J Pharm Sci. 1980 Apr;69(4):455-7.
Distribution of tetracycline in red blood cells.

Jun HW, Lee BH.

The distribution of tetracycline into human red blood cells was studied in vitro at 37 degrees. The drug was taken up rapidly by the cells, and its distribution equilibrium was reached after approximately 10 min of incubation. The steady-state distribution ratio of the drug between the red cells and extracellular fluid of 0.9% NaCl solution was 2.84, while the distribution ratio between the cells and the plasma solution was 0.9. The reduced cellular uptake in plasma was due to binding of the drug to plasma components. Calcium ions in plasma appeared to reduce tetracycline uptake by the red cells. The red cell distribution of tetracycline in dogs was in close agreement with the in vitro data using the washed human red cells. A dog suffering from severe hypoalbuminemia showed greater uptake of the drug by the erythrocytes, while a normal healthy dog exhibited the red cell-plasma distribution ratio of 0.98. The release rate of tetracycline from the preloaded cells into normal saline solution indicated that the release was directly proportional to the cellular concentration of the drug; the first-order release rate was approximately 1.38 hr-1.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7373544&dopt=Abstract antibiotics, tetracycline




Acta Anat (Basel). 1980;106(3):360-9.
Influence of tetracycline on the calcification of epiphyseal rat cartilage. Transmission and scanning electron-microscopic studies.

Levy J, Ornoy A, Atkin I.

Tetracyclines are known to interfere with bone calcification. We therefore studied their effects on matrix vesicle production and initial calcification of cartilage. 15-day-old rats were injected intraperitoneally with oxytetracycline 100 mg/kg, 6 consecutive injections every 12 h. Epiphyseal plates were examined by scanning and transmission electron microscopy and compared to light microscopy findings. It was found that high doses of tetracyclines cause degeneration of the chondrocytes in the proliferating and hypertrophic zones. Chondrocytes had short processes with only few matrix vesicles covering their surface. In the chondrocytic lacunae of the longitudinal septa of hypertrophic and calcifying cartilage there were fewer matrix vesicles as compared to controls, and their ability to aggregate and form mineralized calcospherites was impaired. This was further proven when bones were immersed in 7% NaOCl or ashed, as minerals containing calcospherites were hardly seen. It is therefore presumed that interference with intracellular and probably extracellular accumulation of calcium by tetracycline might inhibit matrix vesicle production and aggregation, thus inhibiting calcification.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7376817&dopt=Abstract antibiotics, tetracycline




Plasmid. 1985 Jul;14(1):37-46.
Worldwide distribution of the conjugative Clostridium perfringens tetracycline resistance plasmid, pCW3.

Abraham LJ, Wales AJ, Rood JI.

The aim of this study was to test the hypothesis that all conjugative R-plasmids of Clostridium perfringens are closely related to the previously characterized tetracycline resistance plasmid, pCW3. Fourteen conjugative R-plasmids derived from 11 C. perfringens strains isolated in Australia, the United States, France, Belgium, and Japan were analyzed. Eleven of the plasmids encoded tetracycline resistance while three carried both tetracycline and chloramphenicol resistance. Each of these plasmids was compared, by restriction analysis, to the reference plasmid, pCW3. Seven of the tetracycline resistance plasmids had EcoRI, XbaI, and ClaI restriction profiles that were identical to those of the corresponding pCW3 digests. The seven remaining R-plasmids were different from pCW3. Comparison of partial restriction maps of these plasmids with a complete map of pCW3 indicated that they contained at least 17 kb of DNA that also was present in pCW3. Hybridization analysis confirmed that these plasmids shared substantial homology with pCW3. The three tetracycline and chloramphenicol resistance plasmids frequently lost a 6-kb chloramphenicol resistance segment during conjugation. Cloning experiments showed that the chloramphenicol resistance determinant was expressed in Escherichia coli and that the chloramphenicol resistance gene of one of these plasmids, pIP401, was contained within a 1.5-kb region of the 6-kb deletion segment. Hybridization analysis indicated that the deletion segment of pIP401 was related to those of the other two chloramphenicol resistance plasmids. During the course of this study, conjugative R-plasmids which appear to be identical to pCW3 or closely related to pCW3 were identified from C. perfringens strains from human, animal and environmental sources in five countries. It is concluded that C. perfringens strains in humans and animals throughout the world have overlapping gene pools and that all the conjugative C. perfringens R-plasmids examined probably evolved from a pCW3-like element.

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Plasmid. 1988 Mar;19(2):113-20.
Hybridization analysis of the class P tetracycline resistance determinant from the Clostridium perfringens R-plasmid, pCW3.

Abraham LJ, Berryman DI, Rood JI.

Department of Microbiology, Monash University, Clayton, Victoria, Australia.

The tetracycline resistance determinant from pCW3, a conjugative plasmid from Clostridium perfringens, has been identified and the structural gene localized to within a 1.4-kb region. Hybridization analysis, which utilized an internal 0.8-kb specific gene probe, showed that eight nonconjugative tetracycline resistant C. perfringens strains all carried homologous resistance determinants. No homology was detected in DNA prepared from tetracycline resistant isolates of Clostridium difficile or Clostridium sporogenes. However, the one strain of Clostridium paraputrificum that was tested did contain an homologous determinant. No homology was found to any of the recognized classes of tetracycline resistance determinants. The C. perfringens tetracycline resistance determinant represents a new hybridization group, Class P.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2901767&dopt=Abstract antibiotics, tetracycline




J Infect Dis. 1985 Nov;152(5):1032-6.
Effect of tetracycline on the attachment of K88+ enterotoxigenic Escherichia coli to porcine small-intestinal cells.

