Ann Clin Res. 1975 Feb;7(1):42-6.
Drug absorption in patients with T-tube after cholecystectomy.

Aukee S, Venho VM, Jussila J, Karjalainen P.

The influence of bile flow on the absorption of tetracycline, doxycycline, sulphadimidine and cycloserine was studied in 13 volunteer patients with t-tubes in their main bile ducts after biliary surgery. Their hepatic functions and bile flows were estimated by giving I131 radioiodinated rose-bengal intravenously. About 80% radioactive tracer was recovered from the bile when the t-tube was open, so most of the bile was diverted outside the intestinal tract. Up to 4 hours after administration serum tetracycline levels were lower when the t-tube was open than when the t-tube was closed. In one patient the serum levels were so much reduced that therapeutic serum tetracycline levels could not be achieved. The serum doxycycline levels were fairly high and bile flow did not have any effect on absorption. The 24-hour biliary excretion of doxycycline was only about 15% of the urinary excretion. The absorption of sulphadimidine and cycloserine was not affected by the presence or absence of bile. The bile salts are important surfactants in man, and modify the absorption rate of tetracycline, but not of doxycycline, sulphadimidine and cycloserine. Even in the absence of intact bile flow therapeutic serum tetracycline levels can be expected with the doses currently used.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1155910&dopt=Abstract antibiotics, tetracycline




Nucleic Acids Res. 1997 Mar 15;25(6):1219-24.
Interaction of tetracycline with RNA: photoincorporation into ribosomal RNA of Escherichia coli.

Oehler R, Polacek N, Steiner G, Barta A.

Institute of Biochemistry, University of Vienna, Vienna Biocenter, Dr Bohrgasse 9/3, A-1030 Vienna, Austria.

Photolysis of [3H]tetracycline in the presence of Escherichia coli ribosomes results in an approximately 1:1 ratio of labelling ribosomal proteins and RNAs. In this work we characterize crosslinks to both 16S and 23S RNAs. Previously, the main target of photoincorporation of [3H]tetracycline into ribosomal proteins was shown to be S7, which is also part of the one strong binding site of tetracycline on the 30S subunit. The crosslinks on 23S RNA map exclusively to the central loop of domain V (G2505, G2576 and G2608) which is part of the peptidyl transferase region. However, experiments performed with chimeric ribosomal subunits demonstrate that peptidyltransferase activity is not affected by tetracycline crosslinked solely to the 50S subunits. Three different positions are labelled on the 16S RNA, G693, G1300 and G1338. The positions of these crosslinked nucleotides correlate well with footprints on the 16S RNA produced either by tRNA or the protein S7. This suggests that the nucleotides are labelled by tetracycline bound to the strong binding site on the 30S subunit. In addition, our results demonstrate that the well known inhibition of tRNA binding to the A-site is solely due to tetracycline crosslinked to 30S subunits and furthermore suggest that interactions of the antibiotic with 16S RNA might be involved in its mode of action.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9092632&dopt=Abstract antibiotics, tetracycline




Infect Immun. 1996 Mar;64(3):825-8.
Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion.

Shapira L, Soskolne WA, Houri Y, Barak V, Halabi A, Stabholz A.

Hebrew University--Hadassah Faculty of Dental Medicine, Jerusalem, Israel.

Septic shock results from excessive stimulation of host immune cells, particularly monocytes and macrophages, by lipopolysaccharide (LPS) released from gram-negative bacteria. Macrophage-derived cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1 beta), have been identified as central mediators in the pathogenesis of septic shock and the resultant mortality. Therefore, these cytokines were targets for experimental therapy for septic shock. Because of tetracycline's ability to intervene in cellular mechanisms involved in cytokine secretion, we tested the effect of tetracycline on LPS-induced septic shock and inflammatory lesions in mice. Tetracycline was found to protect mice against LPS-induced lethality and to abolish clinical signs of LPS-induced inflammatory lesions. This protection correlates with tetracycline's ability to reduce LPS-induced TNF-alpha levels in serum. Furthermore, tetracycline was found to inhibit LPS-induced TNF-alpha and IL-1 beta secretion, but not cytokine mRNA accumulation, in human monocytes in vitro. The results presented here suggest that tetracycline is a potent drug for LPS-induced pathology and that its mechanism of action involves blockage of posttranscriptional events of cytokine production.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8641787&dopt=Abstract antibiotics, tetracycline




Food Addit Contam. 1996 Apr;13(3):287-92.
Residue depletion in tissues and fluids from swine fed sulfamethazine, chlortetracycline and penicillin G in combination.

