Annals of Mechnikov's Institute

Carbapenem resistance shapes the population structure of Klebsiella pneumonia

2024-12-11T11:50:40+02:00

Klebsiella pneumoniae (Kp) is an ubiquitous and highly versatile species from the family Enterobacteriaceae. Remarkable genetic and phenotypic plasticity determines its success in adapting to a wide range of environmental and host-associated niches (e.g., fresh and salt waterwater, soil, plants, insects, birds, and animals, including humans, where it usually persists as a gut commensal, but also can colonize other mucosal surfaces and skin). Certain lineages can cause severe invasive community-acquired (CA) infections, but the majority behave as a typical opportunistic pathogen, persistingasymptomatically till the moment of the host vulnerability. One of the most concerning aspects of Kp's recent evolution is its adaptation to the environment of healthcare facilities. The species is one of the major nosocomial pathogens, and the most frequent cause of neonatal sepsis worldwide. Distinguishing clinical feature of Kp infections is propensity for the development of bacteremia and metastatic spread to unusual and often multiple locations (e.g., hepatic, and non-hepatic abscesses, meningitis, endophthalmitis, necrotizing fasciitis, etc.). Despite such a prominent clinical relevance per se, Kp has been recognized as a global healthcare threat primarily due to its contribution to the current crisis of carbapenem resistance (CR). Certain epidemiologically successful lineages turned out to be incredibly effective in the accumulation, maintenance, and spread of resistance-associated mobile genetic elements (rMGEs) among other clinically relevant Gram-negative organisms. The aggregation of numerous resistance genes (including those, encoding ESBL's and/or carbapenemases) within a specific Kp genetic background has led to the emergence of global hospital outbreak CRKp clones, followed by multispecies outbreaks of difficult-to-treat CR healthcare associated infections (HAI) worldwide. Recent surveillance efforts and molecular epidemiology studies demonstrate a complex population structure of Kp, characterized by hundreds of deeply branching phylogenetic lineages. These lineages exhibit significant differences in the distribution of genes conferring antibiotic resistance and virulence, as well as variable transmissibility within the hospital environment. This review focuses on understanding the evolution of clinically relevant genetic variants of CRKp, which is crucial for the development of effective control strategies.

Diseases of the anorectal zone: hemorrhoids

2025-03-04T18:30:28+02:00

The article provides data on diseases of the anorectal zone, in particular hemorrhoids. The etiology, pathogenesis and methods of hemorrhoid treatment are described. The most common method of treating internal hemorrhoids is the use of suppositories. Rectal suppositories for the treatment of hemorrhoids include local anesthetics, corticosteroids, vasoconstrictors, antiseptics, keratolytics, protective agents (such as mineral oils and cocoa butter), astringents (substances that cause coagulation) and other ingredients. A study of the range of medicinal products for rectal use by type of dosage form in Ukraine indicates that it consists of ointments, creams and suppositories, suppositories prevail - 55.9% and ointments - 35.3%, creams occupy 8.8%. A comparison of the range of drugs for rectal use used to treat hemorrhoids allows us to state that the Ukrainian market is dominated by pharmaceutical products of foreign production - 61.7%, of which 29.4% of the range belongs to suppositories, 23.5% to ointments, and only 8.8% to creams. The main part of the range of products for rectal use of domestic manufacturers is occupied by suppositories - 26.5% and ointments - 11.8%. In the State Institution "Immunology and Microbiology of the NAMS" of Ukraine, suppositories containing 5% hop essential oil and diclofenac sodium have been created for the treatment of diseases of the anorectal zone. According to the literature, biologically active substances of hops, including essential oil, exhibit antimicrobial, anti-inflammatory, antioxidant, sedative, membrane-stabilizing effects. The antibacterial activity of various hop fractions, mainly against gram-positive bacteria, has been known for many years and is well documented. A significant amount of research mainly indicates a high antibacterial potential against gram-positive bacteria, whether it is hop extracts rich in prenylated cylphloroglucins and chalcones, or hop essential oil. To increase the anti-inflammatory effect of hop essential oil, diclofenac sodium was introduced into the composition of the excipients of the drug. The introduction of diclofenac sodium is due to the synergism between NSAIDs and biologically active substances of hop essential oil. Experimental studies have shown that combined suppositories containing hop essential oil and diclofenac sodium exhibit antimicrobial, anti-inflammatory, wound healing and membrane-stabilizing effects, i.e. their use for the treatment of diseases of the anorectal zone is pathogenetically justified.

