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After spinal cord injury (SCI), emergency treatment intervention can minimize tissue damage, which is closely related to the recovery of long-term function. Here, we examined whether the administration of a single dose of riluzole (6 mg/kg) immediately after SCI was a critical window for the drug to exert its regulatory effect and limit long-term neurological deficits. The animals were sacrificed 1 day after administration for investigation of neuronal survival and a potential neuroinflammatory response, and sacrificed in the 6th week for assessment of neurological function. Riluzole applied in a single dose immediately post-SCI decreased the mRNA level of interleukin-1β at 6 h, reduced the destruction of neurons, and reduced the activation of microglia/macrophage M1 expression at day 1 post-SCI. Additionally, riluzole-treated rats showed higher expressions of interleukin-33 and its receptor ST2 in microglia/macrophages of the spinal cord than vehicle-treated rats, suggesting that this signaling pathway might be involved in microglia/macrophage-mediated inflammation. At 6 weeks, riluzole-treated rats exhibited higher motor function scores than vehicle-treated controls. In addition, riluzole-treated rats exhibited higher expression of GAP43 protein and shorter N1 peak latency and larger N1-P1 amplitude in motor-evoked potentials, compared to vehicle-treated rats. Together, these data suggested that early application of riluzole after SCI could be crucial for long-term functional recovery, so it may represent a promising therapeutic candidate within the critical therapeutic window for acute SCI.

To assess the antipyretic and hepatoprotective effects of Rhynchosia cana (Wild.) DC (R. cana) methanol extract in In-silico trials and laboratory animal models. R. cana methanol extract (MERC) was evaluated for antipyretic activity in yeast-induced Pyrexia. R. cana's hepatoprotective ability was evaluated for hepatotoxicity-induced paracetamol albino rats. The GC-MS eluted compound on the protein TGF-β, and PPARα was conducted in silico docking experiments. At doses of 200 and 400 mg/kg, p.o, a single administration of MERC demonstrated strong antipyretic efficacy in albino rats. When the MERC (400 mg/kg) was given preventively for seven days, highly significant hepatoprotective behaviour was also observed. The docking findings of the TGF-β ligand molecule show that the binding affinity of vitexin is -10.3 Kcal/mol, and Silymarin is -10.6 Kcal/mol. Vitexin displayed a binding affinity of -8.8 Kcal/mol for the PPAR alpha protein, and Silymarin showed an affinity of -8.2 kcal/mol. The present research indicates that MERC has substantial antipyretic and hepatoprotective effects, as confirmed in the In Silico and In Vivo tests.

Resumen La presente investigación realiza un recorrido por el concepto de confiabilidad como una de las propiedades psicométricas fundamentales en la Teoría Clásica de los Test. Se desarrolla el concepto y cuáles son sus diferentes aplicaciones prácticas para indagar el grado de confiabilidad de un instrumento de medición. Se centra el estudio en el cálculo de la consistencia interna a partir del alfa y el omega como los coeficientes más utilizados y la importancia de calcularlos mediante la utilización de matrices de correlaciones policoricas (MCP). Como objetivo principal se presenta una guía en español para el cálculo de coeficientes ordinales de confiabilidad al utilizar el programa R/RStudio. Se brinda un ejemplo a nivel empírico que da cuenta la relevancia de calcular este tipo decoeficientes para el cálculo de la confiabilidad de un instrumento. Al emplear una muestra de 266 adultos entre 18 y 63 años (M = 31.91, DE = 11.50), se administró la versión adaptada a argentina del Inventario de Ansiedad de Beck y el Cuestionario de Regulación Emocional. De esta manera, se exponen coeficientes para estimar la confiabilidad de los instrumentos que dan cuenta de sus ventajas y desventajas, al realizar el cálculo mediante MCP, matriz de correlaciones de Pearson y matriz de covarianzas de Pearson. A partir de los resultados, se evidencia que el cálculo mediante MCP proporcionó grados de confiabilidades mayores respecto al cálculo mediante las otras dos matrices. Se espera que el presente documento sea de importancia para investigadores no familiarizados con R. Abstract The present study takes a tour of the concept of reliability as one of the fundamental psychometric properties in Classical Tests Theory. The concept and its different practical applications are developed to investigate the degree of reliability of a measuring instrument. Focusing on the calculation of internal consistency from alpha and omega as the most used coefficients and the importance of calculating these coefficients by using polychoric correlation matrices (PCM). The main objective is to present a guide in Spanish for the calculation of ordinal reliability coefficients using the R/Rstudio program. Providing an example at the empirical level that shows the relevance of calculating this type of coefficients for calculating the reliability of an instrument. Using a sample of 266 adults between the ages of 18 and 63 years (M = 31.91 SD = 11.50), the version adapted to Argentina of the Beck Anxiety Inventory and the Emotional Regulation Questionnaire were administered. In this way, coefficients are exposed to estimate the reliability of the instruments that account for their advantages and disadvantages, performing the calculation using MCP, Pearson’s correlation matrix and Pearson’s covariance matrix. From the results, it is evident that the calculation using MCP provided higher degrees of reliability compared to the calculation using the other two matrices. This document is expected to be of importance to researchers unfamiliar with R.

