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Biomedical subjects

E R Block

Publications and source records attributed to E R Block.

At least 109 records · Page 6Linked to original sources
PubMed1978

Prevention of acute paraquat toxicity in rats by superoxide dismutase.

Paraquat is a widely used herbicide which causes lung injury in man characterized by progressive parenchymal damage that may lead to fatal respiratory failure. The precise mechanism of injury is unknown but is related to the cyclic oxidation and reduction of paraquat in cells with resultant production of free radicals of oxygen. In this study, superoxide dismutase (SOD), an enzyme that catalyzes the dismutations of superoxide free radical (O2-) to less toxic forms, plus reduced glutathione (GSH), and d-propranolol (PROP), were evaluated for their ability to protect against acute paraquat toxicity. Rats maintained at room air were given 50 mg paraquat dichloride/kg body weight in a single intraperitoneal (IP) injection 60 min prior to receiving either 0.2, 2, 10, or 20 mg/kg/d SOD, 3.6, 7.2, or 14.4 mmol/kg/d GSH, 2 or 20 mg/kg/d PROP, or an equal volume of normal saline (controls) LP. in divided doses for 3 d. SOD significantly prolonged and increased survival at doses of 2, 10, or 20 mg/kg/d (p less than 0.05). In addition, histologic lung morphology in SOD-treated rats showed only minimal intra-alveolar hemorrhage and hypercellularity 24, 48, and 168 h after paraquat challenge. Treatment with GSH, PROP or 0.2 mg/kg/d SOD was not protective. Duration of survival, percent survival, and lung morphology in these groups were not significantly different from controls. These results indicate that a) SOD protects against the development of acute paraquat toxicity in rats, b) one mechanism of paraquat poisoning is increased biologic production of O2-, and c) SOD may have a role in the therapy of paraquat poisoning in man.

Animals↗
PubMed1978

Effect of hyperoxia on imipramine uptake and metabolism by the isolated, perfused rat lung.

Imipramine (IMP) is a biologically active amine which is removed from the circulation by the lungs. We evaluated the effect of high partial pressures of O2 on pulmonary uptake and metabolism of IMP. Lungs from rats previously exposed to either air (controls) or 100% O2 at 1 ATA for 12-48 hr were isolated, ventilated and perfused via the pulmonary artery. Uptake of IMP was calculated from the arteriovenous difference of 14C-IMP across the lung and lung effluents and homogenates were analyzed for the presence of metabolites of IMP. IMP was avidly concentrated in the lungs of control rats by a saturable process, and this saturable uptake was not affected by 12-48 hr exposure to 100% O2. 14C-IMP was not metabolized by control of O2-exposed lungs.

Animals↗
PubMed1977

Massive hemothorax complicating heparin anticoagulation for pulmonary embolus.

A case of massive hemothorax complicating heparin anticoagulation for pulmonary thromboembolism is presented. Hemothorax complicating anticoagulant therapy for PTE usually occurs within the first week of treatment and is invariably on the side of the initial clinical symptoms, suggesting intrapleural rupture of a hemorrhagic pulmonary infarct. Late hemothorax is unusual and may not be on the side of the initial symptoms, suggesting a different pathogenesis. Hemothorax may occur as the only bleeding complication of anticoagulation and when coagulation studies are within an acceptable therapeutic range. Cessation of anticoagulation therapy and prompt evacuation of the pleural space are recommended.

Hemothorax↗
PubMed1977

Depression of serotonin clearance by rat lungs during oxygen exposure.