Keywords: hemorrhoids, human, treatment

Eucalyptus-based products range as an example of modern approaches to the creation of herbal drugs

2025-03-03T20:07:28+02:00

Introduction. Given the popularity of eucalyptus leaves and various forms of BAS extracted from this type of raw material, and the current focus of pharmacological action, it is relevant to investigate the Ukrainian pharmaceutical market of eucalyptus raw materials and products based on it. The purpose of the work is to investigate the Ukrainian market of eucalyptus-based products of pharmaceutical, food and cosmetic orientation. Methods: content analysis of information from the compendium, literary sources, pharmacy websites, trading platforms, etc. Results and their discussion. The market contains raw materials (whole, cut, ground and leaf powder) from 23 manufacturers, of which the majority are state (up to 90%). Only 25% of manufacturers indicate the type of plant whose leaves they sell: E. viminalis (5 manufacturers) and E. globulus (1 manufacturer), the rest do not mention the species affiliation. In addition, there are collections, teas and herbal teas (a total of 12 items) which, except to eucalyptus leaves, contain medicinal plant raw materials (MPM), belonging to 21 families. On the pharmaceutical market of Ukraine, essential oil of eucalyptus is available from 21 manufacturers, most of which do not indicate the name of the raw material from which this oil is obtained. Only 6 manufacturers indicated that it is essential oil of Corymbia citriodora, E. radiata and E. globulus (2 manufacturers for each type of raw material). Most often, oil is offered for sale in a volume of 10 ml, but there are options of 5 ml, 30 ml (ounce), and even 50 ml and 100 ml (Aromatics, Ukraine). 54% of manufacturers are Ukrainian, from foreign ones – products from 6 countries are presented, of which manufacturers from Switzerland and France dominate (11.5% each), the Czech Republic and India (7.7% each). There is information about 2 aroma compositions. On the pharmaceutical market, there are medicines with eucalyptus leaf extracts, which are produced by manufacturers from 10 countries (Fig. 5). Two-thirds of the manufacturers are state (67.8%), German ones make up 10.8%, Pakistani ones – 7.5%. The rest are manufacturers from the USA (4.3%), India (3.2%), Turkey (2.2%) and Poland, Vietnam, Spain (1.1% each). The dominant type of forms with eucalyptus leaf extracts are soft (27%), of which more complex and combined balms and ointments. Liquid dosage forms are represented mainly by inhalation solutions (8 options), tinctures: simple (6) and complex (3). Granules (sachets) predominate among solid dosage forms. Cosmetics (9%) are represented by hydrosols, soap, foot serum, skin elixir, bath concentrate and perfume. Conclusions. The variety of products (pharmaceutical, food, cosmetic industries) based on raw materials, extracts from it and essential oil confirms its demand in healthcare, food and cosmetic industries. A certain drawback is the unclear segmentation of the market of pharmaceutical (medicines), food (herbal teas, teas) and cosmetic (hydrolates, extracts) direction, which creates difficulties in consumer orientation. However, the modern Ukrainian market of pharmaceutical products based on eucalyptus leaves and extracts from it presents a variety of dosage forms with different combinations of components, which may be the basis for creating an effective algorithm of approaches to the development of dosage forms of new types of APIs with the relevant direction of action.

