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Biomedical subjects

Z Nagy

Publications and source records attributed to Z Nagy.

At least 217 records · Page 12Linked to original sources

Blood-brain barrier impairment by low pH buffer perfusion via the internal carotid artery in rat.

Krebs-Ringer bicarbonate buffer (KRB) adjusted by lactic acid to low pH levels (6.6, 6.2, 6.0, 5.8, 5.5) was perfused via the internal carotid artery as a bolus into rat brain hemispheres. In one group of animals, the fluid phase tracer horseradish peroxidase (HRP) was perfused immediately following the low pH treatment. In the other group of animals, the brain hemispheres were fixed and the endothelial cells were stained with colloidal iron (CI) at pH 1.8. Widespread extravasation of HRP was detected indicating blood-brain barrier (BBB) opening to this tracer in hemispheres perfused with KRB at pH 6.2, 6.0, 5.8, or 5.5. HRP was seen in pools of endothelial tight junctions. Endothelial cell injury reflected by swelling and influx of HRP into the cytoplasm was occasionally encountered. CI evenly decorated the negatively charged surface of endothelial cells in the control brains, in contrast to markedly diminished iron binding capacity of endothelial cells in low pH-treated hemispheres. Our results suggest that the ionic milieu influences the negatively charged cell surface sialoglycoproteins and glycolipids, which are integral parts of the BBB system.

Acidosis↗

Ca2+ depletion-induced disconnection of tight junctions in isolated rat brain microvessels.

Cerebral microvessels were isolated from rat brains. One part of the microvessel pellets was incubated for 25 or 90 min in Krebs-Henseleit bicarbonate buffer (KHB) at pH 7.5 (control group). The other part of the pellets was treated for the same periods of time with Ca2+-free KHB, containing 2.2 mM EGTA and 2 mM glucose (experimental group). Morphological changes of endothelial tight junctions were evaluated in 100 randomly selected interendothelial clefts from isolated cerebral microvessels of each groups by electron microscopy. Following 25 min of incubation time, either with Ca2+-containing or with Ca2+-free KHB, no significant changes of tight junctions were observed. After 90 min of incubation in Ca2+-free medium, 58% of tight junctions were altered (in 42% partial, and in 16% complete disconnection of tight junctions were found). This contrasted the control group, where only 14% of tight junctions were disconnected (12% partially and 2% completely). Our results are consistent with a role for intercellular Ca2+ in maintaining structural integrity of cerebral tight junctions.

Animals↗

In vitro study of local solubility of uric acid stones with lithium carbonate.

The possibilities of local dissolution of uric acid calculi with Na hydrocarbonate, K carbonate and lithium carbonate were examined in vitro. The most promising results were obtained with lithium carbonate. The necessity for studies of the compound in laboratory animals before its use in humans is emphasized.

Bicarbonates↗

Isolation and physicochemical and functional properties of a calcium binding gluten fraction.

Each milligram gluten protein isolated from bread contains 0.03-0.06 mumol calcium. On theoretical grounds we have concluded that this calcium quantity is bound to the free carboxyl groups not participating in peptide bonds of dicarbonic aminoacids, especially glutaminic acid, making up a large proportion within the aminoacids of gluten. After treatment with EGTA, a well-known calcium complex forming compound, two gluten fractions can be distinguished: water-soluble gluten-ES, and gluten-EP soluble in acetic acid. The aminoacid composition of gluten-ES is similar to that of unfractionated gluten. It is rich in aminodicarbonic acid (glu), aminodicarbonic acid amide (gln) and proline. Further properties of gluten-ES are: immunological similarity to gluten; a molecular mass of 36 000 dalton; an absorption maximum at 275.6 nm; a Ca2+-binding capacity of 0.72 mumol Ca2+/mg protein as measured by atomic absorption spectrophotometry and by Ca2+ ion selective electrode; inhibitory effect of a small quantity (25-30 micrograms) of the compound on the Ca2+-Mg2+ dependent ATPase and Ca2+-uptake of fragmented sarcoplasmatic reticulum. Preliminary experiments have demonstrated that gluten-ES has an influence on other calcium ion mediated systems like actomyosin superprecipitation. We put forward the hypothesis that by its Ca2+-binding capacity, gluten-ES is capable of influencing the level of free calcium and may thus play a part in the pathomechanism of coeliac disease.

Amino Acids↗

Cyclic AMP-dependent protein kinase stimulates the phosphorylation of phosphatidylinositol to phosphatidylinositol-4-monophosphate in a plasma membrane preparation from pig granulocytes.

Plasma membranes prepared from pig granulocytes were incubated in the presence of [gamma-32P]ATP. The dissociated catalytic subunit of cyclic AMP-dependent protein kinase stimulated the incorporation of 32P into both the protein and lipid fractions of the membrane. The SDS gel-electrophoretic analysis of the 32P-labelled proteins showed that the protein kinase phosphorylated preferentially a 24000-Mr protein, though other 32P-labelled proteins were also detected. 32P-labelled membrane lipids were analysed in two different thin layer chromatographic systems. 32P-labelling was found exclusively in polyphosphoinositides. On addition of the protein kinase the 32P-labelling of both polyphosphoinositides was increased but a higher amount of phosphate was incorporated into phosphatidylinositol-4-phosphate than into phosphatidylinositol-4,5-bisphosphate.

Adenosine Triphosphate↗

Applicability of biosuppressin as an urease-inhibitor.