A pharmacokinetic study of the absorption into the bloodstream, bioavailability and excretion of Gamavit from the body after intramuscular administration to laboratory mini-pigs was conducted. Quantitative determination was carried out by HPLC using a fluorimetric detector, for which Gamavit was labeled with Cy5 dye, which was then used for mini-pigs inoculation. The developed methods for determining Gamavit in the blood and feces were validated according to the following validation parameters: selectivity, calibration curve, accuracy, precision, limit of quantitative determination, sample transfer, and sample stability. The confirmed analytical range of the method for Gamavit detection in blood plasma and feces was 1.00…50.0 mcg/ml. Maximum concentration of Gamavit in the blood of mini-pigs after a single intramuscular injection was 30.97 mcg/ml and was reached on average 15 minutes after administration. 24 hours following administration, Gamavit was still detected in the blood in insignificant amounts. The average half-life of Gamavit in the blood is 8.64±3.50 hours. After administration at a dose of 0.1 ml/kg, the clearance of the drug is 1.27 l/kg * h, the excretion rate at an effective concentration of 30 mg/l is 38 mg/kg*h, and the maintenance dose when using the drug 1 time a day is 0.9…1.0 ml. The detection of the label in the feces of the studied animals indicates that one of the ways Gamavit removal is excretion with the help of bile acids, as well as partial excretion with feces.

espanolLa Artritis Reumatoide (AR) es uno de los tipos de Artritis mas frecuentes e importantes, por cuanto se trata de una enfermedad cronica y agresiva que ocasiona dano en las articulaciones, dolor e incapacidad. No tiene cura, sin embargo, existen varias lineas de tratamientos dirigidas a los sintomas y a prevenir el dano en las articulaciones y la incapacidad. De acuerdo con la Organizacion Mundial de la Salud (OMS), la AR es una de las mayores causas de ausentismo y retiro laboral prematuro en el mundo. Afecta entre el 1 y 1.5 % de la poblacion mundial. El proposito fundamental de la presente revision es plasmar las generalidades de los farmacos biologicos usados en el tratamiento de la AR, que son, como se usan, tipos, efectos adversos y recomendaciones para evitar dichos efectos o tratarlos. El modelo de investigacion es una revision de tipo documental bibliografico. De la revision se desprende que los farmacos biologicos se usan como segunda linea de accion, en el tratamiento de pacientes con AR refractaria a los farmacos antirreumaticos modificadores de la enfermedad (FAME) sinteticos. Existen diversos tipos de estos medicamentos que varian de un pais a otro, al igual que la legislacion que los regula y sus costos. Asimismo, su efectividad se encuentra asociada a otros FAME, especialmente cuando se administra acompanado con metotrexato. La combinacion entre FAME presenta mejores resultados que su administracion unica. Estos farmacos biologicos mejoran eficazmente los resultados clinicos, funcionales y radiograficos, y retrasan la progresion radiografica en la mayoria de los casos. Por ultimo, resulta fundamental el monitoreo de estos pacientes durante el tratamiento con FAME ya que es posible la presencia de algunos efectos secundarios. EnglishRheumatoid Arthritis (RA) is one of the most frequent and important types of arthritis, as it is a chronic and aggressive disease that causes joint damage, pain and disability. There is no cure, however there are several lines of treatment aimed at symptoms and preventing joint damage and disability. According to the World Health Organization (WHO), RA is one of the leading causes of absenteeism and premature retirement in the world. It affects between 1 and 1.5% of the world population. The main purpose of this review is to capture the generalities of the biological drugs used in the treatment of RA, what they are, how they are used, types, adverse effects and recommendations to avoid said effects or treat them. The research model is a bibliographic documentary type review. The review shows that biological drugs are used as a second line of action, in the treatment of patients with RA refractory to synthetic disease-modifying antirheumatic drugs (DMARDs). There are several types of these drugs that vary from one country to another, as well as the legislation that regulates them and their costs. Likewise, its effectiveness is associated with other DMARDs, especially when administered with methotrexate. The combination of DMARDs presents better results than its single administration. These biologics effectively improve clinical, functional, and radiographic outcomes, and delay radiographic progression in most cases. Lastly, it is essential to monitor these patients during DMARD treatment since the presence of some side effects is possible.

Clinical relevance: Caffeine intake has been demonstrated to influence several physiological measures, including some related to eye physiology. The ability to focus at different distances is of paramount importance in real-world situations, and thus, the possible impact of caffeine intake on accommodative facility may have important clinical implications. Background: This placebo-controlled, double-blind, balanced crossover study aimed to assess the acute effects of caffeine ingestion on the frequency and precision of the binocular accommodative facility. Methods: Twenty university students (21.9 ± 3.4 years) ingested a capsule of caffeine (4 mg/kg) or placebo (300 mg of corn-starch) on two different days and counterbalanced order. The binocular accommodative facility was objectively assessed, using the WAM-5500 binocular open-field autorefractometer, after 60 min of capsule ingestion (caffeine/placebo). Perceived levels of activation was also assessed in each experimental condition. Results: The ingestion of a single administration of caffeine (~ 4 mg/kg) causes an increase in the number of cycles performed per minute (p = 0.023, Cohen’s d = 0.55), whereas no effects were observed for the mean magnitude of accommodative change between the far and near targets (p = 0.794), and the percentage of incorrect cycles of accommodation and dis-accommodation (p = 0.271 and 0.396, respectively). Participants reported a perceived level of activation of 6.8 ± 1.5 and 7.6 ± 1.8 in the placebo and caffeine conditions, respectively (p = 0.059). Conclusion: Caffeine intake improves quantitative, but not qualitative, measures of accommodative facility. These results corroborate the impact of caffeine on visual function and suggest that this ergogenic effect of caffeine may be used to enhance visual performance in applied situations.

