Pharmacological Groups Research Articles

Development of new methods for predicting hygienic standards for the content of medicines in the air of the working area on the example of non-steroidal anti-inflammatory drugs

Introduction. Experts predict the hygienic standards of medicines in Russia in accordance with the methods common to all medicines (MG 1.1.726-98), developed more than 25 years ago on the basis of experimental materials obtained during the rationing of 66 medicines. By 2023, the content of more than 230 medicines of various pharmacological orientation has already been normalized in the air of the working area. Such an array of experimental materials makes it possible to study the relationship between the values of standard toxicological and pharmacological indicators and hygienic standards approved by law, already within the framework of individual pharmacological groups of drugs with the same mechanism of action, as well as to develop new forecasting approaches taking into account the specifics of pharmacological actions.
 The study aims to evaluate existing and develop new computational methods for predicting hygienic standards for the content of medicines in the air of the working area, taking into account the specifics of pharmacological action on the example of a group of nonsteroidal anti-inflammatory drugs.
 Materials and methods. Scientists studied the pharmacological group of nonsteroidal anti-inflammatory drugs. The main method of the study was a multiple correlation and regression analysis of the relationship between the values of hygienic standards and the values of toxicological and pharmacological parameters. As a mathematical model, the authors adopted a double logarithmic model. We evaluated the suitability of the mathematical model by Fisher's F-criterion, the statistical significance of the regression coefficients by the Student's t-criterion, the quality of approximation by the standard deviation, and the accuracy of the calculation by the average multiplicity of differences.
 Results. Experts have identified in a group of 15 non-steroidal anti-inflammatory substances normalized in the air of the working area, a reliable relationship between the values of toxicometry parameters and the values of therapeutic doses, on the one hand, and the values of hygiene standards, on the other. Scientists have developed and selected the most accurate and statistically significant formulas for calculating the safe concentrations of this group of drugs in the air of the working area. We found that the accuracy of the formulas developed by us, taking into account the specifics of the pharmacological action, is higher than that of the formulas from MG 1.1.726-98. From the formulas developed earlier, equations with greater accuracy for the hygienic rationing of nonsteroidal anti-inflammatory drugs have been identified.
 Conclusion. Taking into account the specifics of the pharmacological action of medicines when developing mathematical models for calculating the hygienic standard increases the accuracy of the forecast.

Physiological and Pathophysiological Aspects of Diabetic Foot Ulcer and its Treatment Strategies.

Diabetes foot ulcers (DFU) are among the most common complications in diabetic patients, leading to amputation and psychological distress. This mini-review covers the general physiology of ulcer healing as well as the pathophysiology of DFU and its therapies. Only a few treatments have been sanctioned and numerous compounds from various pharmacological groups are now being tested at various stages for the prevention and treatment of DFUs. The main objective of this mini-review is to give concise information on how diabetes mellitus impairs the healing of chronic ulcers by disrupting numerous biological systems of the normal healing process, resulting in diabetic foot ulceration, and the current therapeutic approaches. A review of accessible material from systemic searches in the PubMed/Medline, Scopus, Cochrane Database of Systematic Reviews, published review articles, and Clinical Trials databases (US National Library of Medicine) with no period of limitation was conducted. The treatment of DFUs comprises wound dressings, use of matrix metalloproteinase inhibitors in wound dressing, antibiotics, skin substitutes, pressure off-loading growth factors and stem cells, gene therapy, topical oxygen therapy, etc. Conclusion: The majority of these treatments are aimed at treating diabetic foot ulcers and preventing diabetic wounds from becoming infected. Yet, there is no single therapy that can be advised for diabetic foot ulcer patients. Future treatment strategies should be considered an appropriate treatment option for persistent wounds.

Extemporaneous Preparations in the Pharmacotherapy of Nervous System Disorders: Pharmaceutical Management, Marketing, Analysis, Application

Pharmaceutical management, marketing, pharmaceutical analysis, clinical and pharmacological properties for the use of an extemporaneous drug in the pharmacotherapy of nervous system disorders were studied. The previous experience of the author in the development of new combined drugs of various clinical and pharmacological groups was used. The composition of an extemporaneous drug with sedative pharmacological properties (sodium bromide, novocaine, tincture of valerian) is proposed. The manufacturing technology in pharmacy conditions, qualitative and quantitative indicators of active substances, as well as storage conditions and shelf life of the new extemporaneous drug were developed. The search, development, manufacture in a pharmacy and the use of extemporaneous drugs will contribute to the improvement of planning, organization, and control of the processes of medical and pharmaceutical assistance to patients in conditions of armed conflict. Coordination of medical, pharmaceutical, human, financial, natural, technological, and social resources is necessary to meet the challenges of today.

