Conjugates of amiridine and salicylic derivatives as promising multifunctional CNS agents for potential treatment of Alzheimer's disease.

New conjugates of amiridine and salicylic derivatives (salicylamide, salicylimine, and salicylamine) with different lengths of alkylene spacers were designed, synthesized, and evaluated as potential multifunctional central nervous system therapeutic agents for Alzheimer's disease (AD). Conjugates demonstrated high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition (IC: AChE, 0.265-4.

Effect of Long-Term Reduction of Deuterium Content in the Body on Hemoglobin Production and Parameters of Erythropoiesis.

Anemia is the most widespread hematological disease, therefore the search for new approaches to erythropoiesis regulation in the body remains an extremely urgent problem. We studied the effect of long-term reduction of deuterium level in the internal milieu of the body on hemoglobin production and parameters of erythropoiesis in sexually mature male Wistar rats. The animals consumed water with deuterium content decreased to 10 ppm for 2 months.

Effects of Deuterium Depletion on Age-Declining Thymopoiesis In Vivo.

The thymus provides maturation and migration of T cells to peripheral organs of immunity, where they recognize diverse antigens and maintain immunological memory and self-tolerance. The thymus is known to be involved with age and in response to stress factors. Therefore, the search for approaches to the restoration of thymopoiesis is of great interest.

Postnatal Exposure to the Endocrine Disruptor Dichlorodiphenyltrichloroethane Affects Adrenomedullary Chromaffin Cell Physiology and Alters the Balance of Mechanisms Underlying Cell Renewal.

Dichlorodiphenyltrichloroethane (DDT) is a wide-spread systemic pollutant with endocrine disrupting properties. Prenatal exposure to low doses of DDT has been shown to affect adrenal medulla growth and function. The role of postnatal exposure to DDT in developmental disorders remains unclear.

Combining Experimental and Computational Methods to Produce Conjugates of Anticholinesterase and Antioxidant Pharmacophores with Linker Chemistries Affecting Biological Activities Related to Treatment of Alzheimer's Disease.

Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations.

Features of Spleen Development in Newborn Rats Exposed to Endocrine Disrupter Dichlorodiphenyltrichloroethane during the Prenatal Period.

The development of the spleen in newborn male Wistar rats exposed to low-dose endocrine disruptor dichlorodiphenyltrichloroethane during the prenatal period was studied. Histological examination of the spleen revealed a more active development of periarterial lymphoid sheaths and lower granulocyte content in the organ. Cytofluorimetry showed a significantly lower content of B cells.

The effect of substituent position and solvent on thermal Z‒E isomerization of dihydroquinolylazotetrazole dyes: kinetic, thermodynamic, and spectral approaches.

Kinetic and thermodynamic parameters have been investigated for the thermal Z‒E isomerization of dihydroquinolylazotetrazole dyes with alkyl substituents (Me, t-Bu, and Adm) at positions 1 (dyes 2) and 2 (dyes 3) of the tetrazole moiety in two solvents of different polarity, acetonitrile (MeCN) and toluene. The experimental results show crucial dependence of these parameters on a substituent position in the tetrazole moiety and on a solvent. For dyes 2, E and ΔH are lower in MeCN than in toluene that results in a high increase in the lifetimes of the Z isomers: from milliseconds in MeCN to minutes in toluene.

Regulation of Morphogenetic Processes during Postnatal Development and Physiological Regeneration of the Adrenal Medulla.

Regulation of morphogenetic processes during postnatal development of the rat adrenal medulla was studied. Termination of the adrenal medulla growth was found to be associated with decreased chromaffin cell proliferation, activation of canonical Wnt-signaling pathway, and enhanced expression of Sonic Hedgehog ligand. Analysis of transcription factors associated with pluripotency revealed increased percentage of Oct4-expressing cells by the end of medulla growth and no signs of Sox2 expression.