Keywords: eucalyptus, leaves, collections, drugs

Effect of native and L-arginine-modified raspberry shoot extracts on electrocardiogram parameters of rats and status of the antioxidant system under the conditions of experimental doxorubicin cardiomyopathy in rats

2025-02-28T11:39:03+02:00

Introduction. In folk medicine, raspberry (fruits, leaves and shoots) is applied in treatment of influenza, sore throat. But there is no any information about application raspberry as cardio protective medicine. The aim of the work was study of the effect of raspberry shoot extracts on the state of free radical oxidation processes and electrocardiogram (ECG) parameters in rats with experimental doxorubicin cardiomyopathy. Material & methods. The object of the study was extract of shoot raspberry (ERS) and its modified extract with L-arginine ("RubusArg"); antioxidant effect of extracts was determined by catalase, superoxide dismutase, and reduced glutathione assays; cardiomyopathy was induced by doxorubicin model. Results & discussion. The therapeutic and prophylactic administration of the studied extracts, along with the reference drug quercetin, significantly improved animal survival rates. Survival reached 90% with RubusArg, 80% with both ERS and quercetin, and 70% with catechin. RubusArg demonstrated the strongest suppression of free radical oxidation, as evidenced by a significant 2.1-fold reduction in serum 8-isoprostane levels (p≤0.01). Additionally, myocardial homogenate showed a 1.45-fold decrease in TBA-reactive substances compared to the untreated control. The extract also significantly enhanced antioxidant enzyme activity, increasing catalase levels by 1.28-fold in myocardial homogenate and 1.3-fold in blood serum. Superoxide dismutase activity rose by 1.5-fold in myocardial homogenate and 1.68-fold in blood serum, while myocardial glutathione levels significantly increased by 1.35-fold. Conclusion. The conducted study indicates the promising use of the modified L-arginine raspberry shoot extract, which contains ionized forms of (+)-catechin and epicatechin, for the correction of anthracycline-induced myocardial damage. The application of native and modified L-arginine raspberry shoot extracts (RubusArg) contributes to the improvement of the antioxidant-prooxidant index, reduction of FRO intensity, increased activity of SOD, catalase, increased levels of reduced glutathione, improved ECG parameters, and reduced mortality.

Key words: doxorubicin, cardiomyopathy, raspberry shoots, catechins, rats, ECG.

Antitussive codeine medicines in Ukraine: clinical and pharmacological, marketing, regulatory aspects, and forecasts

2025-01-25T21:47:11+02:00

Introduction. The circulation and use of codeine-containing medicines require careful regulation to ensure effective treatment of pain and cough and minimize the risks of misuse. In Ukraine, the availability of such medicines is the subject of regulatory measures aimed at maintaining a balance between accessibility and safety. This study examines the effectiveness, variety of dosage forms and regulatory aspects of codeine medicines in accordance with international standards. Materials and methods. The study was conducted on the basis of a systematic review of scientific literature and regulatory documents on the circulation and use of codeine medicines in Ukraine. The data analysis included a study of dosage forms, prescription rules and restrictions aimed at preventing abuse. Results. The study revealed a significant variety of dosage forms of codeine-containing medicines, with combined forms demonstrating advantages in the treatment of pain and cough. It was found that strict regulatory measures are in place, including mandatory registration, prescription-only dispensing and expiration date restrictions. However, gaps remain in awareness of the risks of misuse and the need for enhanced patient-physician collaboration. Conclusions. The analysis highlights the importance of optimizing the circulation and use of codeine-containing medicines to balance availability and safety. Improved control mechanisms and educational initiatives are essential to reduce the risks of misuse while ensuring effective patient treatment.

Keywords: cough, codeine, codeines medicines, pharmacology, marketing, pharmacotherapy, regulatory barriers, safety

Analysis of extemporal prescription state for dermatological diseases and problem aspects during marital state in Ukraine

2024-12-20T16:53:06+02:00

Introduction. The negative trend of the reduction of pharmacies with the manufacture of medicinal forms in the Western region for the years 2014-2024 during the war was investigated and the need to preserve and expand the number of pharmacies that prepare extemporaneous medicines, which is relevant in the conditions of martial law, was substantiated.

The purpose of this work was to analyze the dynamics of the number of pharmacies that extemporaneously manufacture medicines over the last 10 years during the war in the Western region in order to determine trends. Our task was to study the list of medicinal forms that are actually produced in pharmacies, especially for dermatological diseases. The objects of analysis were documents, orders for pharmacies with compounding departments during last 10 years. The nomenclature of pharmaceuticals from 14 pharmacies that have valid licenses and actually carry out extemporaneous production of drugs in the city of Lviv and the Lviv region was studied. Research methods: historical, bibliographic, documentary, content analysis, systematization and generalization. We have selected a set of 12 dosage forms that were most often produced during the period of martial law during 2022-2024, these prescriptions can be recommended for implementation in the work of production departments of private pharmacies. It was substantiated that the urgent task of harmonizing with EU legislation regarding the work of pharmacies that have extemporaneous production is the need to make changes to the Licensing Conditions of Pharmacies on the mandatory extemporaneous production of medicinal forms in each pharmacy, regardless of the form of ownership.

