Biomedical subjects

K Kolev

Publications and source records attributed to K Kolev.

At least 19 recordsLinked to original sources

PubMed1998

Fibrinolysis with des-kringle derivatives of plasmin and its modulation by plasma protease inhibitors.

Quantitative characterization of the interaction of des-kringle1-5-plasmin (microplasmin) with fibrin(ogen) and plasma protease inhibitors may serve as a tool for further evaluation of the role of kringle domains in the regulation of fibrinolysis. Comparison of fibrin(ogen) degradation products yielded by plasmin, miniplasmin (des-kringle1-4-plasmin), microplasmin, and trypsin on SDS gel electrophoresis indicates that the differences in the enzyme structure result in different rates of product formation, whereas the products of the four proteases are very similar in molecular weight. Kinetic parameters show that plasmin is the most efficient enzyme in fibrinogen degradation, and the kcat/KM ratio decreases in parallel with the loss of the kringle domains. The catalytic sites of the four proteases have similar affinities for fibrin (KM values between 0.12 and 0.21 microM). Trypsin has the highest catalytic constant for fibrin digestion (kcat = 0.47 s-1), and among plasmins with different kringle structures, the loss of kringle5 results in a markedly lower catalytic rate constant (kcat = 0.0076 s-1 for microplasmin vs 0.048 s-1 for miniplasmin and 0.064 s-1 for plasmin). In addition, microplasmin is inactivated by plasmin inhibitor (k" = 3.9 x 10(5) M-1 s-1) and antithrombin (k" = 1.4 x 10(3) M-1 s-1) and the rate of inactivation decreases in the presence of fibrin(ogen). Heparin (250 nM) accelerates the inactivation of microplasmin by antithrombin (k" = 10.5 x 10(3) M-1 s-1 ), whereas that by plasmin inhibitor is not affected (k" = 4.2 x 10(5) M-1 s-1).

Animals↗

PubMed1998

Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases.

The efficiency of plasmin, miniplasmin, and neutrophil leukocyte elastase in fibrin digestion is well characterized in static systems. Since in vivo the components of the fibrinolytic system are permanently exposed to flow, we have developed two in vitro models and studied the effect of shear forces on fibrin dissolution with these proteases. Cylindrical nonocclusive fibrin clots are perfused at various flow rates through their preformed axial channel, and dissolution of fibrin is followed by measuring the absorbance of degradation products released into the circulating fluid phase. In one experimental setting, fibrin surface is degraded with enzymes applied in the recirculating fluid phase; in another setting, clots containing gel-embedded proteases are perfused with enzyme-free buffer. As shear rate at fibrin surface is changed from 25 to 500 s(-1), the rate of product release by recirculated enzymes increases 2.8-, 2.9-, and 4-fold for plasmin, miniplasmin, and porcine pancreatic elastase, respectively. Buffer-perfused fibrin containing gel-embedded plasmin or miniplasmin is disintegrated by shear forces at a relatively early stage of dissolution, and this disassembly is related to the formation of fragment Y (150 kDa) and fragment D (100 kDa) fibrin degradation products. Fibrin clots degraded by incorporated polymorphonuclear leukocyte elastase, which yields different degradation products, do not disassemble abruptly, even at the highest shear rate (500 s(-1)). Our results suggest that fibrin surface degradation is accelerated with increasing shear rate and that plasmin or miniplasmin embedded in the clot promotes the release of particular clot remnants into the circulating phase, whereas polymorphonuclear leukocyte elastase does not.

Animals↗

PubMed1998

Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4.

The inflammatory mediators, cytokines and complement proteins are believed to regulate the sequential events during the development of lesions secondary to ischaemia and reperfusion. The endothelial cell monolayer of the brain microvasculature is the critical interface between the blood-borne mediators and brain tissue. The involvement of these cells in complement production and regulation has not been well documented. In the present study, expression of complement proteins (C1 inhibitor, factor H, factor B, C4) by cultured endothelial cells obtained from human brain microvessels has been characterized. Interferon gamma upregulates the production of all the complement factors studied. Serine proteases, plasmin and miniplasmin induce the expression of C4, decrease the level of ELISA detectable C1 inhibitor, and do not affect the production of factors H and B. These data indicate that complement proteins are expressed locally by the brain microvessels, and may modulate the inflammatory responses of brain tissue.

