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Biomedical subjects

S H Kowalczyk-Bronisz

Publications and source records attributed to S H Kowalczyk-Bronisz.

At least 19 recordsLinked to original sources

Immunotropic activities of benzisoselenazolones and organic diselenides in mice.

We have investigated the immunotropic effects of 23 seleno-organic compounds (8 benzisoselenazolones, 3 benzisoselenazolone oxides and 12 organic diselenides). All of the compounds increased the rosette formation of sheep red blood cells (SRBC) with spleen cells obtained from thymectomized C53BL/6 mice and incubated in vitro in the presence of imuran. Furthermore, 16 of the compounds were also assayed in vitro in the hydrocortisone test performed with C57BL/6 mouse thymocytes. It was found that all of them significantly protected the cells against hydrocortisone induced cytotoxicity. Also in the Jerne's assay, performed in 129Ao/Boy mice pretreated in vivo with 3 selected compounds 5 days before immunization with SRBC, the stimulation of plaque forming cells (PFC) was observed. Only one compound (AE22, an analog of piroxicam) was found to be inhibitory in this assay. In contrast, in the graft versus host (GvH) assay performed in hybrid mice the donor lymphoid cells obtained from C57BL/6 mice pretreated with 9 selected seleno-organic compounds, suppressed the GvH reaction in the recipient hybrid mice. Thus, in all of the immunotropic assays except the GvH reaction in adult mice, the seleno-organic compounds were found to have immunostimulating activities.

Adjuvants, Immunologic↗

Synthesis and immunological activity of mono- and disubstituted derivatives of 2,5-dimercapto-1,3,4-thiodiazoles.

It is presented that the newly synthesized mono- and disubstituted 2,5-dimercapto-1,3,4-thiodiazole derivatives exert immunotropic activity. This effect was evaluated by measuring plaque forming cell number, circulating immunoglobulins level, autologous rosette number, mitogenic activity and by performing popliteal lymph node assay. It is shown that intensity of immunotropic activity depends on chemical structure: mono-substituted derivatives had a strong suppressive effect, disubstituted compounds showed the variable activity. One compound of this group exerted a stimulatory effect. The tested compounds were active in popliteal lymph node assay and had no mitogenic activity.

Animals↗

Immunotropic activity of lupin seeds extracts and fractions from Lupinus angustifolius and Lupinus albus.

The results demonstrated immunotropic activity of seeds extracts and fractions from Lupinus angustifolius and Lupinus albus. Plaque forming cells (PFC) number to SRBC (sheep red blood cells) were elevated by an extract from Lupinus angustifolius and lowered by extracts from Lupinus albus. All preparations obtained from Lupinus angustifolius reduced the number of rosette forming cells (E-RFC). These preparations suppressed also the intensity of graft versus host reaction (GVHR) in case when the donors were treated. Lupinus albus extract suppressed GVH reaction when recipients were treated. Lupin extracts stimulated draining popliteal lymph nodes in PLN assay.

Adjuvants, Immunologic↗

Synthesis and immunological activity of dialkyloamine- and N-piperidinederivatives of dithiocarbamic acid.

A series of aminocarbamic acid derivatives, containing fragments of substituted hydrazine and dithiocarbamic acid, was synthesized. The immunopharmacologic studies showed these that derivatives exerted immunotropic, mainly suppressive effects (PFC, circulating immunoglobulins, E-RFC, A-RFC). Some of these compounds, however, caused significant increase of weight of the popliteal lymph nodes. The immunotropic activity of the newly synthesized preparations is comparable with the action of sodium diethyldithiocarbamate (imuthiol).

Adjuvants, Immunologic↗

Synthesis and immunopharmacological analysis of selected derivatives of N,N'-bis-/3-aziridine/butanoylalkylenediamines and imides of 3-aziridinesuccinic acid. I.

A series of aziridinederivatives of N,N'-bis-butanoylalkylenodiamines (Scheme 1, 1-4) and aziridinederivatives of substituted succinic acid (Scheme 2, 16-19) was obtained. Pharmacological analysis revealed that these compounds were immunotropic, of marked suppressive effect (PFC, RFC, circulating immunoglobulins). Outstanding in this group was phenyloimide of succinic acid (prep. 16) which reduced PFC and RFC number but increased the level of circulating IgG.

Animals↗

Synthesis and immunopharmacological analysis of selected butanic and butanodionic acid amides containing aziridine unit. II.

In the reaction of butanic and butanodionic acid chlorides with amines, amides 1-10 were produced. Addition of aziridine to a double bonds was performed in alkaline medium which resulted in aziridine derivatives of both acids. Pharmacological study revealed that the preparations examined possess immunotropic, strongly suppressive activity (PFC, E-RFC), partly IgG level; they leave the titer of circulating IgM unchanged. It seems that rather the basic system of acids than the substituents introduced to it are responsible for the effect of the compounds.

Animals↗

Immunological profile of animals exposed to pesticide--deltamethrin.

