The Efficacy of a Peptide Product from the Pituitary Gland of Rangifer tarandus as an Antioxidant Agent Under the Combined Effects of Light Desynchronosis and Depriming Toxicant

The possibility of using methods for determining the oxidative status of an organism (enzymatic and non-enzymatic links of the cellular antioxidant system) to assess the antioxidant properties of peptides of the pituitary gland of the reindeer (Rangifer tarandus) were investigated in an experimental study conducted with a combined effect of factors of different nature on rats: a physical factor — prolonged light desynchronosis (different light modes) and a chemical factor - acute severe poisoning with depriving toxicant (sodium thiopental, LD50). The pharmacological correction of the oxidative status of cells in the animals of the experimental subgroups was carried out with the peptide product of the pituitary gland, intranasally injecting the surviving rats with the bioproduct at a dose of 100 µg/kg, once in the first half of the objective day for 14 days after poisoning with sodium thiopental. The surviving animals of the control groups were similarly injected with saline. The effectiveness of the correction of the disruptions of the cellular oxidative status with the peptide product of the pituitary gland was tested 30 days after the onset of the combined effect of stress factors on rats. It was found that the use of this bioactive peptide product in experimental animals exposed to different light modes and a chemical factor contributed to a decrease in the initially increased indicators of lipid peroxidation in rat erythrocytes and an increase in the initially reduced indicators of the enzymatic link of antioxidant protection. The activity of superoxide dismutase, glutathione peroxidase, glutathione transferase, as well as glucose-6-phosphate dehydrogenase increased after pharmacological correction. The concentration of reduced glutathione also increased in erythrocytes. The maximum changes were observed in the experimental subgroup of rats exposed to the combined effects of constant illumination and depriming toxicant. It was also found that the revealed positive changes in the indicators of the enzymatic link of antioxidant protection in animals of the experimental subgroups are associated with the maintenance of a sufficient concentration of reduced glutathione in red blood cells, which contributed to the maintenance of the cellular redox balance, when the conditions of the external lighting regime are violated.

Comparative characteristics of ketamine and sodium oxybutyrate as adjuvant sedation in patients with alcoholic delirium

Annotation. Today, the number of benzodiazepine-resistant alcoholic deliriums is growing. It is actually to search for an optimal scheme of sedation with a combination of two sedatives. The aim of the study was to compare efficacy of standard sedation with added barbiturates and the schemes with using ketamine and sodium oxybutyrate. We tested 60 cases of delirium tremens which were randomized into three groups. In the control group we conducted the traditional sedation with added sodium thiopental. In the first research group we combined the infusion of ketamine with diazepam. In the second one we gave sodium oxybutyrate with diazepam. We evaluated the duration of delirium, hemodynamics parameters, serum cortisol and serotonin, laboratory indicators of kidneys and liver condition. We used such statistical methods as Mann-Whitney test, Wilcoxon T-criterion and Kruskal-Wallis H-criterion. The duration of delirium was significantly lower in research groups in comparison with the control one. There was no difference of the duration of delirium between research groups. It indicates a comparable effect of using either ketamine, or sodium oxybutyrate. All groups showed significant reduction of hemodynamics parameters in the process of the treatment, however we observed more cases of hypertension and tachycardia on the third day of the treatment in the research groups than in the control one. These data suggest an insufficient effect of the combination of diazepam with both ketamine and sodium oxybutyrate on the sympatho-adrenal system. Serum cortisol was significantly reduced in all the groups, there was no difference between control and research groups. Serotonin was equally increased in all the groups on the third day. The obtained results indicate that the effectiveness of the combination of benzodiazepines with both ketamine and sodium oxybutyrate is comparable to the standard sedation regimen and does not differ in the reaction of these biomarkers. The laboratory indicators of kidneys condition on the third day increased only in the research groups, which indicates more negative influence on kidneys by both ketamine and sodium oxybutyrate. The indicators of liver condition were significantly reduced only in the group of ketamine, there were no difference in the rest groups. The use of ketamine and sodium oxybutyrate as adjuvant sedation may reduce the duration of a delirium episode, but has insufficient effect on hemodynamics and may adversely affect renal function.

