Social behavior and spatial orientation in rat strains with genetic predisposition to catatonia (GC) and stereotypes (PM)

Various psychopathologies, including schizophrenia, bipolar disorder and major depression, are associated with abnormalities in social behavior and learning. One of the syndromes that may also take place in these disorders is catatonia. Catatonia is a psychomotor syndrome in which motor excitement, stereotypy, stuporous state, including the phenomenon of “waxy flexibility” (catalepsy), can be observed. Rats with genetic catatonia (GC) and pendulum-like movements (PM) of the anterior half of the body have physiological and behavioral changes similar to those observed in schizophrenia and depression in humans and can be considered as incomplete experimental models of these pathologies. The social behavior of the GC and PM rats has not been previously studied, and the cognitive abilities of animals of these strains are also insufficiently studied. To determine whether the GC and PM rats have changes in social behavior and spatial learning, behavioral phenotyping was performed in the residentintruder test, three-chamber test, Barnes maze test. Some deviations in social behavior, such as increased offensive aggression in PM rats in the resident-intruder test, increased or decreased social interactions depending on the environment in different tests in GC, were shown. In addition, principal component analysis revealed a negative association between catatonic freezing and the socialization index in the three-chamber test. Decreased locomotor activity of GС rats can adversely affect the performance of tasks on spatial memory. It has been shown that PM rats do not use a spatial strategy in the Barnes maze, which may indicate impairment of learning and spatial memory

Non-Alcoholic Fatty Liver Disease in Cardiac Patients with Overweight and Obesity

Aim. In this research, we set out to study organic changes in the heart and blood vessels of obese men suffering from non-alcoholic fatty liver disease (NAFLD) combined with cardiac pathology in the metabolically unhealthy phenotype (MUHP). Another objective consisted in establishing a relationship between liver damage and the pathology of the heart and blood vessels.Materials and methods. A group of 112 men (male)aged 61.2±1.7 diagnosed with the ischemic heart disease (IHD) and stage 1–3 arterial hypertension (AH) were examined during the stationary treatment in the Republican Clinical Diagnostic Centre (Izhevsk, Russia). The patients were divided into 3 groups according to their body mass index (BMI): 29 men with a BMI under 25 kg/m2(I group); 43 overweight men a BMI over 25 of kg/m2(II group); 40 men with obesity and a BMI above 30 of kg/m2(III group). Laboratory and non-invasive instrumental examinations required for the diagnostics of NAFLD and IHD were carried out, including liver ultrasound and FibroScan elastometry. Other examinations included the measurement of the intra-abdominal adipose tissue (IAT) and epicardial adipose tissue (EAT) thickness, the calculation of the visceral adiposity index (VAI), the estimation of endothelial dysfunction indicators, as well as the assessment of the structural and functional parameters of the heart and blood vessels.Results. In obese patients with pronounced NAFLD signs, IAT, EAT and VAI indicators are shown to increase in direct correlation with the parameters of liver steatosis. A relationship is established between the most significant structural and functional indicators of the heart (myocardial mass index, volume of the left atrium), blood vessels (endotheliumdependent vasodilation, the size of the intima-media complex of the common carotid artery) and NAFLD. It is demonstrated that the correlation coefficients grow with the progression of fatty infiltration and liver fibrosis signs.Conclusions. The results of the study have revealeda connection between the NAFLD presence and the main markers of visceral fat depots (IAT, EAT, VAI), which is shown to increase the risk of cardio-vascular complications in such patients. NAFLD is accompanied by endothelial dysfunction and a change in the most significant parameters of cardiac and vascular remodelling. These parameters manifest the progression of pathological changes in the liver parenchyma, which increases the cardio-metabolic risk in patients with MUHP

Safety of Therapy with Tocilizumab and Other Interleukin Inhibitors

Monoclonal antibodies directed against interleukin and interleukin receptors have been successfully used for the treatment of rheumatic diseases since 2001, and since 2020 they have been used as part of complex therapy for patients with severe COVID-19. This raises the question of safety of these products, especially when used for new indications. The aim of the study was to analyse data on potential adverse reactions to tocilizumab and other interleukin inhibitors in order to increase the safety of pharmacotherapy of systemic connective tissue diseases, as well as of severe COVID-19. Literature data suggest that the most frequent adverse reactions to tocilizumab and other interleukin inhibitors are infections, hypercholesterolemia, leukopenia, neutropenia, thrombocytopenia, and increased liver enzyme activity. Hypersensitivity and acute infusion reactions, manifested as pseudoallergic reactions, also pose serious health risks and can even be fatal. However, the identification of undesirable reactions to interleukin inhibitors is challenging, due to their prolonged intake and long intervals between injections. Besides, they are often used in combination with other medicines, such as methotrexate or glucocorticosteroids, which complicates establishment of a reliable correlation between an adverse reaction and a particular medicine. At present, the safety of tocilizumab and other interleukin inhibitors for the treatment of severe COVID-19 has not been studied properly and needs further research with an increased number of participants and a careful analysis of the risk/benefit ratio of these medicines when used for COVID-19 treatment

