Experimental oral foreign body reactions. Commonly employed dental materials.

Foreign bodies and tissue reactions to foreign materials are commonly encountered in the oral cavity. The more common lesions include apical deposition of endodontic materials, mucosal amalgam and graphite tattoos, myospherulosis, oil granulomas, and traumatically introduced dental materials and instruments. Since many foreign materials are unidentifiable histologically, commonly used dental materials were experimentally implanted subcutaneously in rats to assess local host responses and characterize the nature of these materials microscopically. The histologic characteristics of these foreign body reactions are detailed herein. The implanted materials corresponded to reactions seen in human subjects.

Disposition and toxicity of amphotericin-B in the hyperlipidemic Zucker rat model.

The pharmacokinetics and toxicity of the lipophilic antifungal agent, amphotericin-B (AmpB), were studied in the hyperlipidemic obese rat model and compared with lean litter-mates. Serial blood samples were obtained for 36 h following a single intravenous infusion of AmpB (1.2 mg/kg) with pre- and post-drug measurements of renal function. Although triglyceride, cholesterol, HDL-cholesterol and LDL + VLDL-cholesterol levels were elevated in the obese compared with lean rats, protein: lipoprotein ratios were similar. There was a 2-fold increase in the area under the serum concentration-time curve of AmpB in obese rats compared to lean litter-mates (15,600 +/- 6900 v. 7800 +/- 2900 ng. h/ml; P less than 0.05); no differences in elimination rate constants were found between groups. Weight-corrected volume of distribution and total body clearance were significantly lower in obese compared with lean rats; no differences were found in absolute clearance or volume. Kidney levels of AmpB were markedly increased in obese versus lean rats. Similarly, kidney to serum ratios of AmpB were greater in obese compared with lean rats (152 +/- 113 v. 41 +/- 23; P less than 0.001). There was a significant decline in the creatinine clearance from baseline in the obese rats coupled with a rise in serum creatinine; no differences were found in lean rats. Similarities in absolute pharmacokinetic variables and protein: lipoprotein ratios suggest differences in AmpB disposition and toxicity are a result of differences in lipoprotein-mediated transport mechanisms between obese and lean rats.

Round window membrane permeability during experimental purulent otitis media: altered Cortisporin ototoxicity.

Round window membrane (RWM) permeability is the most critical factor influencing cochlear function following otitis media. Because otic drops are frequently used during purulent otitis media (POM), we investigated RWM permeability and ototoxicity of Cortisporin otic suspension after inducing experimental POM. Unilateral POM was induced in eight chinchillas by inoculating type 7F Streptococcus pneumoniae into the right ears. Left ears were inoculated with phosphate-buffered saline (control). When POM resolved, the animals were divided into two groups. The round window niches of group 1 were covered with Cortisporin otic suspension. Compound action potentials were measured before and after drug application. The RWM permeability was measured in group 2 by use of tetraethylammonium (TEA) ions as tracers, and the arrival time of TEA and the slope of the potassium-selective microelectrode response were measured. Animals with otitis media exhibited less susceptibility to ototoxicity of Cortisporin otic suspension and reduced RWM permeability to the medium-sized molecule TEA.

The effect of Gd-dimeglumine on subcutaneous tissues: a study with rats.

Gadopentetate dimeglumine and a saline solution of similar osmolality of 2100 mOs/kg H2O were placed in the paws and in the thigh muscles and subcutaneous tissue of Sprague-Dawley rats weighing 225-250 g. The paws were serially photographed for 4 weeks and the thighs were examined histologically for up to 4 weeks. Gross and histologic reactions to gadopentetate dimeglumine were greater than those to the saline solution, and included tissue sloughs. When risk factors for extravascular extravasation are present, such as infusion sites in the dorsum of the hand or foot, or around the ankle, or when soft tissues are obscured by bandages, caution should be exercised when injecting gadopentetate dimeglumine.

Prevention of neutrophil-mediated injury to endothelial cells by perfluorochemical.

