Presence of the guanylate cyclase in brain capillaries: histochemical and biochemical evidence.
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Biomedical subjects
Publications and source records attributed to I Tóth.
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A surgical procedure for staghorn calculi, which are inaccessible to conservative therapy, is described. It not only provides for complete elimination of the calculus but may also contribute to the prevention of recurrences. The technique of marginal wedge excision of the renal parenchyma, developed in animal studies, is described in detail and 11 surgical cases are reported. Removal of staghorn calculi was successful all throughout, and renal function remained unaffected by the intervention in all of the cases. Recurrences were confined to a single case. The procedure is safe, it involves no greater surgical strain than does marginal nephrotomy, but its short-term metaphylactic results seem more promising. Assessment of the long-term results awaits further observations.
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The properties and the effects of a new steroid muscle relaxant preparation 2 beta,16 beta-bis(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan) were compared to those of pancuronium bromide in a controlled randomized clinicopharmacological study using ataranalgesic anaesthesiological technique. In 45 cases pipecurium bromide, in other 45 cases pancuronium bromide was used as long-acting muscle relaxant in anaesthesia for general surgical procedures. According to the results, pipecurium bromide is approximately 20% more potent than pancuronium bromide, it induces mechanical response characteristic for non-depolarizing muscle relaxants, and the residual neuromuscular blockade can be antagonized completely by neostigmine. There were no ECG alterations or specific serum enzyme (CPK, GOT. LDH) level changes observed. Pipecurium bromide did not influence blood pressure but in contrast to the heart rate increasing effect of pancuronium bromide, it caused mild bradycardia. On the basis of the study the drug can be used for further wide scale clinical investigations.
1. In view of the importance of calcium in triggering the transmitter secretion during nerve stimulation or depolarization, the localization of calcium binding sites was studied in stimulated nerve endings that were fixed in calcium-containing s-collidine buffered paraformaldehyde solution. 2. In cholinergic synapses, such as the superior cervical ganglion of cat, the myoneural junction of rat diaphragm and the electric organ of Torpedo marmorata, a stimulation-dependent accumulation of calcium was found in the mitochondria of presynaptic nerve endings. 3. In synaptosomes prepared from rat cerebral cortex, the activity-dependent accumulation of calcium in mitochondria of pinched off nerve endings was also observed. The mitochondrial accumulation of calcium in synaptosomes was dependent on ATP, temperature and could be inhibited by quercetin. 4. In stimulated synapses, only the mitochondria seemed to accumulate calcium in appreciable amounts, whereas other intra-terminal structures, such as the smooth endoplasmic reticulum and synaptic vesicles were devoid of calcium.
Daily doses of 1320 mg MTDQ have been administered orally to 7 patients for 100 subsequent days. Biological half-life and serum concentration measurements were performed. Function of vital organs, as well as routine laboratory findings revealed that MTDQ did not induce any toxic changes. The effect of MTDQ on the radiosensitivity of hypoxic tumor cells was studied in a combined treatment modality including 12 patients. The action on tumor regression was found encouraging. It has been found remarkable, too, that due to the effect of MTDQ and radiotherapy some of the nonspecific and general symptoms (e. g. pruritus) also disappeared.
Animal experiments were carried out on 12 dogs. Dogs are specially qualified because the choledochus and the pancreatic duct seperately fall into the duodenum. Laboratory tests demonstrated the influence of the choledocholigature on the exocrine function of the pancreas. These findings refer to the unity of the biliary tract and the pancreas. The histologic inquiries of pancreas did not showed any pathologic alterations because the survival time was too short likely.
Donor kidneys were preserved in a Collins-4 solution containing periodate in concentrations of 10(-2) and 10(-4) mole/l, respectively, in an attempt to oxidize the carbohydrate components of the antigen-carrying membrane surfaces and thus to influence the rejection phenomena exhibited by the allogeneic kidney. All kidneys were, however, rejected as a result of a hyperacute reaction indicating that periodate did not react with the hydrophobic membrane structures in vivo. Not only did the antigen thus remain unchanged but the vulnerability of other renal structures to the destructive effect of the killer cells also increased as a result of toxic damage.
