Papers by T-L Mandalian
Journal of Comparative Pathology, 2020
Introduction: Although pain is traditionally considered to be mediated by neurons, recent researc... more Introduction: Although pain is traditionally considered to be mediated by neurons, recent research has shown the important roles of glial cells in pain sensation. Microglial cells have been implicated in such processes, but less is known about the role of astrocytes. Astrogliosis is recognized as a defence reaction, conceivably aimed at limiting tissue damage and restoring homeostasis. This study aimed to assess the expression of glial fibrillary acidic protein (GFAP) in astrocytes from the frontal cortex, hypothalamus and periaqueductal grey matter (PAG) after administration of short-term doses of distinct drugs used for pain management, but without painful stimuli. Materials and Methods: Male Wistar rats received amitriptyline (Amt, 10 mg/kg/day) or gabapentin (Gb, 60 mg/kg/day) for 10 days, by gavage or via the intraperitoneal route, methadone (Me, 4.5 mg/kg/day), morphine (Mo, 10 mg/kg/day), carbamazepine (Cbz, 40 mg/kg/day), fluoxetine (Flx, 10 mg/kg/day), amantadine (Ama, 10 mg/kg/day), S-ketamine (Ke, 50 mg/kg/day), dipyrone (Dip, 16 mg/kg/day) or 0.9% saline solution (daily). Brain samples were collected for GFAP immunohistochemical investigation in the frontal cortex, hypothalamus and PAG. Results: Morphometric analysis showed that all drugs increased GFAP expression and astrocyte size in the frontal cortex and hypothalamus in relation to the saline group. In the PAG this expression was increased in the groups treated with Amt, Me, Mo, Ama, Flx and Ke, but not with Gb, Cbz and Dip. Discussion: Although the precise meaning of such changes remains unclear, astrocytes appeared to react phenotypically to distinct classes of pain modulators in almost all investigated areas, probably influencing neurons and the entire neural microenvironment.
A series of three formulations were prepared in view of experimental and theoretical investigatio... more A series of three formulations were prepared in view of experimental and theoretical investigation of their drug release potential. The morphology of the film formulations, in terms of distribution of drug into the polymeric matrix and the nature of the drug was investigated by scanning electron microscopy and polarized light microscopy techniques. The in vitro drug release has been studied in a medium mimicking the physiological medium. It was established that the drug release is in close correlation with the mass ratio. Assuming that the dynamics of polymer-drug system's structural units take place on continuous and nondifferentiable curves (multifractal curves), we show that in a one-dimensional hydrodynamic formalism of multifractal variables the drug release mechanism (Fickian diffusion, non-Fickian diffusion, etc) are given through synchronous dynamics at a differentiable and non-differentiable scale resolutions. Finally, the model is confirmed by the empirical data
Journal of Comparative Pathology, 2020
International Journal of Advance and Innovative Research, 2022
Kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) is a common contaminant of many food prod... more Kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) is a common contaminant of many food products which are part of humans or animals daily nutrition (sake, soy sauce, cereals, fodder and dairy products). This mycotoxin has demonstrated antibacterial, antifungal, antiparasitic, insecticide, antioxidant and skin whitening effects. In this study, adult zebrafish were divided in 4 groups: Control and 3 kojic acid-treated groups which were exposed to 100 mg/l, 204 mg/l and 284 mg/l kojic acid for 7 days. Histological alterations of the control and kojic acid-treated group were examined and compared, with emphasis on liver, kidney, pancreas, intestine, brain and myocardium. While the Control group had no histological alterations, the kojic acid-exposed zebrafish show hepatocytes hyperhydration/vacuolation, fragmentation of the cell membrane, nuclear karyolysis/pycnosis, a significant shortening of the intestinal villi, myocardiocytes degeneration, a moderatesevere myocardial congestion, an important lipid infiltration of the exocrine pancreas leading to the atrophy of the acini, nephrocyte degeneration and hyalinosis, nuclear hyperhydration, reduction to annulation of the tubular lumens. The histological alterations increase proportionally with the kojic acid dose.
Revista de Chimie
Patulin is a common contaminant of many food products which are part of humans or animals daily n... more Patulin is a common contaminant of many food products which are part of humans or animals daily nutrition: fruits and fruit products, cereals, diary products and sausages. In the present study, adult zebrafish were divided in 2 groups: Control and patulin-treated group which was exposed to patulin (70 �g/L) for 7 days. Histological alterations of the control and patulin-treated group were examined and compared, with emphasis on liver, kidney, pancreas, intestine, brain and myocardium. While the Control group had no histological alterations, the patulin-exposed zebrafish show severe hepatocyte alteration, medium to severe degeneration of urinary epithelium, enterocytes hyalinosis, partial coagulation necrosis of the Langerhans islets and myocardial edema.
