Effect of gamma-oxybutyrate on energy metabolism and the cyclic nucleotide level in nerve tissue in experimental intracerebral hemorrhage

Experimental intracerebral hemorrhage (EICH) was shown to cause a disorder of the functional state of the brain mitochondria. The rate of oxidation of NAD- and FAD-linked substrates in 3 and 4 states decreased 1 and 24 hours after hemorrhage. An injection of gamma-hydroxybutyrate 1 hour before decapitation increased the rate of mitochondrial respiration. EICH was found to increase cGMP level and to decrease cAMP level. A combined action of hemorrhage and gamma-hydroxybutyrate produced a greater lowering of cAMP level and an elevation of cGMP level.     

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer

Despite recent advances in the treatment of metastatic castration‐resistant prostate cancer (CRPC), outcome of patients remains poor due to the development of drug resistance. Thus, new drugs are urgently needed. We investigated efficacy, toxicity and mechanism of action of marine triterpene glycoside frondoside A (FrA) using CRPC cell lines in vitro and in vivo. FrA revealed high efficacy in human prostate cancer cells, while non‐malignant cells were less sensitive. Remarkably, proliferation and colony formation of cells resistant to enzalutamide and abiraterone (due to the androgen receptor splice variant AR‐V7) were also significantly inhibited by FrA. The marine compound caused cell type specific cell cycle arrest and induction of caspase‐dependent or ‐independent apoptosis. Up‐regulation or induction of several pro‐apoptotic proteins (Bax, Bad, PTEN), cleavage of PARP and caspase‐3 and down‐regulation of anti‐apoptotic proteins (survivin and Bcl‐2) were detected in treated cells. Global proteome analysis revealed regulation of proteins involved in formation of metastases, tumor cell invasion, and apoptosis, like keratin 81, CrkII, IL‐1β and cathepsin B. Inhibition of pro‐survival autophagy was observed following FrA exposure. In vivo, FrA inhibited tumor growth of PC‐3 and DU145 cells with a notable reduction of lung metastasis, as well as circulating tumor cells in the peripheral blood. Increased lymphocyte counts of treated animals might indicate an immune modulating effect of FrA. In conclusion, our results suggest that FrA is a promising new drug for the treatment of mCRPC. Induction of apoptosis, inhibition of pro‐survival autophagy, and immune modulatory effects are suspected modes of actions.     

Concise review: Telomere biology in normal and leukemic hematopoietic stem cells

The measurement of telomere length can give an insight into the replicative history of the cells in question. Much of the observed telomere loss occurs at the stem and progenitor cell level, even though these populations express the enzyme telomerase. Telomerase-transfected hematopoietic stem cells (HSC), although able to maintain telomere length, are still limited in terms of ability to undergo sequential transplantation, and other factors require to be addressed to achieve optimal levels of stem cell expansion. Unchecked telomere loss by HSC, meanwhile, would appear to play a significant role in the pathogenesis of bone marrow failure, as observed in the condition dyskeratosis congenita. This heterogeneous inherited condition appears to exhibit telomerase dysfunction as a common final pathogenic mechanism. Although less well-established for acquired marrow failure syndromes, mutations in key telomerase components have been described. The identification of the leukemic stem cell (LSC), along with the desire to target this population with anti-leukemia therapy, demands that telomerase biology be fully understood in this cell compartment. Future studies using primary selected LSC-rich samples are required. A better understanding of telomerase regulation in this population may allow effective targeting of the telomerase enzyme complex using small molecule inhibitors or additional novel approaches. Disclosure of potential conflicts of interest is found at the end of this article.     

Thermo-Optical Studies of Laser Ceramics

A cycle of works on manufacturing and studying laser and magnetooptical ceramics with a focus on their thermo-optical characteristics performed by the research team is analyzed. Original results that have not been published before such as measurements of the Verdet constant in the Zr:TAG, Re:MgAl₂O₄, and ZnAl₂O₄ ceramics are also presented.     

The use of monotherapy in patients with epilepsy: An appraisal of the new antiepileptic drugs

The use of antiepileptic drugs (AEDs) in monotherapy is always preferred to a polytherapy regimen because monotherapy facilitates drug compliance, is associated with a lower risk of toxicity, and is less costly. In addition, the yield of polytherapy to render a patient seizure-free when monotherapy regimens did not is relatively low. The available data derived from randomized controlled trials suggest that standard and new AEDs appear to display comparable antiepileptic efficacy but they differ with respect to tolerability and toxicity, which may be related to their pharmacodynamic and pharmacokinetic properties. New AEDs appear to be better tolerated than standard AEDs and to have fewer pharmacokinetic interactions than standard AEDs. In this article, we review the advantages of using AEDs in monotherapy in patients with newly diagnosed and refractory epilepsies, focusing on the individual properties of the drugs that may make them more appropriate in various patient groups.     

Ultrastructural changes in nerve tissue cells after exposure to blood serum from patients with infantile cerebral palsy in various model systems

Laboratory of Neuro-Ontogeny, I. P. Pavlov Department of Physiology, Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR B. I. Tkachenko.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 6, pp. 563–566, June, 1991.     

Induction of postural asymmetry in an intact recipient by brain extract from a donor with the same syndrome

An attempt was made at the direct transfer of postural asymmetry, following removal of half the anterior lobe of the cerebellum in rats, to a recipient. Asymmetry of the hind limbs was shown to appear in spinal animals after injection of brain extract of pathological donors into their subdural space below the level of transection. The specificity of the resulting asymmetry depending on the side of injury to the donor's cerebellum was revealed. The asymmetry of the recipient completely copied the asymmetry of the donor. Brain extracts from control animals did not induce asymmetry. Additional confirmation was obtained of the polypeptide nature of the factor stimulating the development of postural asymmetry. Treatment of the extract with pronase deprived it of its activity.Laboratory of Physiological Mechanisms of Memory Control, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 8, pp. 147–150, August, 1978.