GLPG1205 is a modulator of GPR84, a G‐protein–coupled receptor reported to be associated with several diseases. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1205 in healthy subjects were evaluated in 2 randomized, double‐blind, placebo‐controlled, single‐site, phase 1 studies. In study 1, 16 (aged 21‐48 years) and 24 (24‐50 years) healthy men received single doses of GLPG1205 10 to 800 mg, and GLPG1205 50, 100, or 200 mg once daily for 14 days, respectively, or placebo. Study 2 evaluated the effect of aging on GLPG1205 pharmacokinetics: 24 healthy men (aged 37–83 years), weight‐matched into 3 age cohorts (65‐74, ≥75, and 18‐50 years), received GLPG1205 50 mg or placebo once daily for 14 days; an open‐label part of this study evaluated a GLPG1205 250‐mg loading dose followed by 50 mg once daily for 13 days in 8 healthy men (aged 68‐74 years). Single (up to 800 mg) and multiple (maximum tolerated dose 100 mg once daily) GLPG1205 doses had favorable safety and tolerability profiles. After single administration of GLPG1205, median time to occurrence of maximum observed plasma concentration and arithmetic mean apparent terminal half‐life ranged from 2.0 to 4.0 and from 30.1 to 140 hours, respectively. Age did not affect GLPG1205 exposure. GPR84 receptor occupancy with GLPG1205 vs placebo confirmed target engagement. These results support further clinical development of GLPG1205.

We studied the effect of an anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice against the background of doxorubicin treatment. It was shown that administration of an anthocyanincontaining complex from S. aucuparia L. prevented the development of anemic syndrome by stimulating regeneration of the erythroid lineage of hematopoiesis after its devastation by single administration of the cytostatic.

Since its outbreak in December, 2019, the novel coronavirus has wreaked a havoc across the world. Stringent measures such as lockdown and self-isolation were imposed in various nations to curb the transmission of the life-threatening virus. India had been under a complete lockdown from 25th March, 2020 to 3rd May,2020, compelling its citizens to stay indoors for an unprecedented amount of time. The ‘stay at home orders’ had serious implications on the mental health of the people. In light of the on-going pandemic, the current study aims to understand the lockdown experience of young married adults and its relationship with their psychological well-being. Also, with a spike in the digital habits of young adults during the Covid-19 lockdown, we intended to explore the impact of technology on the psychological well-being of its users. A convenience sample of 140 married, young adults (20 to 40 years old), staying with their partners in different parts of the country, was selected for the study. A single administration of WHO QOL BREF and self-constructed Lockdown Experience Scale was carried out. A separate list of technology usage items was also presented to the participants. Due to lockdown, the questionnaires were administered through Google forms. Results indicate that Lockdown Experience (Quality of Partner Relationship, sharing of household responsibilities, Personal Space) correlated significantly with Psychological Well Being as well as with Technology Use. Implications and suggestions for future research have been given.

Background/Aim. Organophosphate pesticides (OPs) are used extensively worldwide in agriculture and forestry, and their application represents a major health problem for humans and animals. The aim of this study was to investigate the possibility of the adaptation of an organism to the prolonged administration of a low dose of diazinon. Methods. The study was conducted on a total of 60 male Wistar rats. The first 30 rats were divided into four equal diazinon groups (n = 6) and the control one (corn oil). Diazinon was orally administered once at doses: 200, 400, 600, 800 mg/kg (one dose – one group). The concentration of glucose, the activity of α-amylase and the relative activity of LDH1-LDH5 isoenzymes in the blood were measured 24 hours after the application. The remaining 30 rats were divided into two equal diazinon groups (n = 10) and the control one (corn oil). The first group was treated during 7 days, and the second during 14 days with 55 mg/kg of diazinon (1/10 of previously determined LD50 value). The histopathology of the pancreas and the liver, as well as the relative activities of LDH isoenzymes in the blood, were determined after the completion of both time periods. Results. Single administration of increasing doses of diazinon resulted in a significant increase in the concentrations of glucose, activity of α-amylase and LDH isoenzymes. Subacute application of a low diazinon dose induced histopathological changes in the pancreas manifested by acinar cell necrosis, and in the liver in the form of portal hepatitis and multifocal necrosis. The cumulative doses resulted in statistically significantly lower activities of LDH isoenzymes compared with the single administration of these doses, indicating a lower degree of the cells damage after the subacute diazinon administration. Conclusion. Subacute administration of a low dose of diazinon leads to a different adaptation degree of organs and organ systems to toxic effects caused by this organophosphate. Uvod/Cilj. Organofosfatni pesticidi (OP) se intenzivno koriste širom sveta u poljoprivredi i šumarstvu, a njihova primena predstavlja značajan zdravstveni problem kod ljudi i životinja. Cilj ove studije bio je da se ispita mogućnost adaptacije organizma na prolongiranu primenu niskih doza diazinona. Metode. Studija je sprovedena na ukupno 60 pacova muškog pola Vistar soja. Prvih 30 pacova je podel-jeno u četiri jednake grupe tretirane diazinonom (n = 6) i kontrolnu grupu (kukuruzno ulje). Diazinon je primenjivan jednokratno peroralno u dozama: 200, 400, 600, 800 mg/kg (jedna doza – jedna grupa). Koncentracija glukoze, aktivnost α-amilaze i relativna aktivnost LDH1-LDH5 izoenzima u krvi, određivani su 24 sata nakon aplikacije. Preostalih 30 pacova je podeljeno u dve jednake diazinon grupe (n = 10) i kontrolnu grupu (kukuruzno ulje). Prva grupa je tretirana 7 dana, a druga 14 dana sa 55 mg/kg diazinona (1/10 prethod-no određene vrednosti LD50). Histopatologija pankreasa i jetre i određivanje relativne aktivnosti LDH izoenzima u krvi urađeni su po završetku oba vremenska perioda. Rezultati. Jednokratna primena rastućih doza diazinona rezultirala je statistički značajnim povećanjem koncentracije glukoze, ak-tivnosti α-amilaze i LDH izoenzima. Subakutna primena niske doze diazinona indukovala je histopatološke promene u pankreasu manifestovane acinarnom nekrozom, a u jetri promene su se ispoljile u vidu portalnog hepatitisa i multi-fokalne nekroze. Кumulativne doze diazinona rezultirale su statistički značajno nižom aktivnošću LDH izoenzima u poređenju sa jednokratnom primenom tih doza, što ukazuje na niži stepen oštećenja ćelija posle subakutne primene dia-zinona. Zaključak. Subakutna primena niske doze diazinona dovodi do različitog stepena adaptacije organa i organskih sistema na toksične efekte izazvane tim organofosfatom.