The fine structural characteristics of ZIO reaction was studied in the cerebral and cerebellar cortex and olfactory bulb of the rat and in synaptosomes prepared from rat cerebellar cortex. It was concluded that: 1. Organelles of different nerve cell types exhibit different ZIO reactions provided that the impregnation was carried out under standardized conditions. 2. 6...10 times more synaptic vesicles were stained by ZIO in the inhibitory terminals than in the excitatory ones. 3. ZIO positivity was found in all types of synaptosomes prepared from cerebral cortex. Following electrical or chemical (KCl) depolarization there was a decrease in the number of ZIO positive synaptic vesicles, which decrease was directly proportional to the parameters of stimulation. 4. By x-ray microanalysis Os, Zn and Ca were consistently detected in the ZIO precipitates. Iodine, however, could not always be found. After stimulation the presence of Ca was observed even in those synaptosomes in which the ZIO reaction product was absent. 5. On the basis of the staining characteristics the reaction, under standard conditions, can reflect certain functional states of the nerve terminals.
An electron histochemical study was undertaken to localize calcium with ammonium oxalate precipitation technique in soleus muscle of rat in normal cases and in myopathy induced experimentally by a prolonged treatment of 2,4-dichlorophenoxyacetate (2,4-D). The calcium content of precipitates was detected by energy-dispersive X-ray microanalysis. In normal cases, the electron dense precipitates containing calcium were mainly found in the vesicles of sarcoplasmic reticulum, whereas in 2,4-D induced myopathy the deposits were shifted near the Z line into the myofibrils. Calcium, because the uptake into sarcoplasmic vesicles was inhibited by 2,4-D, could attach to other binding sites, such as to the troponin-C.A long-lasting binding of calcium might lead to a prolonged activation of the actin-myosin system.
Selective angiography post mortem and in vivo, respectively, has been performed in canine kidneys (isolated, autografted or left in situ) for the study of the renovascular changes caused by different perfusates and by reperfusion. The results indicate that inadequate heparinization, the composition of the perfusate, imperfect surgical techniques and even restoration of circulation to the kidney itself, may produce roentgenologically demonstrable renovascular damage the causes and consequences of which are unrelated to those of the closely studied and adequately interpreted phenomena of graft rejection.
The structure of the dog kidney can be preserved in hypothermic intracellular-type solutions, but after 6 hours the appearance of pathologic focal changes such as mild oedema, lesions of the cellular elements, podocyte heteromorphism, vacuolization, disintegration of the basal membrane and of the cytomembrane structrues and even cell degeneration, is unavoidable.
In the autogenous kidney preserved under conditions of hypothermia the development of a partial no-reflow phenomenon is unavoidable after reimplantation. The phenomenon is ascribed to ischaemic lesions induced by preservation. The consequences are functional disorders in the acute period (temporarily pathologic angiogram, nephrogram and proteinuria) and scars due to chronic focal necrosis. These unavoidable changes of the current preservation procedures are mostly of subclinical importance.
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Twenty-five swine kidney xenografts previously flushed with Collins-4 solution were perfused with canine blood and the functional and morphological changes resulting from xenoperfusion were studied. Blood flow of the kidneys practically ceased by the end of 8 minutes parallel with progressive swelling and cyanosis of the organ. Microscopic study of the kidneys revealed gross destruction of the glomerular and tubular apparatus, marked by extensive oedema, interstitial haemorrhages, diffuse capillary thrombosis and damage to the cell membrane.
The possibility of structural and functional preservation of the isolated liver has been studied in dog experiments. A sterile liver preparation left in situ was worked out, having practically no ischaemic period, except during perfusion. Nevertheless, well-defined lesions (perivascular and interstitial oedema, dissociated contraction of the smooth muscle elements of the veins, cellula accumulation in the sinusoids) appeared, accompanied by a gradual reduction (microcirculatory disorders, enzyme derailment) of the function of hepatocytes.
On the basis of own investigations of the testosteron metabolism in hepatopathy must be assumed that the hypogonadism appearing in liver diseases is to be regarded as peripheral form, i.e. it is not centrally evoked by gonadotropin insufficiency. An own pathogenetic concept is discussed.
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