The effect of oxygen (O2) exposure on the ability of the isolated, perfused rat lung to clear serotonin (5-hydroxytryptamine, 5-HT) from the perfusate was evaluated in normal or vitamin E-deficient Sprague-Dawley rats. Rats were exposed to 100% O2 at 1 ATA for 4-48 h. Lungs were subsequently isolated, artificially ventilated, and perfused in a recirculating system with Krebs-Ringer bicarbonate solution, pH 7.4 containing 3% bovine serum albumin and 0.25 muM [14C] 5-HT. 5HT clearance was calculated from the disappearance rate of [ 14C] 5-HT from the perfusate. In normal rats exposed to 100% O2, there was a progressive reduction in the clearance of 5-HT with increasing duration of O2 exposure. Compared to lungs from air-exposed controls, clearance was depressed 20% (P less than 0.01) after 18 h, 22% (P less than 0.01) after 24 h, and 35% (P less than 0.001) after 48 h. With vitamin E-deficient rats, the reduction in 5-HT clearance occurred after a shorter exposure time and was of greater magnitude than in rats on a normal diet. Depression of 5HT clearance by the lungs is an early alteration of lung function fue to hyperoxia and is potentiated by vitamin E deficiency. The most likely mechanism for the depression of 5-HT clearance is interference with the transport properties of lung endothelium.

Animals↗
PubMed1977

Effect of hyperbaric oxygen exposure on pulmonary clearance of 5-hydroxytryptamine.

Clearance of 5-hydroxytryptamine (5-HT) by the lungs of normal and vitamin E-deficient rats was evaluated following a 60-min exposure to 100% oxygen (O2) at 4 ATA (HBO). After exposure, lungs were isolated, ventilated, and perfused, with a recirculating system used for measurement of 5-HT clearance. Control lungs were obtained from rats exposed to air at 1 ATA. In control normal rats, fractional clearance of 5-HT was 0.78+/-0.03 (mean+/-SE). Following HBO 5-HT clearance was 0.55+/-0.04 (P less than 0.01). In control vitamin E-deficient rats. 5-HT clearance was 0.85+/-0.05 and was decreased to 0.46+/-0.03 (P less than 0.001) following HBO. To evaluate the effect of recovery time after HBO on 5-HT clearance, separate groups of rats were killed at varying intervals post-HBO. In normal rats, 5-HT clearance had returned to control levels by 3-4 after HBO; in vitamin E-deficient rats, clearance remained unchanged 4 h after HBO and was only 74% (P less than 0.001) of control values 24 h post-HBO. These results indicate that depression of pulmonary 5-HT clearance occurs in rats due to hyperoxia and is potentiated by vitamin E deficiency. This represents a reversible alteration of lung function which requires vitamin E for complete recovery.

Animals↗
PubMed1977

Effect of superoxide dismutase and succinate on the development of hyperbaric oxygen toxicity.

Prolonged exposure to hyperbaric O2 (HBO) causes seizures and eventual death. The precise molecular basis for O2 toxicity is not known but may be due to increased biological production of superoxide anion (O2-). In the present study, superoxide dismutase (SOD), an enzyme that catalyzes the dismutation of O2- to less toxic forms, was evaluated for its ability to protect against HBO-induced seizures and death, and the results were compared to those concurrently obtained with succinate (SUCC), an agent previously reported to protect against HBO-induced seizures. Preconvulsion time and survival time in normal and vitamin E-deficient rats exposed to 100% O2 at 5 ATA were not significantly prolonged by pretreatment with 2 to 20 mg/kg SOD intraperitoneally (ip) or 0.1 to 1.0 mg/kg SOD intrathecally. In contrast, 12 mmol/kg SUCC ip significantly prolonged preconvulsion time in normal and vitamin E-deficient rats and survival time in normal rats. The ability of SUCC to stimulate ATP production may account for its protective role. Reasons for the failure of SOD to protect against O2 toxicity are discussed.

Animals↗
PubMed1974

5-fluorocytosine and amphotericin B in bronchial secretions.

The penetration into and clearance from bronchial secretions of 5-fluorocytosine and amphotericin B were studied in a dog model. After a single intravenous dose of 35 mg/kg, 5-fluorocytosine intrabronchial concentrations were greater than the minimal inhibitory concentration for 80 to 90% of Candida species. These inhibitory concentrations persisted up to 3 h. In contrast, amphotericin B in intravenous doses of 0.6 and 1.2 mg/kg penetrated the blood-bronchus barrier poorly.

