Antimicrob Agents Chemother. 2000 Nov;44(11):2979-84.
Genetic diversity of the tet(M) gene in tetracycline-resistant clonal lineages of Streptococcus pneumoniae.

Doherty N, Trzcinski K, Pickerill P, Zawadzki P, Dowson CG.

Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom.

The aim of the present study was to examine the stability and evolution of tet(M)-mediated resistance to tetracyclines among members of different clonal lineages of Streptococcus pneumoniae. Thirty-two tetracycline-resistant isolates representing three national (Spanish serotype 14, Spanish serotype 15, and Polish serotype 23F) and one international (Spanish serotype 23F) multidrug-resistant epidemic clones were all found to be tet(M) positive and tet(O), tet(K), and tet(L) negative. These isolates all carried the integrase gene, int, which is associated with the Tn1545-Tn916 family of conjugative transposons. High-resolution restriction analysis of tet(M) products identified six alleles, tet(M)1 to tet(M)6: tet(M)1 to tet(M)3 and tet(M)5 in isolates of the Spanish serotype 14 clone, tet(M)4 in both the Spanish serotype 15 and 23F clones, and tet(M)6, the most divergent allele, in the Polish 23F clone. This indicates that tet(M) variation can occur at the inter- and intraclone levels in pneumococci. Two alleles of int were identified, with int1 being found in all isolates apart from members of the international Spanish 23F clone, which carried int2. Susceptibility to tetracycline, doxycycline, and minocycline was evaluated for all isolates with or without preincubation in the presence of subinhibitory concentrations of tetracyclines. Resistance to tetracyclines was found to be inducible in isolates of all clones; however, the strongest induction was observed in the Spanish serotype 15 and 23F clones carrying tet(M)4. Tetracycline was found to be the strongest inducer of resistance, and minocycline was found to be the weakest inducer of resistance.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11036009&dopt=Abstract antibiotics, tetracycline




Antimicrob Agents Chemother. 2002 May;46(5):1435-40.
Effects of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline triple therapy in the Helicobacter pylori SS1 mouse model after 1 day of dosing: development of an H. pylori lead selection model.

Sizemore CF, Quispe JD, Amsler KM, Modzelewski TC, Merrill JJ, Stevenson DA, Foster LA, Slee AM.

Antimicrobial Research Department, DuPont Pharmaceuticals Company, Wilmington, Delaware 19880-0400, USA.

We evaluated the effect of optimized doses and dosing schedules of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline (BMT) triple therapy with only 1 day of dosing on Helicobacter pylori SS1 titers in a mouse model. A reduction of bacterial titers was observable with 22.5 and 112.5 mg of metronidazole per kg of body weight (as well as BMT) given twice daily and four times daily (QID). Two hundred milligrams of tetracycline per kilogram, given QID, resulted in only a slight reduction of H. pylori titers in the stomach. We argue that optimization of doses based on antimicrobial drug levels in the animal and shortened (1 or 2 days) drug administration can be used to facilitate early evaluation of putative anti-H. pylori drug candidates in lieu of using human doses and extended schedules (7 to 14 days), as can be deduced from the results seen with these antimicrobial agents.

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Indian J Med Sci. 2002 Nov;56(11):553-9.
Effect of minocycline and tetracycline on immunological responses in experimental animals.

Reeta KH, Mediratta PK, Mahajan P, Sharma KK.

Department of Pharmacology, University College of Medical Sciences & GTB Hospital, Shahdara Delhi-110 095.

In recent years, there has been an increase in the use of antibiotics, primarily tetracycline anlogues, like minocy cline to treat rheumatoid arthritis. However, the mechanism of action of these analogues is not clearly defined. The present study investigates the effects of minocycline and tetracycline on some immunological parameters in Wistar rats and Swiss albino mice. Haemagglutination (HA) titre was employed as parameter of humoral immune response and % leukocyte migration inhibition (% LMI) and footpad thickness tests were used as measures of cell mediated immune response. Both minocycline and tetracycline significantly improved humoral immune response in rats as indicated by an increase in anti-SRBC antibody titre. In the LMI test, depending on the time period of drug administration, there was an increase or a decrease in the % LMI. When drugs were administered on days 1-7 after sensitization, both the compounds caused a significant increase in % LMI. However, the % LMI was significantly decreased when the drugs were administered on days 7-13 of sensitization, indicating variable effects of these agents on the Immune mechanism depending on the time of administration in relation to the development of immune responsiveness. Both minocycline as well as tetracycline produced a significant decrease in the paw volume in the footpad-thickness test which indicates a decrease in lymphokine production/release. The present study thus shows that minocycline and tetracycline exhibit immunomodulatory properties, which may contribute significantly to their beneficial effects in rheumatoid arthritis.

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J Vet Pharmacol Ther. 1989 Sep;12(3):267-76.
In vitro activity of five tetracyclines and some other antimicrobial agents against four porcine respiratory tract pathogens.

Pijpers A, Van Klingeren B, Schoevers EJ, Verheijden JH, Van Miert AS.

Department of Herd Health, Faculty of Veterinary Medicine, State University of Utrecht, The Netherlands.