Ecological risk assessment of pharmaceuticals and endocrine disrupting compounds in Brazilian surface waters

Pharmaceuticals and endocrine disrupting compounds are organic micropollutants that can cause adverse effects at low concentrations. Their occurrence in surface waters has been reported in several countries, including Brazil, at concentrations on the order of ngL−1, while the concentrations at which toxic effects are observed are often in the range of mg.L−1 to μg.L −1, however few studies have been undertaken to characterize risks they represent in Brazilian surface waters. Thus, the objective of this study was to evaluate the ecological risk to Brazilian surface waters caused by the presence of pharmaceuticals and natural and environmental estrogens. Twenty-nine pharmaceuticals, hormones and environmental estrogens were included in the risk assessment while twelve were discarded due to insufficient data availability. The endocrine disrupting compounds were the most frequently detected (39.8% of the reported concentrations), followed by non-steroidal anti-inflammatory drugs (16.3%), antibiotics (6.6%), antiseptics (5.1%), analgesics (5.1%), antihypertensives (4.6%), and to a lesser extent, lipid controllers, anticonvulsants, antidepressants, antihistamines, antivirals and corticosteroids. Bisphenol-A was the most frequently detected compound, followed by diclofenac, 17-β-estradiol, 17-α-ethynilestradiol, naproxen, triclosan and 4-n-nonylphenol. Acute ecological risk was predicted in two thirds and chronic risk in one third of the water bodies surveyed. The presence of diclofenac or triclosan was determinant for acute risk while estrogenic hormones proved to be decisive for chronic risk. In addition to natural and synthetic endocrine disruptors, the pharmacological groups estimated to have the highest average associated risks were non-steroidal anti-inflammatory drugs, followed by anticonvulsants. No discharge limits exist for most of the compounds found to contribute to ecological risks, indicating the need for regulatory action by the proper Brazilian authorities.

Medical therapy for conjunctivitis. Literature review

Conjunctivitis, according to various studies, is the most common reason for going to the initial outpatient appointment and can be caused by several factors at the same time. Treatment is carried out comprehensively, depending on the clinical picture, somatic status and anamnesis data. In accordance with the clinical guidelines developed by the Russian Association of Ophthalmologists, the following groups of drugs are recommended for use: antibacterial, antiseptic, antihistamine, nonsteroidal anti-inflammatory drugs.Purpose: to analyze the use of the above groups of drugs in the treatment of conjunctivitis in order to recommend a reasonable prescription of the necessary therapy.Materials and methods. The literature data on the study of the features of the action of the above pharmacological groups in the treatment of conjunctivitis, obtained on the resources of PubMed, eLibrary, Crossref Metadata, mainly over the past 20 years, are presented.Results. The presence of signs of an allergic reaction involves the appointment of antiallergic drugs with multiple pharmacological effects – blockade of histamine receptors, stabilization of mast cell membranes and suppression of eosinophil filtration. Given the different mechanisms of action within this group of drugs, it is necessary to select them individually. When prescribing tablet forms of antihistamines, it must be remembered that with prolonged use, they can cause patients to feel dry in their eyes. In cases where the above antiallergic drugs do not adequately control the allergic inflammatory process, anti-inflammatory drugs are used. Nonsteroidal and steroid anti-inflammatory drugs are used as anti-inflammatory drugs. Usually nonsteroidal anti-inflammatory drugs are recommended for use in chronic conjunctivitis and patients with a history of systemic diseases. Steroid drugs are indicated for severe forms of manifestation of the allergic process on the eyes, as well as the appointment of steroid anti-inflammatory drugs is recommended for use in short courses (up to 2 weeks), and with their longer use, control of intraocular pressure is necessary. Literature data indicate the lack of efficacy of antiviral drugs such as acyclovir and others from this group in the treatment of conjunctivitis of adenoviral etiology. Drugs with an immunomodulatory effect based on interferon or inducers of interferon synthesis are widely used. The prescription of antibiotics should be justified, since in recent years the level of resistance to them has significantly increased. Antiseptics that have a wide spectrum of action (bacteria, viruses, fungi and protozoa) are an alternative to antibiotics, but it must be remembered that this group of drugs often causes allergic reactions.Conclusion. The treatment of conjunctivitis must be approached carefully, taking into account not only the etiology of the disease, but also the somatic and immune status of the patient. To avoid the negative effects of the use of antibiotics, replace them with alternative drugs and do not use them in the treatment of conjunctivitis of a non-bacterial nature.

