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| Scand J Infect Dis, 1976, 8(3), 209 - 12 Interaction between cephaloridine and furosemide in man; Norrby R et al.; The effect of a moderate oral dose of furosemide (80 mg daily) on the serum half-life of cephaloridine was studied . In 14 patients not previously treated with diuretics this dose was found to prolong the half-life significantly . A corresponding decrease of the half-life of cephaloridine was observed when furosemide was withdrawn from 2 patients who were treated with diuretics at admission to hospital . The concurrent treatment with furosemide and cephaloridine did not affect the renal function of the patients studied . From the results obtained it seems possible that even moderate doses of a potent diuretic increase the nephrotoxicity of a cephalosporin. Appl Environ Microbiol, 1976 Jan, 31(1), 143 - 5 Effect of norleucine on mycelial fragmentation in Cephalosporium acremonium; Drew SW et al.; DL-Norleucine, which is known to replace methionine for stimulation of cephalosporin C formation, also mimics methionine's effect on arthrospore formation . Thus, hyphal fragmentation, like antibiotic biosynthesis, is divorced from a sulfur donation role. Can J Microbiol, 1975 Dec, 21(12), 1981 - 96 Differentition of mutants of Cephalosporium acremonium in complex medium: the formation of unicellular arthrospores and their germination; Queener SW et al.; Differentiation of swollen hyphal fragments to unicellular arthrospores accompanied the synthesis of cephalosporin C by a series of Cephalosporium acremonium mutants during propagation in a complex medium . The complex medium supported significantly higher synthesis than the defined medium used in previous studies of differentiation in C . acremonium . The mutants differed in their ability to form unicellular arthrospores and to synthesize cephalosporin C, but a one-to-one correspondence between the two properties was not observed . An inverse relation was observed between the growth rates of the mutants and their ability to synthesize cephalosporin C: each mutant produced more antibiotic but grew more slowly than its parent strain . Germination of the unicellular arthrospores occurred in complex medium but differed significantly from the germination of conidia in seed medium . The unicellular arthrospores were examined by electron microscopy and compared with swollen hyphal fragments and slender hyphal filaments . The unicellular arthrospores had a thicker cell wall, rougher cell surface, and had one or more small identations in their surface . The internal structure of the unicellular arthrospore resembled those of the swollen hyphal fragment and slender hyphal filament . Filaments had lower concentrations of lipid-containing vacuoles which were prevalent in both the swollen hyphal fragments and the unicellular arthrospores. Arch Dermatol . 1975 Dec;111(12):1609. Contact urticaria from cephalosporins; Tuft L; A rare instance of contact-type urticaria resulting from an acquired sensitization to cephalosporin compounds in a chemist is reported . Patch tests elicited an immediate urticarial rather than a delayed contact-type response . Similar control tests to other antibiotics gave negative results . Although the patient's primary complaint was urticaria, prolonged or excessive contact with the cephalosporins caused coryza and dyspnea . Following transfer to another laboratory where the patient worked with other chemicals, there was no recurrence of symptoms. J Antibiot (Tokyo), 1975 Nov, 28(11), 889 - 95 Stimulation of cephalosporin production by methionine peptides in a mutant blocked in reverse transsulfuration; Drew SW et al.; The previously reported inability of methionine to stimulate cephalosporin C production in a cysteine auxotroph is due to cysteine interference with methionine uptake . In such a cse, "illicit transport" of alanylmethionine can be used to demonstrate the efficacy of methionine in such mutants blocked in the path from methionine to cysteine . This result supports the hypothesis that the stimulatory activity of methionine is not due to its ability to donate sulfur to the caphalosporin C molecule. J Antibiot (Tokyo), 1975 Nov, 28(11), 881 - 8 Effect of methionine on cephalosporin C and penicillin N production by a mutant of Cephalosporium acremonium; Komatsu KI et al.; A mutant with enhanced potential to utilize sulfate for cephalosporin C production was isolated from a strain of Cephalosporium acremonium . The mutant displayed potency levels more than twofold