1975
A double-blind study with intra-individual comparisons was carried out to investigate the effects of 15 mg of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH-tropanium bromide(+/-)-tropate (Sch 1000), 15 mg Sch 1000 + 10 mg oxazepam, 10 mg oxazepam and placebo with oral administration in randomized sequence on gastric juice volume, amount of acid, concentration and pH values in 12 healthy volunteers. The secretion parameters were measured during a 1-h basal period and a 2-h stimulation period. The gastric juice was obtained in 15 min portions via stomach tube. Stimulation was effected by 1 mug/kg/h pentagastrin via drip infusion. The Friedman test was used for the comparative statistical evaluation, and individual comparisons were carried out by means of the Wilcoxon test (pair-differences rank). The results show that Sch 1000 and Sch 1000 + oxazepam were equal in effect on basal and stimulated secretion volume. As compared with placebo, it was not possible to establish an effect on secretion volume for oxazepam alone. Sch 1000 and Sch 1000 + oxazepam were found to be equipotent in reducing the amount of basal acid, while oxazepam reduced this quantity only during the first 30 min of basal secretion. None of the three active preparations was capable of inhibiting the stimulated acid, although both Sch 1000 preparations produced a clear trend towards lowered mean values. During the basal secretion period, all three test preparations had an inhibiting action on acid concentration, but none of them had a significant effect during the stimulation period. The pH value was savely increased only by Sch 1000 and Sch 1000 + oxazepam, and this even only during the basal period. The results are discussed.
Symmetrization of ArHgX with EDTA and NH3 24 hr at room temp. in aq. or org.-aq. mixts. gave 40-95% Ar2Hg (Ar = p-Br-, p-Cl-, p-AcNH-, p-NHMe-, Me, p-Et2N-, p-Me2N-, p-MeOC6H4; Ph; m-xylyl, pseudocumyl, pentamethylphenyl, duryl, isoduryl, mesityl, and $\alpha$-naphthyl). Other nucleophiles (e.g. BuNH2) were as effective as NH3, but EDTA was the best chelating agent. [on SciFinder(R)]
A high yield recyclization and pollution free process for the manuf. of diarylmercury compds. is described. The new process enables saving of starting materials and recovery of Hg. [on SciFinder(R)]
Treatment of 4 compds. of the type Ar(HgX)2 and of poly[4-(acetoxymercurio)styrene] with EDTA tetra-Na salt [64-02-8] and NH3 [7664-41-7] resulted in symmetrization and polymn. of the monomers and crosslinking of the polystyrene [9003-53-6] by Hg [7439-97-6]. E.g., 2,5-bis(chloromercurio)thiophene gave poly(mercurio-2,5-thiophenediyl) [57715-35-2]. [on SciFinder(R)]
PhHgOAc is converted into Ph2Hg via a symmetrization process, in the absence of an auxiliary ligand, at 6.5≥pH\textgreater4.0. Arylmercuric salts, in which the arom. rings contain more than 1 electron donating group, symmetrize in the absence of an auxiliary ligand at a basic pH. Both processes proceed in water or in mixts. of org. solvents and water. The factors influencing the symmetrization at different pH values are discussed. [on SciFinder(R)]
Asymmetrical diarylmercury compds., e.g. p-MeOC6H4HgC6H4NMe2-p, were produced together with sym. products via a symmetrization process. The asym. products could not be isolated from the reaction mixt. and their existence was indicated through different analyses (m.p., IR, PMR, mass spectra, elemental analysis and DTA). The asym. products are unstable and disproportionate into two sym. compds. at elevated temps., and in org. solvents even at room temp. [on SciFinder(R)]
The mechanism for the symmetrization of arylmercuric salts in the presence of chelating agents includes 3 main steps: (i) dissocn. of the arylmercuric salt; (ii) formation of a reactive complex between the ionized arylmercuric salt and the chelating agent; (iii) an electrophilic substitution at a C-Hg bond via a 2-electron, 3-center bond type transition state. The effect of chelating agents on the reactions of PhHgOAc with piperidine, BuNH2, or CNS- to give Ph2Hg and of m-MeC6H4HgOAc with tetra-Na ethylenediaminetetraacetate to give (m-MeC6H4)2Hg was discussed. [on SciFinder(R)]
The lysis of group A streptococci by muramidases of Streptomyces albus is strongly inhibited by human, rabbit, and calf serum as well as by human synovial fluids and pus. Rabbit antisera to heat-killed streptococci were no more inhibitory to the lysis of the streptococci by the lytic enzyme than normal rabbit serum. The results indicate that muramidases of S. albus will not be useful for the in vivo treatment of chronic granulomatous lesions which had been induced by insoluble cell wall components of streptococci.