THE EFFECT OF HYDROXYZINE ON AKATHISIA AND OTHER NEUROLOGICAL SIDE EFFECTS OF ANTIPSYCHOTICS IN THE TREATMENT OF PARANOID SCHIZOPHRENIA

Side effects of antipsychotic drugs are the most urgent problem in the pharmacotherapy of schizophrenia. Medications used to correct side effects of various pharmacological groups, including correctors of cholinolytics, tranquilizers-benzodiazepines, have severe side effects, which justifies the search for no less effective and at the same time safer alternatives. The aim of the study was to evaluate the corrective effect of Hydroxyzine on akathisia and other neurological disorders that develop as side effects of antipsychotic therapy. Materials and methods. The study analyzed the severity of side effects in 43 patients suffering from paranoid schizophrenia receiving monotherapy with antipsychotics, before their administration, on the 7th and 21st day after the start of taking Hydroxyzine. The severity of side effects was assessed by the ESRS scales and the scale of evaluating drug-induced akathisia. Results. A significant corrective effect of Hydroxyzine on akathisia and other neurological side effects of antipsychotics was shown on the 7th day of Hydroxyzine therapy, the severity of Parkinsonism, dyskinesia, akathisia and tremor significantly decreased. Patients noted an improvement in general well-being, a decrease in the level of anxiety associated with the disease, staying in a psychiatric hospital, side effects of psychopharmacotherapy. Hydroxyzine significantly reduced the severity of akathisia, assessed both objectively and subjectively by patients. There was a decrease in the need of patients to move, to change the position of the body, improved sleep, reduced emotional stress. In general, Hydroxyzine had a positive effect in the form of a decrease in pathological motor activity and a decrease in the severity of emotional manifestations associated with the side effect of antipsychotics, which persisted on the 21st day of Hydroxyzine therapy in the absence of clinically significant undesirable side effects. Conclusions. The results of the study show the effectiveness of Hydroxyzine for correcting neurological side effects of antipsychotics along with good tolerability and substantiate the possibility of expanding its use in the complex therapy of paranoid schizophrenia.

A Pilot Study for Effectiveness of Non-Pharmacological versus Pharmacological Treatment Strategies for Lumbar Disc Herniation: A Pragmatic Randomized Controlled Trial.

We aimed to compare the efficacy, safety, and cost-effectiveness of non-pharmacological- and pharmacological treatment strategies for Lumbar disc herniation (LDH) in pragmatic clinical settings. This study was a pilot, two-armed, parallel pragmatic randomized controlled trial. Thirty patients aged 19-70 years with a numeric rating scale (NRS) score ≥5 for sciatica and confirmed LDH on magnetic resonance imaging (MRI) were included. Participants were assigned in a 1:1 ratio to non-pharmacological (non-Phm) or pharmacological (Phm) treatment group. They were treated for 8 weeks and a total follow-up period was 26 weeks after randomization. Non-Phm treatment included acupuncture, spinal manual therapy, etc., Phm included medication, injection, nerve block, etc., The primary outcome was a numeric rating scale (NRS) of radiating leg pain. NRS for low back pain, Oswestry disability index, visual analog scale, Fear-Avoidance Beliefs Questionnaire, patient global impression of change, Short Form-12 Health Survey, version 2, 5-level European Quality of Life-5 dimensions (EQ-5D) were also measured. Linear mixed model was used to evaluated the difference in change of outcomes from baseline between two groups. An economic evaluation was conducted using incremental cost-effectiveness ratios. There was no significant difference between the two groups in the intervention period, but non-Phm group showed significantly greater degree of improvement in follow-up of Week 14. Difference in the NRS for sciatica and ODI were 1.65 (95% CI 0.59 to 2.71, p=0.003) and 8.67 (95% CI 1.37 to 15.98, p=0.21), respectively in Week 14. The quality-adjusted life year (QALY) value calculated by EQ-5D and Short Form-6 Dimension were 0.006 (95% CI -0.012 to 0.024, p=0.472) and 0.015 (95% CI -0.008 to 0.038, p=0.195) higher in non-Phm group than in Phm group. The cost was lower in non-Phm group than in Phm group (Difference: -682, 95% CI -3349 to 1699, p=0.563). We confirmed that the non-Phm treatment could be more cost-effective treatments than Phm treatments and feasibility of a large-scale of main study in future.