The minimal inhibitory concentrations (MIC) of five tetracyclines and ten other antimicrobial agents were determined for four porcine bacterial respiratory tract pathogens by the agar dilution method. For the following oxytetracycline-susceptible strains, the MIC50 ranges of the tetracyclines were: P. multocida (n = 17) 0.25-0.5 micrograms/ml; B. bronchiseptica (n = 20) 0.25-1.0 micrograms/ml; H. pleuropneumoniae (n = 20) 0.25-0.5 micrograms/ml; S. suis Type 2 (n = 20) 0.06-0.25 micrograms/ml. For 19 oxytetracycline-resistant P. multocida strains the MIC50 of the tetracyclines varied from 64 micrograms/ml for oxytetracycline to 0.5 micrograms/ml for minocycline. Strikingly, minocycline showed no cross-resistance with oxytetracycline, tetracycline, chlortetracycline and doxycycline in P. multocida and in H. pleuropneumoniae. Moreover, in susceptible strains minocycline showed the highest in vitro activity followed by doxycycline. Low MIC50 values were observed for chloramphenicol, ampicillin, flumequine, ofloxacin and ciprofloxacin against P. multocida and H. pleuropneumoniae. B. bronchiseptica was moderately susceptible or resistant to these compounds. As expected tiamulin, lincomycin, tylosin and spiramycin were not active against H. pleuropneumoniae. Except for flumequine, the MIC50 values of nine antimicrobial agents were low for S. suis Type 2. Six strains of this species showed resistance to the macrolides and lincomycin.

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J Invest Dermatol. 1985 Apr;84(4):262-4.
Photohemolytic potency of tetracyclines.

Bjellerup M, Ljunggren B.

Hemolysis induced by long-wave ultraviolet radiation (UVA) and 8 different commercial tetracycline derivatives was studied in a model using human red blood cells. Demethylchlortetracycline and doxycycline were shown to have pronounced hemolytic properties causing 88% and 85% hemolysis, respectively, at a concentration of 50 micrograms/ml and 72 J/cm2 of UVA. Tetracycline, oxytetracycline, and chlortetracycline caused maximally 18% hemolysis at 200 micrograms/ml and lymecycline only 7% at 100 micrograms/ml. Methacycline showed intermediate hemolytic effect of 36% at 200 micrograms/ml. Minocycline had no hemolytic effect whatsoever. These experimental data correlate very well with clinical reports and comparative phototoxicity trials in humans. Photohemolysis may thus be of value for predicting tetracycline phototoxicity.

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Calcif Tissue Int. 1981;33(2):101-4.
Effects of demineralizing tetracycline-stained human dentine.

Simpson MS.

In view of the belief that tetracycline is removed from bone when it is demineralized, it was decided to investigate the effect of demineralizing agents on human dentine. Teeth which had been stained in vivo with tetracycline were fixed in formalin and demineralized using mineral and organic acids and EDTA at neutral pH. When examined microscopically under ultraviolet light, the tetracycline lines in dentine, although reduced in intensity, were all still present. This indicates that formalin fixation does not appreciably alter the fluorescent effect of tetracycline in teeth and that it is not removed by demineralization. It seems likely therefore that tetracycline is incorporated in both the mineral and organic phases of human dentine.

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J Bacteriol. 1983 Aug;155(2):531-40.
Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline.

George AM, Levy SB.

Increasing levels of resistance to tetracycline and to a number of other unrelated antibiotics, including chloramphenicol, beta-lactams, puromycin, and nalidixic acid, occurred in Escherichia coli after 50 to 200 generations of growth in the presence of subinhibitory concentrations of tetracycline or chloramphenicol. In the absence of selective pressure, resistances fell to low levels within 100 generations of growth. This amplification of resistance was observed in laboratory and naturally occurring E. coli strains as well as in polA and recA strains. With the exception of previously identified cmlA and cmlB mutations, tetracycline or chloramphenicol resistances were not P1 transducible. Coincident with the emergence of resistance was the appearance of a previously cryptic energy-dependent efflux system for tetracycline. The expression of resistance phenotypes and the tetracycline efflux system were temperature sensitive at 42 degrees C.

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Biochem Pharmacol. 1998 Jan 1;55(1):93-100.
Pharmacological effect of tetracyclines on proteoglycanases from interleukin-1-treated articular cartilage.

Steinmeyer J, Daufeldt S, Taiwo YO.

Institute for Pharmacology and Toxicology, Rheinische Friedrich-Wilhelms-Universitat Bonn, Germany.

Based on previous in vivo and in situ studies showing that tetracyclines possess antidegenerative effects on cartilage in conjunction with a reduced proteoglycan (PG) loss from the extracellular matrix, we investigated the effects of doxycycline, minocycline and tetracycline on the degradation and biosynthesis of PGs by bovine articular cartilage explants, both in vitro and in situ. Doxycycline, minocycline and tetracycline dose dependently, although weakly, inhibited PG degrading matrix metalloproteinases (MMPs) in vitro, when tested at concentrations ranging from 1 to 100 microM. Ro 31-4724 proved to be a potent inhibitor of MMP proteoglycanases (IC50 value 1.5 nM). Only at a concentration of 100 microM did doxycycline and minocycline significantly inhibit the interleukin-1 (IL-1)-induced augmentation of PG loss from cartilage explants into the nutrient media. The tetracyclines did not modulate the IL-1-mediated reduced aggregability of PGs, whereas 10 microM Ro 31-4724 partially restored the aggregability of PGs ex vivo. Tetracycline even at this high concentration was ineffective. Compared to the effects of the MMP inhibitor Ro 31-4724, treatment with tetracyclines at therapeutic serum levels of 1 or 10 microM was minimal, with little or no effect on cartilage proteoglycanases and PG biosynthesis. In our experiments, tetracyclines and Ro 31-4724 at doses evaluated had no cytotoxic effects on chondrocytes.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9413935&dopt=Abstract antibiotics, tetracycline