Pharmacological Substances Research Articles

Clinical, radiological and pathochemical substantiation of osteosubstitution by hydroxyapatite ceramics with β-tricalcium phosphate and platelet-enriched autofibrin in fragmentary bone fractures in dogs

Due to the similarity of its composition to bone tissue, bioactive ceramics based on hydroxyapatite are considered the most promising for osteosubstitution of fragmentary fractures, and topical application of pharmacological agents and autologous agents bioactive substances, in particular, platelet-rich fibrin (PRF). The work aims to clinically and radiologically, and pathochemically substantiate osteosubstitution by hydroxyapatite ceramics with β-tricalcium phosphate and platelet-enriched fibrin for fragmentary bone fractures in dogs. A control and two experimental groups of animals were formed, including patients (n = 10) with humerus and forearm fractures. After general and local anesthesia and extracortical osteosynthesis, the first experimental group was injected with platelet-rich autofibrin between bone fragments. The second group was osteosubstituted with a combination of PRF and hydroxyapatite ceramics; in the control group, the defects remained without replacement. For biochemical studies, blood samples were taken after injury no later than 24 hours and on the 3rd, seventh, 14th, 21st, and 42nd day after osteosynthesis. In the postoperative period, clinical and radiological studies were performed. The activity of bone isoenzyme alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TrAP), the level of total calcium (Ca), inorganic phosphorus (P), and total protein were determined in blood serum. It was found that complete recovery of limb function in the experimental groups was 1.2–1.4 times faster (P < 0.001) compared with the control group and radiologically confirmed earlier consolidation of fractures. In both experimental groups, the maximum activity of BAP was observed on the 14th day, in the absence of a significant difference between these groups, while in control – it peaked on the 21st day. In the case of bone injury, the level of TrAP decreased by 1.2 times (P < 0.05) and then gradually increased, which was significant in the control group on the 42nd day, in the first experimental group on the 21st, and the second on the 14th day. On the third day after osteosynthesis, the concentration of P was still lower in the control (P < 0.05) and the first experimental (P < 0.01) group compared with clinically healthy animals. The concentration of Ca on the third day was reduced in all groups by 1.2 times (P < 0.001) and then gradually returned to normal. The use of PRF with calcium-phosphate ceramics for osteosubstitution helps to optimize regeneration processes in the area of bone injury by activating osteoblastic cells and reducing the intensity of the osteoresorption reaction with an earlier reaction of bone regeneration remodeling.

Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system.

Since the beginning of pharmaceutical research, drug delivery methods have been an integral part of it. Polymeric micelles (PMs) have emerged as multifunctional nanoparticles in the current technological era of nanocarriers, and they have shown promise in a range of scientific fields. They can alter the release profile of integrated pharmacological substances and concentrate them in the target zone due to their improved permeability and retention, making them more suitable for poorly soluble medicines. With their ability to deliver poorly soluble chemotherapeutic drugs, PMs have garnered considerable interest in cancer. As a result of their remarkable biocompatibility, improved permeability, and minimal toxicity to healthy cells, while also their capacity to solubilize a wide range of drugs in their micellar core, PMs are expected to be a successful treatment option for cancer therapy in the future. Their nano-size enables them to accumulate in the tumor microenvironment (TME) via the enhanced permeability and retention (EPR) effect. In this review, our major aim is to focus primarily on the stellar applications of PMs in the field of cancer therapeutics along with its mechanism of action and its latest advancements in drug and gene delivery (DNA/siRNA) for cancer, using various therapeutic strategies such as crossing blood-brain barrier, gene therapy, photothermal therapy (PTT), and immunotherapy. Furthermore, PMs can be employed as "smart drug carriers," allowing them to target specific cancer sites using a variety of stimuli (endogenous and exogenous), which improve the specificity and efficacy of micelle-based targeted drug delivery. All the many types of stimulants, as well as how the complex of PM and various anticancer drugs react to it, and their pharmacodynamics are also reviewed here. In conclusion, commercializing engineered micelle nanoparticles (MNPs) for application in therapy and imaging can be considered as a potential approach to improve the therapeutic index of anticancer drugs. Furthermore, PM has stimulated intense interest in research and clinical practice, and in light of this, we have also highlighted a few PMs that have previously been approved for therapeutic use, while the majority are still being studied in clinical trials for various cancer therapies.