Myocardial salvage after reperfusion may be limited by neutrophil-mediated microvascular damage. The effect of the perfluorochemical, Fluosol-DA, and its various components on neutrophil adherence, cytotoxicity, and proteolytic enzyme release was examined on sheep large and small vessel endothelial cells in vitro. Cells were studied under normoxic (N) and anoxic conditions (A). Various concentrations of Fluosol (10%, 25%, and 50%) significantly reduced neutrophil adherence under both experimental conditions [mean 22 +/- 3.25% versus 7 +/- 0.8% (N) and 20 +/- 3.2% versus 7.5 +/- 0.9% (A); P less than 0.01]. The perfluorocarbons, perfluorodecalin (PFD), and perfluoro-tripropylamine (PFTP) in a 50 volume/percent concentration exhibited profound effects on adherence, particularly on cells subjected to anoxia (51% and 69% reduction in adherence, respectively; P less than 0.01). No effect on adherence was observed with other components, including the detergent, pluronic F68. A 25% reduction (P less than 0.02) in endothelial cytotoxicity was noted when neutrophils were preincubated with Fluosol. However, pretreatment of endothelial cells with Fluosol did not inhibit neutrophil adherence. Neutrophils stimulated with cytochalasin B and FMLP showed a significant reduction in lysozyme release after incubation with Fluosol (28 +/- 5% versus 17 +/- 4%; P less than 0.01). This study demonstrates that Fluosol significantly attenuates neutrophil adherence, cytotoxicity, and enzyme release in an in vitro model of microvascular injury. It also suggests that prevention of neutrophil-mediated microvascular damage may be an important mechanism whereby Fluosol enhances myocardial salvage after ischemia and reperfusion.

Safety assessment of gadopentetate dimeglumine in U.S. clinical trials.

Gadopentetate dimeglumine is an intravenous contrast medium used in magnetic resonance imaging. To determine its safety, the authors summarized data concerning adverse reactions, laboratory parameters, and other assessments for 1,068 adult patients who received gadopentetate dimeglumine in United States clinical trials. For all studies, 213 of 1,068 patients (19.9%) who received gadopentetate dimeglumine experienced one or more clinical adverse reactions. Most of these reactions were minor and short-lived. Hematologic, blood chemistry, and urinary evaluations showed no apparent drug-related effects, with the exception of a transient, asymptomatic rise in serum iron and bilirubin levels in some patients. Other safety assessments--electrocardiography, electroencephalography, neurologic examinations, and vital signs--showed no clinically significant trends in change from baseline results. It was concluded that gadopentetate dimeglumine demonstrated a high degree of safety and tolerance.

[The pathomorphological changes in the pleura of rabbits with artificial pneumothorax and uropolin pleurography]. / Patomorfologichni promeni v plevrite na zaitsi pri artifitsialen pnevmotoraks i plevrografiia s uropolin.

The results from artificial pneumothorax in 25 rabbits with intrapleural administration of Uropolin (10 rabbits) as well as of 10% solution of NACl (7 rabbits) were described. Thoracotomy was made on 7th, 14th and 12 21st day and the parietal, diaphragmatic and visceral pleura with underlaying tissues were examined. Proliferation of the mesothelium [correction of mesother] and growth of the connective tissue, which were more manifested in rabbits treated with Uropolin, were established histologically. The authors think that pathohistological examinations confirm the clinical observed favourable effect of intrapleural administration of Uropolin for obliteration of the pleural cavity.

Histopathologic findings and energy dispersive X-ray spectroscopic analysis of experimentally induced foreign-body pneumonias in rats.