Poor regulation, desperation, and misinformation, a countrywide analysis of self-medication and prescription patterns in Ecuador during the COVID-19 pandemic

BackgroundThe rapid spread of the SARS-CoV-2 virus during the early phase of the pandemic led to an unprecedented global health crisis. Various factors have influenced self-medication practices among the general population and unsubstantiated prescribing practices among healthcare professionals. ObjectiveThis study aimed to describe trends in the purchase and sale of medicines during the COVID-19 pandemic period (2020–2022) in Ecuador, by comparing them with pre-pandemic periods. MethodsIn this study, a cross-sectional design was employed to conduct a comprehensive analysis of 28 pharmacological groups, categorized according to the Anatomical Therapeutic Chemical Classification (ATC). Utilizing an integrated drug consumption database, the study examined physician prescribing data, medicine usage, and spending levels in Ecuador during the COVID-19 pandemic. The analysis involved computing absolute differences in monthly resolution, calculating excessive expenditure in comparison to previous yearly averages, and using Defined Daily Dose (DDD) methodology for internationally comparable results. Furthermore, a correlation analysis was performed to investigate potential associations between prescribed and consumed medicines and the number of new cases and deaths. ResultsIn Ecuador, the average yearly expenditure among these groups prior to the pandemic (2017–2019) amounted to $150,646,206 USD, whereas during 2020 and 2021, the same groups represented a total expenditure of $228,327,210, reflecting a significant increase. The excess expenditure during this period reached 51.4%, equivalent to $77,681,004 USD. Notably, 13% of this expenditure consisted of Over the Counter (OTC) Medicines. The study also identified a remarkable surge in sales of ivermectin, which increased by 2,057%, and hydroxychloroquine, which increased by 171%, as measured by DDD. ConclusionsThis study highlights the substantial consumption of medicines by the population in Ecuador during the pandemic. It is concerning that many medications were sold without proven therapeutic indications, indicating that misinformation and desperation may have led to improper prescribing by physicians and patients resorting to ineffective drugs. Moreover, since the sale of these therapeutic drugs requires a prescription, poor regulation, and a lack of control within pharmacies likely contributed to such practices.

Glycyrrhiza glabra L. Extracts and Other Therapeutics against SARS-CoV-2 in Central Eurasia: Available but Overlooked.

In Central Eurasia, the availability of drugs that are inhibitors of the SARS-CoV-2 virus and have proven clinical efficacy is still limited. The aim of this study was to evaluate the activity of drugs that were available in Kazakhstan during the acute phase of the epidemic against SARS-CoV-2. Antiviral activity is reported for Favipiravir, Tilorone, and Cridanimod, which are registered drugs used for the treatment of respiratory viral infections in Kazakhstan. A licorice (Glycyrrhiza glabra) extract was also incorporated into this study because it offered an opportunity to develop plant-derived antivirals. The Favipiravir drug, which had been advertised in local markets as an anti-COVID cure, showed no activity against SARS-CoV-2 in cell cultures. On the contrary, Cridanimod showed impressive high activity (median inhibitory concentration 66 μg/mL) against SARS-CoV-2, justifying further studies of Cridanimod in clinical trials. Tilorone, despite being in the same pharmacological group as Cridanimod, stimulated SARS-CoV-2 replication in cultures. The licorice extract inhibited SARS-CoV-2 replication in cultures, with a high median effective concentration of 16.86 mg/mL. Conclusions: The synthetic, low-molecular-weight compound Cridanimod suppresses SARS-CoV-2 replication at notably low concentrations, and this drug is not toxic to cells at therapeutic concentrations. In contrast to its role as an inducer of interferons, Cridanimod is active in cells that have a genetic defect in interferon production, suggesting a different mechanism of action. Cridanimod is an attractive drug for inclusion in clinical trials against SARS-CoV-2 and, presumably, other coronaviruses. The extract from licorice shows low activity against SARS-CoV-2. At the same time, high doses of 2 g/kg of this plant extract show little or no acute toxicity in animal studies; for this reason, licorice products can still be considered for further development as a safe, orally administered adjunctive therapy.