Mechanistic Aspects of the Asymmetric Transfer Hydrogenation in the Manufacture of Noradrenaline

AbstractMechanistic, stereochemical and stereoelectronic aspects of the asymmetric reduction (via hydrogen or transfer hydrogenation) for the manufacture of N‐benzyl‐noradrenaline from the ketone precursor are studied through catalyst screening and computational evaluations. This reaction provides an efficient and industrially suitable method for the manufacture of enantiomerically pure noradrenaline, an important neurotransmitter which is widely used as a pharmacological substance due to its sympathomimetic properties.

Influence on study outcomes of an inpatient study by the behavior of the study staff (PINgPOng): study protocol for a randomized clinical trial

BackgroundThe placebo effect as the symptom improvement following inert treatments is a fixed component of RCTs to differentiate between specific effects of the tested pharmacological substance from other unspecific effects. The PINgPOng study was set up to analyze the influence of a study team trained to either minimize the placebo response and optimize drug-placebo differences or to maximize the placebo response to increase drug efficacy by unspecific factors on the study results of a RCT in a classical early clinical trial setting.Methods/designPINgPOng is a single-center, prospective, randomized, double-blind, placebo-controlled study in a 3-group, 2-sequence, 2-period cross-over design. The study is conducted according to the principles of ICH-GCP and the Declaration of Helsinki on the Phase I-Unit of the University Hospital Bonn. The primary endpoint is the pain intensity in the cold pressor test before and after the administration of 15 mg oxycodone or placebo. The pain intensity is compared between three study conditions: 32 healthy volunteers in each study arm will be treated either by an untrained study team (arm A), by a study team trained to maximize (arm B), or to minimize placebo responses (arm C). Neuroendocrine factors (alpha-amylase activity, salivary cortisol), characteristic traits (anxiety, depression, stress), and somatic reactions are analyzed as covariates of the pain perception.DiscussionThe PINgPOng study will allow to answer the question whether and to what extent the behavior of a trained study team (neutral vs. maximize vs. minimize placebo responses) will differentially affect placebo responses in a setting of a highly standardized early clinical trial. The results will help to control the placebo effects by education of the clinical study team and to avoid unnecessary high placebo effects in clinical development.Trial registrationGerman Clinical Trials Register DRKS00013586. Registered on December 22, 2017.

Calcium imaging in intact mouse acinar cells in acute pancreas tissue slices.

The physiology and pathophysiology of the exocrine pancreas are in close connection to changes in intra-cellular Ca2+ concentration. Most of our knowledge is based on in vitro experiments on acinar cells or acini enzymatically isolated from their surroundings, which can alter their structure, physiology, and limit our understanding. Due to these limitations, the acute pancreas tissue slice technique was introduced almost two decades ago as a complementary approach to assess the morphology and physiology of both the endocrine and exocrine pancreas in a more conserved in situ setting. In this study, we extend previous work to functional multicellular calcium imaging on acinar cells in tissue slices. The viability and morphological characteristics of acinar cells within the tissue slice were assessed using the LIVE/DEAD assay, transmission electron microscopy, and immunofluorescence imaging. The main aim of our study was to characterize the responses of acinar cells to stimulation with acetylcholine and compare them with responses to cerulein in pancreatic tissue slices, with special emphasis on inter-cellular and inter-acinar heterogeneity and coupling. To this end, calcium imaging was performed employing confocal microscopy during stimulation with a wide range of acetylcholine concentrations and selected concentrations of cerulein. We show that various calcium oscillation parameters depend monotonically on the stimulus concentration and that the activity is rather well synchronized within acini, but not between acini. The acute pancreas tissue slice represents a viable and reliable experimental approach for the evaluation of both intra- and inter-cellular signaling characteristics of acinar cell calcium dynamics. It can be utilized to assess many cells simultaneously with a high spatiotemporal resolution, thus providing an efficient and high-yield platform for future studies of normal acinar cell biology, pathophysiology, and screening pharmacological substances.