Neurodegenerative pathologies affecting the posterior segment of the eye such as diabetic retinopathy, age related macular degeneration and glaucoma are among the main causes of blindness in the world. They have in common that are cronic, multifactorial and in some cases related with the elderly. The treatment of these pathologies require to maintain therapeutic concentrations in the posterior segment thanks to the use of successive intraocular injections which are associated to secondary effects being poor tolerated by patients. Intraocular drug delivery systems emerged as an alternative to frequent injections as they are able to deliver the therapeutic agent in a controlled fashion into the eye after a single administration. Depending on the biomaterial these delivery systems are biodegradable or non biodegradable. Attending to their sizes, drug delivery systems are classified in implants (>1mm), microsystems (1-1000μm) y nanosystems (1-1000nm). Biodegradable microspheres emerge as therapeutic tools of great interest for the treatment of neurodegenerative pathologies as they can encapsulate active substances of distinct nature and provide release profiles tailoring with clinical needs. Furthermore, it is possible to administer different amounts of microspheres which correspond to the most adequated doses of the medicine in a personalized therapy. The simultaneous encapsulation of several active substances in the microspheres are of great interest in the treatment of multifactorial diseases covering different therapeutic targets.

Evaluation of the immunotropic effect of albendazole in low therapeutic doses has been carried out based on testing the ability of CBA × C57BL/6 mice lines to induce a delayed-type hypersensitivity (DTH) and the synthesis of antibodies against the thymus-dependent antigen. It has been shown that albendazole at doses of 2.5 and 5.0 mg/kg had no effect on the immune response of the cellular and humoral type. The DTH indices were 10.1 ± 3.14 and 10.8 ± 2.45%, respectively, and slightly exceeded those in the control by 3.1 and 10.2%. When albendazole was administered to immunized animals at doses of 2.5 and 5.0 mg/kg, log1/2 of the blood hemagglutinin titer was 6.8 ± 0.46 and 7.0 ± 0.47, and effect indices of albendazole were 1.03 and 1.06. The titer of hemagglutinins in the blood of experimental animals exceeded that in the control by 3.0 and 6.1%, respectively. It has been shown that immunocompetent cells, which functionally provide the formation of delayed-type hypersensitivity and the synthesis of antibodies against the thymus-dependent antigen, are tolerant to albendazole. Albendazole at low therapeutic doses of 2.5 and 5.0 mg/kg with a single administration did not have immunotropic activity. At the tested doses, albendazole is not a regulator of cellular and humoral processes since it does not contribute to modulation of the functional activity of immunocompetent cells and their cooperative interaction, which are necessary for the development of an immune response of the cellular and humoral type.

The leaves of Alchornea cordifolia are traditionally used by African populations for the treatment of several diseases. The acute toxicity study concluded that the total aqueous extract of Alchornea cordifolia (ETAAC) is not toxic by single administration and that its LD50 is greater than 5000 mg/kg of body weight (bw). Tests carried out by daily administration of ETAAC did not result in any significant change in the body weight of the animals and the weight of vital organs. After 28 days of treatment, no significant difference was observed in the figurative elements of the blood and in the biochemical parameters. Significant decreases were observed in urea and alanine-amino transferase after 60 days of treatment. Alchornea cordifolia does not affect the functioning of the kidneys, liver and heart. It is therefore not toxic at doses of 100 mg/kg of bw, 200 mg/kg of bw and 400 mg/kg of bw in rats.

