerable difference in myocardial NA content and blood-pressure behaviour, both trained and untrained rats showed the same morphological reactions following administration of A II. These myocardial alterations which largely correspond to the so-called epinephrine myocarditis should not therefore be due solely to NA action; rather, the involvement of A II should be considered also.
The mulitplication of herpes suis virus in neurons, amphicytes, gliocytes, as well as Schwann's and endothelial cells of the spinal ganglion of rabbit was traced by electron microscopy and autoradiography, using tritium-labelled thymidine. Marking of nuclear zone margin, quite common when it comes to ganglion cells, was observed also in the context of mesenchymal cells beyond expectation on the basis of light microscopy, but in the case under review it had no direct relationship with virus synthesis. Repeated markings were recorded from the nucleoli of apparently unchanged ganglion cells which suggested the suitability of the technique for early detection of infectious attack on intact cells. Exogenous 3H-thymidine was supplied three hours and absorbed with specificity by the DNA-forming centres of the nuclei, but the growing virus drew into itself additional cellular or inactive thymidine. The method proved to be highly significant, as in comparison to the nuclear environment there were ten times as many lemnici in the DNA production centres of neurons and Schwann's cells and about six times as many in the amphicytes and gliocytes. Now, there is definite justification in rejecting as unfounded all doubt expressed repeatedly and more recently in the specificity of herpes-dependent intranuclear inclusions.
The peripheral arterial blood vessels in the cerebrum of 36 experimental animals and 9 controls were studied by electron microscopy. In 5 rats of these renal hypertension was produced (the animals were sacrificed 3 to 15 days following the second operation). 24 animals were treated with depot angiotensin (0.02 to 2.5 mg/daily) for 3 hr up to 40 days, and 7 rats were neurotized for 1 to 41/2 months. The alterations of the cerebral vessels were distinctly different within these 3 models already in the early reactions. Thus, even in the first 14 days of the experiment with renal and angiotensinogenic hypertension alterations were observed that did never occur in the neurotized rats. There were always observed disturbances in permeability of the cerebral vessels, but they were never followed by such heavy wall insudations as usually noticed in the splanchnic vessels. The less frequent occurrence of hemorrhages and malacic processes in the rat brain is ascribed aside from the physiological properties of the brain supply, to genetic factors and the absence of arteriosclerotic burden to the vascular wall in the non-dietetically pretreated experimental animals.
Daily s.c. injections of 0.02--10.0 mg angiotensin in depot form for 14 days caused in rats, under defined conditions, pronounced dose-dependent effects, with an unusual tolerance to the drug being observed. The behaviour of the systolic and diastolic blood pressure and heart rate allowed to define 4 dose ranges. In the lowest dose range of 0.02 mg angiotensin-II a lasting borderline hypertension with only straight-line changes of diastolic blood pressure and bradycardia were observed. The doses of 0.15--1.25 mg angiotensin-II caused a continual blood pressure rise and led, between day 4 and 6 of the experiment, to a pronounced lasting resistance high-pressure without appreciable changes in heart rate. The strongest resistance high-pressure, which occurred as early as on day 3, with pronounced tachycardia was achieved with a dose of 2.5 mg angiotensin-II. Higher doses produced pronounced tachycardia but no significant effects on blood pressure. The varying dose-dependent effects of depot angiotensin are discussed, and the possibility is pointed out to study by the angiotensin-II hypertension model various mechanisms of a long-time hypertensive dysregulation.
The concentration of diazepam in two types of suspension vehicles, as prepared from 10-mg tablets was tested over a 14-day period. The suspensions (1 mg/ml) were stored at room temperature in amber glass bottles. In one suspension, consisting of eight triturated tablets, 4.0 ml ethanol, 24.0 ml propylene glycol, 20.0 ml Syrup, USP, and 32.0 ml chocolate syrup, 90% of the diazepam was dissolved. This suspension demonstrated consistently acceptable concentrations of diazepam. In the other suspension, consisting of triturated tablets and Syrup, USP, only 25% of the diazepam was dissolved, and less consistent, subpotent concentrations of diazepam were found. The variation of diazepam concentrations between the suspensions was unrelated to the chemical stability of the drug.
In pigs receiving up to 14 days daily injections of depot angiotensin, repeated daily bloody measurements of the blood pressure at the carotid artery proved unsuitable because of ensueing septic processes, in contrast to the unbloody measurement at the caudal artery. The depot angiotensin, despite the use of preparations with varying content of angiotensin-II and carrier solution, caused immediately after the injections a very strong maximal rise in systolic and diastolic blood pressure that occurred also with longer periods of the experiment; this rise gradually diminished in the course of the day but remained mostly in the hypertonic range and showed daily initial values above normal. The pig proved to be much more sensitive to angiotensin than the rat, for instance. Despite the proved vasoconstricting action of angiotensin, light-microscopic alterations at the vessels, kidneys, and the myocardium could not be observed. Part of the arterioles showed an increased wall thickness in animals killed on the 8th and 15th day of the experiment. The differences in the pathomorphological and blood pressure behaviour from the rat are discussed. The first experimental results qualify the pig as an experimental animal for comparative hypertension studies.
In 55 rats, not accustomed to the process of blood pressure measurement and given daily doses from 1.25 - 10.0 mg angiotensin in depot form for up to 3 days, as much as 70% of the animals died of circulatory failure. Blood pressure increase was either absent or was very low after low doses. Histologically, the myocardium revealed focal destruction of muscle fibres with mesenchymal cell proliferation in many places; the epithelium of numerous renal tubuli was changed hydropically; the liver showed focal necroses of the parenchyma; the adrenal cortex showed stress reactions, and the arterioles of the splanchnic area -- changes of the plasmatic vasculose from the 3rd day of experiment. By contrast, in 51 rats accustomed to the measuring process prior to the experiment and given high doses of angiotensin, only moderate blood pressure rise and scattered cases of death (4%) occurred, low doses caused a strong blood pressure elevation. With otherwise equal histologic organ diagnoses, liver necroses were absent, except for two cases. This differential response of the two animal groups to varying angiotensin doses and the pathogenesis of the changes observed are discussed.