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1.
J Pharm Biomed Anal ; 223: 115125, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36375394

RESUMEN

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with diverse psychopharmacological effects including antidepressant and anxiolytic actions. However, the clinical use of BDNF is limited due to its poor pharmacokinetic properties. The development of low-molecular-weight BDNF mimetics passing through the blood-brain barrier is an emerging strategy for improved managing psychiatric diseases. The present study characterizes a novel dipeptide mimetic of the 2nd BDNF loop named GTS-201, which exhibits psychotropic properties in experimental animal models of anxiety and alcohol dependence. The aim of this work was to study the pharmacokinetics of GTS-201 in rats at a saturating dosage of 5 mg/kg applied by the intraperitoneal route and to characterize the effects on neurotransmitter levels in the blood and brain. The maximum concentration (Cmax) of GTS-201 in the plasma (867 ± 69 ng/ml) was recorded at 35 ± 7.7 min after administration (Tmax) with a half-elimination period (T1/2) of 19.5 ± 1.8 min, while in the brain tissue Cmax was 14.92 ± 3.11 ng/ml, Tmax was 40.0 ± 7.7 min and T1/2 were 87.5 ± 12.7 min. The relative tissue availability of the GTS-201 for the brain reached 2.9%. At the dose applied, GTS-201 induced a significant increase of serotonin (5-fold) and dopamine levels in the brain tissue (8-fold) along with a decrease in cortisol content in blood plasma 45 min after acute administration. In summary, GTS-201 crosses the blood-brain barrier after acute administration and affects the activity of serotonergic and dopaminergic systems, which may underlie its neuropsychotropic effects described previously.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Dipéptidos , Animales , Ratas , Factor Neurotrófico Derivado del Encéfalo/química , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Dipéptidos/química , Cromatografía Liquida , Espectrometría de Masas en Tándem , Dopamina , Neurotransmisores
2.
Front Physiol ; 13: 963301, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36457309

RESUMEN

Studies conducted by I. Altman in the 1960-70s revealed the increase in the individual stress level under isolation and confinement. Altman introduced the term "privacy" as a desired level of personal space that humans need to feel psychologically comfortable. The author also mentioned the dynamic process of boundary regulation that can be accompanied by the increase in conflict tension in the confined groups. In our study with short-term chamber isolation ESKIS, we analyzed behavior, crew interactions, and psychological state of a mixed-gender crew with none or minimal previous isolation experience (4 males and 2 females) who spent 14 days in a small chamber of 50 m3. The study confirmed that the pre-isolation period was particularly stressful for the subjects who felt also significant anxiety during the first days of isolation. Also, some mood and sleep disturbances were detected under isolation and crowding. Psychological stress made the crew more cohesive; they demonstrated the increase in common values. Extraverted subjects who could obtain social support from their partners and Mission Control's duty teams were less interested in psychological support via VR.

3.
Front Physiol ; 12: 751170, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34858207

RESUMEN

Two experiments, with 17-day and 120-day isolation, were carried out within the frame of the Scientific International Research in Unique Terrestrial Station (SIRIUS) international project at the Institute of Biomedical Problems (Moscow, Russia). Manifestations of the "detachment" phenomenon in the crew - mission control center (MCC) communication previously identified in the Mars-500 project were confirmed in this study. As in the Mars-500 experiment, in the SIRIUS-19, the landing simulation in the halfway of isolation caused a temporary increase of crew communication with MCC. We also revealed several differences in the communication styles of male and female crew members. By the end of the experiment, there was a convergence of communication styles of all the SIRIUS crew members and also an increase in crew cohesion.

4.
Biomed Res Int ; 2019: 6821575, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31093501

RESUMEN

Diabetes mellitus (DM) is a chronic disease requiring changes in the behaviour of the entire family. The responsibility for implementing doctor's recommendations falls mainly upon the mother. The aim of this study is to assess the psychosocial functioning of mothers of children with DM compared to mothers of healthy children. The study involved 120 mothers: 60 with children with DM and 60 with healthy children. Data were collected using an original social-demographic questionnaire developed by the authors as well as Antonovsky's Sense of Coherence Scale (SOC-29), Schwarzer and Schultz's Berlin Social Support Scales (BSSS), Rosenberg's Self-Esteem Scale (SES), and Zigmond and Snaith's Hospital Anxiety and Depression Scale (HADS). The assessment scales were standardised and accredited by the Polish Psychological Association. The results suggest that DM in children has no effect on the psychosocial functioning of mothers regarding their self-esteem and sense of coherence. However, mothers of children with DM are well-prepared for living in a difficult situation. Social support offered to mothers of diabetic children helps them to maintain their psychosocial health.


Asunto(s)
Diabetes Mellitus/psicología , Madres/psicología , Adulto , Factores de Edad , Ansiedad/psicología , Niño , Depresión/psicología , Escolaridad , Femenino , Humanos , Renta , Masculino , Estado Civil , Persona de Mediana Edad , Características de la Residencia , Apoyo Social
5.
Int J Mol Sci ; 20(9)2019 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-31035445

RESUMEN

Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.


Asunto(s)
Trastornos Nutricionales/tratamiento farmacológico , Trastornos Nutricionales/etiología , Oligoelementos/deficiencia , Acetato de Zinc/uso terapéutico , Zinc/deficiencia , Animales , Estudios Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Humanos , Imidazoles/química , Ratones , Trastornos Nutricionales/diagnóstico , Trastornos Nutricionales/prevención & control , Resultado del Tratamiento , Acetato de Zinc/química , Acetato de Zinc/farmacología
6.
PLoS Negl Trop Dis ; 12(6): e0006511, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29889829

RESUMEN

BACKGROUND: To establish correlates of human immunity to the live plague vaccine (LPV), we analyzed parameters of cellular and antibody response to the plasminogen activator Pla of Y. pestis. This outer membrane protease is an essential virulence factor that is steadily expressed by Y. pestis. METHODOLOGY/PRINCIPAL FINDINGS: PBMCs and sera were obtained from a cohort of naïve (n = 17) and LPV-vaccinated (n = 34) donors. Anti-Pla antibodies of different classes and IgG subclasses were determined by ELISA and immunoblotting. The analysis of antibody response was complicated with a strong reactivity of Pla with normal human sera. The linear Pla B-cell epitopes were mapped using a library of 15-mer overlapping peptides. Twelve peptides that reacted specifically with sera of vaccinated donors were found together with a major cross-reacting peptide IPNISPDSFTVAAST located at the N-terminus. PBMCs were stimulated with recombinant Pla followed by proliferative analysis and cytokine profiling. The T-cell recall response was pronounced in vaccinees less than a year post-immunization, and became Th17-polarized over time after many rounds of vaccination. CONCLUSIONS/SIGNIFICANCE: The Pla protein can serve as a biomarker of successful vaccination with LPV. The diagnostic use of Pla will require elimination of cross-reactive parts of the antigen.


Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Inmunidad Celular , Inmunidad Humoral , Vacuna contra la Peste/inmunología , Activadores Plasminogénicos/inmunología , Yersinia pestis/inmunología , Adulto , Anciano , Biomarcadores/sangre , Citocinas/biosíntesis , Citocinas/inmunología , Epítopos de Linfocito B/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Peste/sangre , Peste/inmunología , Peste/microbiología , Peste/prevención & control , Células Th17/inmunología , Vacunación , Vacunas Vivas no Atenuadas/administración & dosificación , Vacunas Vivas no Atenuadas/inmunología , Factores de Virulencia
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