Patient-derived xenografts of colorectal cancer for testing new pharmacological substances.

e15612 Background: The purpose of this study was to create a patient-derived xenograft model of human colorectal cancer and to determine its histological and molecular characteristics, including the status of the KRAS, NRAS, BRAF genes and the presence of microsatellite instability factors. Methods: Biological materials obtained from tumors of 4 patients with colorectal cancer were used to create the first-generation in vivo model. The study was performed on immunodeficient Balb/c Nude mice (20 females aged 5-6 weeks). Subcutaneous xenografts were obtained by the implantation of a 3×3×3 mm donor tumor fragment to recipient animals under the skin of the right thigh, 5 samples from each patient. For the second, third and fourth PDX generations, mice of the same strain were used (n = 3 for each generation). All manipulations were performed in accordance with the rules for using laboratory animals. Genomic DNA was extracted from PDX samples, and mutations in exons 2, 3 and 4 of the KRAS and NRAS genes and BRAF V600 mutations were identified by direct sequencing. Microsatellite instability was determined by fragment analysis for five loci Bat-25, Bat-26, NR21, NR24, NR27. Results: Stable transplantable xenografts of colorectal cancer were obtained from two out of four patients. The average waiting time between implantation and growth of the first-generation xenograft was 28 days. The model was confirmed to reproduce the histotype, differentiation and mutational status of the KRAS, NRAS, BRAF genes and microsatellite instability similar to those of donor tumors. Conclusions: The results confirm the possibility of the model use for testing both new pharmacological substances with a cytotoxic effect and drugs based on monoclonal antibodies.

Antitumor effectiveness of combination therapy with platinum and hybrid organotin compound on the Lewis epidermoid carcinoma model with metronomic administration.

e15080 Background: The prevalence of lung malignancies in Russia in 2019 was 100.5 per 100,000 population, which is 2.5% more than in the previous year. Drug therapy remains one of the main methods of treatment of malignant lung neoplasms. An urgent task for specialists in experimental pharmacology and oncology is searching for new antitumor compounds. Hybrid organotin compound (3,5-di-tert-butyl-4-hydroxyphenylthiolate)triphenylol) is a promising candidate for antitumor drugs [Milaeva E.R. et al. Novel selective anticancer agents based on Sn and Au complexes. Pure & Applied Chemistry. 2020, 92, 1201-1216]. The combined administration of platinum antitumor drug and an organotin compound will increase the effectiveness of therapy and reduce the general toxic effect on the body. Methods: The study was conducted on C57bl/6 mice (females, n = 48, each cohort contained 12 mice) on the Lewis epidermoid carcinoma model (subcutaneous transplantation) [Frantsiants E.M. et al. Method for Stimulation of Malignant Growth by Chronic Pain in Rat Lungs. Bulletin of Experimental Biology and Medicine. 2020, 169(2), 290–292]. Cisplatin-Teva (CP) and (3,5–di–tert–butyl–4–hydroxyphenylthiolate)triphenylolol) (Me-5) were used as chemotherapeutic agents. Groups of animals were formed as follows: I (experimental) - CP at a dose of 1 mg/kg + Me-5 at a dose of 25 mg/kg; II (comparison group) - CP at a dose of 1 mg/kg; III (comparison) - Me-5 at a dose of 25 mg/kg; IV (control group) - without pharmacological substances. All manipulations were carried out according to the European Convention for ETS 123. The compounds were administered intraperitoneally daily during 10 days. 21 days after the subinoculation of tumor cells all animals were euthanized. The antitumor effect was estimated by the percentage inhibition of tumor growth by weight. Results: The combination of the studied substances has a more pronounced antitumor effect. The percentage of reduction in the mass of the primary focus in group I was 38.1%, in group II - 20.4%, in group III - 12%. The obtained results showed that the percentage of inhibition of tumor growth by weight with a tenfold combined administration of Cisplatin-Teva and Me-5 on the Lewis epidermoid carcinoma model was significantly higher than the previously obtained result when studying the combination of Cisplatin-Teva and Me-5 with a five-fold administration [Dodokhova M.A. et al. Effect of cisplatin and hybrid organotin compound in low doses on the growth and metastasis of lewis epidermoid carcinoma in experiment. Eksperimental'naya i Klinicheskaya Farmakologiya. 2021, 84(8), 32–35], which is 38.1% and 25%, respectively. Conclusions: The research suggests a multifactorial mechanism of action of hybrid organotin compounds.

