Biomedical subjects
Publications and source records attributed to N A Semenova.
Magnetic resonance spectroscopy revealed structural modifications of human plasma lipoproteins during peroxidation induced by copper sulfate in vitro. Decreased molecular mobility of fatty acid chains in lipoprotein lipids was demonstrated.
The pool of low-molecular-weight metabolites was studied in patients with breast cancer by high-resolution 1H-NMR spectroscopy. In order to predict the efficiency of treatment, mathematical regression analysis was carried out with consideration for some clinical morphological characteristics of patients, chemotherapy protocols, and the degree of therapeutic pathomorphosis. The efficiency of drug therapy was largely determined by metabolic status of tumors in untreated patients with breast cancer.
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Disturbances of energy metabolism in rat brain after frontal lobectomy and post-traumatic effects of monosialic ganglioside GM1 on brain energy metabolism were studied by 31P NMR in vivo. Frontal lobectomy caused the statistically significant reversible decrease of ATP and increase of ADP during the compensatory period. In a presence of GM1 these post-operational effects were not observed. The mean value of normalized correlation coefficients between NMR-measured phosphomonoesters, P(i), pH, phosphocreatine, gamma-ATP + beta-ADP, alpha-ATP + alpha-ADP +NAD/NADH + diphosphodiesters and beta-ATP for a given group of animals (Z-index) was used to estimate brain energetic status. It has been shown that the variation of the Z-index correlates with the dynamics of locomotor activity during the compensatory period. The Z-index increased by more than 100% for the subgroup with an increased moving activity and only by about 20% for the subgroup with a decreased activity. Moreover, the compositions of these subgroups were almost the same as those from the solution of the reverse task, i.e., the studied group was divided into two subgroups by the Z-index. The Z-index is proposed as a possible criterion of pathology detection in brain energetics.
The role of fructose 2,6-bisphosphate in the interconversion of sedoheptulose 7-phosphate and sedoheptulose 1,7-bisphosphate in rat liver cytosol fractions was studied by means of phosphorus magnetic resonance spectroscopy. When the activity of 6-phosphofructo-1-kinase was inhibited by a high concentration of ATP, the addition of fructose 2,6-bisphosphate led to a marked decrease in sedoheptulose 7-phosphate levels, accompanied by an increased concentration of ADP. Fructose 2,6-bisphosphate essentially inhibited both the decrease in sedoheptulose 1,7-bisphosphate concentration and the accumulation of Pi in the incubation mixture. The data provided evidence that fructose 2,6-bisphosphate can regulate the substrate cycle: sedoheptulose 7-phosphate<-->sedoheptulose 1,7-bisphosphate in the liver, and thus control the flux through the nonoxidative stage of the pentose phosphate pathway.
Changes in relative levels of brain phosphates and intracellular pH at selected time intervals after total gamma-irradiation of a rat at a single dose of 6.5 or 300 Gy were studied by 31P NMR in vivo. Irradiation yielded only minor changes in the spectra. Irradiation at a dose of 6.5 Gy caused a reversible decrease in Pi and an alkaline pH shift of 0.2 units after day 1, with no change in ATP. The signal, which consisted of alpha-ATP, alpha-ADP, NAD+/NADH and diphosphodiesters, declined after day 6, possibly due to a fall in NAD+/NADH concentration. Irradiation at a dose of 300 Gy led to an increase in ATP from 10 to 13% of total phosphates after day 1. Homeostasis of brain energy metabolism was characterized by the Z-index (normalized sample correlation coefficients averaged over the correlation matrix for NMR-measured phosphomonoesters, Pi, pH, phosphocreatine, gamma-ATP+beta-ADP, alpha-ATP+alpha-ADP+NAD+/NADH+diphosphodiesters and beta-ATP). The Z value rose from -0.18 +/- 0.02 to -0.02 +/- 0.02 by day 6 or from -0.19 +/- 0.02 to -0.07 +/- 0.02 by day 1 after irradiation at a dose of 6.5 or 300 Gy, respectively. This may indicate a pathological state of brain energetics as a system and a decrease in its stability.
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The method of 31P nuclear magnetic resonance was used to study in vivo the level of phosphorus-containing metabolites in P388 leukemia cells sensitive or resistant to rubomycin (daunomycin) and its nitroxyl analog-emoxyl. It was shown that decreased content of phosphomonoesters (PME) is characteristic of the resistant strains in comparison with the parent cells. Rubomycin and emoxyl were established not to affect practically the pool of phosphorus-containing metabolites in the cells of the resistant strains, but caused considerable increase of PME level in the cells of the parent strain.
