Thyroid metastasis of vaginal leiomyosarcoma: a case report and review of the literature.

Metastasis of vaginal leiomyosarcoma to the thyroid gland is an extremely rare event. Here, we report a case of thyroid metastasis of vaginal leiomyosarcoma. A 65-year-old female patient presented with a multinodular toxic goiter. 5 years earlier the patient has undergone a radical vaginal resection followed by chemotherapy due to high-grade vaginal leiomyosarcoma. Fine-needle aspiration cytology of the right thyroid lobe was suggestive of the benign thyroid lesion. As the diagnosis was not clear, following a multidisciplinary team discussion the decision was made to proceed with a total thyroidectomy. Pathologic assessment of the tumor confirmed thyroid metastasis of vaginal leiomyosarcoma.

Parathyroid carcinoma: a case report.

Parathyroid carcinoma (PC) is an uncommon cause of primary hyperparathyroidism (pHPT). The tumor is mostly functioning with following high serum calcium and parathyroid hormone (PTH) levels. Consideration of PC in differential diagnosis of pHPT is important because the mortality and the prognosis depend on early recognition and surgical approach. A case of PC in 51-year old female patient with persistent pHPT is reported. A patient, referred with anterior cervical hematoma, dysphagia, underwent neck ultrasound, barium X-ray swallow test and neck computed tomography. On the posterior surface of left thyroid lobe, close to the esophagus the heterogenic lesion with irregular margins was found. The preoperative calcemia was slightly elevated. The patient underwent cervical exploration with parathyroidectomy. Histological exam showed parathyroid lesion with immunohistochemical confirmation of PC. After 2 months follow-up there are no signs of a residual-recurrent disease. Although laboratory tests revealed pHPT preoperatively, no clinical effects of elevated calcium and PTH concentration levels were presented. As histological features are not specific for the differential diagnosis between the parathyroid adenoma and PC, the immunohistochemistry remains the only useful tool for the definite diagnosis.

Erratum to: "Amphipathic CRAC-Containing Peptides Derived from the Influenza Virus A M1 Protein Modulate Cholesterol-Dependent Activity of Cultured IC-21 Macrophages" [Biochemistry (Moscow), 83, 982 (2018)].

This corrects the article DOI: 10.1134/S0006297918080096.

Aggregation of Influenza A Virus Nuclear Export Protein.

Influenza A virus nuclear export protein (NEP) plays an important role in the viral life cycle. Recombinant NEP proteins containing (His)6-tag at either N- or C-terminus were obtained by heterologous expression in Escherichia coli cells and their high propensity for aggregation was demonstrated. Dynamic light scattering technique was used to study the kinetics and properties of NEP aggregation in solutions under different conditions (pH, ionic strength, presence of low-molecular-weight additives and organic solvents). Using atomic force microscopy, the predominance of spherical aggregates in all examined NEP preparations was shown, with some amyloid-like structures being observed in the case of NEP-C protein. A number of structure prediction programs were used to identify aggregation-prone regions in the NEP structure. All-atom molecular dynamics simulations indicate a high rate of NEP molecule aggregation and reveal the regions preferentially involved in the intermolecular contacts that are located at the edges of the rod-like protein molecule. Our results suggest that NEP aggregation is determined by different types of interactions and represents an intrinsic property of the protein that appears to be necessary for its functioning in vivo.

A case report of late local relapse of adrenocortical carcinoma 18 years after adrenalectomy.

Adrenocortical cancer is an extremely rare tumor presenting with extensive locoregional spread at the time of diagnosis. Due to the diagnostic difficulties preoperatively and a lack of effective treatment options, patients have poor prognosis. Patients succumb to metastases within a couple of months. Only 20 cases have been so far reported in the literature with a medium disease-free survival up to 2 years. We present a case of a locoregional recurrence of adrenocortical cancer 18 years after left adrenalectomy.

Amphipathic CRAC-Containing Peptides Derived from the Influenza Virus A M1 Protein Modulate Cholesterol-Dependent Activity of Cultured IC-21 Macrophages.