Brain↗

PubMed1998

Perturbation of the integrity of the blood-brain barrier by fibrinolytic enzymes.

The action of fibrinolytic enzymes (plasmin, miniplasmin, neutrophil leukocyte elastase) on the blood-brain barrier is investigated. The binding and the effects of the fibrinolytic enzymes are studied in the first subcultivation of human brain capillary endothelial cells. 125I-labeled plasmin, miniplasmin and neutrophil leukocyte elastase bind to confluent monolayers of cultured endothelial cells with dissociation constants of 1 x 10(-8) mol/l, 4.8 x 10(-7) mol/l and 1.8 x 10(-8) mol/l, respectively, and the number of binding sites varies between 2.3 x 10(5) and 7.5 x 10(6) per cell. Following treatment of the cultured cells with purified and active-site titrated proteases, the changes in morphology of individual cells are analyzed with computerized morphometry. At low concentrations (in nanomolar range) all studied fibrinolytic proteases induce reduction of the cell area; the minimal size is achieved in 20-80 min after the application of an enzyme and the effect is completely reversed in 15 min after its removal. A possible in-vivo consequence of these in-vitro findings is studied in an organ-perfusion model: rat hemisphere is perfused with a protease solution followed by a circulating phase-borne tracer (horse-radish peroxidase). In perfused rat hemisphere, the fibrinolytic enzymes open the blood-brain barrier to the circulation-borne tracer. These results support the concept that fibrinolytic enzymes interact with the brain microvascular endothelium and thus affect the integrity of the blood-brain barrier through active cell contraction.

Blood-Brain Barrier↗

PubMed1997

Functional evaluation of the structural features of proteases and their substrate in fibrin surface degradation.

A new model has been introduced to characterize the action of a fluid phase enzyme on a solid phase substrate. This approach is applied to evaluate the kinetics of fibrin dissolution with several proteases. The model predicts the rate constants for the formation and dissociation of the protease-fibrin complex, the apparent order of the association reaction between the enzyme and the substrate, as well as a global catalytic constant (kcat) for the dissolution process. These kinetic parameters show a strong dependence on the nature of the applied protease and on the structure of the polymerized substrate. The kinetic data for trypsin, PMN-elastase, and three plasminogen-derived proteases with identical catalytic domain, but with a varied N-terminal structure, are compared. The absence of kringle5 in des-kringle1-5-plasmin (microplasmin) is related to a markedly lower kcat (0.008 s-1) compared with plasmin and des-kringle1-4plasmin (miniplasmin) (0.039 s-1). The essentially identical kinetic parameters for miniplasmin and plasmin with the exception of kdiss, which is higher for miniplasmin (81.8 s-1 versus 57.6 s-1), suggest that the first four kringle domains are needed to retain the enzyme in the enzyme-fibrin complex. Trypsin, a protease of similar primary specificity to plasmin, but with a different catalytic domain, shows basically the same kcat as plasmin, but its affinity to fibrin is markedly lower compared with plasmin and even microplasmin. The latter suggests that in addition to the kringle domains, the structure of the catalytic domain in plasmin also contributes to its specificity for fibrin. The thinner and extensively branched fibers of fibrin are more efficiently dissolved than the fibers with greater diameter and lower number of branching points. When the polymer is stabilized through covalent cross-linking, the kcat for plasmin and miniplasmin is 2-4-fold higher than on non-cross-linked fibrin, but the decrease in the association rate constant for the formation of enzyme-substrate complex explains the relative proteolytic resistance of the cross-linked fibrin. Thus, the functional evaluation of the discrete steps of the fibrinolytic process reveals new aspects of the interactions between proteases and their polymer substrate.

Aminocaproic Acid↗

PubMed1997

Myosin as cofactor and substrate in fibrinolysis.