Keywords: extemporaneous production, dosage forms, pharmacy, martial law, substances, dermatological forms, acne, dermatitis

Analysis of phenolic compounds of willow extracts by HPLC method

2025-03-04T18:14:03+02:00

Abstract. In Ukraine, special energy plantations of fast-growing, highly productive willow varieties are being actively established. Most often, domestic and Swedish-selected varieties and hybrids of rod-shaped willow are used. An analysis of available scientific sources reveals that data on the pharmacognostic studies of 'energy willow' raw materials remain significantly limited. The aim of our work is to analyze the composition of phenolic compounds of willow extracts obtained from raw materials collected on an energy plantation. Materials and methods. Willow shoots were harvested from an energy plantation in the Rivne region. The samples were analyzed by HPLC using a Shimadzu HPLC system under the following conditions: a Phenomenex Luna C18(2) column (250 × 4.6 mm, particle size – 5 μm); column temperature – 35 °C; detection wavelengths – 330 nm (for hydroxycinnamic acids and flavonoid glycosides), 370 nm (for flavonoid aglycones), 280 nm (for tannins), and 340 nm (for coumarins); mobile phase flow rate – 1 ml/min; injection volume – 5 μl. The mobile phase consisted of eluent A (0.1% trifluoroacetic acid solution in water) and eluent B (0.1% trifluoroacetic acid solution in acetonitrile) in various ratios. Component identification was performed based on retention times and the compliance of UV spectra with reference substances. Results. The chemical composition of willow bark extracts (50%, 70%, 96% ethanol and 80% methanol) was investigated by HPLC, and 12 phenolic compounds were identified and quantified: flavonoids catechin, apigenin-7-glucoside, quercetin, rutin, hyperoside, quercitrin, phenolic acids chlorogenic, neochlorogenic and caffeic acids, gallic and ellagic acids, coumarin scopoletin. The raw material of "energy willow" is a promising plant raw material as a source of bioactive compounds for pharmaceutical purposes and requires further research.

Key words: Salix viminalis L. cormus, high performance liquid chromatography (HPLC), compounds of phenolic nature

Research of mineral composition of Populus angulate ait.

2025-02-25T11:41:04+02:00

RESEARCH OF MINERAL COMPOSITION OF POPULUS ANGULATA AIT.

Introduction. In recent years, the significance of forest plantations and restored forests has been steadily increasing, as poplar raw materials (Populus spp., family Salicaceae Mirb.) have become an increasingly attractive source of bioenergy and a promising renewable resource for biotechnology and bioprocessing projects. Particular attention is given to poplars of the Aigeiros Duby section, as species, clones, and varieties from this group are most commonly used in plantation cultivation. This creates promising opportunities for the rational and sustainable use of poplar-derived medicinal plant raw materials. Consequently, pharmacognostic studies of "black poplars," including research on the mineral composition of Populus angulata Ait. raw materials, are highly relevant. Such studies play a crucial role in standardization the raw materials. Aim. Study of the mineral composition of shoots, leaves and buds of Populus angulata Ait, and to determine total ash content in this raw material. Materials and methods. The objects of the study were shoots, leaves, buds of Populus angulata Ait. section black poplar Aigeiros Duby, family Salicaceae Mirb. The mineral composition analysis was carried out on the basis of the State Scientific Institution "Institute for Single Crystals" of the National Academy of Sciences of Ukraine (Kharkiv). Macro- and microelement composition of the raw material was determined by atomic emission spectrometry with photographic registration. The total ash content in the raw material Populus angulata Ait. by the gravimetric method according to the State Pharmacopoeia of Ukraine 2.0. Results. For the first time, the content of 19 mineral elements was determined by atomic absorption spectrometry in the raw material of Populus angulata Ait., cultivated in Ukraine, 5 of which are classified as macro- (K, Na, Ca, P, Mg) and 14 as microelements (Fe, Mn, Al, Si, Zn, Mo, Cu, Pb, Sr, Co, Ni, As, Cr, Hg), 10 of which are essential. It was established that the raw material of Populus angulata Ait. in terms of the content of heavy metals and total ash meets the requirements of the State Pharmacopoeia of Ukraine 2.0. The obtained data will contribute to further research and the development of quality control methods for poplar raw materials.