Antitumor pharmacological activity of hybrid organotin compounds on the Lewis epidermoid carcinoma model.

e15004 Background: New antitumor agents based on organic metal derivatives are intensively determined and created by now. Tin compounds are of great interest among them [Milaeva E.R.et al. Novel selective anticancer agents based on Sn and Au complexes. Pure & Applied Chemistry. 2020, 92, 1201-1216]. The results of studies on cell line models allowed us to conclude that cytotoxic effect of organotin compounds is pronounced, so it is advisable to hold their further studies on biological models in vivo [ Dodokhova M.A. et al. Pharmacotherapeutic potential’s evaluation of organotin compounds in vivo Biopharmaceutical journal, 13(3), 30 – 34 (2021); doi: 10.30906/2073-8099-2021-13-3-30-34]. For the specialists of experimental pharmacology and oncology is relevant to rate the antitumor activity of hybrid organotin compounds on experimental malignant tumors. Methods: The study was held on C57Bl/6 mice (females, n = 36, each cohort contained 12 mice) on a Lewis epidermoid carcinoma model (subcutaneous transplantation) [Kit O.I. et al. Influence of chronic neurogenic pain on the dynamics of the no-system functioning during melanoma B16/F10 growth in male mice. Siberian Journal of Oncology, 2021, 20(3), 67–75]. Bis-(3,5-di-tert-butyl-4-hydroxyphenyl)dimethyl tin(Me-3) and (3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenyl tin (Me-5) were used as chemotherapeutic agents. Groups of animals were formed as follows: I (experimental) - Me-3 at a dose of 75 mg / kg; II (experimental) - Me-5 at a dose of 50 mg / kg; III (control group) - without pharmacological substances. The doses were characterized as the most effective according to the results of a pharmacological activity screening study. The compounds were injected intraperitoneally daily for 5 days. All animals were euthanized since 21 days after the tumor cells transplantation. The antitumor effect was estimated by the percentage of tumor growth inhibition by weight (%). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Results: After the intraperitoneal injection of chemical substances Me-3 and Me-5, there was revealed an inhibition of growth by weight of Lewis epidermoid carcinoma’s primary node for all experimental groups, 23.7% and 28% respectively. Conclusions: The injection of organotin compounds with different ligand groups allows us to suggest a biocidal activity of the organotin component on the primary tumor node cells.

Antimetastatic effect of benzimidazole derivative on the model of melanoma B16 in the experiment.

e21562 Background: Study of the influence of a pharmacological substance dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a] benzimidazole on the tumor growth on a model of experimental transplantable B16 melanoma in mice. Methods: B16 melanoma strain were transplanted subcutaneously to 80 female C57/Bl6 mice weighing 18-20 g. Intragastric dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a] benzimidazole injections (0.5 ml a day) began 48 h after tumor transplantation once a day for 10 days at single doses of 50, 220 and 500 mg/kg (groups 1, 2 and 3, respectively). Mexidol was used for comparison, and saline as control (injected at similar regimens and doses). Results: Intragastric enoxifol injections did not significantly inhibit the melanoma growth. Only group 2 showed inhibition of the tumor growth by 48.7 % on day 22. Median survival of mice in all experiment groups was similar to that in the control group. The number of metastatic nodes in the lung tissues in groups 1, 2 and 3 decreased by 2.1, 4.8 and 2.5 times, respectively, compared to controls. The average index of metastasis inhibition was 71.3 % in all groups being 1.3 times higher than in the mexidol group (54.2 %). Conclusions: The revealed significant changes in parameters of the metastatic activity of the tumor suppose that dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a] benzimidazole at all studied doses has a greater effect on the development of spontaneous lung metastases and metastasis rates than on the growth of primary B16 melanoma in mice.