Myosin accelerates plasminogen activation by tissue-type plasminogen activator (tPA), and is degraded extensively by plasmin. Myosin binds both tPA and plasminogen, and enhances activation of des1-77-plasminogen by tPA but not by urokinase-type plasminogen activator (uPA). Myosin decreases K(M) and increases k(cat) for des1-77-plasminogen activation by tPA, to yield catalytic efficiencies in excess of 8000 M-1 s-1. The effect of myosin is attributed to its C-terminal portion, the myosin rod. With a K(M) of 3 microM, myosin is a high-affinity substrate for plasmin. The findings indicate that myosin is a cofactor for plasminogen activation and a substrate for plasmin.

Animals↗

PubMed1996

Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain.

Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-alpha, IL-1-alpha and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-alpha, IL-1-alpha) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.

Biological Factors↗

PubMed1996

Quantitative comparison of fibrin degradation with plasmin, miniplasmin, neurophil leukocyte elastase and cathepsin G.

The relative contribution of plasmin, miniplasmin, PMN-elastase and cathepsin G to the fibrin-gel dissolution is studied. The global kcat/KM ratios are determined as a measure of the fibrinolytic catalytic efficiency using spectrophotometric kinetic analysis of the competition between fibrin and synthetic peptide substrates for the proteases, turbidimetric assay for fibrin dissolution and gel-filtration of the partially degraded fibrin. When the substrate is fibrin polymerized in the presence of 3 mM Ca2+, the value of this ratio is 4.3 x 10(5) M-1.s-1 for plasmin, 1.9 x 10(5) M-1.s-1 for miniplasmin, 5.0 x 10(4) M-1.s-1 for PMN-elastase and 2.2 x 10(3) M-1.s-1 for cathepsin G. When fibrin is polymerized without addition of Ca2+, the kcat/KM values are increased by a factor of 2.3 for plasmin, 2.0 for miniplasmin and 1.6 for cathepsin G, whereas that of PMN-elastase is unchanged. Progressive cross-linking of fibrin decreases the catalytic action of all studied proteases, but no change in their relative contribution to fibrinolysis is observed. When plasmin inhibitor (at physiological concentration) is also cross-linked to fibrin, the most efficient fibrinolytic enzymes are miniplasmin and PMN-elastase. The effect of 6-aminohexanoate on the formation of fibrin degradation products by plasmin and miniplasmin suggests that the high-affinity lysine binding site in the N-terminal kringle domain of plasmin is involved in the interactions with the native polymerized fibrin, whereas the fifth kringle found in both enzymes participates in binding to newly exposed lysine residues. These results provide a quantitative basis for the evaluation of fibrinolytic efficiency and support the concept of synergistic fibrinolysis.

Amino Acid Sequence↗

PubMed1995

Dual effect of synthetic plasmin substrates on plasminogen activation.

The effect of plasmin substrates D-valyl-L-leucyl-lysine-p-nitroanilide (S-2251) and H-D-norleucyl-hexahydrotyrosyl-lysine-p-nitro-anilide (Spectrozyme-PL) on the rate of activation of native human plasminogen in physiological salt solution is studied. Plasminogen activation by two-chain urokinase-type plasminogen activator (urokinase), two-chain tissue-type plasminogen activator (tc-tPA) or trypsin, but not by single chain tPA (sc-tPA) is increased 5- to 10-fold by both substrates, as determined by electrophoretic and spectrophotometric kinetic analysis. The amidolytic activity of sc-tPA, on the other hand, is inhibited by the plasmin substrates in a non-competitive manner (K1 of 6.4 . 10(-4) M for S-2251 and 2.9 . 10(-4) M for Spectrozyme-PL), whereas urokinase and tc-tPA activities are not affected. It is concluded that plasmin substrates containing a lysine residue have a general capacity to enhance plasminogen activation presumably by inducing a conformational change in the native zymogen in a manner similar to 6-aminohexanoate, while the same substrates are inhibitory both on the amidolytic activity of sc-tPA and the activation of native and des1-77-plasminogen by sc-tPA.