Applied Sciences
Machine learning is a branch of artificial intelligence that allows computer systems to learn dir... more Machine learning is a branch of artificial intelligence that allows computer systems to learn directly from examples, data, and experience. Statistical modeling is more about finding connections between variables and consequently the impact of these relationships, while also catering for prediction. It should be clear that these two methodologies are different in terms of their purpose, despite the fact that they use similar means to get there. The evaluation of the machine learning algorithm uses a set of tests to validate its accuracy. Although, for a statistical model, the analysis of regression parameters by confidence intervals, significance tests and other tests can be used to assess the legitimacy of the model. To demonstrate the applications and usefulness of this theory, an experimental study was conducted on zebrafish exposed to mycotoxin. Methods: Patulin (70 µg/L) and kojic acid (100 mg/L, 204 mg/L, and 284 mg/L) were administered by immersion to zebrafish once daily for...
Applied Sciences, 2022
Machine learning is a branch of artificial intelligence that allows computer systems to learn dir... more Machine learning is a branch of artificial intelligence that allows computer systems to learn directly from examples, data, and experience. Statistical modeling is more about finding connections between variables and consequently the impact of these relationships, whilst also catering for prediction. It should be clear that these two methodologies are dissimilar in their objective, despite using alike means to arrive there. The valuation of the machine learning algorithm uses a test set to validate its accuracy. Though, for a statistical model, analysis of the regression parameters via confidence intervals, significance tests, and other tests can be used to evaluate the model’s legitimacy. To demonstrate the applications and utility of this theory, we performed an experimental study on zebrafish exposed to the mycotoxin. Methods: Patulin (70 µg/L) and kojic acid (100 mg/L, 204 mg/L, and 284 mg/L) were administered by immersion to zebrafish once daily for 7 days period before the behavior testing. The following behavioral tests were performed: Novel Tank test (NTT) (to assess the explorative behavior and anxiety); Y Maze test (which measures the spontaneous explorative behavior). Behavioral tests were performed on separate days. For the behavior tests, the statistical analysis was performed using ANOVA variation analysis (two-way ANOVA). All results are expressed as the mean ± standard error of the mean. The values of the general index F for which p <0.05 were considered statistically significant. Results: Y-maze - Patulin exposure led to an intensification of the locomotor activity, an increased traveled distance and number of arm entries. By increasing the spontaneous alternation between the aquarium’s arms, Patulin has shown a stimulating effect on spatial memory. In the case of zebrafish exposed to 100 mg /l kojic acid, the traveled distance was shorter by 27% than the distance attained by those in the control group. The higher doses of kojic acid (204 mg / l and 284 mg / l) lead to an increased locomotor activity, distance traveled, number of arm entries and the spontaneous alternation. The increase in spontaneous alternation demonstrates that 204 mg/l and 284 mg/l kojic acid doses had a stimulating effect on spatial memory. Novel Tank test - Compared to the control group, the traveled distance of the patulin exposed fish is slightly reduced. Compared to the control group, the traveled distance of the kojic acid exposed fish is reduced, due to a shorter mobile time (by 25-27% in the case of fish exposed to 204 mg / L and 284 mg / L kojic acid). Patulin and kojic acid exhibits toxic effects on zebrafish liver, kidney, myocardium and leads to severe alteration. We continued the analysis trying some machine learning algorithms on the classification problems in the case of the two behavioral tests MAZE and NTT, after which we concluded that the results were better in the case of the NTT test relative to the MAZE test and that the use of decision tree algorithms leads to amazing results, knowing that their hierarchical structure allows them to learn signals from both classes. Conclusions: The groups exposed to patulin and kojic acid show histological changes in the liver, kidneys, and myocardial muscle tissue. The novel tank test, which assesses the explorative behavior, proved to be conclusive in the behavioral analysis of fish that were given toxins, proving that intoxicated fish had a decreased explorative behavior and an increased anxiety. We have managed to detect an automatic learning algorithm, from the category of decision trees, which can be trained to classify the behavior of fish that were administered a toxin from the category of those used in the experiment, only by analyzing the characteristic features of the NTT behavioral test.
