Are bacterial toxins involved in arthritis induced in rats?
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Biomedical subjects
Publications and source records attributed to L Cuzzolin.
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The changes in the pattern of bacteria in root canal after repeated washing with NaOCl and endodontic instrumentation were evaluated. Samples were obtained from the root canals of patients before and after endodontic instrumentation, and analyzed according to the usual microbiological techniques. Washing with NaOCl and endodontic instrumentation act against bacteria such as Peptostreptococci, Streptococcus sanguis, Actinomyces israelii, Proteus mirabilis, Bacteroides, whereas Streptococcus lactis and Aerococcus were present before and after endodontic instrumentation. Environmental conditions such as low pH could be responsible for the persistence of gram-positive bacteria. The use of topical treatment and the associated endodontic instrumentation seem useful in the eradication of some bacteria in the root canal.
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The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to favorable therapeutic result.
Some studies on the relationships among toxic effects in rat liver, kidney and intestine have been carried out. Indomethacin caused a marked reduction in microsomal enzymes, such as cytochrome P450, cytochrome b5 and aminopyrine N-demethylase in the kidney and the liver, greater in the former and for a shorter time than in the latter. Indomethacin induced intestinal lesions and marked overgrowth of intestinal bacteria, mainly of aerobic bacteria in the first 24 hours after its administration and anaerobic bacteria such as Clostridii in the second day. These findings enable us to suggest that the drug induces multisystem lesions through different mechanisms involving either a direct effect on the tissue or other microbiological or pharmacological factors.
Imipenem serum pharmacokinetics, lung tissue and pericardial fluid concentrations were measured in 10 patients undergoing thoracotomy, following a 1 g intravenous infusion of imipenem-cilastatin. The serum concentrations of imipenem 0.5 h and 4 h after the end of the 40 min infusion were 53.3 (+/- 16.7) and 2.0 (+/- 0.3) mg/l, respectively. The concentration of imipenem in lung tissue at 1 h was lower than in pericardial fluid and at 2.25 h the mean concentration of imipenem in pericardial fluid was 10.5 mg/l, vs. 0.28 mg/kg of lung tissue. Imipenem concentrations in pericardial fluid remained above 5 mg/l, well above the MIC for most pathogens, for 1 h whereas in pericardial fluid the concentration was 10.5 mg/l at 2.25 h.
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The pharmacokinetics of ceftriaxone were studied for seven patients with pleural effusion of various etiologies. All patients received 1 g of antibiotic, administered as an intravenous bolus. The pleural fluid had a high total protein content (6.0 g/dl). Ceftriaxone levels in plasma and in pleural fluid were determined by the agar well diffusion technique. Total and free drug concentrations in pleural fluid reached 7 to 8.7 and 3.8 to 2.3 micrograms/ml, respectively, in 4 to 6 h. The disappearance of the drug from the pleural fluid was very slow. In these patients, therapeutic ceftriaxone levels were present for at least 53 h in pleural fluid.
The penetration of ceftazidime in pericardial fluid and lung tissue was investigated in 14 thoracotomized patients, who had normal renal function and did not receive any antibiotic treatment before thoracotomy. The drug (28 mg/kg) was given by i.v. Blood, pericardial fluid and lung tissue samples were taken over the next 5 hours. Concentrations of ceftazidime in the lung tissue were very high in the first hour and over the 200 and 300 min time interval, the ratio between serum and lung tissue levels was 0.7. The correlation coefficient between pericardial fluid, serum ratio and time was calculated to be of 0.99 (P less than 0.001). From these data we can observe that ceftazidime rapidly diffuses into the pericardial space and lung tissue where good concentrations (5.4 mcg/g) persist for at least 5 hours.
Feces samples of 35 children, aged between 3 and 24 months (mean age 12 months), were analyzed. Sixteen children who had no therapy were considered as "control samples"; an antibiotic therapy was administered to 8 subjects for at least 5 days for extraintestinal pathology (ampicillin, orally, at a dose of 100 mg/kg/die in three doses). Finally, the same antibiotic therapy with the addition, from the beginning over 5 days, of the oral preparation of Bacillus subtilis spores (4 X 10(9) die) was administered to 11 patients. During antibiotic therapy, the number of stools per day increased, but not for those patients taking B. subtilis spores. Regarding the bacterial flora, the subjects treated with antibiotic therapy alone showed a significant decrease of all aerobic species, except for fungi, anaerobic total count and aerobic cocci. After oral bacteriotherapy together with ampicillin, we observed an increase of saccharolytic flora, aerobic and anaerobic, while proteolytic flora did not show any changes.
The gastrointestinal effects of single and repeated administration of ferrous sulphate was evaluated measuring faecal flora modifications and histology of stomach and duodenum of the rat. The acute experiments showed reversible histopathological lesions of stomach and duodenum with iron deposition and increase in faecal Cl. perfringens toxin after treatment with a high dose of FeSO4. The chronic experiment at lower doses showed no relevant histological damage, some iron deposition and strong alterations in faecal flora. A strong impact of oral FeSO4 on gastrointestinal environment was demonstrated.
The effects of nitroflurbiprofen (NFP), a new non-steroidal anti-inflammatory drug containing a nitroxybutyl moiety, on rat aortic rings were compared with those of flurbiprofen (FP) and glyceryl trinitrate (GTN). NFP and GTN relaxed, in a dose-dependent manner, either intact or rubbed aortic rings precontracted with epinephrine. Pretreatment with FP did not influence the relaxant activity of NFP in both endothelium-intact and -denuded arteries. In unrubbed preparations, FP did not affect contraction induced by epinephrine, while in rubbed ones a moderate relaxation was observed. Methylene blue and oxyhaemoglobin completely reversed the vasodilating effect of NFP in both rubbed and unrubbed preparations. Moreover, the addition of cysteine 5 mmol l-1 at the end of the cumulative application of NFP resulted in a further relaxation of aortic rings. These results indicate that NFP possesses vasodilatory activity which appears to be dependent on the release of nitric oxide or nitric oxide derivatives.
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