Herbal Immunomodulator in View of Omicron Virus - A Review

The COVID-19 pandemic has caused a global medical crisis of unprecedented proportions. The death rate and infected people is rising on a daily basis all over the world. This situation is so much worse because of the potential for disasterous situations with variety of social and economic factors. Effective infection monitoring is still being developed, and efforts are being made to integrate traditional interventions with standard of care. With special reference to respiratory health, the Ministry of Aayush recommends the self-care guidelines for preventive health measures and boosting immunity. Ayurvedic literature and scientific publications back up these claims. There is a lot of research on natural substances that can affect immune function in addition to plant compounds. There are some examples suggest by Ministry of Aayush such as Gargle with a pinch of turmeric and salt in warm water. Gargling can also be done with water boiled with Triphala (dried fruits of Emblica officinalis, Terminalia chebula, and Terminalia bellerica) or Yashtimadhu (Glycyrrhiza glabra). Once or twice a day, apply medicated oil (Anu taila or Shadbindu Taila), plain oil (Sesame or Coconut), or nasal application of cow's ghee (Goghrita), especially before going out and after returning home. Antimicrobials, or "immune-boosters," are a class of plants that work directly on bacteria or viruses while also boosting the immune system's overall performance. Volatile oils are common, yet active pharmacological substances are numerous and complex. Herbs such as: Allium sativum (Garlic), Baptisia tinctoria (Wild Indigo), Echinacea sp. (Echinacea), Thuja occidentalis (Thuja), Usnea sp. (Old Man’s Beard).

Experimental approach to obtaining subcutaneous xenograft of non-small cell lung cancer

Purpose of the study. Was was the creation of a Patient Derived Xenograft (PDX) model of non‑small cell lung cancer in immunodeficient mice adapted to growth in immunodeficient mice.Materials and methods. The study was performed using the tumor material from 14 donors implanted subcutaneously to 132 immunodeficient Balb/c Nude mice. Xenografts were maintained until the third passage. PDXs in the third passage from 3 patients were used to assess the model sensitivity to cisplatin. A histological analysis and genetic tests for the presence of EGFR mutations were performed for donor tumors from 3 patients and the corresponding xenografts in the third passage.Results. We observed a noticeable PDX growth already on the 8th day after the tumor material implantation. Successful xenograft engraftment was noted in 21 of 42 mice (50 %), which were rather successful results. A comparative histological analysis of tumor material from 3 patients showed that the PDX models retained the original histotype. We also demonstrated the identity of the EGFR mutations in the established xenografts from 3 patients and the donor tumors, which proved the value of these PDX models for preclinical studies of substances with potential antitumor activity. The analysis of the xenograft sensitivity to cytostatic cisplatin showed a statistically significant decrease in the growth rate in the xenografts obtained from 2 out of 3 patients, in comparison with the control.Conclusions. The created PDX models can be recommended as test systems for preclinical studies of the effectiveness of new pharmacological substances with potential antitumor activity.

Model design for networks of heterogeneous Hodgkin–Huxley neurons

We present a novel modular, scalable and adaptable modelling framework to accurately model neuronal networks composed of neurons with different dynamic properties and distinct firing patterns based on a control-inspired feedback structure. We consider three important classes of neurons: inhibitory Fast spiking neurons, excitatory regular spiking with adaptations neurons, and excitatory intrinsic bursting neurons. We also take into consideration two basic means of neuronal interconnection: electrical and chemical synapses. By separating the neuronal dynamics from the network dynamics, we have developed a fully flexible feedback structure that can be further augmented to incorporate additional types of neurons and/or synapses. We use an augmented version of the Hodgkin–Huxley model to describe the individual neuron dynamics and graph theory to define the network structure. We provide simulation results for small fundamental neuron motifs as well as bigger neuronal networks and we verify the accuracy, flexibility and scalability of the proposed method. Therefore, we provide the basis for a comprehensive modelling framework that is able to imitate the dynamics of individual neurons and neuronal networks and is able to replicate basic normal brain function. The structure of the proposed framework is ideal for applications of control and optimization methods both for modelling the effect of pharmacological substances as well as for modelling diseased neuron and network conditions.