Keywords: Populus angulata Ait., atomic emission spectrometry, mineral elements

Trends in pharmaceutical waste management as an important element of pharmaceutical safety

2025-01-09T19:04:21+02:00

Introduction. Pharmaceutical waste (PhW), when released into the environment, poses risks to the human body and other biological species and poses a challenge to the pharmaceutical safety of the state. The aim of the work. To investigate the status and prospects of PhW management as an important element of pharmaceutical safety. Materials and Methods. The work used general scientific methods: content analysis, abstraction, interpretation and generalization. The materials selected were 30 scientific publications obtained from the electronic databases Google Scholar and PubMed, a guideline from the FIP/WHO, five European and five Ukrainian regulatory documents, as well as Eurostat statistical data and corporate information from a foreign research and analytical company and four domestic pharmaceutical enterprises and public organizations. Results. Analyzing the risks posed by uncontrolled accumulation of PhW, as well as the volume of the global market for its management, the importance of proper management of PhW as a basic element of pharmaceutical safety is highlighted. The achievements of Ukrainian scientists on the issue of PhW management are shown. The global nature of the problem of household PhW and the peculiarities of their management in Europe and Ukraine are indicated. It presents current views on PhW management that are aligned with the European Green Deal, the European Strategic Approach to Pharmaceuticals in the Environment, and the Pharmaceutical Strategy for Europe. Considering the importance of the circular economy, Ukrainian innovative technology is described using the example of paracetamol, which will contribute to reducing the negative impact on the environment and increasing the efficiency of PhW management. It is shown that an important task is the harmonization of national legislation with European regulatory documents in the field of PhW management. Attention is paid to the need to develop a national concept on this. Conclusions. Based on the theoretical generalization of scientific research, international guidelines, European and Ukrainian regulatory documents, as well as statistical and corporate information, the article shows contradictory trends in the management of PhW, including household PhW, as an important component of pharmaceutical safety, as well as the significant problems of this management in Ukraine. Based on the multifaceted nature and complexity of PhW and the need to ensure an adequate level of pharmaceutical safety in the state, the issue of developing a national concept of PhW management on the basis of harmonizing national legislation with European legislation is updated and its eight main theses are identified.

Key words: pharmaceutical waste, medicine, management, pharmaceutical safety, utilization, national concept.

Virtual screening of the properties of a series of 5- arylidene derivatives of 3- (benzo[d]thiazol-2-ylamino)-2-thioxothiazolidin-4-one