The contraceptive choice at the time of a surgical and pharmacological abortion: a possible and effective option thanks to a dedicate counselling

The percentage of repeat abortion in Italy is about 25%. It is therefore important to implement the strategies that can facilitate the adoption of the most effective contraceptive methods. Long-acting reversible contraceptive methods are currently considered the most effective and with the highest rates of 12-months continuation, with a reported reduction of recurrent abortion. Our study has the aim to evaluate the contraceptive choice of women requesting abortion, when an accurate and dedicate counselling is offered and the availability of a LARC method is given immediately after pregnancy termination, both in case of surgical and medical abortion. LARC methods were chosen both in case of surgical and medical abortion, by an high percentage of patients. We reported no differences between the surgical and pharmacological groups on the choice of LARC and SARC. Our observational study shows the feasibility to perform an accurate, dedicate, and personalised counselling on contraception at time of abortion. This approach has enabled a high number of women to have a LARC method inserted at the time of abortion, as a valid strategy to prevent the risk unplanned pregnancy.

An investigation on availability and efficacy of anti-anemic drugs for pigs in the Ukrainian pharmaceuticals

Antianemic drugs are used to prevent anemia, majorly iron deficiency anemia. Drugs with such pharmacological action are especially relevant for piglets, as animals of this species at this age are particularly sensitive to iron deficiency. The present investigation aimed at studying the pharmaceutical market of antianemic drugs registered in Ukraine during 2017-2022. It should be noted that if the drug is registered, it has been checked for safety according to the food industry standards of Ukraine. In 2017, the national market of veterinary iron-containing drugs was represented by 13 drugs from the group QB03A “Antianemic drugs. Drugs of iron”, according to the АТС-vet classification. The range of these drugs by 38 % was provided by pharmaceutical products of Ukrainian manufacturers: "O.L.KAR-AgroZooVet-Service", "Pharmaton", "Brovapharma", "Experimental production of the Institute of Epizootology", "Biopharm", and "Vetsintez". Imported products (62 %) were represented by Pharmacosmos, Merial, Koofavet , "Vugen B&G" , "Biovet Pulawy", "Interchem Verken De Adelaar", and "Bioveta". In general, the modern pharmaceutical market of veterinary drugs in Ukraine during 2017–2022 was sufficiently provided with antianemic drugs for pigs and mostly imported drugs. The percentage of antianemic drugs of Ukrainian production prevailed in 2020, however the imported drugs of this pharmacological group's was higher in 2022. It can be concluded that the drugs of non-Ukrainian production predominated among antianemic drugs in Ukraine during 2017-2022. Based on the obtained results, we can state that in Ukraine there is a need for the development and/or production of domestic anti-anemic drugs. They must be effective and ensure a reduction in the dependence of the national pharmaceutical market of drugs of this group on foreign manufacturers.

Resistance to antimicrobials of the microflora extracted in acute postpartum endometritis in cows