The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination.

Preterm birth (PTB) represents 15 million births every year worldwide and is frequently associated with maternal/fetal infections and inflammation, inducing neuroinflammation. This neuroinflammation is mediated by microglial cells, which are brain-resident macrophages that release cytotoxic molecules that block oligodendrocyte differentiation, leading to hypomyelination. Some preterm survivors can face lifetime motor and/or cognitive disabilities linked to periventricular white matter injuries (PWMIs). There is currently no recommendation concerning the mode of delivery in the case of PTB and its impact on brain development. Many animal models of induced-PTB based on LPS injections exist, but with a low survival rate. There is a lack of information regarding clinically used pharmacological substances to induce PTB and their consequences on brain development. Mifepristone (RU-486) is a drug used clinically to induce preterm labor. This study aims to elaborate and characterize a new model of induced-PTB and PWMIs by the gestational injection of RU-486 and the perinatal injection of pups with IL-1beta. A RU-486 single subcutaneous (s.c.) injection at embryonic day (E)18.5 induced PTB at E19.5 in pregnant OF1 mice. All pups were born alive and were adopted directly after birth. IL-1beta was injected intraperitoneally from postnatal day (P)1 to P5. Animals exposed to both RU-486 and IL-1beta demonstrated microglial reactivity and subsequent PWMIs. In conclusion, the s.c. administration of RU-486 induced labor within 24 h with a high survival rate for pups. In the context of perinatal inflammation, RU-486 labor induction significantly decreases microglial reactivity in vivo but did not prevent subsequent PWMIs.

Исследование общей и специфической токсичности рекомбинантного ангиогенина человека

Angiogenin exerted no toxic effects in acute toxicity tests, all animals successfully endured the maximally attainable dose 12 g/kg intragastrically. To assess the long-term/chronic toxicity, the gel-based composition containing 0.01 % of angiogenin was daily applied to the scarified skin areas of rats for 1 month. No significant changes or differences between the treated and control groups were detected by common biochemical, hematological and histological assays. No local irritating effects of 0.0025 % angiogenin gel were detected in appropriate tests using outbred chinchilla rabbits. Angiogenin did not cause neither sensibilization of guinea pigs in active cutaneous anaphylaxis test nor delayed hypersensitivity reaction in mice. No detectable immuno- and embryotoxicity of the preparation were observed. Angiogenin was proved to lack mutagenic and carcinogenic capabilities, as well as the capability of stimulating the tumor growth upon intratumoral administration. The tested preparation of angiogenin showed no toxic effects, including systemic, local irritating, sensibilizing and skin-resorptive ones, and, thus, recombinant human angiogenin is a safe pharmacological substance. 10.30906/2073-8099-2022-14-2-40-53

Therapeutic ultrasound and essential oil of melaleuca alternifolia interfere with muscle regeneration?

Currently the Essentials oil of Tea Tree is used in healing, for possessing various medicinal properties. Phonophoresis is a method used in physiotherapy, where pharmacological substances associated with a coupling agent, are induced by ultrasonic waves in the underlying tissues. Our objectives are aimed at monitoring and qualitative analysis of the lesion treated with the compound and the method accuracy phonophoresis. We used twenty (20) rats, which are divided into two (2) different groups: Group I: Rats harmed without intervention and Group II: Rats victims treated with the compound by Phonophoresis. Histological analysis showed the material collected in samples from animals in group I, an extensive and diffuse inflammation, unconnected with large amounts of inflammatory cells, as in group 2 inflammation comes in mild areas with limited, there is also muscle fiber regeneration. The results seem to demonstrate the efficacy of Melaleuca alternifolia essential oil by phonophoresis in the muscle fiber in the lesion region.