Experience of Using Remdesivir in Patients with Novel Coronavirus Infection

Timely, effective, and safe antiviral therapy in COVID-19 patients reduces complications, disability and mortality rates. The greatest concern with remdesivir is the risk of drug-induced liver injury, including in patients whose liver function is compromised by COVID-19.The aim of the study was to investigate the efficacy and safety of remdesivir in patients with confirmed SARS-CoV-2 infection who had been admitted to an infectious diseases hospital in the Volgograd region in March 2022. Materials and methods: the authors carried out an open, non-randomised, single-arm study using medical records of 234 patients who had been diagnosed with “U07.1 COVID-19, virus identified” and prescribed remdesivir upon admission. The effectiveness of therapy was evaluated using two criteria: the need for oxygen supplementation or ventilatory support, or mortality. The authors conducted the evaluation on days 7, 14, and 28 using the six-point ordinal severity scale by Y. Wang et al. The safety of therapy was assessed on the basis of complaints and changes in laboratory findings.Results: for the patients prescribed remdesivir at admission, the 7-day mortality rate was 3.0%, the 14-day mortality rate was 5.6%, and the 28-day mortality rate was 7.3%. With the exception of a patient with myocardial infarction, all the patients who had been hospitalised with mild COVID-19 and prescribed remdesivir did not require oxygen therapy and/or transfer to intensive care and were discharged following recovery. The patients with moderate to severe COVID-19 had the 14-day mortality rate of 6.4% and the 28-day mortality rate of 8.6%. 17 patients (7.2%) discontinued remdesivir prematurely for various reasons, including adverse drug reactions. Remdesivir therapy of 5-10 days was associated with an increase in ALT activity by 2.7 ± 0.8 times in 15.9% of patients with mild COVID-19, by 3.8 ± 1.8 times in 20.4% of patients with moderately severe COVID-19, and by 4.8 ± 2.7 times in 24% (12/50) of patients with severe COVID-19. In two patients (0.9%), the increase exceeded 10-fold the upper limit of normal.Conclusions: the obtained results support recommending remdesivir to patients with mild, moderate and severe COVID-19, including those with moderately elevated baseline activity of hepatic transaminases

Expression of catecholaminergic genes in the midbrain and prepulse inhibition in rats with a genetic catatonia

The GC rat strain (from the words "genetic" and "catatonia") was created by selection for predisposition to passive-defensive reaction of catatonic freezing in response to stressing stimuli. Rats of the GC strain have previously demonstrated a number of biochemical and behavioral properties similar to those of patients with schizophrenia and depression. Prepulse inhibition (PPI) is widely explored as an important indicator, a decrease of which may be indicative of psychopathology, including schizophrenia. It has been established that the brain noradrenergic system influences the manifestation of PPI, in particular through the activation of central alpha-adrenoreceptors. Also known is the association between PPI and expression of catechol-O-methyltransferase. This study focuses on the reaction of prepulse inhibition in rats of the inbred GC strain, being considered as a hypothetical model of schizophrenia, as well as on the relation of prepulse inhibition to mRNA expression of tyrosine hydroxylase, catechol-O-methyltransferase, alpha1A- and alpha2Aadrenergic receptors in the midbrain of GC rats. For the first time, a decrease of PPI in GC rats compared with WAG rats was shown, both with a prepulse power of 75 dB and at 85 dB, which may indicate a violation of filtration of sensorimotor information into the central nervous system in GC rats. Real-time PCR showed a decrease in mRNA level of Adra1A in intact rats with genetic catatonia when compared to control WAG rats. There was observed no correlation between the expression of mRNA of the Adra1A, Adra2A, Th, and Comt genes in the midbrain and the PPI reaction in GC rats. The reduction of prepulse inhibition in GC rats indicates functional similarity of this genetic model of schizophrenic psychopathology with a prototype. © AUTHORS, 2017.Russian Foundation for Basic Research, RFBR: 16­04­013250324­2016­0002This study was supported by the Russian Foundation for Basic Research, project 16­04­01325, and State Budgeted Project 0324­2016­0002