Enzyme Activation↗

PubMed1995

Contraction of human brain endothelial cells induced by thrombogenic and fibrinolytic factors. An in vitro cell culture model.

BACKGROUND AND PURPOSE: Vasogenic brain edema is a frequent complication of ischemic stroke. The mechanism of the blood-brain barrier opening that underlies the edema formation is poorly understood. In the present study we examined the response of endothelial cells cultured from adult human brain to thrombogenic and fibrinolytic factors that possibly accumulate in the occluded vascular segments in ischemic stroke. METHODS: The changes in the morphology of cultured human brain microvascular endothelial cells were observed by phase-contrast light microscopy and quantified with computerized morphometry. RESULTS: Active proteases (eg, thrombin, plasmin, urokinase) as well as heparin and protamine, but not fibrinogen and antithrombin III, produced significant changes in endothelial cell morphology. Two shape patterns of contraction were observed: protamine treatment resulted in rounded cells with a decrease in both cell perimeter and area, whereas all other agents induced spiderlike cell morphology with increased perimeter and reduced area. The rate of contraction was dose dependent, and at comparable enzyme concentrations plasmin produced faster contraction than thrombin. The observed changes were reversed 3 hours after abrogating the treatment. CONCLUSIONS: In an in vitro model we have demonstrated that factors involved in thrombus formation and dissolution induce endothelial cell contraction, which could affect focally the permeability of the blood-brain barrier by opening paracellular avenues between endothelial cells in vivo. Thus, the genesis of brain edema in thromboembolic stroke or occasionally during fibrinolytic therapy can be attributed in part to the contact of these factors with the microvascular endothelium.

Brain↗

PubMed1994

Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin, and miniplasmin by plasma protease inhibitors.

The effect of solid-phase fibrin on the inactivation of plasmin, miniplasmin, and neutrophil leukocyte elastase (PMN-elastase) by plasma protease inhibitors (alpha 2-antiplasmin, alpha 1-protease inhibitor, alpha 2-macroglobulin) was studied. In Hanks' balanced salt solution, fibrin reduces the second-order rate constant for the inhibition of PMN-elastase by alpha 1-protease inhibitor from 8,760 x 10(4) to 4 x 10(4) M-1.s-1 and by alpha 2-macroglobulin from 121 x 10(4) to 1.8 x 10(4) M-1.s-1. The rate constant for miniplasmin inactivation by alpha 2-antiplasmin decreases from 99 x 10(4) to 1 x 10(4) M-1.s-1, by alpha 2-macroglobulin from 78 x 10(4) to 1.8 x 10(4) M-1.s-1, and by alpha 1-protease inhibitor from 0.11 x 10(4) M-1.s-1 to 0. Plasmin bound to fibrin is completely protected against alpha 2-macroglobulin and alpha 1-protease inhibitor, whereas the rate constant for the inactivation by its primary plasma inhibitor alpha 2-antiplasmin is reduced from 430 x 10(4) to 1.08 x 10(4) M-1.s-1. The competition of substrate and inhibitor for the enzyme was also studied, using fibrin preincubated with inhibitor. Under our pseudo-first-order experimental conditions, fibrin completely eliminates those interactions, the second-order rate constant of which is 1.1 x 10(5) M-1.s-1 or less in a system without fibrin surface.

Binding, Competitive↗

PubMed1994

Heparin modulation of the fibrinolytic activity of plasmin, miniplasmin and neutrophil leukocyte elastase in the presence of plasma protease inhibitors.

