TAMI-77. CHARACTERIZATION OF METABOLIC DIFFERENCES IN MENINGIOMAS USING TUMOR TISSUE AND PATIENT-DERIVED CELL LINES

As more information emerges on metabolic changes in brain pathologies, mass spectrometry methodologies are needed to investigate cellular changes in primary brain tumors. Many approaches use technologies that lack sensitivity and selectivity, which hinders discovering potential novel diagnostic and prognostic features. Fresh frozen tissue from 26 patients (57% women, 43% men, age 21-67) underwent surgical resection for newly diagnosed meningiomas. We used patient-derived cell lines and arachnoid cells to validate and compare metabolic differences in patient tumor tissue. Primary metabolism (GC-TOF), lipidomics, and biogenic amines (RPLC and HILIC-HRMS) were analyzed using 10 mg of tissue and 1x106 cells. RESULTS: Primary metabolism and lipidomics showed significant differences between Grade I and Grade II tumors. We identified over one thousand total metabolites through authentic standards and MS2 fragmentation patterns. Ascorbic Acid was enriched in Grade I tumors compared to Grade II and enriched in tumors compared to non-neoplastic dura tissue from the same patient. Lysosomal activation in atypical meningiomas is indicated by a 2-fold increase (compared to Grade I tumors) of Bis(monoacylglycero)phosphate metabolites. We grouped metabolites into fifteen classes based on chemical ontology and function. Statistically significant differences were observed in total amino acids (AA), basic AA, cyclic AA, sulfur-containing AA, branched-chain AA, dipeptides, histidine-containing dipeptides, vitamins and cofactors, glutathione metabolites, acylcarnitine’s, sphingomyelins, phosphatidylethanolamines, phosphatidylinositol’s, cardiolipins, and nucleic acids. Thymine-containing nucleic acids and biogenic monoamines were 2-fold higher in Grade I compared to Grade II tumors. Using novel untargeted metabolomics, we found multiple classes of metabolites that were enriched in Grade II meningiomas compared to Grade I. This points towards possible pathways that drive malignancy and biomarkers that could be useful for diagnosis, grading, and treatment selection.

A PROSPECTIVE RANDOMIZED STUDY OF COMPARISON OF PROPHYLACTIC KETAMINE, CLONIDINE AND TRAMODOL FOR THE CONTROL OF SHIVERING UNDER NEURAXIALANAESTHESIA

Background: Thermoregulatory system coordinates defenses against environmental temperature to maintain internal core temperature within a narrow range, thus optimizing normal body function and homeostasis in humans. Anaesthetic induced thermoregulatory impairment and hence hypothermia in cold environments. Shivering is an important complication of hypothermia. Shivering is an involuntary, oscillatory muscular activity that augments metabolic heat production upto 600% above basal level to increase temperature. It is associated with substantial adrenergic activation, discomfort and can double or even triple oxygen consumption and carbon dioxide production. Potent anti-shivering properties have been attributed to numerous drugs including biogenic monoamines, cholinomimetics, cations, endogenous peptides and possibly N-methyl-D- aspartate (NMDA) receptor antagonists like ketamine, tramadol and clonidine. Aim: To evaluate the effectiveness of prophylactic use of intravenous ketamine, clonidine and tramadol in control of shivering and to note any side-effects of the drugs used. Methods: A total number of 120 ASA I and 2 patients of either sex belonging to age group 18-60 years posted for Lower Abdomen and Lower Limb surgeries under subarachnoid block were divided into four groups of 30 each. Group P (control group): Patients received 10mL of normal saline IV as placebo. Group K: Patients received Inj. Ketamine 0.5mg/kg BW IV diluted to 10ml in Normal Saline. Group C: Patients received Inj. Clonidine 75mcg IV diluted to 10ml in Normal Saline. Group T: patients received Inj. Tramadol 0.5mg/kg BW IV diluted to 10ml in normal saline. Results: We conclude that giving Ketamine 0.5mg/kg,Clonidine 75mcg or tramadol 0.5mg/kg i.v. prophylactically just before subarachnoid block significantly decreased the incidence of shivering without causing any major side effects. Conclusion: Ketamine, Tramadol or Clonidine decrease shivering during spinal anesthesia.