Microencapsulation of Lysiphyllum strychnifolium extract using pectin as a carrier matrix and its characterization

Lysiphyllum strychnifolium (Craib) A. Schmitz (LS, Fabaceae) is one of the folklore medicines in Thailand. The previous studies have demonstrated several pharmacological activities and high polyphenolic substances possessed by this plant. However, the suitable encapsulation of LS extract has not been discovered. This study aimed to develop LS microcapsules using spray-drying technique with pectin as a carrier. Moreover, the powder analysis and characterization were also conducted. The effects of inlet temperatures (80, 100, and 120°C) and carrier concentrations (1, 5, and 10 %w/v) on the encapsulation yield (EY), encapsulation efficiency (EE), total phenolic content (TPC), and main markers (trilobatin and yanangdaengin) of LS microcapsules were studied. Finally, the characterization was investigated by Fourier transform infrared (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The obtained results indicated that S2 microcapsule formulation, pectin to extract ratio 10:1 (w/w) at inlet temperature of 100°C, was chosen as the optimal condition because of the positive tendency to acquire higher EE as pectin level was increased. On the contrary, the level of TPC and markers was reduced due to the more addition of pectin. The FTIR, XRD, and DSC results suggested that the well-encapsulated microcapsules were obtained for S2 formulation and SEM represented the semi-spherical structure of its microstructures. The development of LS microcapsules with the proximity to gain the advantageous powder analysis and characteristic has been achieved. Therefore, this approach could be used for the subsequent manufacturing of LS extract.

INVESTIGATION OF THE IMMUNOTOXIC PROPERTIES OF STRAWBERRY GARDEN LEAF EXTRACT DRY

Abstract: The main task of the preclinical study of the effect of potential drugs on the immune system is to prove or exclude the possibility of developing an immunotoxic effect caused by a pharmacological agent or its metabolites in an animal experiment. The proposed approach to assessing the immunotoxic effect of pharmacological agents consists in the study of a number of integral immunological functions that allow, taking into account the results of hematological and morphological studies of lymphoid organs, to assess the possible risk when using a new pharmacological agent. Mandatory testing for immunotoxicity should be subject to new, original pharmacological agents, as well as well-known drugs for which there is no data on the study of immunotoxicity, recommended for use in long repeated courses; use in pediatric practice, as well as for the treatment of pregnant women and when prescribed during lactation; as prophylactic agents and contraceptives; for use without a doctor's appointment among the general population [2,3]. Strawberry garden leaf extract dry (strawberry garden extract) is one of the potential substances for obtaining safe medicines for the prevention and treatment of diseases of the urinary tract, as it has diuretic and anti-inflammatory activity [4]. The study of the immunotoxic properties of strawberry garden extract is an obligatory part of the preclinical safety assessment of a new pharmacological substance for obtaining safe medicines with it. In this regard, studies on the study of the immunotoxic properties of strawberry leaves of dry extract in the framework of preclinical studies and substantiation of the use of the substance for the further development of medicines based on it are relevant.

The Effect of Noise-Masking Earbuds (SleepBuds) on Reported Sleep Quality and Tension in Health Care Shift Workers: Prospective Single-Subject Design Study.

