ABSTRACT
We described specific MRI features of MS presenting with acute partial transverse myelopathy. We reviewed the clinical histories and MRI studies of brain and spinal cord of 24 patients, using axial and sagittal images of the spinal cord to define patterns of signal abnormality in the context of clinical presentation, course, and vertebral column structural pathology. The heterogeneity of spinal cord tract involvement was greater than previously reported, with signal abnormality identified within the central cord, crossing the gray-white junction, and involving all four major funiculi. Correlation between spinal cord MRI findings and neurologic deficits was strong (100% by axial images; 96% by sagittal images). Serial spinal cord MRI demonstrated the dynamic nature of the signal abnormalities over time and in response to high-dose steroid treatment. No cranial MRI abnormality initially was seen in 36% of cases with evidence of demyelinating disease on concurrent spinal MRI.
Subject(s)
Magnetic Resonance Imaging , Multiple Sclerosis/diagnosis , Multiple Sclerosis/physiopathology , Spinal Cord Diseases/diagnosis , Adult , Child , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Retrospective Studies , Spinal Cord/pathologyABSTRACT
Seven derivatives of 2-methyl-1,4-naphthoquinone were compared to an equivalent series of 6-methyl-1,4-naphthoquinone derivatives for their abilities to interact with mitochondrial membranes and enzyme systems. The substituents on the methyl groups included various electron-withdrawing and -donating groups. The 6-methyl quinones were, in general, more potent inhibitors of NADH-oxidase and succinoxidase, depleted sulfhydryl groups more completely, produced greater rates of cyanide (CN-)-insensitive respiration (respiratory bursts), and induced more severe large-amplitude mitochondrial swelling than the analogous 2-methyl quinones. The NADH-oxidase system was more sensitive than succinoxidase to inhibition by both series, suggesting that Complex I is the primary site of inhibition by these quinones.
Subject(s)
Mitochondria, Heart/drug effects , Naphthoquinones/pharmacology , Animals , Antineoplastic Agents/pharmacology , Cattle , Cyanides/pharmacology , In Vitro Techniques , Mitochondria, Heart/metabolism , Mitochondrial Swelling/drug effects , Multienzyme Complexes/antagonists & inhibitors , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Naphthoquinones/toxicity , Oxidoreductases/antagonists & inhibitors , Oxygen Consumption/drug effects , Structure-Activity RelationshipABSTRACT
The physicochemical properties of a series of 1,4-naphthoquinones were correlated with their activities against Sarcoma-180 by Hodnett et al. [J. med. Chem. 26, 570 (1983)]. Redox potential was the most important molecular parameter determining antitumor activity in this series of compounds, suggesting that interference with electron transport contributes to their cytotoxicity. We evaluated this same series of quinones for their abilities to inhibit the beef heart mitochondrial succinoxidase and NADH-oxidase enzyme systems. They exhibited a broad range of inhibitory potencies. There was a strong relationship between succinoxidase inhibition, antitumor activity (T/C ratio), and redox potential. The redox potentials of the quinones which inhibited succinoxidase lay within the narrow range of endogenous components of the respiratory chain. In contrast, inhibition of NADH-oxidase was related to redox potential but did not significantly predict antitumor activity. These results suggest that inhibition of mitochondrial succinoxidase may be a useful preliminary screen for antitumor activity.
Subject(s)
Mitochondria, Heart/drug effects , Naphthoquinones/pharmacology , Animals , Cattle , Multienzyme Complexes/antagonists & inhibitors , Multienzyme Complexes/metabolism , NADH, NADPH Oxidoreductases/antagonists & inhibitors , NADH, NADPH Oxidoreductases/metabolism , Oxidation-Reduction , Oxidoreductases/antagonists & inhibitors , Oxidoreductases/metabolism , Oxygen Consumption/drug effects , Structure-Activity RelationshipABSTRACT
UNLABELLED: Glomerular filtration rate (GFR) is an important index of renal function. Twenty-four-hour creatinine clearance overestimates GFR in patients with poor renal function. Inulin and iothalamate clearances are accepted reference standards for determining GFR but are expensive and laborious. We have previously reported that GFRs obtained by measuring the disappearance of 99mTc-DTPA from ultrafiltered (protein-free) samples of plasma were virtually identical to those obtained by the iothalamate method. However, the subjects used in that study had normal to only moderately decreased renal function. METHODS: The accuracy of measuring GFR by plasma clearance of 99mTc-DTPA was determined in subjects where renal function varied from normal to severely impaired. In all subjects, GFR was established by clearance of 125I-iothalamate from urine and serum and was used as the standard of reference. RESULTS: For subjects with normal to moderately diminished renal function (GFR > 20 ml/min), the correlation between values of GFR obtained by the DTPA and iothalamate methods was high (n = 18, r = 0.966). The difference between the pairs of GFR values obtained by the two methods was not statistically significant (p > 0.1). In patients with severe renal insufficiency (GFR < 20 ml/min), the correlation between the DTPA and iothalamate methods was poor (n = 11, r = 0.236), and the GFR values obtained by the two methods were statistically different (p < 0.01). CONCLUSION: These results suggest that GFR can be determined accurately by plasma clearance of 99mTc-DTPA in all patients except those with severe renal insufficiency.