Iron deficiency anemia (IDA) treatment is done to eliminate the causes of iron deficiency, iron supplementation, and rarely red blood cell transfusion. Divalent iron salts are the first line of oral treatment, but their use lead to frequent gastrointestinal adverse reactions. Iron is administered intravenously in the event of contraindications, intolerance, or inefficiency of oral therapy, but the parenteral route of drug delivery is not easily accepted by the patients. Intravenous preparations for single administration of a large dose of iron have a good therapy safety profile, but are more expensive than oral and are usually administered in a hospital setting. The availability of new iron compounds: sucrosomial iron, ferric citrate complexes, and ferric maltol widen the possibilities of IDA therapy and enable the better selection of iron preparations in various clinical situations. The innovative structure of sucrosomial iron leads to absorption in different ways (through endocytosis, the paracellular pathway, M cells of Peyer's patches), ensures high bioavailability, and good tolerance of therapy. Ferric citrate, in addition to iron supplementation, reduces phosphate levels, and is beneficial to chronic kidney disease. Ferric maltol is currently being studied for IDA treatment with various comorbidities. Some studies indicate that new iron formulas may be used where intravenous intake has been recommended so far. So, we can expect treatment with iron nanoparticles and drugs that affect the intestinal microflora in the future. The paper presents current knowledge about new iron preparations that are already available in everyday practice, but also those that are at various stages of pre-clinical and clinical studies.

Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core-shell microneedles-which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics-for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.

Objective We utilized a computerized order entry system–integrated function referred to as “void” to identify erroneous orders (ie, a “void” order). Using voided orders, we aimed to (1) identify the nature and characteristics of medication ordering errors, (2) investigate the risk factors associated with medication ordering errors, and (3) explore potential strategies to mitigate these risk factors. Materials and Methods We collected data on voided orders using clinician interviews and surveys within 24 hours of the voided order and using chart reviews. Interviews were informed by the human factors–based SEIPS (Systems Engineering Initiative for Patient Safety) model to characterize the work systems–based risk factors contributing to ordering errors; chart reviews were used to establish whether a voided order was a true medication ordering error and ascertain its impact on patient safety. Results During the 16-month study period (August 25, 2017, to December 31, 2018), 1074 medication orders were voided; 842 voided orders were true medication errors (positive predictive value = 78.3 ± 1.2%). A total of 22% (n = 190) of the medication ordering errors reached the patient, with at least a single administration, without causing patient harm. Interviews were conducted on 355 voided orders (33% response). Errors were not uniquely associated with a single risk factor, but the causal contributors of medication ordering errors were multifactorial, arising from a combination of technological-, cognitive-, environmental-, social-, and organizational-level factors. Conclusions The void function offers a practical, standardized method to create a rich database of medication ordering errors. We highlight implications for utilizing the void function for future research, practice and learning opportunities.

Background:Psilocybin is a serotonergic psychedelic found in “magic mushrooms” with a putative therapeutic potential for treatment-resistant depression, anxiety, obsessive-compulsive disorder, and addiction. In rodents, psilocybin acutely induces plasticity-related immediate early genes in cortical tissue; however, studies into the effects on subcortical regions, of different doses, and the subsequent translation of corresponding proteins are lacking.Methods:We examined the acute effects of a single administration of psilocybin (0.5–20 mg/kg) on the expression of selected genes in the prefrontal cortex and hippocampus. In total, 46 target genes and eight reference genes were assessed using real-time quantitative polymerase chain reaction. Corresponding protein levels of the three most commonly regulated genes were assessed using Western blotting.Results:In the prefrontal cortex, psilocybin increased the expression of Cebpb, c-Fos, Dups1, Fosb, Junb, Iκβ-α, Nr4a1, P11, Psd95, and Sgk1, and decreased the expression of Clk1. In the hippocampus, psilocybin strongly increased the expression of Arrdc2, Dusp1, Iκβ-α, and Sgk1 in a dose-dependent manner, and decreased the expression of Arc, Clk1, Egr2, and Ptgs2. Protein levels of Sgk1, Dusp1, and Iκβ-α showed only partial agreement with transcriptional patterns, stressing the importance of assessing downstream translation when investigating rapid gene responses.Conclusion:The present study demonstrates that psilocybin rapidly induces gene expression related to neuroplasticity, biased towards the prefrontal cortex, compared to the hippocampus. Our findings provide further evidence for the rapid plasticity-promoting effects of psilocybin.

The aim of this study was to determine if a single administration of dinoprost tromethamine before each test enhances sexual behaviour in inexperienced rams, and if the possible effect is maintained after the rams gain sexual experience. The study was conducted in northeaster Mexico during autumn (breeding season). The study was performed with 26 Saint Croix rams (16.1 ± 1.1 months old). Rams were allocated to two treatments, which were subjected to 15 tests with 2 restrained non-oestrous ewes. While rams from one group (group DIN) received a single dose of dinoprost (10 mg im, Lutalyse, Zoetis) immediately before the test, the other rams remained untreated (group CON). Sexual behaviours were recorded during 5 min. The data were analysed with a mixed model that included the treatment, number of test and their interaction as main effects, and the individual as a random effect. DIN rams displayed less ano-genital sniffings (6.6 ± 0.8 vs 9.7 ± 0.8, P = 0.007), matings (0.11 ± 0.05 vs 0.29 ± 0.05, P = 0.03), and had a lower mating/total mounts ratio (0.05 ± 0.03 vs 0.16 ± 0.03, P = 0.006) than CON rams. There were no other treatment effects, but there were significant effects of time and interactions between treatment and time in all the behaviours. Overall, administration of a single dose of dinoprost before testing did not have positive effects in the development of rams' sexual behaviour, and even, might have negative effects. However, it should be considered that in this study only one prostaglandin analogue, one dose of this analogue, administered immediately before the tests was used, so more studies involving other analogues, doses, and/or regimes of administration should be done.

