J Clin Periodontol. 2001 May;28(5):446-52.
The long-term effect of systemic tetracycline used as an adjunct to non-surgical treatment of advanced periodontitis.

Ramberg P, Rosling B, Serino G, Hellstrom MK, Socransky SS, Lindhe J.

Department of Periodontology, Faculty of Odontology, Goteborg University, Sweden.

AIM: In the present study both the short- and the long-term effects were evaluated of a treatment that, during the phase of basic therapy, included administration of systemic tetracycline and non-surgical intervention. MATERIAL AND METHODS: 35 adult human subjects with advanced periodontitis, 19 females and 16 males, aged between 24 and 60 years, were included in a test group. 80 age- and sex-matched adult periodontitis subjects were recruited for a control group (42 females and 38 males). A baseline examination included assessment of the following parameters: number of teeth, plaque, bleeding on probing, probing attachment level, probing pocket depth. In radiographs, the distance between the cemento-enamel junction and the alveolar bone crest was determined at all interproximal sites. The subjects were given oral hygiene instruction. The members of the test group were provided with tablets with 250 mg of tetracycline hydrochloride and were instructed to take 1 tablet 4x per day for a period of 3 weeks. No antibiotic was given to the subjects in the control group. During the 3-week interval, all participants received 4-6 sessions of non-surgical periodontal therapy. All subjects were subsequently enrolled in a maintenance care program and were provided with supportive periodontal therapy (SPT) 3-4x per year. Clinical re-examinations were performed after 1, 3, 5 and 13 years. RESULTS: The present investigation demonstrated that tetracycline administered during a 3-week period concomitant with non-surgical treatment enhanced the outcome of mechanical therapy. At the re-examination 1 year after active therapy, there was in the test group an average gain in probing attachment that was almost 3x higher than the gain that occurred in an age and sex matched Control group. Re-examinations after 3, 5, and 13 years of SPT disclosed that this short-term benefit was not maintained in the longer perspective. CONCLUSION: The beneficial effect of systemically administered tetracycline on probing attachment level occurred in the first year post-therapy. Annual rates of probing attachment level change from 1 to 13 years did not differ between groups.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11350508&dopt=Abstract antibiotics, tetracycline

nimr.mrc.ac.uk

In order to evaluate the efficiency of the tetracycline-regulated gene expression system in Drosophila, we have generated transgenic lines expressing a tetracycline-controlled transactivator protein (tTA), with specific expression patterns during embryonic and larval development. These lines were used to direct expression of a tTA-responsive promoter fused to the coding region of either the beta-galactosidase or the homeotic protein Antennapedia (ANTP), under various conditions of tetracycline treatment. We found that expression of beta-galactosidase can be efficiently inhibited in embryos and larvae with tetracycline provided in the food, and that a simple removal of the larvae from tetracycline exposure results in the induction of the enzyme in a time- and concentration-dependent manner. Similar treatments can be used to prevent the lethality associated with the ectopic expression of ANTP in embryos and, subsequently, to control the timing of expression of the homeoprotein ANTP specifically in the antennal imaginal disc. Our results show that the expression of a gene placed under the control of a tetracycline-responsive promoter can be tightly controlled, both spatially by the regulatory sequences driving the expression of tTA and temporally by tetracycline. This provides the basis of a versatile binary system for controlling gene expression in Drosophila, with an additional level of regulation as compared to the general method using the yeast transcription factor GAL4.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9584119&dopt=Abstract antibiotics, tetracycline




Antimicrob Agents Chemother. 2002 Sep;46(9):2996-3000.
16S rRNA mutation-mediated tetracycline resistance in Helicobacter pylori.

Gerrits MM, de Zoete MR, Arents NL, Kuipers EJ, Kusters JG.

Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, The Netherlands.