Korsrud GO, Papich MG, Fesser AC, Salisbury CD, MacNeil JD.

Health of Animals Laboratory, Agriculture and Agri-Food Canada, Saskatoon, Saskatchewan, Canada.

Twenty-four hogs were fed a ration for 14 days containing three times the recommended label dose of a combination drug which included sulfamethazine, chlortetracycline and penicillin G. Groups of six hogs were slaughtered 0, 2, 4, or 8 days after withdrawal. Six untreated control hogs were slaughtered 5 days before the first group, of six treated hogs, were slaughtered. Residue concentrations were determined in kidney, liver, muscle, serum and urine. At zero withdrawal the kidney from one hog contained 0.018 mg penicillin G per kg and the serum from the same hog contained 0.016 mg penicillin G per litre. Penicillin G was not detected in any other samples that were analysed. Chlortetracycline concentrations in tissues at zero withdrawal time were below accepted Canadian Maximum Residue Limits (MRL) for chlortetracycline of 1 mg/kg in muscle, 2 mg/kg in liver and 4 mg/kg in kidney and were below the limit of quantitation in all tissues 4 days after withdrawal. Sulfamethazine persisted in the tissues longer than penicillin G or chlortetracycline. Sulfamethazine concentrations were above the Canadian MRL of 0.1 mg/kg at zero withdrawal time and did not decrease to below the MRL until 8 days after withdrawal. Our results suggest that, if the label withdrawal period of 10 days is observed, an increase in the dosage of up to three times the recommended rate is unlikely to increase significantly the risk that residues would occur in the tissues of treated hogs at concentrations which exceed MRLs. Sulfamethazine concentrations in all matrices decreased after storage at -76 degrees C for 6 months.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8718743&dopt=Abstract antibiotics, tetracycline




Int J Dermatol. 1996 Jun;35(6):413-6.
Treatment of actinic prurigo in Chimila Indians.

Duran MM, Ordonez CP, Prieto JC, Bernal J.

Dermatology Unit, Javeriana University, Bogota, Colombia.

BACKGROUND: Actinic prurigo has a high prevalence in women of child-bearing age. Its treatment has been, among others, with thalidomide. To avoid the deleterious effects of this drug on the embryo, therapeutic alternatives have been sought. Among these, tetracycline and vitamin E have been investigated as to their influence on the symptoms of actinic prurigo. Both these drugs affect superoxide radicals that are thought to be involved in the pathogenesis of actinic prurigo. MATERIALS AND METHODS: Patients (Chimila Indians with a high prevalence of actinic prurigo) received either (a) tetracycline, 500 mg three times daily, for 6 months, or (b) vitamin E, 100 IU daily, for 6 months. The patients were seen once monthly. There were eight patients in each group. RESULTS: Both drugs used were effective. Pruritus was remarkably improved by either treatment. None of the side effects were severe enough to lead to interruption of treatment, but the observation period posttreatment was relatively short, 4 months for tetracycline and 2 months for vitamin E. The improvement occurred in spite of the continuation of extensive exposure to the sun. CONCLUSIONS: Tetracycline and vitamin E are efficacious in relieving the pruritus of actinic prurigo. Preliminary trials of a combination treatment with these two drugs is a new avenue which has shown in preliminary trials to yield synergistic effects which might allow the dosage of tetracycline to be reduced.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8737876&dopt=Abstract antibiotics, tetracycline




Biochem J. 1996 Aug 1;317 ( Pt 3):855-60.
Antibiotic interactions with the hammerhead ribozyme:tetracyclines as a new class of hammerhead inhibitor.