BackgroundShift work is associated with sleep disorders, which impair alertness and increase risk of chronic physical and mental health disease. In health care workers, shift work and its associated sleep loss decrease provider wellness and can compromise patient care. Pharmacological sleep aids or substances such as alcohol are often used to improve sleep with variable effects on health and well-being.ObjectiveWe tested whether use of noise-masking earbuds can improve reported sleep quality, sleepiness, and stress level in health care shift workers, and increase alertness and reaction time post night shift.MethodsEmergency medicine resident physicians were recruited for a prospective, single-subject design study. Entrance surveys on current sleep habits were completed. For 14 days, participants completed daily surveys reporting sleep aid use and self-rated perceived sleepiness, tension level, and last nights’ sleep quality using an 8-point Likert scale. After overnight shifts, 3-minute psychomotor vigilance tests (PVT) measuring reaction time were completed. At the end of 14 days, participants were provided noise-masking earbuds, which they used in addition to their baseline sleep regimens as they were needed for sleep for the remainder of the study period. Daily sleep surveys, post–overnight shift PVT, and earbud use data were collected for an additional 14 days. A linear mixed effects regression model was used to assess changes in the pre- and postintervention outcomes with participants serving as their own controls.ResultsIn total, 36 residents were recruited, of whom 26 participants who completed daily sleep surveys and used earbuds at least once during the study period were included in the final analysis. The median number of days of earbud use was 5 (IQR 2-9) days of the available 14 days. On days when residents reported earbud use, previous nights’ sleep quality increased by 0.5 points (P<.001, 95% CI 0.23-0.80), daily sleepiness decreased by 0.6 points (P<.001, 95% CI –0.90 to –0.34), and total daily tension decreased by 0.6 points (P<.001, 95% CI –0.81 to –0.32). These effects were more pronounced in participants who reported worse-than-average preintervention sleep scores.ConclusionsNonpharmacological noise-masking interventions such as earbuds may improve daily sleepiness, tension, and perceived sleep quality in health care shift workers. Larger-scale studies are needed to determine this interventions’ effect on other populations of shift workers’ post–night shift alertness, users’ long-term physical and mental health, and patient outcomes.

Evaluation of supramolecular complex of fenbendazole effect on embryonic development

The purpose of the research is to study the embryotropic effect of supramolecular complex of fenbendazole (SMСF).Materials and methods. The experiment to assess the embryotropic properties of SMCF was carried out on 40 white female and 20 male rats in accordance with the Guidelines for the experimental (preclinical) study of new pharmacological substances. Pregnant female rats were divided into 3 experimental and one control groups. SMCF was administered intragastrically on the 1–6 days of embryogenesis (group 1); on the 7–14 days (group 2) and on the 15–19 days (group 3) in three times therapeutic dose – 6,0 mg/kg of active substance. The animals of the control group received saline from the first to the 19th days of pregnancy. Rats were euthanized on the 20th day of pregnancy. The uterus with fetuses was removed after laparotomy, the number of corpora lutea, implantation sites, the number of living, dead and resorbed fetuses were recorded, the weight and diameter of the placenta were determined. The embryos were examined, weighed, the craniocaudal sizes were determined, the levels of total embryonic, preimplantation and postimplantation embryo death were calculated. The fetuses were examined for abnormalities of internal organs and changes in the skeletal system according to the methods of J. G. Wilson (1965) and A. B. Dawson (1926), modified in the department of embryology of the IEM of the USSR Academy of Medical Sciences.Results and discussion. As a result, SMCF does not induce toxic effects on the fetus: mortality rates, size and weight of embryos were at the level of the control group in a threefold therapeutic dose 6,0 mg/kg at intragastric administration on the 1–6; 7–14 and 15–19 days of pregnancy. SMCF did not cause external and internal malformations.

Бенфотіамін як антиоксидант у дренажній зоні ока при поєднаному моделюванні глаукоми та діабету

During experimental glaucoma with diabetes in rabbits, in the filtering tissues of the eye, a state of oxidative stress is formed manifested by a significant decrease in the activity of antioxidant enzymes and the accumulation of products of free radical oxidation of lipids and proteins. Administration of a lipid-soluble form of vitamin B1 benfotiamine effectively reduced the manifestations of oxidative stress in the tissues of the anterior chamber of the animal eyes. This biologically active substance increased antioxidant capacity in tissues by activating antiradical protection enzymes: superoxide dismutase activity increased by 51%, catalase by 36% and glutathione peroxidase by 45% compared to the untreated animals. In addition, the processes of lipid peroxidation and oxidative destruction of protein molecules were decreased under the influence of benfotiamine. The level of malondialdehyde (MDA) was reduced by 47%, and the marker of oxidative damage to proteins of CO-groups by 35% relative to the untreated group. The results obtained may be a basis for further studies of the pharmacological substance benfotiamine in the clinic of glaucoma accompanied by diabetes, which will expand the arsenal of pathogenetically sound therapy of this serious disease.