Most Helicobacter pylori strains are susceptible to tetracycline, an antibiotic commonly used for the eradication of H. pylori. However, an increase in incidence of tetracycline resistance in H. pylori has recently been reported. Here the mechanism of tetracycline resistance of the first Dutch tetracycline-resistant (Tet(r)) H. pylori isolate (strain 181) is investigated. Twelve genes were selected from the genome sequences of H. pylori strains 26695 and J99 as potential candidate genes, based on their homology with tetracycline resistance genes in other bacteria. With the exception of the two 16S rRNA genes, none of the other putative tetracycline resistance genes was able to transfer tetracycline resistance. Genetic transformation of the Tet(s) strain 26695 with smaller overlapping PCR fragments of the 16S rRNA genes of strain 181, revealed that a 361-bp fragment that spanned nucleotides 711 to 1071 was sufficient to transfer resistance. Sequence analysis of the 16S rRNA genes of the Tet(r) strain 181, the Tet(s) strain 26695, and four Tet(r) 26695 transformants showed that a single triple-base-pair substitution, AGA(926-928)-->TTC, was present within this 361-bp fragment. This triple-base-pair substitution, present in both copies of the 16S rRNA gene of all our Tet(r) H. pylori transformants, resulted in an increased MIC of tetracycline that was identical to that for the Tet(r) strain 181.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12183259&dopt=Abstract antibiotics, tetracycline




J Assoc Off Anal Chem. 1991 Nov-Dec;74(6):894-6.
Limited survey of residual tetracyclines in tissues collected from diseased animals in Aichi Prefecture, Japan.

Oka H, Ikai Y, Kawamura N, Hayakawa J.

Aichi Prefectural Institute of Public Health, Nagoya, Japan.

Tissues were collected to survey the actual conditions of tetracycline antibiotics (TCs) residues in slaughtered animals that did not pass inspection at slaughterhouses in Aichi Prefecture, Japan, because of the presence of disease symptoms. Tissues were analyzed by liquid chromatography. Among 271 samples, 49 (18.1%) were positive for oxytetracycline (OTC), 5 (1.8%) for chlortetracycline (CTC), and 5 (1.8%) for doxycycline (DC), respectively. One sample (cattle kidney) was positive for both OTC and DC. However, tetracycline was not detected in any samples. Percentage frequencies of TCs residues were 29.1% (37/127) and 15.2% (22/144) for cattle and hogs, respectively. Kidney samples showed higher incidence of TCs residues and 1.5-7 times higher residual concentrations than liver and miscellaneous samples.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1757409&dopt=Abstract antibiotics, tetracycline




Antimicrob Agents Chemother. 1991 Aug;35(8):1591-5.
Structural requirements of tetracycline-Tet repressor interaction: determination of equilibrium binding constants for tetracycline analogs with the Tet repressor.

Degenkolb J, Takahashi M, Ellestad GA, Hillen W.

Lehrstuhl fur Mikrobiologie, Friedrich-Alexander Universitat Erlangen-Nurnberg, Federal Republic of Germany.

We used the Tn10-encoded Tet repressor, which has a highly specific binding capacity for tetracycline, to probe contacts between the drug and protein by chemical interference studies of the antibiotic. For that purpose, the equilibrium association constants of modified tetracyclines with the Tet repressor and Mg2+ cations were determined quantitatively. The results confirm the previous notion that Mg2+ probably binds with the oxygens at positions 11 and 12 and is absolutely required for protein-drug recognition. Modifications were introduced at positions seven, six, five, and four of the drug, and anhydrotetracycline was also studied. Substitutions or eliminations of functions at these positions influenced binding to the Tet repressor up to 35-fold. The introduction of an azido function at position seven in 7-azidotetracycline and epimerization of the substituents at position four in 4-epitetracycline lead to a 2- or 25-fold reduction, respectively, of Tet repressor affinity in those compounds. Anhydrotetracycline bound about 35-fold more strongly than tetracycline did, indicating that the oxygen at position 11 may be involved in Tet repressor recognition. This increased binding is in contrast to the lower antibiotic activity of anhydrotetracycline and indicates that the Tet repressor and ribosomes recognize the drug differently.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1929330&dopt=Abstract antibiotics, tetracycline




Res Commun Chem Pathol Pharmacol. 1991 Apr;72(1):39-51.
Fluxes and accumulation of tetracyclines by human blood cells.