Murray JB, Arnold JR.

Department of Biology, University of Leeds, U.K.

A screening of a range of common laboratory antibiotics for inhibition of the hammerhead ribozyme has shown that in addition to certain aminoglycosides (most notably neomycin B) the tetracyclines are also effective inhibitors, with chlorotetracycline being more effective than tetracycline. Inhibition by chlorotetracycline is not as strong as that by neomycin B but is more complicated, with at least two binding sites apparent. As with hammerhead inhibition by neomycin B, chlorotetracycline inhibition can be overcome by raising the concentration of the Mg2+ ion cofactor. We find that around six Mg2+ ions will displace neomycin B, compared with twelve for chlorotetracycline. Inhibition observed in the presence of mixtures of neomycin B and chlorotetracycline is consistent with separate binding sites on the hammerhead for these two classes of antibiotic. Under certain conditions of the mixing order and low concentration of chlorotetracycline, enhancement of single-turnover hammerhead cleavage by up to 20% is observed, with higher concentrations of antibiotic being inhibitory. We have also found that the presence of 2.5% (v/v) DMSO causes a 30% enhancement of the single-turnover cleavage. These results thus extend the range of known inhibitors of hammerhead cleavage, and also demonstrate how the cleavage can be accelerated.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8760373&dopt=Abstract antibiotics, tetracycline




Anal Biochem. 1996 Mar 15;235(2):195-201.
Tetracycline-controlled gene expression system achieves high-level and quantitative control of gene expression.

Yin DX, Zhu L, Schimke RT.

CLONTECH Laboratories, Inc., Palo Alto, California 94305, USA.

The tetracycline-controlled gene expression system utilizes the control elements of the tetracycline resistance operon encoded in TnlO of Escherichia coli to control gene expression in eukaryotic cells. Here we demonstrate the quantitative control of the expression of the luciferase gene, dihydrofolate reductase gene, and bcl-2 gene in HeLa S3 or Chinese hamster ovary AA8 cells using the tetracycline-controlled gene expression system. Regardless of the host cell lines or the genes being expressed, there is a common range of tetracycline concentration within which the expression of genes is most sensitively regulated. In addition, the maximal gene expression level of the tetracycline-controlled gene expression system is higher than that of the wild-type CMV promoter/enhancer-driven system. Nonetheless, careful selection of stably transfected clones is necessary to achieve the optimally regulated gene expression using this system.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8833328&dopt=Abstract antibiotics, tetracycline




Antibiotiki. 1977 Apr;22(4):340-4.
[Effect of successive cyclic administration of oleandomycin and tetracycline on the immunogenic reactivity and indices of non-specific bodily resistance in experimental staphylococcal sepsis]

[Article in Russian]

Plaksina AN, Plaksin AI.

The effect of subsequent cyclic administration of oleandomycin and tetracycline on the titer of the complement, the content of lysozyme, the bactericidal properties of the serum and the presence of the antibiotic specific antibodies in the blood serum found in the Hoigne reaction were studied on rabbits. It was found that the subsequent cyclic administration of the antibiotics to both the intact animals and the animals with experimental staphylococcal sepsis was accompanied by an increase in the titer of the complement only on the 7th day of administration of oleandomycin, the first antibiotic. The subsequent administration of tetracycline and especially discontinuation of the antibiotics use resulted in a significant, stable and prolonged decrease in the complement titer. The cyclic subsequent administration of oleandomycin and tetracycline for 7 days was accompanied by an increase in the lysozyme content and serum bactericidal properties. Changes in the factors of non-specific resistance under the effect of the subsequent cyclic administration of oleandomycin and tetracycline on both the intact animals and the animals with experimental staphylococcal sepsis were accompanied by an appearance, progressive increase and prolonged preservation in the serum of the antibiotic specific antibodies found in the Hoigne reaction. A possibility of producing specific antibodies simultaneously to the 2 antibiotics, i. e. oleandomycin and tetracycline in their administration in subsequent 7-day cycles was shown.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=883787&dopt=Abstract antibiotics, tetracycline