that of the parent in the presence of sulfate but its productivity was severely inhibited by more than 0.5% of methionine which gave high cephalosporin C production with the parent . In a complex medium norleucine stimulated cephalosporin C production by the mutant in the presence of sulfate, whereas it showed no effect on the parent . In an incubation system with sulfur-starved cells of the mutant, L-methionine, but not the D-isomer, gave lower cephalosporin C production and a delayed production of penicillin N . However, it exhibited a stimulatory effect in the presence of valine or alpha-aminoadipic acid, the constituent amino acids of the antibiotic . Norleucine showed a similar effect to that of L-methionine in the presence of sulfate . On the basis of these results, characteristics of the mutant are discussed in connection with the effect of methionine. Am J Hosp Pharm, 1975 Nov, 32(11), 1116 - 21 Drug usage review and inventory analysis in promoting rational parenteral cephalosporin therapy; Simon WA et al.; Drug usage review and inventory analysis data on the cephalosporin antibotics were presented by the pharmacy to a hospital pharmacy and therapeutics committee in an effort to promote rational use of these drugs and decrease drug costs . The committee recommended that cefazolin be the parenteral cephalosporin of choice . Cephalothin was placed on a limited formulary status for ophthamology patients and patients with renal impairment . Efforts by the committee to promote physician compliance with its recommendations are discussed. Eur J Biochem, 1975 Aug 1, 56(1), 57 - 65 The catalytic activity and penicillin sensitivity in the liquid and frozen states of membrane-bound and detergent-solubilised transpeptidase of Streptomyces R61; Dusart J et al.; The Km, app . values of the membrane-bound transpeptidase of Streptomyces R61 for the donor Ac2-L-Lys-D-Ala-D-Ala and the acceptor Gly-Gly are not affected by temperature variations when the reaction mixtures are incubated in liquid suspensions . At -5 degrees C, the incubation can be carried out either in the liquid or in the frozen state . The enzyme is active in the latter state . In the frozen state, the Km, app . value for the acceptor remains unchanged but there is a 3-fold increase in the maximum velocity, a 10-fold decrease of the Km, app . value for the donor and a 10-fold increase of the benzylpenicillin concentration required to inhibit the enzyme activity by 50% (ID50 value) . Temperatures of -35 degrees C or below are required to completely inhibit the membrane-bound enzyme in the frozen state . Cetyltrimethylammonium bromide extracts the transpeptidase both from the isolated membranes and, with a much higher yield, from the intact mycelium . The extracted enzyme is not active in the frozen state, requires detergent for activity, has decreased Km, app . values for both donor and acceptor, exhibits the same sensitivity to benzylpenicillin and cephalosporin C as the membrane-bound transpeptidase (in liquid suspensions) and, like this latter enzyme, has no DD-carboxypeptidase activity . The detergent-extracted transpeptidase penetrates gels of Sephadex-100 and is not sedimented at 200 000 X g. Antibiotiki, 1975 Jun, 20(6), 510 - 4 {Biological and physicochemical properties of the alpha- and beta-forms of cephaloridine}; Iakobson LM et al.; Alfa- and delta forms of cephalosporin were compared . Biological activity, lantimicrobial spectrum and innocuousness of the forms and their physico-chemical properties were investigated with the methods of infrared and ultraviolet spectrophotometry and derivatography . No significant differences in the biological properties of alfa- and delta forms of cephalosporin were found . However, the ingrared spectrum of the delta-form was indicative of higher stability of its molecule, which was confirmed by higher thermostability of delta-cephalosporin. J Med Chem, 1975 Apr, 18(4), 408 - 17 Electronic structures of cephalosporins and penicillins . 