Entry of many viral and bacterial pathogens into host cells depends on cholesterol and/or cholesterol-enriched domains (lipid rafts) in the cell membrane. Earlier, we showed that influenza virus A matrix protein M1 contains amphipathic α-helices with exposed cholesterol-recognizing amino acid consensus (CRAC) motifs. In order to test possible functional activity of these motifs, we studied the effects of three synthetic peptides corresponding to the CRAC-containing α-helices of the viral M1 protein on the phagocytic activity of cultured mouse IC-21 macrophages. The following peptides were used: LEVLMEWLKTR (M1 α-helix 3, a.a. 39-49; further referred to as peptide 1), NNMDKAVKLYRKLK (M1 α-helix 6, a.a. 91-105; peptide 2), and GLKNDLLENLQAYQKR (M1 α-helix 13, a.a. 228-243; peptide 3). We found that all three peptides modulated interactions of IC-21 macrophages with non-opsonized 2-µm target particles. The greatest effect was demonstrated by peptide 2: in the presence of 35 µM peptide 2, the phagocytic index of IC-21 macrophages exceeded the control value by 60%; 10-11 mM methyl-ß-cyclodextrin abolished this effect. Peptides 1 and 3 exerted weak inhibitory effect in a narrow concentration range of 5-10 µM. The dose-response curves could be approximated by a sum of two (stimulatory and inhibitory) components with different Hill coefficients, suggesting existence of at least two peptide-binding sites with different affinities on the cell surface. CD spectroscopy confirmed that the peptides exhibit structural flexibility in solutions. Altogether, our data indicate that amphipathic CRAC-containing peptides derived from the viral M1 protein modulate lipid raft-dependent processes in IC-21 macrophages.

Heterologous Expression and Isolation of Influenza A Virus Nuclear Export Protein NEP.

Influenza A virus nuclear export protein NEP (NS2, 14.4 kDa) plays a key role in various steps of the virus life cycle. Highly purified protein preparations are required for structural and functional studies. In this study, we designed a series of Escherichia coli plasmid constructs for highly efficient expression of the NEP gene under control of the constitutive trp promoter. An efficient method for extraction of NEP from inclusion bodies based on dodecyl sulfate treatment was developed. Preparations of purified NEP with either N- or C-terminal (His)6-tag were obtained using Ni-NTA agarose affinity chromatography with yield of more than 20 mg per liter of culture. According to CD data, the secondary structure of the proteins matched that of natural NEP. A high propensity of NEP to aggregate over a wide range of conditions was observed.

[Sobering up agents influencing toxicodynamics of ethanol].

The pathogenetic mechanisms of acute alcoholic intoxications are examined and is based the expediency of the search for the amethystic agents, which influence neurotransmitter systems. Promising should be considered the agents, which modulate GABA-systems (partial reverse agonists of benzodiazepine receptors), glutamate (antagonists of metabotropic receptors mGluR2/3), opioid neuropeptides (antagonists of opioid receptors), acetylcholine (reversible inhibitors of acetylcholinesterase and M-cholinoagonists), adenosine (selective antagonists of A(2A)-receptors). The amethystic effect manifest also the substances, which modify the second messengers systems (calcium, nitrergic and cascade of arachidonic acid). The most of the means examined possesses the moderate amethystic potential, and effectiveness is manifested predominantly during the preventive application.

[Substantiation of possibility of use GABA-receptor's chloride channel blockers for modelling of the temporal epilepsy].

In work the review of some clinik-morphological and pharmacological researches devoted to a temporal epilepsy and its experimental models is resulted. On the basis of the analysis of existing problems in working out antiepileptic drugs and in studying of mechanisms epilepsy necessity of development of new chronic experimental models of a temporal epilepsy is proved. The basic criteria of experimental model of a temporal epilepsy are generalised. It is shown that parametres of acute toxicity and the remote consequences of an intoxication convulsive agents from group GABA-receptor's chloride channel blockers correspond to the basic criteria a post-epistatus of model of a temporal epilepsy. The conclusion is presented on use possibility GABA-receptor's chloride channel blockers in quality agents for modelling of a temporal epilepsy.

[Involvement of brain neurotrophic factors in the pathogenesis of chemical dependences].

The involvement of brain neurotrophic factors (BNF) in the development and maintenance of the syndrome of psychic dependence on psychoactive substances is discussed. The implication of BNF in the pathogenesis of psychic dependence syndrome is supported by changes of the addictive power of psychostimulants, ethanol and morphine in conditions of metabolism modulation of these peptides as well as in rodents with defects in neurotrophin genes. Glial cell line derived BNF and tumor necrosis factor-alpha reduce the addictive potential of cocaine, methamphetamine, morphine and ethanol. Brain-derived neurotrophic factor, on the contrary, increases the addictive activity of cocaine suppressing the development of the syndrome of psychic dependence on ethanol. Thus, the BNF must be considered as an important group of neuroactive peptides implicated in the pathogenesis of chemical dependences.

[Genetic transformation of sugar beet: evolution of theoretical and experimental approaches].