To document the diagnostic features of foreign-body pneumonias, four commonly used orally administered medicaments were instilled into the lungs of Sprague-Dawley rats. Rats in each group received a single 0.4 ml dose of either barium sulfate suspension (BaSO4), mineral oil, Pepto-bismol, or Kaopectate inoculated into a lung via a mainstem bronchus. The other lung served as a non-inoculated control. Rats were euthanatized on post-inoculation day 2 or 7 in order to document fully-developed acute pulmonary lesions and developing, chronic pulmonary lesions, respectively. Light microscopic features of BaSO4-inoculated lungs were distinctive from changes in mineral oil-inoculated lungs at both post-inoculation days. On post-inoculation day 2, rats inoculated with BaSO4 had pneumonia characterized by large numbers of alveolar macrophages containing green-to-brown granular material. There was minimal interstitial involvement. On post-inoculation day 2, mineral oil caused pneumonia characterized by giant cells and alveolar macrophages that had cytoplasms distended with variably-sized clear vacuoles. Lungs inoculated with BaSO4 or mineral oil had changed little on post-inoculation day 7 compared to the light microscopic features observed on day 2. On post-inoculation day 2, rats inoculated with either Pepto-bismol or Kaopectate had broncho-interstitial pneumonia with areas of necrosis and hemorrhage. On post-inoculation day 7, lungs inoculated with Pepto-bismol or Kaopectate had extensive fibrosis within alveolar lumens. Energy dispersive spectroscopy performed on sections of lung from rats given BaSO4, Pepto-bismol, and Kaopectate yielded a unique elemental spectrum for each compound in situ on post-inoculation days 2 and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

[The myoelectrical activity of the gastroduodenal area in ulcer formation due to serotonin]. / Mioélektricheskaia aktivnost' gastroduodenal'noi zony pri iazvoobrazovanii, vyzvannom serotoninom.

The effects of prolonged subcutaneous administration of serotonin on the myoelectric activity of the gastroduodenal junction were investigated in conscious rabbits. Serotonin produced the duodenogastric discoordination by increasing duodenal activity and decreasing the activity of stomach and pylorus. This discoordination resulted in gastric ulceration. Atropine prevented both duodenogastric discoordination and ulceration. These results indicate that serotonin ulceration is related to duodenogastric discoordination.

The effects of dietary iron supplementation on the toxicity of piroctone olamine in the growing rat.

Weanling Charles River CD rats of both sexes were fed 300 mg/kg/day of Piroctone Olamine, an anti-bacterial agent, and were supplemented with 0, 50, 100 or 200 ppm dietary iron as FeSO4.7H2O for six weeks. However, analytical data indicated that Piroctone was degraded in the diet so that the rats received only 225 mg/kg/day. The rats given Piroctone Olamine without iron gained significantly less body weight and ate significantly less feed than controls, with the effect being more pronounced in the males. They also developed severe microcytic, hypochromic anemia. The rats supplemented with all three levels of dietary iron grew at a rate similar to controls. The rats supplemented with 50 ppm dietary iron had anemia with all of the hematological iron-associated factors being significantly depressed. The 100 ppm supplement restored all hematologic factors to normal in the females, but slight reductions remained in the males. The 200 ppm supplement of iron restored all parameters to values similar to the controls in both sexes. These results suggest that the mechanism of the toxicity of Piroctone Olamine is the prevention of dietary iron absorption by in situ chelation.

Prophage induction by 4 antimalaria drugs (daraprim, fansidar, nivaquine and camoquine) and in combination with aflatoxin B1.

The abilities of 4 antimalaria drugs (Daraprim, Fansidar, Nivaquine and Camoquine) on their own and in combination with aflatoxin B1 to induce prophage in tester strains E. coli D21 and D22 were studied. The 4 drugs were found to induce prophage in the tester strains; Daraprim and Fansidar without the need for activation by liver mixed function oxidases (S9 microsomal fraction), while Nivaquine and Camoquine did require activation by this system. Aflatoxin B1 was used as a positive control in all the tests. The combined effects of each of the drugs with aflatoxin B1 were lower than that of the individual drugs acting alone. From these results, it may be concluded that the drugs may, on their own, pose a carcinogenic hazard to the population in the Nigerian environment exposed to them. In addition, the depression of prophage induction observed when the drugs were combined with aflatoxin B1 may be indicative of a common target site of action in the tester strains.

Mediastinal fibrin glue: hemostatic effect and tissue response in calves.