In the article, the authors presented data on the species structure of the microflora isolated from cows with acute postpartum purulent-catarrhal endometritis. In acute postpartum endometritis, representatives of 8 genera of microorganisms were isolated in washings from the cervical canal. Identification of isolates to the species showed that Streptococcus pyogenes, Escherichia coli and Staphylococcus aureus were most often isolated from sick cows. These microorganisms were more common in associations: Escherichia coli + Streptococcus pyogene; Staphylococcus aureus + Streptococcus pyogenes. And Proteus vulgaris + Staphylococcus epidermidis. The disk diffusion method tested Streptococcus pyogenes, Escherichia coli and Staphylococcus aureus for resistance to 9 pharmacological groups of antimicrobial agents. In total, 48 isolates of 15 antibacterial drugs were tested in the work. The studied isolates of microorganisms showed multiple drug resistance. The authors revealed resistance to drugs of three or more pharmacological groups. Microorganisms showed high resistance (80% or more of isolates that did not show growth zone retardation) to drugs: neomycin (aminoglycosides) and benzylpenicillin (penicillins) - Staphylococcus aureus and Escherichia coli; vancomycin (glycopeptides), polymyxin (polymyxins) - Streptococcus pyogenes and Escherichia coli; ampicillin (penicillins), tetracycline (tetracyclines), cefazolin (cephalosporins), ciprofloxacin (fluoroquinolones) - only Staphylococcus aureus; lincomycin (lincosamides), tylosin (macrolides) - only Escherichia coli; streptomycin (aminoglycoside) - only Streptococcus pyogenes.

Pathophysiology and clinical management of pellagra - a review.

Pellagra is a rare disease caused by niacin deficiency or a disruption of its metabolism. Its manifestations are dermatitis with pronounced photosensitivity, gastrointestinal symptoms, and neuropsychiatric ailments. Currently pellagra is developed in people who chronically abuse alcohol or are treated with medications from specific pharmacological groups (immunosuppressive and anti-tuberculosis drugs). Although the root cause of the disease was established in the mid-twentieth century, a detailed explanation of the processes leading to the development of symptoms has not yet been proposed. They include complex abnormalities at the molecular, metabolic, and immunological levels. Diagnostics is based primarily on the clinical presentation of the disease, while auxiliary tests play secondary role. The low prevalence of the disease, meaning that physicians are unfamiliar with its recognition, often leads to delays in diagnosis and appropriate treatment. The therapy is causal and based on administering niacinamide. Failure to implement treatment in the early stages of the disease leads to the patient's death. The aim of this literature review is to summarize the current state of knowledge on the pathomechanisms of pellagra, highlighting the clinical implications, and key elements of diagnostic and therapeutic management that are important in the treatment of pellagra patients.

Efficacy of Off-Label Use of Anticancer Drugs in Oncology

The off-label use of anticancer drugs is widespread in modern oncology. The potential advantages of such prescriptions are associated with exceeding the expected clinical benefi ts over the risks of complications. The off-label use of anticancer drugs demonstrates the inconsistent efficacy of this approach depending on the type of malignancy, the reasons for prescribing these agents and their belonging to a particular pharmacological group. In a number of situations, the clinical benefits of off-label drugs are more convincing than in case of authorized indications. Currently, prescribing the “old” registered anticancer drugs, used in everyday clinical practice, is seen routine. However, labeling does not reflect the full range of indications with strong evidence of safety and efficacy. The paradigm shift toward molecularly targeted therapy and immunotherapy in various malignancies may increase the off-label use of the specified agents. Lack of treatment options for rare forms of malignancies and exhaustion of the possibilities for registered therapy are the major reasons for off-label prescribing targeted drugs based on the identifi ed molecular genetic disorders. In such cases, the concept of precision therapy is oft en implemented by using agents, the clinical efficacy of which is confi rmed by data with a low level of evidence or with no evidence. Studying the eff ectiveness of the off-label use of anticancer agents is necessary to systematize information and develop algorithms for making decisions about the prescription of these drugs in routine clinical practice.

#5458 HISTOLOGICAL STUDY OF KIDNEY INJURY ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITORS COMBINED WITH CHEMOTHERAPY IN A MURINE MODEL

