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M R Montgomery

Publications and source records attributed to M R Montgomery.

69 records · Page 4Linked to original sources
PubMed1975

Determination of diphenylhydantoin in human serum by spin immunoassay.

A spinn immunoassay for diphenylhydantoin is reported, which appears to give an accurate and precise estimate of serum diphenylhydantoin concentrations, as judged by the disappearance of [14C]diphenylhydantoin from the serum of a rabbit. The assay also appears to be a reliable technique for routine diphenylhydantoin determinations, as judged from our experience with 28 patients. Serum diphenylhydantoin concentrations in the range of 1.0-50.0 mg/liter are easily determined on a 50-mul sample. Except for primidone, no significant cross reactivity was observed with eight drugs that are commonly used in conjunction with diphenylhydantoin therapy. This fast, simple, and precise method therefore appears to be readily applicable to routine determination of diphenylhydantoin.

Animals↗
PubMed1975

Application of electron spin resonance to determination of serum drug concentrations.

Displacement of spin-labeled drugs from drug-specific antibodies in human serum can be measured by use of electron spin resonance. This "spin immunoassay" has advantages of speed, simplicity, and small volume requirements over other standard techniques such as gas-liquid, liquid-liquid, or thin-layer chromatography. Unlike radioimmunoassay, there is no need to separate free and bound label and there are no radiation hazards. We present clinical and experimental data showing how this method can be applied to the routine determination of morphine and diphenylhydantoin concentrations in serum.

Antigen-Antibody Reactions↗
PubMedDate not supplied

Impairment in pulmonary bioenergetics following chlorphentermine administration to rats.

Biochemical alteration in pulmonary oxidative metabolism and morphological integrity of lung mitochondria were examined in rats following administration of chlorphentermine (30 mg/kg, ip, 5 days per week) for 1 or 2 weeks. During the first week of treatment, body weight gain and food intake were decreased markedly but returned to control levels during the second week. Phospholipid content of the lung was increased 31% and 110% after 1 and 2 weeks of treatment, respectively. This was accompanied by a striking intraalveolar accumulation of hypertrophic alveolar macrophages. The metabolism of both (1-14C)- and (6-14C)-glucose was decreased 27% and 26%, respectively, after 2 weeks of drug treatment. In rat lung mitochondria, chlorphentermine significantly lowered the RCR and ADP/O ratio and stimulated state 4 respiration. State 3 respiration and uncoupled state respiration were unaffected. These data indicate that chlorphentermine functions as a true uncoupler of oxidative phosphorylation when administered in vivo. Furthermore, disruption of mitochondrial membranes was observed frequently in lung mitochondria from treated animals. These combined data indicate that the induction of pulmonary phospholipidosis by chlorphentermine is accompanied by marked alterations in subcellular bioenergetics and mitochondrial structure.

Animals↗
PubMedDate not supplied

Biochemical and morphological correlation of oxidant-induced pulmonary injury: low dose exposure to paraquat, oxygen, and ozone.

The authors compared the temporal pattern of low-dose oxidant-induced lung injury in rats after exposure to either 1 ppm ozone or 100% oxygen for 24 hr or from treatment with paraquat (20 mg/kg, intraperitoneally). Histological abnormalities in airways, parenchyma, and blood vessels were evaluated from coded and randomized sections and compared with appropriate controls. Drug metabolism by lung endoplasmic reticulum was studied in similarly treated rats as another index of lung injury. Exposure to oxygen caused no discernible morphological or biochemical abnormalities. Exposure to ozone caused histological lesions which appeared early and resolved by 7 to 14 days, whereas paraquat-induced lesions were first evident at about 7 to 14 days. Abnormalities in drug metabolism followed a similar pattern. Low-dose oxidant exposure from ozone and paraquat produce similar histological and biochemical lesions in rat lungs but with distinct temporal patterns.

Animals↗
PubMedDate not supplied

Severe acute oxidant exposure: morphological damage and aerobic metabolism in the lung.

Groups of male rats were exposed to acute doses of oxygen, ozone, or paraquat which produced equivalent mortality (25-30%) over a 28 day post-exposure period. Quantitative evaluation of morphological changes indicated the primary response to be edema and inflammation with only slight fibrosis being apparent by the end of the observation period. Aerobic pulmonary metabolism was inhibited in lungs from animals exposed to oxygen and ozone as evidenced by decreased oxygen consumption; however, this was transient and O2 consumption returned to normal within 24 hours after removal from the exposure chamber. Conversely, treatment with paraquat caused an immediate, transient stimulation of O2 consumption. Glucose metabolism was unaltered by the gas exposures and, as previously reported, was initially stimulated by paraquat treatment. In vitro, only paraquat altered both O2 consumption and glucose metabolism when added to lung slice preparations; ozone had no effect. Oxygen did not alter O2 consumption but caused a slight biphasic response in glucose metabolism. Aerobic metabolism is relatively unchanged by these doses of oxygen and ozone which result in the death of 25-30% of all treated animals. Even though paraquat produces similar morphologic changes, it may represent a more severe metabolic insult than "equivalent" doses of oxygen or ozone. Also, if interstitial pulmonary fibrosis is a desired result of experimental exposure, rats may not be a suitable model for oxidant induced lung injury.

Aerobiosis↗
PubMedDate not supplied

The relationship between paraquat accumulation and covalent binding in rat lung slices.

The accumulation and covalent binding of paraquat in rat lung slices were both linear for 6 hr in room air incubations. Binding continued to increase in slices transferred to paraquat-free buffer after 3 hr of incubation in paraquat although accumulated paraquat decreased. Binding in 100% O2 was decreased slightly. Active accumulation in 100% N2 did not occur, but binding proceeded at one-third the rate observed in room air. Ascorbate decreased accumulation in room air, although binding was unaffected. Reductants had no effect on binding in 100% nitrogen. Paraquat binding in slices of various organs was in the order of lung greater than liver greater than heart greater than kidney cortex. Mitochondrial proteins were found to have the highest concentration of bound paraquat in lung slices followed in order by microsomal protein greater than nuclear protein = cytosolic protein. The binding of paraquat is postulated to involve a reduced species, presumably the monovalent radical.

Animals↗
PubMedDate not supplied

Disposition of the pulmonary toxin, bleomycin.

The disposition of bleomycin in rats was investigated with the use of a 57Co-labeled bleomycin radioimmunoassay. Bleomycin (1 mg/kg, ip) reached a peak serum level of 0.7-1.0 microgram/ml in 54 +/- 4 min (mean +/- SE) and was eliminated with a t 1/2 of 32 +/- 1 min. The apparent volume of distribution in rats was 184 +/- 11 ml/kg. No change in t 1/2 was observed when rats were pretreated with phenobarbital (1 mg/ml in drinking water for 4 days) or exposed to ozone (3 ppm, 24 hr). Probenecid (0.2 g/kg, ip) given 20 min prior to bleomycin administration increased the t 1/2 2-fold. The order of tissue distribution of 57Co-labeled bleomycin 2 hr after ip administration was: kidney greater than liver greater than lungs greater than spleen greater than heart greater than thymus. The affinity of 57Co-labeled bleomycin for homogenates of lungs, liver, or kidney was equal.

Animals↗