Neurotransmitter changes in the rat brain under combined intoxication induced by alcohol and morphine

We investigated the levels of biogenic monoamines and their metabolites in the rat hypothalamus, midbrain and cerebellum in acute complex intoxication with morphine and alcohol. The distinctive features of neurotransmitter disorders in various parts of the rat brain under a single exposure to ethanol and morphine, as well as the differences between acute morphine-alcohol and alcohol-morphine intoxication were established. Complex intoxication with alcohol and morphine resulted in signs of dopamine consumption only in the hypothalamus, regardless of the order of alcohol and morphine administration. Under conditions of alcohol-morphine intoxication an increase in the level of metabolites of the serotonergic system was noted in the investigated parts of the brain. In the midbrain and cerebellum the manifestation of combined action of ethanol and morphine is mainly determined by the effect of the last of the administered substances. There are features of changes in the indices of the dopaminergic and serotonergic systems in these experimental conditions, confirmed by the processes of dopamine catabolism and a decrease in the norepinephrine and serotonin concentration in the hypothalamus, which are not observed under individual action of ethanol and morphine.

THE ACID-BASE PROCESSES' CHANGES IN THE BODY OF WHITE RATS UNDER THE INFLUENCE OF NITROGEN-CONTAINING SURFACE-ACTIVE MATERIAL

Relevance. Everyday contact of the population with surfactants (SAS) in drinking water poses the problem of timely and prompt substantiation of pre-nosological highly sensitive indicators of early manifestations of biological activity of detergents and operational control over the health of the population and the environment. But today the mechanisms of biotransformation, toxicodynamics, toxicokinetics, and metabolic processes that underlie the formation of structural and metabolic disorders when exposed to a surfactant, taking into account possible long-term effects, have not yet been fully elucidated. Objective: to investigate the effect of nitrogen-containing surfactants on redox processes in the body of experimental animals. Materials and methods. The experiments were carried out on 620, and acute experiments on 128 white rats (weight 180-220 g). We used four ionic nitrogen-containing surfactants with specified technical and physicochemical characteristics: FOM 9, FOM 9-4, FOM 9-12, and FOM 9-20. Doses were chosen so as to determine the lethal effect in the lethal dose (LD) range from 0 to 100. The LD50 was calculated. The substances were introduced into the stomach in pure form using a metal probe. The animals were observed for up to 15 days. The time of death of the animals and the total amount of the introduced substance was recorded. The animals were subjected to postmortem examination. Redox processes were qualitatively assessed by the activity of enzymes: cholinesterase, cerulose plasmin, lactate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, peroxidase, catalase, cytochrome oxidase, by the content of SH-groups in the blood, by the concentration of biogenic monoamines. Results. Nitrogen-containing surfactants caused a change in peroxidase activity both upwards and downwards. In all cases, 1/1000 LD50 was inactive. On the 15th day of the experiment, neonol FOM 9-12 reduced the activity of the enzyme, and other substances did not affect it. By the end of the subacute experiment, neonol FOM 9-4 and neonol FOM 9-12 were reduced, and neonol FOM 9-20 increased peroxidase activity. A similar effect was on the activity of catalase: in all groups, except 1/1000 LD50, on day 30 there was a decrease in its activity. Cholinesterase activity increased. For the content of SH-groups in the blood on the 15th day, there was a tendency to decrease, which turned into significant differences on the 30th day in 1/10 LD50. The effect of 1/100 and 1/1000 LD50 did not violate the content of SH-blood groups. A similar effect was on the content of glutathione in the blood. In a subacute experiment, in groups, 1/10 and 1/100 LD50, the content of norepinephrine, tryptophan, serotonin in the liver increased and DOPA and dopamine decreased. The dynamics of adrenaline did not change. The content of dopamine and norepinephrine increased to a lesser extent in the brain; DOPA and adrenaline did not differ from the control; tryptophan increased only under the influence of FOM-9. 1/1000 LD50 did not affect the dynamics of the content of biogenic monoamines. The tested drugs have a similar effect on the body. Conclusions. A more toxic substance in a subacute experiment is FOM-9. The severity of violations in the dynamics of monitoring the activity of enzymes has a close dose-dependence. The effective dose is set at 1/10, the threshold – 1/100, and the inactive – 1/1000 LD50. Common features of the biological action of nitrogen-containing surfactants are the violation of redox processes, bioenergy, oxidative phosphorylation, which under appropriate conditions lead to the pathology of vital organs, functions, and systems of the body.