Pharmacological Correction of Long-Term Effects of Acute Severe Poisoning with Sodium Thiopental under Chronic Light Desynchronosis

We experimentally studied the possibility of using a peptide extract from the pituitary gland of a reindeer (Rangifer tarandus) to correct the functional state of the body under the combined effect of acute severe poisoning with sodium thiopental in rats, at a dose of LD50 under long-term light desynchronosis. The research was conducted using the statistical method of two-factor analysis of variance. It was found that, under constant light, a peptide extract from the pituitary gland of a reindeer affects such parameters as diene conjugates concentration, the activity of glutathione-S-transferase and glucose-6-phosphate dehydrogenase. Under prolonged darkness, the extract under study affected the activity of glutathione-S-transferase, glutathione peroxidase and glucose-6-phosphate dehydrogenase.

Adequacy of maternal anesthesia depth with two sodium thiopental doses in elective caesarean section: a randomized clinical trial

Background Administration of an optimal dose of anesthetic agent to ensure adequate depth of hypnosis with the lowest risk of adverse effects to the fetus is highly important in cesarean section. Sodium thiopental (STP) is still the first choice for induction of anesthesia in some countries for this obstetric surgery. We aimed to compare two doses of STP with regarding the depth of anesthesia and the condition of newborn infants. Methods In this clinical trial, parturient undergoing elective Caesarian section were randomized into two groups receiving either low-dose (5 mg/kg) or high-dose (7 mg/kg) STP. Muscle relaxation was provided with succinylcholine 2 mg/kg and anesthesia was maintained with O2/N2O and sevoflurane. The depth of anesthesia was evaluated using isolated forearm technique (IFT) and bispectral index (BIS) in various phases. Additionally, infants were assessed using Apgar score and neurobehavioral test. Results Forty parturient were evaluated in each group. BIS was significantly lower in high-dose group at skin incision to delivery and subcutaneous and skin closure. Also, significant differences were noticed in IFT over induction to incision and incision to delivery. Apgar score was significantly lower in high-dose group at 1 min after delivery. Newborn infants in low-dose group had significantly better outcomes in all three domains of the neurobehavioral test. Conclusion 7 mg/kg STP is superior to 5 mg/kg in creating deeper hypnosis for mothers. However, it negatively impacts Apgar score and neurobehavioral test of neonates. STP seems to has dropped behind as an acceptable anesthetic in Cesarean section. Trial registration IRCT No: 2016082819470 N45, 13/03/2019.

STUDYING SEDATIVE ACTIVITY OF COMBINED TINCTURE OF MOTHERWORT AND ST JOHN'S-WORT

The paper presents studying sedative activity of the combined tincture of motherwort and St. John's wort. The combined tincture of motherwort and St. John's wort was obtained by percolation method in a ratio 1:10. Standardization of the obtained tincture was carried out with quality indicators: description, content of active ingredients and ethanol, relative density, dry residue. According to all quality indicators, the tincture obtained met the requirements of the State Pharmacopoeia of the Republic of Belarus. Specific sedative activity of the combined tincture of motherwort and St. John's wort was assessed by barbiturates hypnotic effect prolongation (sodium thiopental), by the rate of falling asleep in animals and by animals staying in lateral position in relation to the control group to which sodium thiopental was injected. In the studies carried out it was found that injection of the combined tincture of motherwort and St. John's wort at a dose of 0,1 ml / kg increases sleep by 125,63% and also accelerates the process of falling asleep by 327,75% compared with the separate injection of motherwort and St. John's wort tincture at doses of 0,1 ml/kg. It was shown that the injection of the combined tincture of motherwort and St. John's wort at a dose of 0,1 ml/kg exhibits a potentiated effect and enhances the hypnotic effect of sodium thiopental administered at a dose of 10 mg/kg.