The effect of deltamethrin (10- or 30-day exposure) on selected parameters of humoral and cellular immune response in mice was studied. In parallel also hematologic and histologic examinations were performed. It was found that deltamethrin exerts negligible immunotropic effect. The prevailing was suppressive effect, and in some cases also stimulatory effect (PFC, GvH, Il-1, exogenous CFU-s). This negligible activity on the immunological system may be attributed to low toxicity of deltamehtrin in relation to the cells of immunological system or to too short exposure of the animals to its effect.

Animals↗

Immunopharmacological indices of piroxicam.

The activity of piroxicam to the selected cellular immune reactions was studied. The drug was shown to modulate these processes, with the prevailing role of suppressive component. It was found that the mechanism of its effect partly consists in an interference in the activity of suppressor cells and mediators of immunological reactions.

Animals↗

Studies on aziridine derivatives. III. Synthesis and immunopharmacological activity of aziridine derivatives of propionic acid.

Several new aziridine derivatives of propionic acid were synthesized (10-15, 19, 20). o-, m-, p-Chloroanilide of chloroacetic acid 1-3 and chloride of 3-/p-chlorobenzoyl/acrylic acid 16 were the substrates. The compounds 1-3 in reaction with nicotine aldehyde or p-chlorobenzaldehyde were transformed into appropriate anilides of 2,3-epoxypropionic acid 4-9. These, in turn reacted with ethylenimine giving the appropriate 3-aziridine derivatives 10-15. Acid chloride 16 in reaction with amines gave the appropriate amides 17 and 18 which formed 2-aziridine derivatives 19 and 20 when under the influence of ethylenimine. Pharmacological analysis revealed that the aziridine derivatives 12-15, 19 and 20 modulate some immunological reactions with the prevailing effect of the suppressive component (PFC, RFC, IgM level, cellular response to SRBC). The stimulatory effect was observed with some compounds on the level of circulating IgG and GvH reaction. The mechanism of these compounds consists in their interference with the activity of Ts cells and mediators of the immunological reactions.

Animals↗

Studies on the derivatives of aziridine. II. Synthesis and immunopharmacological analysis of substituted amides and anilides of alpha-aziridinyl-beta-/p-chlorobenzoyl/-propionic acid.

Several new amides and anilides of alpha-aziridinyl-beta-/p-chlorobenzoyl/-propionic acid were synthetized. The beta-/p-chlorobenzoyl/-acrylic acid 2 was used as the substrate. This compound was converted by reaction with appropriate amine into amides and anilides of beta-/p-chlorobenzoyl/-acrylic acid (3-10). These compounds react with ethylenoimine giving appropriate amides and anilides of alpha-aziridinyl-beta-/p-chlorobenzoyl/-propionic acid (11-18). When pharmacologically analyzed, they appeared to possess marked immunotropic activity. The derivatives in question modulated both humoral as well as cellular immune response, the effect being related to the type of substitutent in the amide group.

Animals↗

[The influence of immunomodulators on lymphokine secretion of radiation-damaged lymphocytes].

Spleen lymphocytes derived from guinea pigs loose their ability to secrete lymphokines induced by Con A after treatment with irradiation (500 and 750 mC/kg). In the presence of the immunomodulator isoprinosine, levamisole and the thymosine-like factor TFX the lymphocytes are again capable of secreting lymphokines. After treatment with isoprinosine, levamisole and TFX in dosages between 10 and 100 micrograms/ml the migration inhibition activity for macrophages and the chemotactic activity for polymorphonuclear granulocytes produced by lymphocytes were restored.

Adjuvants, Immunologic↗

Studies on the derivatives of aziridine. I. synthesis and immunopharmacological analysis of amides of alpha-aziridinyl- beta-/p-chlorobenzoyl/-propionic acid.

Several new aziridinyl derivatives of beta-/p-chlorobenzoyl/propionic acid were synthesized (3, 5, 7, 14-18). The gamma-/p-chlorophenyl/-dihydrofuran-2-one 2 and beta-/p-chlorobenzoyl/acrylic acid 4 were used as the substrates. Compound 2 reacts with ethylenimine yielding aziridinylamide of beta-/p-chlorobenzoyl/-propionic acid 3. The sodium salt of acid 4 and methyl ester 6 were converted by reactions with ethylenimine into appropriate alpha-aziridinyl derivatives 5 and 7. The acid 4 in the reaction with phosphorus pentachloride gives the acid chloride 8 which is transformed under the influence of appropriate amines into corresponding amides 9-13. These amides react with ethylenimine giving the appropriate alpha-aziridinyl derivatives of beta-/p-chlorobenzoyl/-propionic acid 14-18. Pharmacological analysis revealed that the compounds studied possessed immunotropic activity; they modulate both humoral as well as cellular immune response. Their effect has been shown to be related to chemical structure and to substituents of the carboxyl group in particular.