The effect of heparin on the inactivation rates of fibrin-bound plasmin, miniplasmin and neutrophil leukocyte elastase (PMN-elastase) by their plasma inhibitors was studied. While plasmin and miniplasmin bound to fibrin are not inactivated by antithrombin, heparin (800 nM) makes these enzymes available for the inhibitor; the second-order rate constant increases from zero to 1.3 x 10(3) M-1 s-1 and 3.3 x 10(3) M-1 s-1, respectively. Heparin slightly increases the rate of fibrin-bound enzyme inactivation by plasmin inhibitor. alpha 1-Protease inhibitor, on the other hand, is unable to inactivate plasmin or miniplasmin bound to fibrin and heparin has no facilitating effect. In the case of PMN-elastase, heparin (300 nM) further increases enzyme protection against alpha 1-protease inhibitor; the rate constant decreases from 41 x 10(3) M-1 s-1 to 23 x 10(3) M-1 s-1. alpha 2-Macroglobulin inhibits fibrin-bound miniplasmin and PMN-elastase with a second-order rate constant of 1.8 x 10(4) M-1 s-1 and heparin (300 nM) increases the rate insignificantly for miniplasmin and by a factor of two for PMN-elastase. It is remarkable that plasmin bound to fibrin is not inhibited by alpha 2-macroglobulin independently of the presence of heparin. On the basis of the reported kinetic data a lifespan of 420 s for plasmin, 66 s for miniplasmin and 4 s for PMN-elastase was calculated, when the enzymes are bound to fibrin in the presence of the four protease inhibitors at physiological plasma concentration. If heparin is present (300 nM) these values decrease to 240 s for plasmin and 42 s for miniplasmin, whereas that of PMN-elastase is unchanged. Thus, the present in vitro kinetic model suggests an antifibrinolytic effect of heparin in a plasma milieu.

Antifibrinolytic Agents↗

PubMed1988

Albendazole treatment of human cystic echinococcosis.

The effect of albendazole was investigated in 20 patients with single or multiorgan hydatid cyst disease. Albendazole was used at a dose of 10 mg/kg daily in cycles of 28 d for four cycles with 15 d between cycles. Follow-up ranged from 12-18 months. Response varied according to the organ involved, the most successful results being with liver and peritoneal cysts. A positive response was seen in 47% of 34 cyst sites and a partial response was seen in a further 38% of sites. Overall response was classed as completely successful in 30% of patients, and partially successful in 60% at the end of follow-up. Adverse events were rare, although occasional abnormalities of liver function were seen.

Adult↗

PubMed1987

Interaction of antithrombin III and thrombin-antithrombin III complex with cultured aortic endothelial cells.

The binding of antithrombin III, thrombin, thrombin-antithrombin III complex to endothelial cells was investigated. While the rate of the binding of thrombin to these cells was very rapid, that of antithrombin III was relatively slow and the thrombin-antithrombin III complex was intermediate. Binding kinetics indicated that antithrombin III, like thrombin, showed high affinity to endothelial cells; with a Kd of 3 X 10(-8) M and with 5 X 10(4) binding sites per cell. The dissociation of the inhibitor molecule was also rapid, i.e., approximately 70% bound antithrombin III was released in 2 minutes. Heparin, in a 100-fold molar excess to antithrombin III, or the modification of lysine residues of the inhibitor involved in the interaction with heparin, did not influence the association of antithrombin III with endothelial cells. In addition, antithrombin III did not compete with thrombin blocked in its active center for binding to endothelial cells. It is suggested that the binding sites of endothelial cells are different for thrombin and antithrombin III, and antithrombin III does not bind to these cells through its heparin binding domain.

Animals↗

PubMed1987

[Sensitivity of Salmonellae isolated from poultry to bacteriophage O1].

Studied were a total of 200 bacterial strains that agglutinated with the group B, C, D and E Salmonella sera. The organisms were isolated from viscera (liver, gallbladder, spleen, ovaries, and heart) and bone marrow from dead birds, from embryos, eggs, and washings from hatcheries, etc. in 1982-1985 in the district of Stara Zagora. It was found that the strains behaved biochemically as typical Salmonellae. Serologically typed of group B were 40 strains (S. typhimurium--34, and S. lagos--6); of group C--61 strains (S. oranienburg--38, S. isangi--7, S. montevideo--4, Salmonella II 6.7:gmst: 1.5--5, S. thompson--2, and S. newport--5); of group D--89 strains (S. gallinarum--57, S. gallinarum var. duisburg--23, S. pullorum--1, and S, enteritidis--8); and of group E--8 strains (S. senftenberg--4, S. anatum--4). Two of the strains were in the R form. Sensitive to the phage proved 89 +/- 5.7 per cent of the strains including the two R-form ones and those that were resistant of group C (S. oranienburg--5.4 per cent) and of group D (S. gallinarum--23 per cent, and S. gallinarum var. duisburg--26.1 per cent). The high sensitivity to the phage substantiated the phage identification of the strains as an adjunct, supplementary method in the complex diagnostics of diseases of a Salmonella etiology after the preliminarily determined phage for the respective region was made known.

