摘要:

Alkenyl groups were attached to heterocyclic nitrogens of uracil ring assuming that the adjacent carbonyl groups might potentiate their (Nitrogen atoms) inductive effect to an extent enough to polarise the unsaturated double bond. The resulting N-alkenyl uracil derivatives react at room temperature with mercapto ethanol in an anti- Markownikoff’s manner yielding abnormal thioethers. The increased reactivity of the alkenyl group of the uracil compounds towards the SH group of mercapto ethanol led to the examination of their effect on the SH enzyme alcohol-dehydrogenase activity. Results with the virostatic l-allyl-3,5-di-ethyl-6-chlorouracil (Acluracil®) have now shown that it inhibits the enzyme activity to ∼70% at concentration of 2.98 ×10-3 mol/l; the 50% inhibition being achieved at 1.14×10-3 mol/l of the inhibitor concentration. Despite the fact that in vitro the alkenyluracils react with SH groups and the enzyme alcohol-dehydrogenase being an SH enzyme, the present studies do not afford evidence for the involvement of the prosthetic or other sulfhydryl groups of the enzyme protein in inhibition of the enzyme ac

ISSN:0009-3157    

DOI:10.1159/000220684

出版商:S. Karger AG    

年代:1970

数据来源: Karger

摘要:

Cyclacillin was compared with cephalex-in and ampicillin for activity against various patho- gens in vitro and the corresponding infections they produce in mice. Cyclacillin was superior to cephalex- in in vitro and in vivo against penicillin-sensitive S. aureus and Strep, pyogenes. Against penicillin- ase-producing staphylococci, cyclacillin was clearly superior to cephalexin in vivo, while in vitro cephalexin was the more active of the two. Cyclacillin and ampicilin were about equally active in vivo against Strep, pyogenes, D. pneumoniae and penicillin-sensitive staphylococci, while in vitro cyclacillin was somewhat less active than ampicillin. Against penicillin-resistant staphylococci, cyclacillin was active while ampicillin was not. Against gram-negative organisms cyclacillin was less active both in vitro and in vivo than ampicillin. Faced with an increasing challenge by the penicillin-sensitive cocci (i. e., treatment of mice infected with 100 to 100,000 LD95), cyclacillin was clearly and consistently superior to ampicillin. The high order of therapeutic activity exhibited by this agent cannot be predicted from the in vitro susceptibility data. There is no satisfactory explanation for this disparity, which is known to occur also with some other antimicrobial agents. The present results confirm the need for careful consideration of all the relevant biologic parameters before extrapolating in vitro data to the clinical situation.

ISSN:0009-3157    

DOI:10.1159/000220685

出版商:S. Karger AG    

年代:1970

数据来源: Karger

摘要:

Two hundred strains of Streptococcus pyogenes were isolated at random from septic lesions not associated with the respiratory tract and nose and throat in 19 centers throughout Poland and typ-ed by T-agglutination. The prevalent types of S. pyogenes were: 8, 25, Imp. 19 complex in 29% (with occurrence of the 25, Imp. 19 type in 14%, 3, 13, B 3264 complex in 24.5% (type 3 only in 12%), 5, 11, 12, 27, 44 complex in 24 % (type 12 only in 7.5 %), and type 4 in 10.5 %. Other types constituted 11.5 %. These strains were tested for their susceptibility towards 30 antibiotics, of which the most effective occurred: natural and semisynthetic penicillins, cepha-lotin, rifamycins, erythromycin, spiramycin, pristinamycin and lincomycin. Twenty-two per cent of strains were tetracycline-resistant, 13.5 % – chloramphenicol-resistant and 30.5 % – novobiocin-resistant. All strains were not susceptible to streptomycin and the neomycin group of antibiotics at concentrations available in the organism. Distribution of serotypes among antibiotic-resistant strains is described. Prevalence of serotypes of S. pyogenes recognized in this study was compared with occurrence of serotypes in 2451 strains of S. pyogenes isolated from non-epidemic and epidemic-infections caused by this microorganism during the 1950–1965 p

ISSN:0009-3157    

DOI:10.1159/000220686

出版商:S. Karger AG    

年代:1970

数据来源: Karger

摘要:

Six strains of multiple-antibiotic resistant, DNase-positive Staph. epidermidis were found to be sensitive to chloramphenicol and gentamicin sulfate; although cephalothin alone was ineffective, the combination of chloramphenicol and cephalothin resulted in an additive effect against four of the isolates in vitro. However, two strains proved refractory to the combination of these two drugs, emphasizing the need for careful in vitro antibiotic sensitivity studies, especially so in the case of multiple-drug resistant organisms.

ISSN:0009-3157    

DOI:10.1159/000220687

出版商:S. Karger AG    

年代:1970

数据来源: Karger

摘要:

Mice harbouring a measured load of cul-turable Mycob. bovis in the lungs were treated either with rifampicin or INH in high doses over prolonged periods of time. Observed differences in the ultimate incidence of resistant infections were related to the assessed number of resistant units of mycobacteria which were present at the start of the treatment. It followed that the superior efficacy of rifampicin was based on the fact that the bacterial population used for the infection contained approx. 200 times less rifampicin-resistant than INH-resistant bacterial units. There was no indication of a difference in the infectivity of the rifampicin- and INH-resistant mutants in this bacterial strain.

ISSN:0009-3157    

DOI:10.1159/000220688

出版商:S. Karger AG    

年代:1970

数据来源: Karger

摘要:

Following our earlier findings with ex-tracts from the plant Arctium Lappa, arctigenin, one of the constituents was re-isolated and a series of analogues synthesized. Arctigenin (semi)mustard, the only member possessing considerable potency, gave the following inhibitions: Amytal sarcoma(ascites) 76 %; Ehrlich carcinoma(ascites) 7 %; NK lympho- ma(ascites) 50 %; sarcoma 180(solid) 9 %; sarcoma 37(solid) 59%; Ehrlich carcinoma(solid) 37 %. The total dosage given was 500 mg/kg in 10 days, except the lymphoma with 450 mg/kg in 9 days. The size of the inoculum was 4 × 106 cells or 3 mg tumour tissue, respectively. In the survival experiments, complete «cure» was established at a total dosage of 500 mg/kg given in 10 days to animals inoculated with 2 × 106 amytal(ascites)-sarcoma cells. At a dose level of 25.6 LD50/ml incubate, a «sterilizing» effect on amytal ascites sarcoma cells was observed. The relative potencies to HN2 and 6-MP were 1:1 in the SDI test. The compound has a curare-like acute toxicity with an LD50 of 236 and MTD of 136 mg/kg. The repeated-dose toxicity studies in non-tumour bearing mice revealed an invariability of the erythrocyte concentration and a drop in the leucocyte (18,220/µl to 10,630) as well as in the TNBMC count (11.46 m/20 g body weight to 2.76). Referring to the mechanism of action, the eventual joint responsibility of both monofunctional mustard and nearby y-lactone moieties was cons

ISSN:0009-3157    

DOI:10.1159/000220689

出版商:S. Karger AG    

年代:1970

数据来源: Karger

ISSN:0009-3157    

DOI:10.1159/000220690

出版商:S. Karger AG    

年代:1970

数据来源: Karger

ISSN:0009-3157    

DOI:10.1159/000220691

出版商:S. Karger AG    

年代:1970

数据来源: Karger