Features of anesthesia during ophthalmic interventions in children with perinatal lesions of the central nervous system

Purpose. To study the frequency and severity of hypertensive-hydrocephalic syndrome in children planning to undergo ophthalmic surgery, to assess the adequacy of the anesthesia performed. Material and methods. The clinical material was selected by the method of continuous sampling from 4 637 children. Of these, two age groups were formed. The 1st group consisted of 220 children under the age of 6 years, to whom the induction of anesthesia was carried out with the drug «Sevoran». Group 2 included 56 older children (from 7 to 17 years old), who received anesthesia induction with propofol or sodium thiopental. Both groups were comparable in terms of the severity of the hypertensive-hydrocephalic syndrome. Results. Throughout the entire operating period, no complications arose in any case. Within 1–3 hours after waking up, 32 children of the 1st group and 6 children of the 2nd group complained of an isolated headache. Postoperative nausea and vomiting were observed in 22 children of the 1st group and 6 children of the 2nd group. In 30% of cases in children of the 1st group, postoperative reactions were expressed by aggressive behavior, disorientation in place and time, violation of behavioral reactions. In group 2, such reactions were detected only in 10% of cases. All negative manifestations were arrested by parenteral administration of midazolam at a dose of 3–5 mg. Conclusion. For the induction of anesthesia in young children with the presence of hypertensive-hydrocephalic syndrome, the optimal use of the drug «Sevoran». The drugs of choice for anesthesia in children over 6 years of age are propofol and sodium thiopental. The use of artificial ventilation in a moderate hyperventilation mode avoids an increase in intracranial pressure. Adequate analgesia avoids many adverse reactions. Keywords: hypertensive-hydrocephalic syndrome, general inhalation anesthesia, ophthalmic surgery.

Experimental research of cerebroprotective activity of the new 4-aminobutatanoic acid derivative

The aim. To study the cerebroprotective activity of a new derivative of 4-aminobutanoic acid the compound KGM-5 on the effect on survival and behavioural responses, cognitive impairment and neurological deficits in rats with acute cerebrovascular accident. Materials and methods. Acute cerebrovascular accident (ACVA) was simulated in rats by irreversible unilateral carotid occlusion (UCO) under anesthesia with sodium thiopental (35 mg/kg, intraperitoneally, IP). Five groups of animals were used: intact control (IC, n=6), a group of animals with ACVA, which were not treated (control pathology, CP, n=13); group of animals with ACVA, which were treated for 5 days after surgery (first injection 30 min before surgery) with the compound KGM-5 (ACVA+KGM-5, n=14) at a conditionally effective dose of 30 mg/kg body weight of animals, a group of animals with ACVA (ACVA+CD “Picamilon”, n=13), who received IP for 5 days, the comparison drug (CD) “Picamilon” at a dose of 17 mg/kg and pseudo-operated animals (POA), n=8), which were operated without ligation of the carotid artery, which allows to level the effect of anesthesia and surgery on the studied indicators. The cerebroprotective effect of the studied agents was assessed by an integral criterion – survival of animals (throughout the experiment), indicators of neurological deficit (24, 48, 72, 94 hours after ACVA modelling), the state of cognitive functions in the test of extrapolation escape test (EET) (72 hours after ACVA modelling) Results. The KGM-5 compound contributed to a significant reduction in the severity of neurological deficit, as evidenced by significant differences in this indicator compared with CP, respectively, the first (0.5 points vs. 1.25 points, p<0.05), the third (0.0 points against 1.0 point, p<0.05) and the fourth day (0.0 points vs. 0.5 points, p<0.05) after OCO. Under the influence of CD “Picamilon” reduction of neurological deficit compared with CP was observed on the first, third and fourth days, but these differences were insignificant (p>0.05). Both studied agents - the compound KGM-5 and CD “Picamilon” contributed to the improvement of cognitive functions of rats with ACVA, as evidenced by a significant reduction (p<0.05) of the latent period of diving in the EET, respectively, 1.8 and 1.7 times compared with CP and did not show a significant effect on animal survival. Conclusion. The cerebroprotective activity of a new 4-aminobutanoic acid derivative in the conditions of acute cerebrovascular accident in rats was established in terms of the ability to reduce the severity of neurological deficits and improve cognitive functions in the extrapolation escape test. The severity of cerebroprotective activity of the new compound is not inferior to GABA-ergic drug “Picamilon”.