Derivatives of 9-phosphorylated acridine as butyrylcholinesterase inhibitors with antioxidant activity and the ability to inhibit β-amyloid self-aggregation: potential therapeutic agents for Alzheimer's disease.

We investigated the inhibitory activities of novel 9-phosphoryl-9,10-dihydroacridines and 9-phosphorylacridines against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CES). We also studied the abilities of the new compounds to interfere with the self-aggregation of β-amyloid (Aβ) in the thioflavin test as well as their antioxidant activities in the ABTS and FRAP assays. We used molecular docking, molecular dynamics simulations, and quantum-chemical calculations to explain experimental results.

Changes in Secretion of the Thyroid and Pituitary Glands with a Gradual Decrease in Deuterium Body Content.

We studied changes in the secretion of thyroid hormones and pituitary thyroid-stimulating hormone (TSH) in young mature male Wistar rats during gradual decrease in deuterium body content. The rats received deuterium-depleted water ([D]=10 ppm) instead of tap water for 21 days. As soon as after 1 day, an increase in the secretion of thyroid hormones was recorded.

Bilateral Shifts in Deuterium Supply Similarly Change Physiology of the Pituitary-Thyroid Axis, but Differentially Influence Na/I Symporter Production.

Deuterium, a stable isotope of hydrogen, is abundant in organisms. It is known to produce various biological effects. However, its impact in thyroid hormone synthesis and secretion is poorly studied.

Emerging Role of Deuterium/Protium Disbalance in Cell Cycle and Apoptosis.

Deuterium, a stable isotope of hydrogen, is a component of water and organic compounds. It is the second most abundant element in the human body after sodium. Although the concentration of deuterium in an organism is much lower than that of protium, a wide variety of morphological, biochemical, and physiological changes are known to occur in deuterium-treated cells, including changes in fundamental processes such as cell division or energy metabolism.

Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla.

Dichlorodiphenyltrichloroethane (DDT) is the most widespread persistent pollutant with endocrine-disrupting properties. DDT has been shown to disrupt secretory and morphogenetic processes in the adrenal cortex. The present investigation aimed to evaluate transcriptional regulation of postnatal growth of the adrenal medulla and formation of the pools necessary for self-renewal of medullary cells in rats that developed under low-dose exposure to DDT.

Conjugates of Tacrine and Salicylic Acid Derivatives as New Promising Multitarget Agents for Alzheimer's Disease.

A series of previously synthesized conjugates of tacrine and salicylamide was extended by varying the structure of the salicylamide fragment and using salicylic aldehyde to synthesize salicylimine derivatives. The hybrids exhibited broad-spectrum biological activity. All new conjugates were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE.

Caspase-3, Caspase-8 and XIAP Gene Expression in the Placenta: Exploring the Causes of Spontaneous Preterm Labour.

A better understanding of the pathogenesis of preterm birth (PTB) will allow us to lower the PTB rate, reducing perinatal morbidity and mortality. This article presents the hypothesis that premature placenta apoptosis could be a potential cause of PTB. We evaluated gene expression involved in apoptosis: caspase-3, caspase-8, and XIAP (X-linked inhibitor of apoptosis) in the placenta during pregnancy (n = 41), at the onset of preterm labour (n = 42), after preterm (n = 44) and term (n = 32) labour.

Reactive Alterations in Thymic Lymphocytopoiesis to Short-Term Decrease in Deuterium Content in the Body.

We studied changes in thymic lymphocytopoiesis induced by a short-term decrease in deuterium content in the body. The experiment was performed on adult male Wistar rats receiving water with lower deuterium content [D]=10 ppm. Increased relative weight of thymus was found after 24 h of consumption.

Developmental Exposure to Endocrine Disrupter DDT Interferes with Age-Related Involution of Thymus.

The impact of endocrine-disrupting chemicals on the development and involution of the immune system is a possible reason for the increased incidence of disorders associated with inappropriate immune function. The thymus is a lymphoid and also an endocrine organ, and, accordingly, its development and functioning may be impaired by endocrine disruptors. The aim was to evaluate age-related thymus involution in mature rats exposed to the endocrine disruptor DDT during prenatal and postnatal ontogeny.