The review is dedicated to several aspects of sugar beet (Beta vulgaris L.) biotechnology: in vitro cultivation, callus induction, plant regeneration and genetic transformation. Media composition, methods of plant regeneration via somatic embryogenesis and protoplast culture are analysed. The use of Agrobacterium tumefaciens and gold particle bombardment is the base for modern genetic transformation methods.

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice.

Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.

[Molecular aspects of pharmacological activity of naltrexone and naloxone]. / Molekuliarnye aspekty farmakologicheskoi aktivnosti naltreksona i naloksona.

Naltrexone and naloxone, being competitive antagonists of opioid receptors, have found therapeutic applications in medicine. The experiments with mutant receptors showed that many amino acid residues within transmembrane domains play an important role in binding these drugs. Using the site-directed mutagenesis technique, it was established that even single mutations (replacing single amino acid residues) can significantly modify the affinity of antagonists to receptors, sometimes even imparting agonist-like properties to the compounds studied. Chronic administration of naltrexone and naloxone leads to an increase in the density of opioid receptors and in the sensitivity to agonists. This hypersensitivity and overdose risk in heroin abusers after chromic naltrexone treatment are discussed.

[Neurochemical basis of ultra rapid opioid detoxication]. / Neirokhimicheskie osnovy ul'trabystroi opiatnoi detoksikatsii.

Ultra rapid opioid detoxification (UROD) is a new technique with the use of mu-opioid receptor antagonists to precipitate withdrawal. The scientific literature on UROD techniques in opiate addicts are reviewed, but little has been published on its neurochemical aspects. It is discussed that exposure to naloxone ore naltrexone during UROD is associated with development of increasing in opioidergic neurotransmission. On the other hand, ultra rapid opioid detoxification can be accompanied by normalization of joined brain neurotransmitter systems: noradrenergic, serotoninergic, GABAergic, cholinergic and glutamatergic neurotransmission systems. The neurochemical aspects of the new method detoxification are discussed.

The influence of ethanol on the functional status of GABA(A) receptors.

Gamma aminobutyric acid (GABA) is one of the main inhibitory neurotransmitters in the mammalian brain. Its effects are realized via GABA(A), GABA(B), and GABA(C) receptors. GABA(A) is the most abundant type of GABA receptors. It consists of six classes of subunits, alpha, beta, gamma, delta, epsilon, and chi. Acute and chronic exposures to ethanol are accompanied by changes in structure and function of GABA(A) receptors. These changes may be a basis for altered behavior seen in alcoholism.

Genetic variability of somatic embryogenesis in tissue cultures of sugar beet breeding lines.

Genetic variability of callus initiation and plant regeneration has been investigated among three sugar beet genotypes. It was found that TDZ has a genotype-independent effect on callus initiation and is responsible for more than a two-fold increase in the friable callus induction rate and more than a three-fold increase in the shoot regeneration rate from this callus. Along with the genotype-independent organogenesis, regeneration from callus occasionally went through the process of somatic embryogenesis in a highly genotype-specific manner. Despite fast and uncontrollable conversion of embryos to normal plants, it was possible to select and maintain repetitive embryogenic culture without loosing regeneration and root formation capabilities. Extensive experimenting with medium composition and culture conditions resulted in an optimal medium for maintenance of repetitive embryos. Comparing with BAP, low concentrations of TDZ provide higher level of adventitious shoot formation and do not induce vitrification of tissues.

Cloning of a human tRNA isopentenyl transferase.

A cDNA of human origin is shown to encode a tRNA isopentenyl transferase (E.C. 2.5.1.8). Expression of the gene in a Saccharomyces cerevisiae mutant lacking the endogenous tRNA isopentenyl transferase MOD5 resulted in functional complementation and reintroduction of isopentenyladenosine into tRNA. The deduced amino acid sequence contains a number of regions conserved in known tRNA isopentenyl transferases. The similarity to the S. cerevisiae MOD5 protein is 53%, and to the Escherichia coli MiaA protein 47%. The human sequence was found to contain a single C2H2 Zn-finger-like motif, which was detected also in the MOD5 protein, and several putative tRNA transferases located by BLAST searches, but not in prokaryotic homologues.

[Acamprosate--a novel treatment for alcoholism]. / Akamprosat--novoe lekarstvennoe sredstvo dlia lecheniia alkogolizma.

The properties of acamprosate (calcium acetylhomotaurate), a new remedy for the treatment of alcoholism, are reviewed. The efficacy of this drug has been verified by numerous clinical tests in West Europe. The pharmacological activity of acamprosate is related to the drug action upon central neuromediator systems. No side or addiction effects of the drug were reported. Data on the clinical and pharmacological characteristics of acamprosate are summarized.