Influence of a new derivative of 4-aminobutanoic acid on the level of neuromediatory aminoacids, neuromediators and the state of the rats’ hypocamp in conditions of brain ischemia

The aim: to investigate the effect of a new derivative of 4-aminobutanoic acid (compounds KGM-5) on the level of neurotransmitters and neurotransmitter amino acids and the structural-functional state of the hippocampus of rats with acute cerebrovascular accident (ACVA). Materials and methods. ACVA was reproduced in rats by occlusion of the left carotid artery under anesthesia (sodium thiopental (35 mg/kg) intraperitoneally (i/p). 5 groups of animals were used: intact control (IC, n=6), untreated animals with ACVA (CP, n=13); animals with ACVA (n=14), which were treated for 5 days with KGM-5 at a dose of 30 mg/kg i/p, animals with ACVA (n=13), who received i/p comparison drug “Picamilon” (17 mg/kg). There was a group of pseudo-operated animals (POA, n=8). Withdrawal of animals from the experiment was performed on day 6 after modeling ACVA by painless euthanasia under anesthesia. Histological examinations of CA1 and CA3 zones of the ventral hippocampus were performed with staining of sections with thionine by the method of Nissl and hematoxylin, eosin. In the rat brain, neurotransmitter amino acids and neurotransmitters were identified. Statistical processing was performed using the W-Shapiro-Wills test to verify the normality of the distribution and the nonparametric Mann-Whitney U-test. The accepted significance level is p<0.05. Results. Under the influence of the compound KGM-5 and “Picamilon” in the CA1 zone of the hippocampus, the number of normochromic neurons increased by 20 % and 16.6 %, respectively, hyperchromic pycnomorphic neurons and shadow cells decreased respectively by 5.8; 2.9 times and 6.3; 3.5 times, the index of alteration of neurons decreased by 6 times and 4.8 times, respectively, the area of ​​the perikaryon of these neurons increased by 39.7 % and 77.8 %, respectively, compared with KP (p<0.05). Both studied agents showed a less pronounced normalizing effect on the CA3 area of the hippocampus. The new compound KGM-5 showed a normalizing effect similar to “Picamilon” on the level of neurotransmitter amino acids and neurotransmitters in the brain of rats with ACVA. Conclusions. Therapeutic administration of KGM-5 increases the survival of ventral hippocampal neurons, reducing the relative proportion of irreversibly altered cells, and helps to restore impaired levels of neurotransmitter amino acids and neurotransmitters in the brain of rats with ACVA. The neuroprotective effect of the new compound KGM-5 corresponds to this comparison drug “Picamilon”

Comparison of the efficacy of ketamine– propofol versus sodium thiopental–fentanyl in sedation: a randomised clinical trial

BackgroundMany sedative regimens have been studied with controversial efficiencies. This study tried to assess the desirable and adverse effects of sodium thiopental–fentanyl (TF) with ketamine–propofol (KP) for procedural sedation and analgesia in the emergency department.MethodsAfter signing written consent, patients were enrolled in this randomised double-blind trial to receive either KP or TF to reach the desired sedation level. The respiratory and haemodynamic complications, nausea and vomiting, recovery agitation, patient recall and satisfaction, provider satisfaction and recovery time were compared.ResultsOf the participants, 47 in the KP group and 49 in the TF group were enrolled. The mean and SD scores were 6.91±1.93 and 8.34±1.25 for patients’ satisfaction and 7.55±1.54 and 8.65±1.00 for satisfaction of physicians performing the procedures in TF and KP groups, respectively (p=0.000). Moreover, 39 (79.59%) and 18 (38.29%) of patients declared that they had recalled the procedures in the TF and KP groups, respectively (p=0.000). Transient hypoxia was reported in 2.1% and 8.1% in the KP and TF groups leading to perform 4.2% vs 8.1% airway manoeuvres, respectively, without the need for endotracheal intubation or further admission.ConclusionsKP and TF combinations were effectively comparable although KP resulted in higher patient and provider satisfaction. This study did not detect a difference regarding adverse respiratory or haemodynamic effects. It is estimated that the TF combination can be potent and efficacious with possible low adverse events in procedural sedation.