Morphological manifestations of experimental paclitaxel-induced sciatic neuropathy under correction of 2-ethyl-6-methyl-3-hydroxypyridine succinate

Paclitaxel is an effective chemotherapeutic agent for many cancers, but it has a number of limiting side effects that not only significantly reduce the quality of life of patients, but also limit their further treatment. Peripheral neuropathy is one of these, but there are currently no proven effective druHS for the prevention or treatment of paclitaxel-induced neuropathic pain (PINP) in particular, or chemotherapy-induced peripheral neuropathy (CIPN) in general. 2-ethyl-6-methyl-3-hydroxypyridine succinate (HS) is a derivative of succinic acid with neuroprotective, antihypoxic, membrane-protective, nootropic, sedative effects. The aim of the study was to study the effect of the neuroprotective agent HS on the pathomorphogenesis of the sciatic nerves under conditions of paclitaxel-induced peripheral neuropathy in the experiment. Materials and methods. The experiment was carried out on 80 white rats, which were injected intraperitoneally with paclitaxel (Actavis, Romania), previously dissolved in isotonic saline at a dose of 2 mg / kg of body weight four times every other day until a total dose of 8 mg / kg was reached. Then forty of these animals were injected intraperitoneally with 2-ethyl-6-methyl-3-hydroxypyridine succinate at a dose of 10 mg / kg (the remaining 40 rats received intraperitoneal water for injection). Morphological studies were carried out on the first, seventh, fifteenth, twenty-eighth, sixtieth, ninetieth and one hundred and twentieth days after the last injection of the drug. We investigated the pharmacological potential of HS in the prevention and treatment of CIPN at the level of sciatic nerve (SN) morphology. Results. The maximum value of the average profile area of myelinated nerve fibers with the use of HS is significantly lower than with uncorrected flow, and is (78.12±2.24) μm2 compared to (94.04±1.03) μm2 (p <0.001). The introduction of HS provides a stable content of the value of the ratio of the areas of the axial cylinder and the fiber within 0.39±0.01 (first day) - 0.44±0.01 (ninetieth day), and a rapid recovery of the indicator value to normal values during the final 30 days of the experiment. the maximum value of the index of the profile area of the myelin sheath with the introduction of HS is 1.4 times less than with an uncorrected flow, and is, respectively, (49.01±1.59) μm2 and (69.77±1.87) μm2 (p <0.001). HS provides a more intensive restoration of the indicator of the area of the myelin sheath during the 90th - 120th day of the experiment. Conclusions. Our results allow us to conclude that the introduction of HS creates a protective effect against paclitaxel-induced peripheral neuropathy (PIPN) by acting on both the axial cylinder and the myelin sheath of the heart failure. Due to the known pathophysiological mechanisms of the development of neuropathy, this method can be a promising therapeutic agent for the prevention and treatment of PIPN

К. Schaffer: Zur feineren Struktur der Hirnrinde und über funktionelle Bedeutung der Nervenzellenfortsätze. Arch. f. Mikrosk. Anatomie. XLVIIL 4 Heft. 1897. S. S. 550—572

The author's research refers to the anterior cerebral cortex of a newborn dog. The author studies in detail the so-called tiny pyramidal cells, lying between the pluripolar cells of the molecular layer and the small (true) pyramidal cells. Already R. y Cajal drew attention to polygonal or core-shaped cells, the cells that lie behind the layer of the outermost cells (pluripolare Nervenzellen von R. y Cajal), but did not separate them into a special group, believing that these cells were gradually changing vid, go into the small pyramids, to which he numbered them. Schaffer separates these cells into a special group, calling it the layer of surface polymorphic cells. These cells have a dark variety of shapes (fusiform, oval, roundish, pear-shaped, polygonal) and lie in approximately four (4) rows. Dendrites go then, mainly, in two opposite directions (for fusiform cells), then they move radially in all directions (for round and polygonal cells). The number of dendrites is sometimes strikingly abundant. Dendrites going to the surface of the brain reach it, while dendrites of the opposite direction sometimes go down to the ammonium formations of the cerebral cortex. Special attention should be paid to the axial cylinder of the disassembled cells; on the basis of the features of this appendix, the author distinguishes 3 types of disassembled cells.

Cluster Analysis of Myelin Nerve Fibers of the Periferal Nerve

One of the unsolved issues in neuromorphology is the classification of myelin nerve fibers (MNF). Objective: to use cluster analysis to classify the sciatic nerve MNF. Material and methods. The work was performed using 5 one-year-old male Wistar rats. Semi-thin sections were stained with methylene blue. MNF morphometry was performed using ImageJ, and statistical processing – using the software environment R. Results of the study. Ward’s and k-means methods were used to cluster the MNF. Three clusters of MNFs are defined and their parameters are determined. The presented algorithm for adapting the literature data to the format of the obtained results includes determining the total average for the combined set of each indicator and the total variance, which is the sum of intragroup and intergroup variances. Conclusions: 1) for the classification of MNF it is advisable to use cluster analysis; 2) clustering should be performed according to the transsection areas of the axial cylinder and myelin sheath; 3) the number of clusters is determined by the agglomerative method of Ward, and their metrics – by the iterative method of k-means; 4) three clusters of MNF of the rat sciatic nerve differ in the transsection areas of the fibers, the axial cylinder and the myelin sheath and the percentage of nerve fibers; 5) when comparing identical indicators according to the obtained and literature data, the results were equivalent in the areas of the axial cylinder and myelin sheath and their shape coefficients, despite the fact that the classification of myelin fibers and their morphometry was performed using different methods.

Ultrastructural analysis of initial stages of dedifferentiation of root explants of Gentiana cruciata seedlings

The studies were carried out on isolated roots of 10-day old seedlings of <em>Gentiana cruciata</em>, which were placed and cultured on induction medium of Murashige and Skoog (1962) supplemented with 1.0 mg/dm³ dicamba + 0.l mg/dm³ NAA + 2.00 mg/dm³ BAP + 80.0 mg/dm³ adenine sulphate. Changes in explants from the 3rd to the l lth day of culture with the help of light and electron microscope were observed. Observations showed gradual dedifferentiation of root tissues, which was seen earliest in cortex at the proximal end of the explant and shifted gradually inwards the root and towards distal parts of its elongation zone. The most intensive callus formation appeared at cut surface of explant, where proliferation of cells in both cortex and axial cylinder was recognised. In the distal part of the elongation zone, cell divisions occurred only in endoderm and in axial cylinder. The meristematic part of the root was inactive. Finally, the following areas were distinguished in the explant: (I) an area of intensive cell divisions, i.e., the elongation zone; (II) an area of cell dispersion; and (III) the inactive meristem. The ultrastructure brought evidences of cell reorganisation as the meaning of cell readiness to the division. Observations showed an increased activity of mitochondria and Golgi structures, thickening of walls and disappearance of plasmodesmal connections. Amyloplasts and lipid bodies in tissues in which they had been scarce or had not appeared before founding. Intensively dividing cells showed features of meristematic cells. They had dense cytoplasm with numerous organelles, large centrally located nuclei, and "nucleolar vacuoles" inside nucleoli. Cortex-derived callus formed aggregates. Both pericycle and endoderm produced callus of characteristic dense structure and regular type of divisions.