Mechanisms of Suppression of Epinephrine Production in Rats by Low-Dose Developmental Exposure to DDT.

We studied the mechanisms underlying decreased production of epinephrine by adrenal glands in rats developmentally exposed to endocrine disruptor DDT was performed on the basis of assessment of morphology, fine structure, and function of the adrenal medulla and medullary cells. It was found that the main mechanisms of disruptive action of DDT leading to a decrease in epinephrine secretion into systemic circulation are a decrease in the growth rate of the adrenal medulla, a decrease in the number of mitochondria in adrenal cells, especially under the outer cytoplasmic membrane, destructive changes in mitochondria, and a progressive decrease in the synthesis of tyrosine hydroxylase. The decrease in the number of mitochondria and suppression tyrosine hydroxylase synthesis in adrenal cells predominate during the pubertal period, while slowdown of the growth of the adrenal medulla and progressive decrease in the synthesis of tyrosine hydroxylase seem to be the most evident mechanisms after puberty.

Impact of Prenatal and Postnatal Exposure to Endocrine Disrupter DDT on Adrenal Medulla Function.

Epinephrine is the most abundant catecholamine hormone, produced by the nervous system and adrenal glands. Endocrine disruption of epinephrine synthesis, secretion and signaling is less studied than steroid and thyroid hormones. Dichlorodiphenyltrichloroethane (DDT) is recognized as one of the most prominent environmental contaminants with a long half-life.

Dichlorodiphenyltrichloroethane and the Adrenal Gland: From Toxicity to Endocrine Disruption.

Endocrine disruptors are exogenous compounds that pollute the environment and have effects similar to hormones when inside the body. One of the most widespread endocrine disruptors in the wild is the pesticide dichlorodiphenyltrichloroethane (DDT). Toxic doses of DDT are known to cause cell atrophy and degeneration in the adrenal zona fasciculata and zona reticularis.

Impact of Reduced Deuterium Intake on Thermoregulation.

The role of stable hydrogen isotopes in the thermoregulation and its regulation is poorly studied. We analyzed fluctuations in body temperature and changes in thermoregulation parameters in mice under conditions of reduced deuterium intake. The study was performed on male C57BL/6 mice that consumed water with a low (10 ppm) and normal (146 ppm) deuterium content.

Matrix metalloproteinases MMP-2 and MMP-9 as markers for the prediction of preeclampsia in the first trimester.

Introduction: Preeclampsia is a life-threatening condition for the mother and foetus. Globally, it is dia-gnosed in 10 mil. women every year, which accounts for 3% to 8% of all pregnancies.

Response of Pituitary-Thyroid Axis to a Short-Term Shift in Deuterium Content in the Body.

We studied functional changes in rat pituitary-thyroid axis after a short-term shift in deuterium body content. Male Wistar rats consumed deuterium-enriched (500,000 ppm) or deuterium-depleted water (10 ppm) for 24 h. Rats of both experimental groups demonstrated elevated concentration of bound with transport proteins thyroxine and reduced level of thyroid-stimulating hormone in serum.

Low-Dose Exposure to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) Affects Transcriptional Regulation of Adrenal Zona Reticularis in Male Rats.

The study examined transcriptional regulation of adrenal zona reticularis development in male Wistar rats exposed to low doses of endocrine disruptor dichlorodiphenyltrichloroethane (DDT) prenatally and postnatally. At pubertal age, zona reticularis demonstrated a retarded growth with a low proliferative activity of its cells. At this age, zona reticularis was characterized with overexpression of β-catenin by steroid-producing cells; a high percentage of cells with membrane and cytoplasmic localization of β-catenin, and reduced number of cells with nuclear β-catenin attesting to insufficient activation of Wnt signaling.