Acrylates↗

Immunobiological and antiinflammatory properties of 1-phenylo-2-thioxo-3-diethylo-aminoethylo-4-ox o-7-methylpyrimido- [4,5-c]-pyrimidine hydrochloride (compound I).

Immunological and pharmacological properties of 1-phenylo-2-thioxo-3-diethylo-aminoethylo-4-oxo- 7-methylpyrimido [4,5-c]-pyrimidine hydrochloride were evaluated. The preparation was observed to exert immunotropic, predominantly suppressive effect as well as nonspecific antiinflammatory effect. This was accompanied by hardly perceptible central component and slight, reversible effect on the circulatory system. The trials to elucidate mechanism of activity of the immunotropic preparation revealed that it attacked immunologically committed cells. However, it does not act on suppressor cells.

Animals↗

Pharmacological activity of 3-(5-barbiturylo)-propanesulfonic acids derivatives.

Pharmacological activity of 6 newly synthetized water-soluble derivatives of barbiturylo propanosulfonic acids, was evaluated. The compounds were obtained under the conditions of the Ritter reaction. The experiments were performed with the aim to determine the anti-inflammatory and immunotropic activities as well as the central action of the new derivatives; indomethacin was a reference preparation. 5-Allyl-2,4,6-trioxo-5-hexahydropyrimidine-beta-sulfooxy+ ++-propanesulfonic acid displayed pronounced anti-inflammatory and analgesic activity accompanied by immunosuppressive effect observed in the in vitro tests. An introduction of the cyclohexyl group by nitrogen in position 1 of the barbituric ring deprived the new compound of numerous properties; its activity was preserved only in Jerne's test, PFC number was reduced by 50%. On the other hand, the presence of two cyclohexyl groups and beta-hydroxypropanesulfonic and beta-sulfatopropanesulfonic in position 5, conditioned the anti-inflammatory and immunotropic activity of the new derivative. 1,3-Dicyclohexyl-2,4,6-trioxo-hexahydropyrimidine-5, 5-di(beta-hydroxy-propanesulfonic acid) (prep. 5) as the only one in this group, almost completely suppressed the post-carageenin edema. It also diminished the number of RFC and PFC and weakened the cellular response to SRBC. The preparation also increased the viability of multipotential stem cells exposed to Rtg irradiation (the number of endogenous CFU-s increased by 50%). The preparations examined displayed various anti-inflammatory and immunotropic activity dependently on the chemical structure and in some experimental models they appeared more effective than indomethacin.

Adjuvants, Immunologic↗

Chemical, pharmacological and oncostatic properties of 5-(4'-hydroxybenzylidenoimino)-4, 6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole (compound IP-10).

Advanced preclinical studies on IP-10 preparation (4,6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole) were carried out. The drug was shown to be devoid of the irritating local effect, mildly toxic and hardly absorbing when administered per os. The toxic effect showed tendency toward cumulation. In the long-term exposure it did not affect either the elements of peripheral blood or parenchymatous organs. It exerted slight hypotensive effect on the circulatory system but only after intravenous administration. In relation to the smooth muscle organs and central nervous system, IP-10 was only slightly active. Weak effect of the compound was observed with bacteria and fungi. In the case of transplantable tumors, its activity was differentiated. It exerted a significant effect in relation to leukemia, melanoma B-16, Ehrlich carcinoma and Nemeth-Kellner lymphoma. As other isothiasole derivatives, IP-10 exhibits an interesting pharmacological, easy to render activity; particular attention should be paid to its oncostatis activity.

Animals↗

Syntheses and pharmacological analysis of new derivatives of tetrahydro-[1,3]-thiazine and 2-thiobarbituric acid.

Three groups of compounds:1,3-thiazine derivatives, 2-thiobarbituric acid derivatives and noncyclic thioureide were obtained as a result of condensation of some N, N1-derivatives of thiocarbamide and malonyl dichlorides, depending on the reaction conditions and chemical character of reagents. It was observed that the substituents beside nitrogen atoms of thiocarbamides, the kind of acid chloride and reaction conditions influenced the course of reaction. The structure of the newly synthesized compounds was proved by the analysis of PMR spectrum and the interpretation of IR spectrum. In the performed pharmacological examination immunotropic and anti-inflammatory activity of these compounds was determined. Among 1,3-thiazine derivatives, 5,5-diallyl-2-phenylimino-3-phenyl-2,3,4,5-tetrahydro-[1,3]-thiazine-4,6-dione and 5,5-diethyl-2-phenylimino-3-naphtyl-2,3,4,5-tetrahydro-[1,3]-thiazine-4,6-dione exhibited anti-inflammatory activity. The compounds also contained the immunotropic component, either stimulatory or suppressive, 2-thiobarbituric acid derivatives displayed stronger anti-inflammatory activity correlated mostly with the immunosuppressive activity. Some interdependence between chemical structure and biological activity in the group of the investigated 1,3-thiazines and 2-thiobarbituric acid derivatives was observed.

Animals↗