Effects of pot fishing on the physical condition of snow crab (Chionoecetes opilio) and southern Tanner crab (Chionoecetes bairdi)

The effects of commercial fishing with crab pots on the physical condition of the snow crab (Chionoecetes opilio) and southern Tanner crab (C. bairdi) were investigated in the Bering Sea and in Russian waters of the Sea of Okhotsk. In crabs that were subjected to pot hauling, the presence of gas embolism and the deformation of gill lamellae were found in histopathological investigations. Crab vitality, which was characterized subjectively through observation of behavioral responses, depended on not only the number of pot hauls but also the time between hauls. Immediately after repeated pot hauls at short time intervals (≤3 days), we observed a rapid decline in vitality of crabs. When hauling intervals were increased to >3 days, the condition of crabs did not significantly change. After repeated pot hauls, concentration of the respiratory pigment hemocyanin ([Hc]) was often lower in the hemolymph of crabs than in the hemolymph of freshly caught animals. Our research indicated that changes in [Hc] in crabs after repeated pot hauls were caused by the effects of decompression and not by starvation of crabs in pots or exposure of crabs to air. We suggest that the decrease in [Hc] in hemolymph of snow and southern Tanner crabs was a response to the adverse effects of decompression and air-bubble disease. The decrease in [Hc] in affected crabs may be a result of mechanisms that regulate internal pressure in damaged gills to optimize respiratory circulation

Omega-3 Polyunsaturated Fatty Acids: the Role in Prevention of Atrial Fibrillation in Patients with Coronary Artery Disease after Coronary Artery Bypass Graft Surgery

Aim. To estimate the role of omega-3 polyunsaturated fatty acids (PUFAs) administration in atrial fibrillation (AF) prevention after planned coronary artery bypass graft (CABG) surgery.Material and Methods. Studied were 306 patients divided into two groups: patients of group I didn’t receive PUFAs (158 patients, 82.7% males) and patients of group II received PUFAs (148 patients, 89.3% males). PUFAs were prescribed in daily dose 2000 mg 5 days before surgery and in daily dose 1000 mg in postoperative period during 21 days.Results. Postoperative AF (POAF) occurred in 29.7% patients in group I and in 16.9% patients in group II (р=0.009). We found that after CABG in patients of the I group median IL-6 level was 39.3% higher (p=0.001), interleukin-10 – 20.2% higher (p=0.01), superoxide dismutase – 78.9% higher (р<0.001), malondialdehyde – 33.8% higher (p=0.03), docosahexaenoic acid – 31.8% lower (p=0.01) and omega-3 index – 43.4%    lower (p=0.04) than in patients of the II group.According to multivariate regression analysis we found significant association between the factors of inflammation, oxidative stress and the risk POAF development.Conclusions. In patients who took PUFAs, we found less activation of inflammation, oxidative stress, the increasing of docosahexaenoic acid and omega-3 index accompanied by the decreasing of POAF development rates up to 12.8%

Состояние новорожденных после конверсии эпидуральной анальгезии в анестезию при кесаревом сечении: проспективное рандомизированное исследование

АКТУАЛЬНОСТЬ: При проведении эпидуральной анальгезии (ЭА) в родах в случае необходимости оперативного родоразрешения встает вопрос о выборе дальнейшей тактики регионарной анестезии. В статье рассмотрены особенности влияния местных анестетиков на состояние новорожденного при проведении конверсии ЭА в анестезию при необходимости выполнения операции кесарева сечения в зависимости от используемого местного анестетика. ЦЕЛЬ ИССЛЕДОВАНИЯ: Оценить состояние новорожденного при проведении конверсии ЭА в родах через естественные родовые пути в анестезию при кесаревом сечении в зависимости от применяемого местного анестетика. МАТЕРИАЛЫ И МЕТОДЫ: Проведено проспективное рандомизированное исследование 143 детей, рожденных от матерей, которым проводили конверсию ЭА в анестезию для оперативного родоразрешения методом кесарева сечения. В зависимости от используемого местного анестетика пациенток распределили на три группы, в 1-й группе в эпидуральное пространство вводили 20,0 мл 2 % раствора лидокаина в комбинации с 0,1 мг эпинефрина, во 2-й группе — 20,0 мл 0,5 % раствора бупивакаина, в 3-й — 20,0 мл 0,75 % раствора ропивакаина. Оценку состояния новорожденных проводили по шкале Апгар на 1-й и 5-й минутах жизни и по шкале NACS в первые 15 мин, через 2, 24 и 72 ч после рождения. РЕЗУЛЬТАТЫ: Оценка новорожденных по шкале Апгар независимо от применяемого местного анестетика при эпидуральной анестезии на 1-й и 5-й минутах соответствовала 7 баллам и более (р > 0,05). Психоневрологическое состояние новорожденных при оценке по шкале NACS статистически значимо не различалось во всех группах и на всех этапах исследования. Внутри каждой группы между этапами исследования средние значения оценок по NACS статистически значимо увеличивались по сравнению с предыдущим. ВЫВОДЫ: Конверсия ЭА в родах через естественные родовые пути в анестезию при кесаревом сечении безопасна для плода и новорожденного при использовании 20,0 мл 2 % раствора лидокаина в комбинации с 0,1 мг эпинефрина или 20,0 мл 0,5 % раствора бупивакаина либо 0,75 % раствора ропивакаина в объеме 20,0 мл