1-Substituted (2S,4S)-4-amino-5-oxoprolines have been obtained by nucleophilic substitution of bromine in dimethyl (2S,4RS)-4-bromo-N-phthaloylglutamate followed by isolation of the predominant (2S,4S)-diastereomer and removal of protecting groups. The psychotropic activity of the obtained compounds has been studied after a single administration in experimental animals. 4-Amino-1-(4-bromophenyl)-5-oxoproline and especially 4-amino-1-(4-aminophenyl)-5-oxoproline showed pronounced anxiolytic activity in the Elevated plus maze test. (2S,4S)-4-Amino-5-oxoprolines containing 4-methylphenyl, 4-bromophenyl, 4‑aminophenyl, and 2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl substituents at the 1-position exhibited nootropic activity: they improved the formation and retention of the memory trace in the Passive avoidance test and the Active avoidance test (Extrapolation escape test).

Local radiation injuries in the form of radiation ulcers resulting from the local exposure to ionizing radiation are characterized by a long wave-like course, poor prognosis for self-healing and require specialized high-tech treatment techniques. Damage to vessels of the microvasculature being a component of their pathomorphogenesis along with the damage to the epithelial and connective tissue cells, is one of the reasons for the morphological features of this type of damage. Gene induction of the vascular growth in the microvasculature can be a component of the local treatment of local radiation injuries. The aim of the study was to assess the effect of a pro-angiogenic gene therapeutic preparation based on pl-vegf165 (Neovasculgen, Russia) on the healing process of simulated long-term nonhealing severe local radiation injuries (ulcers). Material and methods. The study included white male rats (n=40), which were divided into 4 groups, 10 animals in each group: a control group, a group with a single administration of the preparation in 14 days after irradiation, a group with a double administration of the preparation in 14 and 27 days after exposure, and a group with a single late administration of the preparation in 35 days after exposure. Macroscopic planimetry was the main criterion for assessing the healing process. Routine histological and morphometric investigations were also performed. Results . The study results demonstrated that statistically significant differences in the dynamics of local radiation injury healing on the criterion “the ulcer surface area” were registered between the control group and experimental groups in the long-term period – in more than 60 days. Conclusion. The results obtained can be due to the development of new blood vessels of the microvasculature resulting from the gene induction of angiogenesis.

The objective of ovarian superstimulatory treatments in cattle is to obtain the maximum number of viable embryos by stimulating growth of antral follicles and ovulation of competent oocytes. While factors inherent to the donor animal are critical, an increased knowledge of ovarian physiology, gonadotropin biochemistry and the ability to manipulate ovarian function have provided alternatives for the design of simple and successful protocols for superovulation in cattle. Recent protocols have also been made more user-friendly and allowed for the grouping of donors for successful superovulation. Although the number of reports associating FSH profiles with superovulatory response is limited, studies designed to reduce the number of FSH treatments necessary to induce superstimulation may provide guidance for the development of optimized gonadotropin treatment protocols. Although high peak levels of circulating FSH following a single administration of Folltropin-V have been shown to be associated with a reduced superstimulatory response, the ideal treatment protocol would seem to be to increase circulating FSH levels to values comparable to those required for the induction of follicle wave emergence, and to maintain these levels for at least 72 h (or 36 h for superstimulation prior to ovum pick-up) to allow follicles to reach an ovulatory size and acquire the capacity to ovulate.

The effects of a proteolytic enzyme found in papaya milk juice (caripazim) on the rate of lymphatic drainage of tissues and the pharmacokinetics of cefotaxime were studied in experiments on rabbits and mice. During the study, caripazim was administered to experimental animals, and the rate of removal of Evans blue from the mesentery of mice, as well as the concentration of cefotaxime over time in the blood plasma of rabbits and the blood plasma, intestinal tissues, and livers of mice, after 1.5 and 24 h of antibiotic administration following injection of caripazim, were determined. Thus, the lymphostimulatory properties of caripazim were revealed. Its preliminary administration increased the concentration of cefotaxime in the blood plasma of rabbits in comparison with single administration of an antibiotic at all points of the study (1.5, 3, 4.5, 6, 8, 12, and 24 h). This coincides with the data from the study of the level of antibiotic in the blood plasma of mice. Administration of cefotaxime after injection of caripazim leads to an increase in its content in the intestinal tissue, after both 1.5 and 24 h, but does not affect at the accumulation of the antibiotic in the liver. The concentration ratio liver tissue / blood in mice in the main group was significantly lower than that in the control group, both 1.5 and 24 h into the experiment, which indirectly indicates a decrease in hepatic antibiotic extraction. The data obtained indicates that caripazim has the properties of an endolymphatic conductor.