2025-01-18T13:19:46+02:00

Introduction. The importance of in silico analysis has been recognized due to the high reliability of predicted results. Virtual screening is based on the relationship between properties of a molecule and its structure. Certain online resources enable the prediction of a compound’s behavior in the human body by calculating important descriptors. The use of computer programs to calculate the physicochemical parameters of molecules, predict their pharmacokinetic properties, and assess "drug-likeness" is advantageous at the early stages of Drug Development, as it requires minimal time and financial investment. In molecular Drug Design, scientists are particularly interested in non-condensed bi- and polycyclic heterocycles, among which rhodanine derivatives with benzothiazole moeity demonstrate significant potential biological activity. To identify compounds with an optimal ADME (Absorption, Distribution, Metabolism, Elimination) profile, we selected 5-arylidene-substituted derivatives. The aim of the work was virtual screening and evaluation of the ADME properties of variously substituted 5-arylidene derivatives of 3-(benzo[d]triazol-2-ylamino)-2-thioxothiazolidin-4-one using the freely available SwissADME computer program. Materials and methods. The study materials included previously synthesized compounds (1–6) with pre-confirmed in vitro antitumor activity and virtually modeled derivatives (7–21) based on 3-(benzo[d]triazol-2-ylamino)-2-thioxothiazolidin-4-one. Methods: The research method is a freely available Swiss web tool SwissADME, hosted at http://www.swissadme.ch/. Results and discussion. A virtual design of a derivatives series and their screening was conducted. Comprehensive in silico studies made it possible to assess the potential of a structurally similar compounds. A range of physicochemical and pharmacokinetic parameters of the molecules, as well as their bioavailability (BS) and synthetic accessibility (SA), were determined. According to SwissADME predictions, most of the parameters are acceptable, which makes 5-arylidene derivatives interesting research targets. The similarity of the molecules to existing drugs was confirmed by their successful passage through the Lipinski filter. Sufficient bioavailability and synthetic accessibility of the derivatives are evidenced by calculated criteria (BS = 0.55; SA = 3.75–4.81). The least violations of optimal molecular descriptor values are predicted for compounds 1 and 7, while the greatest are for compounds 3, 6, and 18. The oral bioavailability of the molecules is limited by violations of two or more parameters, including saturation, polarity, lipophilicity, water solubility, size, and flexibility. Compound 7 is the most similar to those with high oral bioavailability. Brain penetration of the studied molecules is not expected, and low permeability through the skin is predicted (Log Kp from -3.53 to -6.10 cm/s). Most derivatives in the series (except compounds 19 and 21) are likely not P- glycoprotein substrates, which may contribute to their therapeutic efficacy, and selectively inhibit isoforms of cytochrome P450. Conclusions. The violations of some parameters of 5-arylidene-substituted derivatives are not critical according to modern Drug Design criteria. Overall, the predicted ADME profile of the compounds is acceptable. The molecular structures can be optimized, or alternative administration routes should be explored. The results of in silico predictions confirm the prospects for further research on this class of heterocycles, which are valuable for medicinal chemistry.

Keywords: rhodanine, benzothiazoles, 5-arylidene derivatives, in silico screening, SwissADME.

Multisymptom long COVID in a patient with psoriatic arthritis: a case report

2024-12-10T11:25:14+02:00

A 62-year-old female patient diagnosed with psoriasis involving the skin and nails, psoriatic arthritis, and enthesitis; arterial hypertension, stage II, grade 2, moderate risk, NYHA II. She received secukinumab 150 mg subcutaneously once every 4 weeks for the treatment of psoriasis. Blood pressure (BP) was controlled with carvedilol 12.5 mg/day.

She was vaccinated against COVID-19 (3 doses in 2021) and fell ill with COVID-19 in September 2022. She was treated as an outpatient. No lung damage was detected on X-ray. The deterioration of the condition began 2 months after the onset of COVID-19 (hair loss, increased shortness of breath, progression of weakness). After 3 months - increased weight, unstable blood pressure (initially increased, then decreased to normal values), inappropriate sinus tachycardia. The dose of carvedilol was reduced to 3.125 mg/day. She could not take ivabradine because of the proarrhythmogenic effect. The patient also developed skin itching and recurrent herpetiform rashes on the lips. The patient assessed them as Herpes labialis. Over the course of six months, these rashes recurred 4-5 times, tachycardia and a tendency to decrease blood pressure persisted. Ten months after acute COVID-19, unbearable skin itching, bullous rashes with a flaccid membrane, serous contents, positive Nikolsky's symptom throughout the body, eosinophilia appeared. The dermatologist diagnosed pemphigus and prescribed methylprednisolone 32 mg / day. In June 2024 (1 year and 9 months after the onset of the disease), she began to notice interruptions in the heart, shortness of breath, intolerance to minor stress, both physical and emotional, due to the appearance of attacks of palpitations. With daytime monitoring of the heart rate - against the background of sinus rhythm with an average daily heart rate of 81 beats / min. rare (at least 14) supraventricular (atrial polytopic) extrasystole are determined, in particular as part of a triplet; frequent (more than 5.0 thousand, up to 522 per hour) polymorphic ventricular parasystole. Takes carvedilol 3.125 mg / day, etacizin 100 mg / day. Also in October 2024, skin itching and a single blister on the lip appeared again (she used betimethasone ointment), parasystole persists.