4 . Modeling acylation by the beta-lactam ring; Boyd DB et al.; Molecular orbital calculations by the CNDO/2 method are used to study the molecular and electronic details involved in the initial phases of the opening of the beta-lactam ring of a model cephalosporin structure, 7-amino-3-acetoxymethyl-3-cephem . The effect of a simple nucleophile, OH-, approaching the carbonyl carbon center of the beta-lactam ring is monitored by following the charge redistributions that occur in the bicyclic system and in the 3 side chain . A migration of electron density to the ester oxygen of the CH2OAc group is observed with concomitant weakening of the CH2-OAc bond . The results are discussed in relation to the mechanism of acylation of bacterial cell wall enzymes by beta-lactam antibiotics and in relation to the hydrolysis of these molecules . The results indicate that the ability of the 3' substituent of cephalosporins to stabilize electron density transferred to it, i.e., the leavability of the 3' moiety, can be an important factor in activating the beta-lactam toward nucleophilic attack. Cancer Res, 1975 Mar, 35(3), 801 - 6 Interaction of chemotherapeutic agents with methotrexate and 5-fluorouracil and its effect on de novo DNA synthesis; Bruckner HW et al.; The transport of methotrexate is known to be affected by corticosteroids and vincristine in L1210 leukemia cells . The deoxyuridine suppression test was used to measure the metabolic consequences of using these drugs with the antimetabolites, methotrexate and 5-fluorouracil, in both L1210 leukemia cells and normal human marrow cells . The deoxyuridine suppression test can be utilized as a sensitive measure of methotrexate and 5-fluorouracil biological activity in producing defective de novo DNA synthesis . The deoxyuridine suppression test was found to detect changes in biological activity equal to 20 ng (0.044 nmole) of methotrexate and 200 ng (1.94 nmoles) of 5-fluorouracil . Hydrocortisone and prednisone, but not dexamethasone or prednisolone, decreased the methotrexate effect to one-half in both L1210 and human cells as measured by the deoxyuridine suppression test . 5-Fluorouracil biological activity was not affected by any steroid studied . Vincristine produced variable results, but on the average it decreased the methotrexate effect in human marrow . Vincristine consistently decreased the methotrexate effect in L1210 systems . Cephalosporin, 75 mug/ml (0.214 mumole), had no effect . In parallel studies, hydrocortisone decreased the uptake of methotrexate, but no folic acid, in human and L1210 cells . The deoxyuridine suppression test warants further investigation as a method of screening drugs for interaction with antagonists of de novo DNA synthesis . This tudy extends earlier evidence of drug interaction with methotrexate in a murine system to human cells and demonstrates that there is a metabolic consequence, reduced potency of methotrexate, as a result of reduced transport produced by certain corticosteroids. Z Orthop Ihre Grenzgeb, 1975 Feb, 113(1), 40 - 5 {Gentamicin in orthopedic surgery}; Kramer J et al.; Like in other operative disciplines also in orthopedic surgery we can see an icrease of infections with gramnegative bacterial like ps . pyocyanea . Gentamicin is in general very effective against these infections . There are following indications for the use of Gentamicin in orthopedic surgery: 1 . Parenteral administration only is indicated if there is no other less toxic antibiotic . If it is used a high dosage is necessary because the bone levels which we investigated were very low . Side effects have to be observed . 2 . For local therapy Gentamicin is used in the suction and perfusion system in addition to a systemic therapy with Penicillin, Ampicillin or Cephalosporin . Gentamicin can also be used for the wound perfusion . 3 . Added to bone cement Gentamicin should only be taken, when an infected total hip is exchanged or if a hospitalism with ps . pyocyanea is known- The administration of Gentamicin is less indicated : 1 . Asthe only antibiotic for parenteral therapy in bone infection . 2 . Added to bone cement for a general prophylaxis in all endoprosthetic operations. Antonie Van Leeuwenhoek, 1975, 41(1), 59 - 68 An inducible beta-lactamase in a strain of Escherichia coli; Dale JW; The production of beta-lactamase (penicillin/cephalosporin beta-lactam amidohydrolase, E.C.3.5.2.6) was found to be inducible in a clinically isolated strain of Escherichia coli . This is the first report of an inducible beta-lactamase in E . coli . The optimal concentration of inducer was 400 mug/ml of ml of benzylpenicillin, or 800 mug/ml of 6-aminopenicillanic acid . About fiftyfold induction was achieved . Maximum induction took ninety minutes from the time of adding the inducer . Induction was abolished by the presence of chloramphenicol(10 mug/ml) . The enzyme has a molecular wieght of 23,000, and is inhibited by rho-chloromercuribenzoate and by iodine . It is active against a wide range of substrates, including cephaloridine and cloxacillin.
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