Deneke CF, Thorne GM, Larson AD, Gorbach SL.

The attachment of six strains of K88+, porcine pathogenic, enterotoxigenic Escherichia coli to isolated porcine intestinal mucosal cells was decreased following growth in the presence of concentrations of oxytetracycline below the minimal inhibitory concentration (MIC). The decrease in binding by the wild-type strains was detected at concentrations of drug as low as 0.001 microgram/ml, which was greater than four orders of magnitude below the MIC. When drug resistance was induced in these six strains, there was still a decrease in binding when the bacteria were grown in the presence of tetracycline. This decrease was comparable to the decrease in binding capacity of the wild-type strains caused by growth in the presence of tetracycline. In contrast, when one strain (G1108E) was made tetracycline resistant by the introduction of the R16 plasmid, the antibiotic had less effect on the binding of this strain than on the wild-type strain; however, growth in the presence of antibiotic still decreased adhesion. Overall, oxytetracycline decreased the adhesion of wild-type, induced-resistant, and genetically resistant K88+ enterotoxigenic E. coli to porcine small-intestinal cells, and this effect occurred at antibiotic concentrations several orders of magnitude below the MIC.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3900235&dopt=Abstract antibiotics, tetracycline




J Clin Oncol. 1985 Dec;3(12):1678-82.
Tetracycline sclerosis in the management of malignant pericardial effusion.

Shepherd FA, Ginsberg JS, Evans WK, Scott JG, Oleksiuk F.

Twenty-two patients with malignant pericardial effusion were seen at the Toronto General Hospital between 1979 and 1984. Under ECG monitoring, an indwelling Kifa catheter was inserted into the pericardial sac and then connected to a Hemovac system and allowed to drain for 12 to 24 hours. Xylocaine hydrochloride, 100 mg, was first instilled intrapericardially, followed by tetracycline hydrochloride, 500 to 1,000 mg, dissolved in 20 mL normal saline. The catheter was clamped for one to two hours and then allowed to drain into the Hemovac. This procedure was repeated every 24 to 48 hours until the net drainage was less than 25 mL/24 hours. Nine men and 13 women were treated (median age, 55 years). The primary malignancy included lung in 15 patients, breast in two patients, and carcinoma of the stomach, ovary, pleural mesothelioma, chronic granulocytic leukemia, and adenocarcinoma of unknown primary in one patient each. Twenty patients received one to five instillations of tetracycline. In one patient the catheter could not be inserted into the pericardial sac, and in one patient the catheter clotted before tetracycline instillation. Minor complications included transient arrhythmia in two patients, postinjection pain in four patients, and self-limited temperature elevation greater than 38.5 degrees C in two patients. fifteen patients had good control of their malignant pericardial effusion for more than 30 days (median survival, 160 days; range, 38 to 275 days). Three patients died before 30 days without evidence of effusion, and no patient surviving longer than 30 days developed recurrent effusion or pericardial constriction. Intrapericardial tetracycline instillation is a safe and efficacious treatment for malignant pericardial effusion and should be considered the first treatment modality in this situation.

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Gene. 1983 Nov;25(1):83-92.
Sequence homology between the tetracycline-resistance determinants of Tn10 and pBR322.

Nguyen TT, Postle K, Bertrand KP.

The Tn10 tetracycline resistance gene, tetA, encodes a tetracycline-inducible protein with an apparent Mr of 36 X 10(3). We have determined the nucleotide sequence of the Tn10 tetA gene. The extent of the tetA gene was determined by analysis of amino-terminal and carboxy-terminal deletion mutants. We conclude that a single Tn10 gene, the tetA gene, is sufficient to confer tetracycline resistance. The predicted Mr of the tetA protein is 43.2 X 10(3). The sequence homology between the Tn10 tetA gene and the pBR322 tetracycline resistance determinant (49% nucleotide homology, 44% amino acid homology) indicates that these phenotypically distinct tetracycline-resistance determinants must have evolved from a common ancestral sequence. The markedly hydrophobic character of the predicted amino acid sequences of the Tn10 tetA and pBR322 tet-coded proteins suggests that a substantial portion of these proteins may be embedded within the cytoplasmic membrane.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6319234&dopt=Abstract antibiotics, tetracycline




Arzneimittelforschung. 1981;31(12):2118-20.
Comparative evaluation of the effects of tetracycline and doxycycline on blood and liver lipids on male and female mice.

Bocker R, Estler CJ, Maywald M, Weber D.

The effects of tetracycline and doxycycline (10-100 mg/g i.v.) on the triglyceride and cholesterol contents of liver and blood were studied comparatively in male and female mice. Only tetracycline increased the triglyceride content of the liver. The cholesterol content of the liver was raised by both tetracycline and doxycycline. Tetracycline and doxycycline increased the concentration of unesterified cholesterol and decreased esterified and total cholesterol in the serum. Most effects were more consistent or more pronounced in females than in males.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7199310&dopt=Abstract antibiotics, tetracycline