Abstract Background and Aims The most current lines of cancer treatment aim to increase efficacy and decrease adverse effects. In this sense, one of the main therapeutic strategies is immunotherapy. Immune checkpoint inhibitors (ICIs) constitute the most relevant immunotherapeutic pharmacological group in the clinical setting. Despite their greater safety than conventional therapies, these agents still cause adverse events. Renal effects, although rare, have been shown to worsen the prognosis of patients. In addition, immune and chemotherapy combination have been approved nowadays. Although they have improved efficacy, they have increased risk of suffering nephrotoxic side effects. Our hypothesis is that kidney damage caused by ICIs could be subclinical, and therefore, not evidenced by the classic clinical biomarkers (plasma creatinine and urea). The aim of this work was the histological evaluation of renal damage associated with anti-CTLA-4 in combination with cisplatin. Method An experimental model was designed in C57BL/6 mice treated with the combined therapy of cisplatin (10 mg/kg, single dose) and anti-CTLA-4 (10 or 15 mg/kg/day, for 6 days) administrated by intraperitoneal injection. In addition, groups treated with drug monotherapies and a control group were included. On the day of sacrifice (day 6) the kidneys were collected and histological sections were made and stained with hematoxylin-eosin. Histological quantification of kidney damage was performed blindly following a tissue damage quantification protocol. For this, 10 photos were taken per kidney (600X), 5 of the external cortex and 5 of the corticomedullary region. Each photo was segmented into 6 areas and a score was assigned to each area as follows. 0: no damage, 1: damage up to 1/3 of the area, 2: damage between 1/3 and 2/3 of the area, and 3: damage over 2/3 of the area. Subsequently, the mean scores of the kidneys from the same experimental group were calculated, as well as the standard error of the mean. Data was analyzed with the statistical software SPSS®. Results Our results showed tubular renal damage associated with cisplatin treatment. It was more pronounced in the external cortical area. However, no structural alterations associated with ICI treatment were found. Co-treatment with both drugs potenciated renal structural damage from cisplatin. Conclusion This potentiation was more evident in the corticomedullary region, so it seems that the drugs combination causes a deeper lesion in the kidney than cisplatin monotherapy. Our study suggests that the combined therapy of anti-CTLA-4 and cisplatin could induce generalized tubular lesions.

Pharmaco-EEG Analysis of Regulatory Neuropeptides with Nootropic Properties in Cats

Informative parameters of normalized electrograms of the brain of cats under the action of regulatory neuropeptides with nootropic properties were established using the example of the Semax drug. The results obtained were confirmed by a comparative pharmaco-EEG analysis with various pharmacological agents of directed action. The pronounced stable activating and nootropic effects of this pharmacological group in brain electrograms are distinguished by a unidirectional action that coincides with the data of pharmacodynamics and pharmacokinetics.

IMPACT OF RENAL DENERVATION TREATMENT ON LEFT VENTRICLE REMODELING IN RESISTANT HYPERTENSIVE PATIENTS: THREE YEARS FOLLOW-UP

Objective: Evaluation of effects of RDN on left ventricle remodeling in patients with resistant hypertension and heart failure with preserved ejection fraction. Design and method: The study enrolled 125 hypertensive patients, who after 3-week of standardized treatment with Losartan, Amlodipine and Indapamide and confirmation of their drug resistance, were randomly assigned into three groups depending on medication supplemented to previously administered: group I - selective I1-imidazoline agonist Moxonidine, group II - cardioselective beta-blocker Bisoprolol and group III - renal denervation. All patients underwent a transthoracic echocardiogram at baseline, one, two and three years follow-up. Renal denervation was performed in the main renal arteries and their branches. Results: Transthoracic echocardiography at baseline revealed LV hypertrophy in all patients. The majority of patients in all three research groups had concentric hypertrophy (52% versus 60% and 56% in group I, II and III, respectively), the normal pattern not being recorded in any group. An authentic reduction in LV mass index was noted from 1-year follow-up in all three observational groups, the progressive reduction being maintained until the end of the study, the group of patients undergoing renal denervation manifested a net superior effect to both pharmacological groups. So, at 3-years follow-up LV mass index was 128,57±4,91 g/m2 in Moxonidine group versus 126,0±5,34 g/m2 in Bisoprolol group and 94,44±3,90 g/m2 in RDN group, p < 0.001. Analyzing the impact of various therapeutic regimes on the geometric pattern of the LV, we can note the fact that both treatment schemes with SNS blockers and RDN favored LV reverse remodeling, its normal pattern being regained by 5 (10%) patients from group I and 7 (28%) patients from group III. This time as well RDN demonstrated absolute superiority over both pharmacological treatment regimens (Figure 1). Conclusions: The obtained data confirm the benefit of RDN treatment on the reverse remodeling of the LV by significantly reduction in LV mass index and inducing the recovery of its normal physiological pattern in practically a third of treated patients at 3 years post-procedurally.