Background Amblyomma americanum and Rhipicephalus sanguineus (sensu lato) nymphs commonly feed on and transmit pathogens to dogs (Canis familiaris). Control of immature and adult tick life stages is necessary to fully protect animals. We evaluated efficacy of oral fluralaner (Bravecto®) against induced infestations with A. americanum and R. sanguineus (s.l.) nymphs on dogs in two experiments. Methods In each experiment, 10 dogs were administered oral fluralaner chewable tablets one time on Day 0 at a targeted minimum dose of 25 mg/kg body weight and 10 dogs remained non-treated controls. Dogs were infested with two groups of 50 A. americanum nymphs and two groups of 50 R. sanguineus (s.l.) nymphs on Days -1, 6, 28, 56 and 84. At 48 h and 72 h post-infestation, nymphs were collected from dogs, assessed as live or dead, and enumerated into categories defining attachment and engorgement status. Fluralaner efficacy was determined in separate analyses against all live nymphs and against live-fed nymphs, i.e. live nymphs that were attached to dogs at the time of collection and/or were engorged. Fluralaner was considered effective when mean numbers of live ticks were reduced in fluralaner-treated dogs by ≥ 90%. Results Fluralaner efficacy against all live and live-fed A. americanum nymphs in the first experiment was > 94% on all collection days. Efficacy against all live R. sanguineus (s.l.) nymphs in the first experiment was > 96% on all collection days excluding the 48 h counts for infestations on Days 28 (83.7%), 56 (82.9%) and 84 (86.7%); efficacy against live-fed R. sanguineus (s.l.) nymphs was > 95% on all 48 h/72 h count days. Fluralaner efficacy against all live A. americanum nymphs in the second experiment was > 93% on all collection days for 8 weeks excluding the 48 h count for infestation on Day 56 (87.8%); efficacy against live-fed A. americanum nymphs was > 91% on all count days for 8 weeks. Efficacy against all live R. sanguineus (s.l.) nymphs in the second experiment was > 91% on all 72 h collection days except for infestations on Days 28 (76.8%) and 56 (86.3%); efficacy against live-fed R. sanguineus (s.l.) nymphs was 100% on all 72 h count days. Conclusions A single administration of oral fluralaner to dogs is effective against A. americanum and R. sanguineus (s.l.) nymphs for up to 12 weeks.

To discuss the potential use of transcranial direct current stimulation (tDCS) to improve motor behavior after brain injury. Despite evidence that tDCS can improve motor function following brain injury, meta-analysis studies have largely failed to find conclusive support for tDCS as a viable treatment. In part, these inconsistencies arise from widespread variability in individuals’ responsiveness to tDCS because of biological and experimental factors. Properly designed smart clinical studies are still needed to determine the optimal stimulation parameters and combinations of tDCS. However, some patterns of “best practice” have begun to emerge: (1) pairing tDCS concurrently with high-intensity motor training as opposed to before, after, or in the absence of physical practice, (2) repeating sessions of stimulation in close succession over a single administration, (3) administering stimulation during more acute periods of recovery over chronic states, and (4) utilizing modeling techniques based on individual anatomy to tailor electrode placement and optimize current flow.

Purpose Electricity utilization at electricity peak hour may differ from every single administration region, for example, mechanical region, business territory and residential zone. This paper introduces a demand-side load management (DSM) strategy, which is one of the utilization of smart grid (SG) that is fit for controlling loads inside the residential working so that the client fulfillment is augmented at least expense. Design/methodology/approach In this paper, a heuristic algorithms-based energy management controller is intended for a residential region in a SG. Here, Antlion Optimization technique is used for DSM techniques such as load shifting, peak clipping, and valley filling in the residential sectors for 24 h with the help of stochastic function to determine the detection of random distribution of the load. Findings This proposed algorithm offered the greatest fulfillment and least expense caused by the consumers when compared to the traditional cost by taking the individual consumer preferences for the loads and the ideal time scheduling for the load, which is obtained from the rebuilding trap. Originality/value Simulation results demonstrate that the comparison of the cost incurred by the users obtained by the DSM techniques is satisfiable.

This study was to compare the pharmacokinetic characteristics of domestic altrenogest oral solution (DAOS) or imported altrenogest oral solution (IAOS) in healthy sows. A single administration (1 mg/kg body weight) of DAOS or IAOS was performed in sixteen healthy sows according to a two-period crossover design. Plasma concentrations of altrenogest (AT) were measured by high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) and the concentration-time data of AT was analyzed by WINNONLIN 5.2. It was suggested that the main pharmacokinetic parameters of DAOS and IAOS were as follows

Long-acting drug delivery system is a development in pharmaceutical technology to minimize the disadvantages of other routes of administration such as oral, transdermal, and injectable administration. The major advantage of this system is the ability to maintain the drug concentration in plasma between the therapeutic ranges after a single administration. Consequently, multiple administrations are no longer required. Long-acting delivery can be achieved through nanoparticles, long-acting depot, and implantable devices. Several aspects related to the long-acting and implantable delivery system are comprehensively discussed in this chapter, including classification and drug release mechanism from the systems, and materials and fabrication method that can be used to prepare them. Finally, the recent updates on implantable devices design are also presented in this chapter.