Gabler WL.

Department of Biochemistry, School of Dentistry, Oregon Health Sciences University, Portland.

Tetracyclines (Tc's) have anti-inflammatory properties unrelated to their antibiotic activities. Their anti-inflammatory property, in part, results from the ability of members of this family of antibiotic to inhibit neutrophil functions. There are marked differences in the ability of different Tc's to suppress neutrophils which may relate to their ability to cross the plasma membrane. To gain insight into the mechanism of Tc inhibition of neutrophils and the reason for the differences in antineutrophil effect of Tc's, we studied the flux and sequestration of Tc's in blood cells. Using centrifugation and a dibutylphthalate scrubber system we found that doxycycline (Dc) was rapidly taken up by blood cells reaching intracellular concentrations several times that found in the medium. Dc also rapidly effluxed when antibiotic loaded cells were placed in drug free medium. While Ca2+, Mg2+ nor protein separately were effective inhibitors of Dc influx, when divalent cations and proteins were combined Dc uptake was markedly suppressed. Tc uptake by blood cells ranked Dc greater than chlortetracycline = tetracycline greater than oxytetracycline, a ranking similar to that reported for neutrophil inhibition by members of the Tc family, suggesting that intracellular accumulation of drug is an important facet of Tc suppression of neutrophil function.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2052748&dopt=Abstract antibiotics, tetracycline




Scand J Infect Dis Suppl. 1988;53:7-11.
In vitro susceptibility to tetracycline and doxycycline in clinical isolates of Haemophilus influenzae.

Ringertz S, Dornbusch K.

Department of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.

The most common indication for the use of tetracyclines in Sweden is respiratory tract infections. Among the tetracyclines, doxycycline dominates with about 75% of the consumption. It is therefore used for routine susceptibility testing, while tetracycline is the test drug in most other countries. Six hundred strains of Haemophilus influenzae isolated from different parts of Sweden were tested for susceptibility to doxycycline and tetracycline. The results were compared with those from earlier reports on resistance rates in Sweden and other countries. The MIC50's of the strains were slightly lower for tetracycline than for doxycycline, but some strains with reduced susceptibility to tetracycline were fully susceptible to doxycycline. The level of resistance to doxycycline in H. influenzae was very low (less than 1%) and has not changed significantly over the past ten years, making doxycycline a suitable antibiotic for instance in the treatment of chronic bronchitis when H. influenzae is involved.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3262234&dopt=Abstract antibiotics, tetracycline




Diagn Microbiol Infect Dis. 1987 Jan;6(1):53-8.
Ovine pulmonary transit of tetracycline and minocycline.

Cohen SH, Hoeprich PD, Gunther R, Merry JM, Franti CE.

Following cannulation of the right external jugular vein and the efferent duct of the right caudal mediastinal lymph node (the caudal end of this node was ligated to cut off the inflow of systemic lymph, i.e., 90%-95% of the efferent lymph was of pulmonary origin), sheep were given either tetracycline or minocycline as single doses of 5 mg/kg body weight infused intravenously over 30 min. Venous blood plasma and pulmonary lymph collected contemporaneously before infusion and from 5 min to 24 hr postinfusion were assayed by a well-agar diffusion method using Bacillus cereus. Peak concentrations of both drugs were observed in both plasma and lymph at 5 min postinfusion. Tetracycline penetrated into the lymph better than minocycline (percent penetration 67.3% of cf. 38.2%). The concentration of tetracycline was significantly higher in lymph during and 5 min postinfusion (p less than 0.01), a factor that may be of importance when selecting a tetracycline for the treatment of a pulmonary infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3802746&dopt=Abstract antibiotics, tetracycline