LIPOPROTEIN (A): TREATMENT IN THE METABOLIC CONTEXT

Objective: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor but is closely associated with other similar risk factors that are manageable with appropriate treatment and guidance. We aimed to study the impact of using combined therapy for managing Lp(a) levels in patients at high cardiovascular risk but without major adverse cardiovascular events, in primary prevention. Design and method: We conducted a retrospective observational study in 516 patients randomly selected from a group of 1677 patients who attended cardiovascular risk and metabolism consultations between 1995 and 2015. The disorders observed and therapies used were classified into nosological and pharmacological groups, respectively. Cardiovascular risk was calculated based on the Framingham risk score, the European Society of Cardiology's SCORE and the American College of Cardiology's ASCVD Risk Estimator, and changes in patients’ lifestyle were assessed. Results: Significant differences (p<0.001) were found in almost all metabolic variables, except fasting insulin and C-peptide. Lp(a) levels were also significantly reduced (p<0.001). Carotid intima-media thickness improved, decreasing from 2.90 mm to 1.40 mm; however, there was no reduction in the number of cases of vascular stenosis. Of patients with hepatic steatosis (85.5%), 40.7% presented hepatomegaly, but liver function was only altered in a few patients (14.5%). Lipid-lowering therapy, especially statins, significantly decreased Lp(a), benefiting from synergy with other treatments aimed at other metabolic situations associated. Conclusions: Lp(a) is a key overall indicator of vascular risk and should be considered a target in context of combined therapy. Besides a healthy lifestyle, primary prevention should include combined drug therapies to address all cardiovascular risk factors and to delay the atherosclerotic process.

The effect of silver nanoparticles and preparations of various pharmacological groups on the bactericidal activity of S. enteritidis ATCC 13076.

The effect of silver nanoparticles and preparations of various pharmacological groups on the bactericidal activity of S. enteritidis ATCC 13076.

THE INFLUENCE OF GLP-1RAS (ORAL SEMAGLUTIDE) ON TENSIONAL CONTROL IN DIABETIC PATIENTS WITH CHRONIC RENAL DISEASE

Objective: GLP-1 receptor agonists (GLP-1RAs) represent one of the pharmacological groups of choice for the diabetic management of patients with cardiovascular disease and chronic kidney disease (CKD). Their hypotensive effect has not been sufficiently evaluated in association with the usual antihypertensive drugs. The main objective is to study the hypotensive effect of oral semaglutide at a maintenance dose of 7mg per day in a cohort of patients with stage 3b CKD (glomerular filtration rate -GFR- 44 to 30ml/min by CKD-EPI) with poor diabetic control and without previous treatment with GLP-1 receptor agonists or iSGLT2. Design and method: Sixteen patients of both sexes were selected and divided into two follow-up arms of eight patients each. In one arm, the combination of oral semaglutide with an angiotensin receptor blocker (ARB) (such as losartan at a maintenance dose of 50-100mg per day) is evaluated, and in the other, dietary measures are intensified together with ARB at the same doses. After 4 months of treatment, the primary and secondary variables were assessed: body weight, glycosylated haemoglobin (HbA1c), renal function and albuminuria (albumin/creatinine ratio - ACC). Results: Mean age was similar in both groups (69 vs 70 years). The reduction in mean blood pressure (BP) values obtained with standardised measurements in a nephrology consultation in the semaglutide + ARB arm was -12mmHg (systolic) and -5mmHg (diastolic) compared to those in the ARB arm alone (-5mmHg systolic and -3mmHg diastolic), with statistical significance (p<0.05). The other comparative variables between the two groups were: reduction in body weight (-2.5kg vs -0.5kg, p<0.05); reduction in mean HbA1c (-1.2% vs -0.1%, p<0.05); changes in eGFR (+2ml/min/1.73m2 vs -3ml/min/1.73m2, p>0.05) and mean reduction in ACC (-257mg/g vs +12mg/g, p<0.05). Conclusions: Orally administered GLP-1 receptor agonists (semaglutide) are drugs with a hypotensive potential complementary to renin angiotensin system inhibitors in diabetic renal patients. This property, together with their antiproteinuric effect, makes them an ideal choice in situations of hypertension and moderate renal dysfunction. Larger, controlled studies are needed to measure the renal effect alongside the various antihypertensive groups.