There is continued controversy regarding the effectiveness and potential adverse effects of fibrin glue. Thus, we chose to evaluate it in a model of experimental calf aortic valve replacement that has been previously well established. Concentrated fibrinogen and topical thrombin were sprayed to form a thin layer of fibrin glue over the mediastinal tissues of 20 consecutive calves undergoing aortic valve replacement. Chest tube outputs of these animals were compared with those of the preceding 20 consecutive calves undergoing aortic valve replacement without fibrin glue. All procedures were performed by the same surgeon, and no other technical changes were made between the two series. Total postoperative chest tube output (mean +/- standard error) was 553 +/- 50 mL for the calves treated with fibrin glue and 1,155 +/- 103 mL for the control calves (p less than 0.001). On histological examination of mediastinal tissues from 5 treated calves killed 6 weeks after operation, there was no evidence of inflammation, fibrosis, or residual fibrin. To our knowledge, this is the first controlled laboratory study to show that fibrin glue spray is an effective hemostatic agent and that it produces no long-term tissue reaction.

[Comparative morphological characteristics of the pulp reaction to direct coating with therapeutic packings]. / Sravnitel'naia morfologicheskaia kharakteristika reaktsii pul'py na priamoe pokrytie razlichnymi lechebnymi prokladkami.

In experiments performed on green monkeys the molar pulp response to direct coating with calmecin and polycarboxylate cement saturated with the potassium nitric solution. Compared, the results of morphological pulp investigation showed the polycarboxylate cement with saturated potassium nitrate solution coating to be most effective. It had a rather good odontotropic effect and increased the protective action of the pulp. Polycarboxylate cement with saturated potassium nitrate solution coating is recommended for clinical trials to treat occasional pulp denudation.

Hemodynamic abnormalities during coronary angiography: comparison of Hypaque-76, Hexabrix, and Omnipaque-350.

The hemodynamic effects induced by coronary angiography in dogs with low osmolar ionic dimer Hexabrix (HB) and nonionic Omnipaque-350 (OM) were compared to the standard ionic contrast medium, Hypaque-76 (H76), both in the normal heart and in one with simulated severe cardiac disease. Left coronary angiography was performed in 12 "normal" closed-chest dogs with 10-cc injections of H76, HB, and OM in a randomized, blinded fashion. The maximal change in the left ventricular (LV) systolic pressure (SP), mean aortic pressure (MAP), left ventricular end diastolic pressure (LVEDP), and LV dp/dt were recorded. The LVSP and MAP fell 30 +/- 3 mm Hg and 26 +/- 4 mm Hg with H76, 22 +/- 2 mm Hg and 19 +/- 2 mm Hg with HB, and 7 +/- 1.5 mm Hg and 5 +/- 1 mm Hg with OM (P less than .001). The LVEDP increased 4.8 +/- 0.5 mm Hg with H76, 3 +/- 0.5 mm Hg with HB, but only 0.2 mm Hg with OM (P less than .001). The LV dp/dt decreased 392 +/- 63 mm Hg/sec with H76 and 235 +/- 21 mm Hg/sec with HB, but increased 411 +/- 50 mm Hg with OM (P less than .001). In eight additional open-chest dogs, left coronary angiography was performed 1 hr after occlusion of the proximal LAD coronary artery and in the presence of a critical circumflex coronary artery (CX) stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential risk of thrombosis during coronary angiography using nonionic contrast media.

The influence of contrast media on coagulation has an important association with thromboembolic complication during coronary angiography. In this study, whole blood was methodically mixed with nonionic contrast medium, Iohexol (IOH), conventional ionic contrast medium, Hypaque-76 (H76), and low osmolar ionic dimer Hexabrix (HB) in vitro. The thrombotic propensity of contrast agents can be evaluated by measuring the clot formation of the mixtures. The experiments were repeated with whole blood after systemic heparinization. In the in vitro study, 5 ml of canine (N = 10) and 3 ml of human (N = 11) whole blood was incubated for 30 min in glass tubes with equal volumes of IOH, H76, HB, and 0.9% NaCl before heparinization. Clot formation with IOH and 0.9% NaCl were seen both in dogs (4.0 +/- 0.7 gm and 5.6 +/- 0.8 gm) and in patients (1.4 +/- 0.9 gm and 2.9 +/- 1.3 gm), whereas no clot was seen with H76 or XB. Following heparinization, no clot was visualized in any mixture of whole blood with contrast media or 0.9% NaCl. Similar results were observed in the catheter-syringe system with canine blood (N = 11) mixed with the contrast agents. Blood clots found in 15 min and 30 min of IOH were 0.07 +/- 0.08 gm and 0.44 +/- 0.20 gm (P less than 0.01) and of NaCl were 0.29 +/- 0.37 gm and 0.69 +/- 0.38 gm (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation enhancement of lung nodule formation in mice is not potentiated by treatment with a perfluorochemical emulsion and carbogen.