Amphotericin B↗
PubMed1973

Experimental therapy of cladosporiosis and sporotrichosis with 5-fluorocytosine.

Cladosporium trichoides and Sporothrix schenckii are fungi known to be pathogenic for man. No effective chemotherapy is available for cladosporiosis, and systemic sporotrichosis can be very resistant to antifungal chemotherapy. Experimental infections of mice with these fungi resembled their respective infections in man and provided a model for evaluating a new antifungal agent, 5-fluorocytosine (5-FC). Our results with four isolates of C. trichoides demonstrated a statistically significant dose-related therapeutic effect with 5-FC. Mortality was significantly reduced in all treatment groups, and survivors showed no clinical sign of disease despite positive brain cultures. Results with a single isolate of S. schenckii were less encouraging. Fatality rate was significantly decreased in all treatment groups, but no trend was noted with increasing 5-FC dosage. Survivors manifested the signs of active disease, and all liver and spleen cultures were positive for S. schenckii. These results indicated that (i) 5-FC may be the first drug useful in the treatment of cladosporiosis, and (ii) 5-FC may have only limited therapeutic benefit in systemic sporotrichosis.

Animals↗
PubMed1973

5-fluorocytosine resistance in Cryptococcus neoformans.

Isolates of Cryptococcus neoformans from six patients were obtained before and after unsuccessful therapy with 5-fluorocytosine (5-FC). Post-therapy isolates exhibited massive and stable 5-FC resistance. The frequency of drug-resistant mutants in susceptible isolates of C. neoformans was <0.001% (70.4 +/- 17.9 per 10(7) cryptococci), whereas mutant frequencies in resistant isolates approached 100%. Non-drug-induced, spontaneously appearing 5-FC resistant mutants were documented in four susceptible isolates of C. neoformans by use of the statistical method of fluctuation analysis. Mutation rates on these same four isolates ranged from 1.2 x 10(-7) to 4.8 x 10(-7). Total intracellular uptake and incorporation of cytosine-5-(3)H (CyH(3)) and 5-fluorocytosine-2-(14)C (5-FC(14)) into a trichloroacetic acid-insoluble fraction were markedly reduced in six isolates with in vivo-acquired resistance when compared with susceptible pretreatment strains from the same patients. Five of these six isolates also had acquired massive resistance to 5-fluorouracil (5-FU), suggesting that a mutation in the uridine-5'-monophosphate pyrophosphorylase was responsible for drug resistance. The sixth isolate, which remained susceptible to 5-FU, appeared to have a defect in a cytosine-specific permease accounting for 5-FC resistance. A single isolate with in vitro-acquired 5-FC and 5-FU resistance had no reduction in uptake or incorporation of CyH(3) or 5-FC(14). The mechanism of resistance in this isolate is discussed.

Antifungal Agents↗
PubMed1973

Variables influencing susceptibility testing of Cryptococcus neoformans to 5-fluorocytosine.

The minimum inhibitory concentration (MIC) of 5-fluorocytosine (5-FC) was determined for 65 isolates of Cryptococcus neoformans by using a twofold serial tube dilution method. The MIC was profoundly influenced by incubation temperature, inoculum size, and duration of incubation. By using a standard set of test conditions, 100% of 49 pretreatment isolates of C. neoformans were susceptible to 10 mug of 5-FC per ml or less, and 9 (56%) of 16 isolates recovered during or after 5-FC therapy were massively drug resistant (MIC > 320 mug/ml). With the standard test conditions recommended here, the tube dilution method was found to be both accurate and reproducible, and the results correlated with the treatment status of patients.

Antifungal Agents↗
PubMed1973

Stability of amphotericin B in infusion bottles.

Intravenous solutions of amphotericin B in 5% dextrose water with or without hydrocortisone or heparin demonstrated no appreciable loss of activity when exposed to fluorescent light for up to 24 h at 25 C (room temperature).

Amphotericin B↗