Bestanchuk E., Gozhenko A., Kashchenko O., Narbutova T., Berezovskyi O., Zаkharova V. Cardiotoxic effect of bleomycin with a single administration in the experiment. Journal of Education, Health and Sport. 2021;11(10):242-251. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.10.022 https://apcz.umk.pl/JEHS/article/view/JEHS.2021.11.10.022 https://zenodo.org/record/5636149 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 30.09.2021. Revised: 12.10.2021. Accepted: 29.10.2021. Cardiotoxic effect of bleomycin with a single administration in the experiment E. Bestanchuk1, A. Gozhenko2, O. Kashchenko3, T. Narbutova3, O. Berezovskyi4, V. Zаkharova5 1Odessa Regional Oncological Dispensary, Odessa, Ukraine 2Ukrainian Research Institute of Transport Medicine of the Ministry of Health of Ukraine, Odessa, Ukraine 3Odessa National Medical University, Odessa, Ukraine 4"ODREX" Medical Center, Odessa, Ukraine 5Amosov National Institute of Cardiovascular Surgery, Kiev, Ukraine The aim of the study was to evaluate the effect of a single injection of bleomycin on the heart Material and methods. The study was conducted in the Research Institute of Transport Medicine during 2016-2021. The experimental model of the cardiotoxic effect of the bleomycin was performed using the medication "Bleocin" manufactured by Nippon Kayaku Co., Ltd. (Japan). According to the task, the study was performed on 10 mature rats of both sexes of the Wistar line with a body weight of 237 ± 20 g. Rats were housed in standard vivarium conditions of Odessa National Medical University. Animals were divided into 2 groups: experimental group (n = 5) and control (n = 5). Bleomycin animals of the experimental group were obtained intraperitoneally at a dose of 0.5 IU / kg once. Withdrawal of animals from the experiment was performed on the 5th day of the experiment, followed by morphological and morphometric examination. Statistical processing of the obtained data was performed by methods of variance, correlation and regression analysis using Statistica 14.0 software (TIBCO, USA) Results. Single administration os bleomycin causes changes in macroscopic parameters (myocardial weight, visual changes) are minimal. The main changes at the microscopic level are represented by contractural degeneration with segmental and / or partial-lateral lysis, ie there is not total but partial myocardial damage. Conclusion. A single injection of bleomycin can cause inflammatory-dystrophic changes of the myocardium. Key words: cardiotoxicity; low dose; single dose; pathology; bleomucin; experimental study

Psychedelics have inspired new hope for treating brain disorders, as they seem to be unlike any treatments currently available. Not only do they produce sustained therapeutic effects following a single administration, they also appear to have broad therapeutic potential, demonstrating efficacy for treating depression, post-traumatic stress disorder (PTSD), anxiety disorders, substance abuse disorder, and alcohol use disorder, among others. Psychedelics belong to a more general class of compounds known as psychoplastogens, which robustly promote structural and functional neural plasticity in key circuits relevant to brain health. Here we discuss the importance of structural plasticity in the treatment of neuropsychiatric diseases, as well as the evidence demonstrating that psychedelics are among the most effective chemical modulators of neural plasticity studied to date. Furthermore, we provide a theoretical framework with the potential to explain why psychedelic compounds produce long-lasting therapeutic effects across a wide range of brain disorders. Despite their promise as broadly efficacious neurotherapeutics, there are several issues associated with psychedelic-based medicines that drastically limit their clinical scalability. We discuss these challenges and how they might be overcome through the development of non-hallucinogenic psychoplastogens. The clinical use of psychedelics and other psychoplastogenic compounds marks a paradigm shift in neuropsychiatry toward therapeutic approaches relying on the selective modulation of neural circuits with small molecule drugs. Psychoplastogen research brings us one step closer to actually curing mental illness by rectifying the underlying pathophysiology of disorders like depression, moving beyond simply treating disease symptoms. However, determining how to most effectively deploy psychoplastogenic medicines at scale will be an important consideration as the field moves forward.

Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies (n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.

The reaction of 2-chloroethylisocyanate and 2-amino-1,3-propanediol in MeCN–MeOH yielded 2-[3-(2-chloroethyl) ureido]-1,3-propanediol, which was nitrosated using sodium nitrite in 50% formic acid to obtain 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol (chlonisol). A single administration of chlonisol at a non-toxic dose of 15 mg/kg increased by 170% the median life expectancy of mice with P-388 leukemia and cured 100% of rats with Walker 256 carcinosarcoma.

We report the case of a 4-year-old boy who presented with cyclic esotropia in the setting of a Chiari type I malformation. He was treated with a single administration of botulinum toxin and remained orthotropic at 7-months. To our knowledge, this is the first reported case of cyclic esotropia with Chiari I malformation successfully treated using botulinum toxin.

The purpose of the study is to determine the pharmacokinetic parameters of a new ester derivative of indomethacin — codenamed indomenthyl — after its administration to rats. Indomenthyl was administered into stomach of rats as a solution in flaxseed oil: single administration at a dose of 12.5, 25 and 50 mg/kg, or multiple administration once a day at a dose of 50 mg/kg for 7 days. Blood plasma levels of indomenthyl and its active metabolite indomethacin were detected using a high-performance liquid chromatograph with the ultraviolet spectrophotometric detector. It was shown that the value of the systemic exposure AUC of indomenthyl and indomethacin, released during its hydrolysis, increases linearly in the dose range of 12.5–50 mg/kg. On repeated (7-fold) administration indomenthyl and indomethacin do not cumulate in the organism. Thus, indomenthyl may be considered a safe retarded release form of indomethacin for the treatment of inflammatory diseases.