Development and validation of CAPS-marker associated with the <i>Rf2</i> gene in sorghum (<i>Sorghum bicolor</i> (L.) Moench)

Background. The development of heterotic hybrids based on cytoplasmic male sterility (CMS) is the leading strategy in breeding sorghum (Sorghum bicolor (L.) Moench). The trait of pollen fertility restoration in forms with CMS A1 (milo), predominantly used in sorghum breeding, is determined by at least two dominant complementary genes Rf1 and Rf2, and also gene Rf5. The development of accessible molecular markers of sorghum Rf genes is highly relevant for hybrid breeding, since they can significantly accelerate the process of creating female sterile forms (A lines), sterility maintainers (B lines) and pollen fertility restorers (R lines).Material and methods. The studied material included 36 sorghum accessions from the VIR collection, which differed by the ability to restore pollen fertility in forms with A1-type CMS. The nucleotide polymorphism of 935 bp fragments of the PPR genes Sobic.002G057050, Sobic.002G054100, and Sobic.002G054200 located at the chromosome 2 was studied.Results. The fragments obtained with the use of a pair of 2459403fw and 2459403 primers were 935 bp long and included parts of three genes: Sobic.002G057050, Sobic.002G054100, Sobic.002G054200. For identifying the sequence variant Sobic.002G057050-1090 associated with the Rf2 gene, Tru9 I restrictase was chosen, which allows obtaining a 572 bp fragment unique for all the studied R lines. Such a marker was found in 10 sorghum lines from West China and Kyrgyzstan, which are widely used in breeding as fertility restorers. The fragment was found neither in three lines with sterile cytoplasm and their fertile analogues, nor in 7 accessions of kafir sorghum, which lacked functional alleles of Rf genes.Conclusions. It has been demonstrated that the marker can be used for selection and checking purity of R and B/A lines. It is also applicable for verifying hybridity of F1 seeds and analyzing hybrid populations from crosses of R lines 924-4, 928-1, 929-3, 931-1, 933-1/6, 1237-3, 1243-2, 1251, 1150-1, F10BC2 with A lines Nizkorosloe 81s, А-83 and А-10598. It may be suggested that the ability to restore pollen fertility in R lines, which lack the marker CAPS- 572, is determined by another Rf gene. The studied 935 bp fragment of Sobic.002G057050 harbours 22 SNP, therefore the development of CAPS-markers for their identification and differentiation can be promising

Antibiotic Dosing in Chronic Kidney Disease

Infectious process is an important cause of morbidity and mortality among patients with chronic kidney disease. Prescription of antibacterial drugs should take into account the pharmacokinetic parameters of the medicine and the individual characteristics of the patient. Adequate antibiotic dosing is crucial for positive treatment outcome and minimisation of side effects. The aim of the study was to analyse scientific literature on factors affecting the dosing of antibacterials in patients with chronic kidney disease. Since most antibacterial medicines are eliminated by the kidneys, a decrease in glomerular filtration rate or kidney function should be followed by the dose adjustment in order to prevent the medicine accumulation and reduce the risk of side effects. Antibiotic dosing in such patients should be accompanied by kidney function assessment and be adjusted to ensure effective and safe treatment, as well as prevention of bacterial resistance. The review provides data on the dosing of some antibiotic groups (beta-lactams, aminoglycosides, fluoroquinolones) at different creatinine clearance rates. Extrarenal excretion of medicines does not usually require the dose adjustment in patients with chronic kidney disease