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The peculiarities of brain energy metabolism were studied in male rats before and during cerebral ischemia of various severity elicited by bilateral common carotid arteries ligation. A multidimensional analysis was applied. In the rats which died after the ischemia, the NAD + NADH+/phosphocreatine (PCr) ratio and ATP content before ligation were higher than those in the surviving group. Also the strength of relationships between parameters of NMR spectra in each correlation matrix were 10 times higher and the variability of elements in each matrix was significantly lower in victims than those in the surviving group. The development of severe ischemia and the animals death were accompanied by an increase in the inorganic phosphate content, decrease in pH and stepwise disappearing of PCr and ATP. In animals surviving the same brain ischemia model, the changes in 31P spectra parameters pointed to some increase in the ratio of NAD + NADH+ only to ATP + ADP but not to PCr, and to an increase in summarized strength of correlation between 31P spectra parameters with the variability of elements decreased within each correlation matrix. Detection of these changes can be helpful in the diagnosis of mild ischemia without neurological deficit which already needs preventive therapy against more severe ischemia.
Initial levels of phosphate brain metabolites were measured using 31P NMR spectroscopy in rats which subsequently died or survived under bilateral ligation of common carotid arteries. A multidimensional analysis was applied. In the rats which died after the brain ischemia: (1), NAD and NADH+ concentrations were much higher than those of creatine phosphate or ATP (i.e. baseline dysbalance existed between the systems of hydrogen acceptors and major macroergic substances); (2), the force of relationships between parameters of NMR spectra in each correlation matrix were 10 times higher and the variability of elements in each matrix was significantly lower than those of the surviving group. These regularities can be used in detection of special groups at high professional risk and in designing individual procedures of prevention and treatment of cerebral circulation disorders. The data are valuable in terms of development of drugs which would correct the dysbalance between hydrogen acceptors and macroergic systems thus providing a metabolic defense for the ischemic brain.
The method of 31P nuclear magnetic resonance has been used to study in vivo the level of phosphorus-containing metabolites in cells of two strains of murine leukemia P388 with the phenotype of the multidrug resistance and in cells of the parent strain. Cells of both resistant strains showed a depressed level of phosphomonoesters in comparison with the parent one. The influence of rubomycin and emoksil on the level of phosphorus-containing metabolites of drug-resistant and -sensitive strains has been evaluated. The drugs were established not to affect practically the pool of these metabolites of the resistant strains. Both drugs significantly increased the pool of phosphomonoesters in the parent strain cells.
A technique of 7-day formation of an intramuscular abscess which is clinically and morphologically similar to that frequently encountered in clinical practice has been tried on 39 rabbits. The standard model proposed involves the following stages: trauma of the spinal erector 2.5-3 cm to the right or to the left from the midline between the second and fourth lumbar vertebra which is produced by a lumbar puncture under either anesthesia with a pulp extractor brought into the muscle up to 1.5 cm and rotating at an angle of 45 degrees; 24 h after the puncture the skin at its site is to be dissected involving subcutaneous fat, superficial and lumbar fasciae, the incision being 1.4-1.6 cm long and parallel to the body axis. The operation is terminated with an introduction of ribbon gauze (10-12 mm in diameter) previously saturated with 24 h suspension culture of staphylococcus (10 ml, concentration of the microorganisms 1.5.10(6] into a pocket made by the clamp tip in the muscle's depth (1.3-1.6 cm) with the help of the handles which produced the opening of 1.2 cm wide. The endpoint is the wound tight layer-by-layer suture.
Twenty rabbits and fourty male rats were used for the development of the autodermoplasty model: two symmetrical semilunar skin incisions, turned to one another, with 1 cm space between the ends of the arches, were made on the back of the animal. The skin with subcutaneous fat was exfoliated from above the muscular tissue in the area between the incisions. Elastic arched net-shaped fluoroplastic plate, matching to the size of the exfoliated skin graft and raising it 1.5 cm above the wound surface was introduced into the cavity emerged. As soon as any method of wound surface purification was used, the plate was removed and the the skin graft above (conditional autodermograft) was applied and fixed to the edges of the wound with 4 interrupted sutures. It was stated that the model used for testing various methods of preparing the wound surface for autodermoplasty not only decreased the duration of experiment and the number of animals employed but cut their keeping and dressing expenditures.