The ability of intravenously-injected mouse mammary tumor cells to form lung tumors is increased by irradiation of the thorax 24 h previously. We examined the effects of treatment with a perfluorochemical emulsion (Fluosol-DA, 20%) plus carbogen before and during irradiation on the radiation-induced enhancement of lung nodule formation. We found no evidence that treatment with Fluosol plus carbogen altered the development of tumor nodules in irradiated mouse lungs.

Effects of emulsified perfluorochemicals on liver cytochromes P-450 in rats.

1. The effects of intravenous (i.v.) injection of various perfluorochemical (PFC) emulsions or different fractions of the non-ionic poloxamer surfactant, Pluronic F-68, have been studied separately in male and female rats. 2. Injection of 10 ml/kg body wt of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding effect occurred in response to injection of Oxypherol (FC-43). 3. Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43. 4. Mean liver microsomal cytochromes P-450 concentrations in male rats were increased 2-3 fold at 72 hr after injection of either F-DA or the novel emulsion with a less pronounced increase also seen at 7 days in animals receiving the novel emulsion. No significant alterations in cytochrome concentration occurred in response to injection of FC-43 or either commercial grade or purified pluronic solution. 5. Liver cytochromes P-450 concentrations in female rats were unaffected by any of the experimental treatments. 6. These results show that injection of a single low dose of emulsified PFCs into male rats can increase hepatic microsomal cytochromes P-450 concentration but the response is highly variable, depending on composition of emulsion injected.

A screening method using tissue culture for evaluation of potential retinal adhesives.

Several adhesives have been tested for their potentially toxic effects on embryonic retinal tissue. The authors have characterized the effects of the adhesives on neurofilament extension and also on surgical-wound "re-knitting." While none of the adhesives in the sample (including those in current surgical use) seem to be ideal, the model advanced has application for the continuing development of better 'bio-adhesives'. The most immediate application is within the field of vitreoretinal surgery in situations where conventional procedures currently seem inadequate.

The pyrogenicity of pertussis vaccine in mice and the factors in the vaccine responsible for this effect.

The injection of whole cell pertussis vaccine into mice produced a biphasic fever reaction with two peaks appearing after about one and four hours, respectively. A method for the quantitative determination of each peak fever activity was developed and the factor responsible for each activity was investigated. The first and the second peak fever activities did not parallel each other in individual vaccines. The earlier fever activity appeared to correlate with endotoxin activity in individual vaccines while the later appeared to correlate with histamine-sensitizing factor (HSF) activity. The later peak fever activity was greatly reduced by heating the vaccine at 100 degrees C for 30 min while the first was little affected by such treatment. It was concluded that the fever activity of pertussis vaccine in mice may be ascribed to the combined actions of endotoxin and a heat-labile substance, possibly HSF.

[Experimental study of the antitumor properties and mechanism of action of kortifen]. / Eksperimental'noe izuchenie protivoopukholevykh svoistv i mekhanizma deistviia kortifena.

Cortiphen, a newly developed hormonal cytostatic ester of 11-desoxy-17 alpha-hydroxycorticosterone and chlorophenacyl, is described. It was studied in transplantable, spontaneous and induced tumors of 7 sites: hemoblastosis (5), hepatoma (3), mammary gland (5), lung (2), gastrointestinal tract (3), sarcoma (2) and melanoma. Practically all the tumors were shown to respond to cortiphen action. Among the antitumor effects of the drug were: long-term inhibition of tumor growth or tumor regression, contribution to longer survival, antimetastatic action and sustained action during repeated courses of administration. Cortiphen was found to interact with glucocorticoid receptors in both animal and human tumors. The role of the hormonal component of the drug's molecule in the realization of its antitumor effect is discussed.