Revista de Chimie
Natural contaminants, especially mycotoxins, pose a challenge since they are found in a wide rang... more Natural contaminants, especially mycotoxins, pose a challenge since they are found in a wide range of agricultural crops and differ significantly in chemical structure and symptomatology in humans and signs of disease in animals following exposure to these chemical agents. Mycotoxins are toxic metabolites produced by a diverse group of fungi that contaminate agricultural crops prior to harvest or during storage post-harvest and different species including humans, poultry, swine and fish. Food contamination by mycotoxins is a risk to human and animal health being responsible for significant economic losses and can exhibit a broad range of effects including carcinogenicity, neurotoxicity and developmental toxicity. In the present paper was tested the influence of patulin (PAT, 70 mg/L) and kojic acid (KA, 100, 204 and 284 mg/L) on the activity of antioxidant enzymes (CAT and GPX), MDA (lipid peroxidation marker) but also on memory and anxious behavior in the Danio rerio experimental m...
UNIVERSITY POLITEHNICA OF BUCHAREST SCIENTIFIC BULLETIN, 2020
A series of three formulations were prepared in view of experimental and theoretical investigatio... more A series of three formulations were prepared in view of experimental and theoretical investigation of their drug release potential. The morphology of the film formulations, in terms of distribution of drug into the polymeric matrix and the nature of the drug was investigated by scanning electron microscopy and polarized light microscopy techniques. The in vitro drug release has been studied in a medium mimicking the physiological medium. It was established that the drug release is in close correlation with the mass ratio. Assuming that the dynamics of polymer-drug system's structural units take place on continuous and nondifferentiable curves (multifractal curves), we show that in a one-dimensional hydrodynamic formalism of multifractal variables the drug release mechanism (Fickian diffusion, non-Fickian diffusion, etc) are given through synchronous dynamics at a differentiable and non-differentiable scale resolutions. Finally, the model is confirmed by the empirical data.
Revista de Chimie , 2020
Patulin is a common contaminant of many food products which are part of humans or animals daily n... more Patulin is a common contaminant of many food products which are part of humans or animals daily nutrition: fruits and fruit products, cereals, diary products and sausages. In the present study, adult zebrafish were divided in 2 groups: Control and patulin-treated group which was exposed to patulin (70 µg/L) for 7 days. Histological alterations of the control and patulintreated group were examined and compared, with emphasis on liver, kidney, pancreas, intestine, brain and myocardium. While the Control group had no histological alterations, the patulin-exposed zebrafish show severe hepatocyte alteration, medium to severe degeneration of urinary epithelium, enterocytes hyalinosis, partial coagulation necrosis of the Langerhans islets and myocardial edema.
Conference Presentations by T-L Mandalian
Journal of Comparative Pathology, 2020
Introduction: Although pain is traditionally considered to be mediated by neurons, recent researc... more Introduction: Although pain is traditionally considered to be mediated by neurons, recent research has shown the important roles of glial cells in pain sensation. Microglial cells have been implicated in such processes, but less is known about the role of astrocytes. Astrogliosis is recognized as a defence reaction, conceivably aimed at limiting tissue damage and restoring homeostasis. This study aimed to assess the expression of glial fibrillary acidic protein (GFAP) in astrocytes from the frontal cortex, hypothalamus and periaqueductal grey matter (PAG) after administration of short-term doses of distinct drugs used for pain management, but without painful stimuli. Materials and Methods: Male Wistar rats received amitriptyline (Amt, 10 mg/kg/day) or gabapentin (Gb, 60 mg/kg/day) for 10 days, by gavage or via the intraperitoneal route, methadone (Me, 4.5 mg/kg/day), morphine (Mo, 10 mg/kg/day), carbamazepine (Cbz, 40 mg/kg/day), fluoxetine (Flx, 10 mg/kg/day), amantadine (Ama, 10 mg/kg/day), S-ketamine (Ke, 50 mg/kg/day), dipyrone (Dip, 16 mg/kg/day) or 0.9% saline solution (daily). Brain samples were collected for GFAP immunohistochemical investigation in the frontal cortex, hypothalamus and PAG. Results: Morphometric analysis showed that all drugs increased GFAP expression and astrocyte size in the frontal cortex and hypothalamus in relation to the saline group. In the PAG this expression was increased in the groups treated with Amt, Me, Mo, Ama, Flx and Ke, but not with Gb, Cbz and Dip. Discussion: Although the precise meaning of such changes remains unclear, astrocytes appeared to react phenotypically to distinct classes of pain modulators in almost all investigated areas, probably influencing neurons and the entire neural microenvironment.
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Papers by T-L Mandalian
Conference Presentations by T-L Mandalian