The lysis of 14C-labeled bacteria by hydrolases of human and rabbit leukocytes was studied in vitro. While Staphylococcus albus, Streptococcus faecalis, and Streptococcus mutans were highly susceptible to lysis, Staphylococcus auresus was intermediate in its susecptibility to lysis by the leukocyte enzymes. Group A Streptococcus, Listeria monocytogenes, Shigella flexneri, Escherichia coli, and Mycobacterium smegmatis were very resistant to degradation by these enzymes. The lytic activity of leukocyte lysates from human and rabbit blood was probably due to acid hydrolases of polymorphonuclear leukocytes. Extracts of human blood monocytes and of rabbit peritoneal and lung macrophages were less lytic for the bacteria tested. Lymphocytes and platelet extracts were not bacteriolytic. The lytic effect of the leukocyte lysates was not inhibited by KCN or sodium azide, but was abolished to a large extent by cationic polyelectrolytes such as protamine sulfate, histone and leukocyte cationic proteins, and poly-lysine, as well as by the anionic polyelectrolytes such as heparin, chondroitin sulfate, DNA, carrageenin, alginate sulfate, dextran sulfate, and ploy-L-glutamic acid. Other potent inhibitors of bacteriolysis were trypan blue, congo red, phosphatidic acid, normal immunoglobulins, and components of streptococcal cell wall.
Isaac Ginsburg, Ne’eman, N. , Duchan, Zvia , Sela, Michael N, James, J. , ו Lahav, Meir . 1975.
“The Effect Of Leukocyte Hydrolases On Bacteria : Iv. The Role Played By Artificial Enzyme "Cocktails" And Tissue Enzymes In Bacteriolysis”. Inflammation, 1, Pp. 41-56.
תקציר Acid hydrolases of human blood leukocytes are highly lytic toStaph. albus, Staph. aureus, andStrep. faecalis. On the other hand, group A and viridans streptococci, encapsulated staphylococci, a variety of Gramnegative rods, andMyc. smegmatis are highly resistant to lysis by leukocyte extracts. The lytic effect of the leukocyte extracts can be mimicked by an artificial "cocktail" which contains crude trypsin, lysolecithin, phospholipase C, and lysozyme. This enzyme mixture is lytic to certain Gram-negative bacteria and encapsulated staphylococci which are resistant to lysis by leukocyte enzymes. Both the leukocyte lysates and the artificial cocktail are more lytic to bacteria harvested from the logarithmic phase of growth than to older cells.Staph. albus andStrep. faecalis, which are not lysed to any appreciable extent by extracts of rabbit intestines, lymphocytes, and platelets, undergo extensive lysis upon the addition of lysozyme, indicating that these cells contain preparatory prolytic agents which are activated by lysozyme. On the other hand, the lysis ofStaph. aureus by extracts of all these cells is less dependent upon lysozyme, indicating that other non-lysozyme-dependent lytic factors are involved in the lysis of this microorganism by certain tissue extracts. It is suggested that the resistance to lysis by leukocyte enzymes of bacterial cell-wall constituents may contribute to the pathogenesis of chronic sequellae, and that artificial enzyme cocktails be used for in vivo treatment of certain chronic inflammatory processes induced by bacteria.
Michael N Sela, Lahav, Meir , Ne’eman, N. , Duchan, Zvia , ו Ginsburg, Isaac . 1975.
“The Effect Of Leukocyte Hydrolases On Bacteria : V. Modification Of Bacteriolysis By Antiinflammatory Agents And By Cationic And Anionic Polyelectrolytes”. Inflammation, 1, Pp. 57-69.
תקציר Lysis of(14)C-labeledStaph. aureus by human blood leukocyte lysates, by extracts of rabbit small intestines and pancreas, and by the "cocktail" of enzymes (containing trypsin, lysolecithin, and lysozyme) is strongly inhibited by anionic polyelectrolytes (e.g., heparin, chondroitin sulfate, liquoid (polyanethole sulfonic acid), and DNA). Most of the lytic agents employed were inhibited by cationic polyelectrolytes (e.g., histone, protamin sulfate and polylysin), as well as by gold thiomalate, normal human serum, synovial fluids obtained from patients with knee-joint trauma, extracts of coffee, tea, and cocoa, Ultracorten- and Dexamethasone. On the other hand, some antiinflammatory agents tested (e.g., indomethacin, aspirin, hydrocortisone acetate and succinate, and prednisolone acetate and tributyl acetate) were not inhibitory. All the cationic polyelectrolytes employed and liquoid were also strong inhibitors of lysozyme. Since mixtures of cationic and anionic polyelectrolytes at equimolar concentrations failed to inhibit bacteriolysis, it is postulated that the balance between charged macromolecular substances, which are likely to accumulate in inflammatory foci, may determine the fate of cellular components of bacteria in inflamed tissues. The possible role played by lysosomal enzymes and by tissue inhibitors in tissue damage and in the survival of bacteria in chronic inflammatory lesions is discussed.