Prevention of the formation of struvite and carbonate-apatite calculi, which rapidly increase in size and tend to recur, is of prime importance. One of the urease inhibitors, hydroxycarbamide, was studied in vitro. The results are favourable and justify further studies aimed at the local application of the inhibitor.

Ammonia↗

Ethanol-soluble substances isolated from Escherichia coli culture filtrate induce polymorphonuclear chemotaxis.

Substances chemotactic (CT) for human PMN were isolated from the culture medium of Escherichia coli O2 : Kl grown to stationary phase. The ethanol soluble fraction of the lyophilized culture filtrate, which contained the bulk of CT activity, was gel filtrated on Sephadex G-10. The 5 X 10(3) molecular weight fraction showed the highest CT activity. On the basis of partial chemical characterization the active CT substances probably consist of glycopeptides and lipids originating from the cell envelope.

Amino Acids↗

Effect of zinc on the local Shwartzman phenomenon.

Local Shwartzman reaction is substantially reduced in intensity by zinc administered locally before and after preparation of the reaction. The endotoxin-induced accumulation of PMN leukocytes is inhibited by zinc rubbed in the skin.

Animals↗

Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions.

Infusion of hyperosmolar solutions into the internal carotid artery causes opening of blood-brain barrier to macromolecules. Ultrastructural tracer studies indicate that extravasation of macromolecules takes place primarily in segments of large penetrating cortical blood vessels. The purpose of the present study was to examine fracture faces of cerebral endothelium in normal and hyperosmolar mannitol-treated rat brains in an attempt to elucidate: (a) the organization of endothelial cell junctions in various segments of the cerebral vascular bed and (b) the structural basis of blood-brain barrier opening in hyperosmotic conditions. We found that in control rat brains: (a) capillary endothelium is provided with complex networks of continuous multistranded tight junctions; (b) continuous capillary-type tight junctions extend, although in a simpler beltlike fashion, into the endothelium of postcapillary venules; (c) the endothelium of collecting veins possess widely discontinuous single- or double-stranded tight junctions associated with gap junctions; (d) arteries have endothelial tight junctions containing focal discontinuities associated with gap junctions. In hyperosmolar mannitol-treated rat brains, there appeared focal distensions of compartments but no definitive structural discontinuities in capillary-type tight junctions. Our data suggest that the blood-brain barrier consists of: (a) an extended tight region (comprising both capillaries and postcapillary venules) and (b) focal, potentially leaky regions (restricted to collecting veins and possibly arteries). Our studies furnished no direct evidence for the structural basis of blood-brain barrier opening in hyperosmolar mannitol-treated rat brains.

Animals↗

Charge-related alterations of the cerebral endothelium.

In a short-term rat brain perfusion model, the luminal surface of cerebral endothelium was exposed to the following solutions: (a) the polycation protamine sulfate (PS) in a dose of 50, 100, and 500 micrograms/ml for 1 or 2 minutes; (b) PS in a dose of 100 micrograms/ml (or 500 micrograms/ml) for 1 or 2 minutes followed by the polyanion heparin in an equivalent dose of 12 units/ml (or 60 units/ml) for 1 or 2 minutes; (c) heparin alone for 1 or 2 minutes, and (d) Krebs-Ringer-bicarbonate solution as control for 1, 2, or 4 minutes. We studied in the cerebral endothelium: (a) structural alterations by electron microscopy, (b) permeability changes to horseradish peroxidase (HRP) by light and electron microscopy, and (c) charge alterations of luminal surface visualized with colloidal iron at pH 1.8 by electron microscopy. We found that: (a) PS resulted in extravasation of HRP throughout the perfused hemispheres in a time- and dose-dependent fashion. In this experimental group, colloidal iron binding decreased on the luminal surface of the cerebral blood vessels; (b) heparin perfusion following PS reversed the colloidal iron staining but failed to prevent the blood barrier opening to HRP; (c) heparin perfused alone also induced extravasation of HRP in the treated brain hemispheres; (d) in Krebs-Ringer-bicarbonate-perfused control brains extravasation of HRP was encountered only in occasional vascular segments. In all brain hemispheres showing tracer extravasation, electron microscopy revealed HRP reaction product in compartments of endothelial tight junctions suggesting opening of interendothelial routes as the structural basis of blood-brain barrier opening. Endothelial cell death reflected by swelling and influx of HRP into endothelial cytoplasm in PS- and/or heparin-perfused hemispheres was probably an additional mechanism explaining tracer extravasation into the neuropil. Our results indicate a correlation between the effect of polycation PS and a decrease in the anionic sites of cerebral endothelium. The relationship between charge alteration and barrier opening in the short-term rat brain perfusion model is not clear.

Animals↗

Combined oral and local therapy for the dissolution of urinary calculi.

The factors underlying the formation of Ca-phosphate and struvite calculi, as well as the present possibilities for oral and local therapy, their advantages and drawbacks are discussed in the light of published evidence. In this context a clinical case of multiple injuries is reported in which practically complete chemolitholysis has been achieved by combined oral and local therapy. The rapid growth of the calculi and their alarming tendency to recurrence in case of inadequate treatment is emphasized. The therapeutic method used in this case is regarded as suitable for practical purposes.

Administration, Oral↗

[Further indications for corneal incision].

The results of operations for disjunctio epithelialis corneae following recurrent keratitis herpetica and injury are reported. The operation is indicated in every chronic or recurrent corneal disease where circumstances do not allow keratoplasty to be carried out; the pain can be alleviated by incisio corneae.

Cornea↗