Animals↗

PubMed1987

Unusual microscopic forms of experimental mesotheliomas.

A lightmicroscopic study is made on 36 pleural and 68 peritoneal experimental mesotheliomas induced in white rats by intrapleural and intraperitoneal introduction of asbestos dust. The experimental tumors were compared with 10 spontaneous human mesotheliomas (8 pleural and 2 peritoneal mesotheliomas). The analysis revealed 4 types of morphologically specific experimental mesotheliomas, which could not be referred to the classifications used. In this group are included: a) large cell alveolar, b) small cell alveolar; c) adenocystic; d) with squamous metaplasia and keratinization. The observed unusual experimental lightmicroscopic forms of mesotheliomas support the opinion for great plastic abilities of mesothelium, and the presence of squamous metaplasia with keratinization may be a reason for considering it as a variant of epithelium.

Animals↗

PubMed1986

[Etiology and chemotherapy of suppurative surgical infection in horses and cattle].

A total of 24 horses and 42 cattle with a variety of local suppurative processes (wounds, abscesses, phlegmons, tendovaginitis, etc.) were studied under conditions of the clinic with regard to the most commonly found microbial species and the opportunity to work out antibioticogrammes in terms of the effectiveness of 11 of the chemotherapeutic agents widely used in the practice. It was found that prevailing in horses were staphylococci and streptococci. In cattle Corynebacterium pyogenes was predominantly established. Besides, there was a rising trend in the part played by representative agents of the occasionally pathogenic microflora (Ps. aeruginosa, Pr. vulgaris, Escherichia coli) as the causative species of local suppurative processes. These organisms were fairly often isolated in association with other species, while they were more rarely found as the only acting ones in a particular case. Best effects of the antibiotics tested could be expectedly produced by gentamycin (82.5 per cent), carbenimycin (74.2 per cent), oxacyllin (72.7 per cent), ampicillin (68.2 per cent), and canamycin (61.8 per cent). At the same time, the effectiveness produced by some of the antibiotics widely employed in the practice, such as chloramphenicol, tetracycline, streptomycin, and penicillin was below 50 per cent.

Animals↗

PubMed1986

[Hygienic evaluation of the occupational risk in working with Bulgarian bentonite raw material].

The use of bentonite in various branches of industry, and first of all, in foundry workshops, grows rapidly. The literature data on health injuries by bentonite dust are rather contradictory: due primarily, to the changeable mineralogical composition of the raw material from different deposits. That requires a specific hygienic assessment of each deposit in exploitation. The authors studied the mineral composition, quantitative ratio of the mineral components and morphology of the particles from the respirable fraction of aerosol in the extraction of Bulgarian bentonite. The microscopic mineralogical analysis in phase contrast, established a basic mass of clay minerals, confirmed by the X-ray structural analysis. The free silicic oxide is presented by low-temperature crystobalite and quartz, more rarely opal and chalcedony. Its quantity does not surpass 1-2%. The experimental studies on experimental animals confirmed fibrosis, degree I and II, according to Belt and King. The clinical studies on the workers established the presence of reticular changes in the lungs, type S and L, according to ILO-UC classification. The hygienic characteristic of the Bulgarian bentonite provided grounds for its broad application as a substitute for more dangerous raw materials, quartz sand in the foundries, in particular. Regardless of its advantages, bentonite is not harmless. The adherence to MAC for dustiness and periodic control of the quartz content in the raw material and aerosol in the working environment, are compulsory.

Air Pollutants, Occupational↗