The place of combined mucoactive drugs in the treatment of acute respiratory infections in children

The problem of respiratory diseases and their therapy options still retains much of its urgency. Respiratory diseases in children are still super common. According to the data on infectious morbidity among children in the Russian Federation for the period 2018–2020, current trends have not changed, and the acute respiratory infections (ARI) are still ranked number one in terms of the frequency of registered diseases. According to the official records, the frequency of ARI in children among infectious diseases is 71,850.02 per 100,000 population, or 71%. Such well-known symptom as cough is one of the most frequent manifestations of respiratory diseases. It causes the greatest discomfort for both the little patients and their parents, the quality of life of the children and those around them worsens, many domestic and foreign authors mention this symptom in their works. And it is this problem that doctors of various specialties most often face. The cough is currently treated with drugs with different effects depending on the characteristics and manifestations of the disease. Systematic reviews and multicenter studies show that prescription of mucoactive drugs to treat cough in children with underlying ARI is substantiated and feasible. The authors substantiated the necessity of using combinations of various drugs aimed to reduce inflammation of the airways, improve mucociliary clearance, thin out and promote sputum discharge and, accordingly, reduce cough. The article briefly discusses the mechanisms of the development of cough in ARI, the action of drug substances included in the combination drugs used to treat cough in children, the possibility of using the combination of muco- and bronchoactive drugs of synthetic and plant origin.

Advantages of “Soft Steroids” in the Treatment of Inflammatory Eye Diseases. Оverview

The purpose to assess the benefits of using soft steroids in the treatment of inflammatory eye disorders according to literature data.Methods. The literature review concerning the administration of the gluco-corticosteroids and combination drugs based on gluco-corticosteroid for the treatment of inflammatory eye disorders. Both Russian and foreign sources for the 1980–2021 period were analyzed.The results. The combination drugs containing anti-infective drugs and gluco-corticosteroids are actively applied for the treatment of inflammatory eye disorders. That exerts joint ethiopathogenetic effect on the disorder. However, gluco-corticosteroid being a part of such drugs (predominantly dexamethasone) as often as not leads to ocular hypertension. In order to deal with this problem the so-called soft steroids (also classified as gluco-corticosteroids) were introduced. They lessen the possibility of the ocular hypertension and are marked by high efficiency and increased safety profile. One of the representatives of soft steroids is fluorometholone. There is a large evidential base in the modern literature that confirms much lesser influence of fluorometholone on ocular pressure if compared to dexamethasone. At the same time, dexamethasone has a higher anti-inflammatory activity, while on the other hand, its systemic immunosuppressive activity is lower. What is more, in terms of influence on the ocular surfaces, dexamethasone has an additional advantage which is causing mucin expression in conjuctival and corneal epithelium. The above mentioned merits of dexamethasone served as basis for its inclusion into the combination drug called Floas-T which is essentially the combination of tobramycin 0.3 % and fluorometholone 0.1 %. It is used in the treatment of inflammatory eye diseases and diseases of eye appendages, as well as for profylaxis of the diseases in the postoperative period.Conclusion. Combination drugs containing anti-infective components and gluco-corticosteroids seem to be highly promising for the treatment of inflammatory eye diseases. One of them worth highlighting is Floas-T classified as soft steroids containing tobramycin and fluorometholone. It compares to dexamethasone favourably in terms of efficiency, while contributing less to ocular hypertension.

Enzyme Inhibitors: The Best Strategy to Tackle Superbug NDM-1 and Its Variants

Multidrug bacterial resistance endangers clinically effective antimicrobial therapy and continues to cause major public health problems, which have been upgraded to unprecedented levels in recent years, worldwide. β-Lactam antibiotics have become an important weapon to fight against pathogen infections due to their broad spectrum. Unfortunately, the emergence of antibiotic resistance genes (ARGs) has severely astricted the application of β-lactam antibiotics. Of these, New Delhi metallo-β-lactamase-1 (NDM-1) represents the most disturbing development due to its substrate promiscuity, the appearance of variants, and transferability. Given the clinical correlation of β-lactam antibiotics and NDM-1-mediated resistance, the discovery, and development of combination drugs, including NDM-1 inhibitors, for NDM-1 bacterial infections, seems particularly attractive and urgent. This review summarizes the research related to the development and optimization of effective NDM-1 inhibitors. The detailed generalization of crystal structure, enzyme activity center and catalytic mechanism, variants and global distribution, mechanism of action of existing inhibitors, and the development of scaffolds provides a reference for finding potential clinically effective NDM-1 inhibitors against drug-resistant bacteria.

Study of the composition of drugs for the treatment of diseases of the nose cavity

Drugs of group R01, according to the АTC- classification used in the treatment of diseases of the nasal cavity by composition and dosage form, were studied. The dependence of the therapeutic effect of drugs on the chemical structure of the active substance, possible combinations of active substances belonging to different pharmacological groups (sympathomimetics, corticosteroids, and antihistamines), which determine their specific effect on the human body, are analyzed. These active substances are found in both mono- and multi-component drugs. In combination drugs, other compounds of natural and synthetic origin are also used to enhance the therapeutic effect.

Targeting Tumor Cells with Nanoparticles for Enhanced Co-Drug Delivery in Cancer Treatment

Gastric cancer (GC) is a fatal malignant tumor, and effective therapies to attenuate its progression are lacking. Nanoparticle (NP)-based solutions may enable the design of novel treatments to eliminate GC. Refined, receptor-targetable NPs can selectively target cancer cells and improve the cellular uptake of drugs. To overcome the current limitations and enhance the therapeutic effects, epigallocatechin-3-gallate (EGCG) and low-concentration doxorubicin (DX) were encapsulated in fucoidan and d-alpha-tocopherylpoly (ethylene glycol) succinate-conjugated hyaluronic acid-based NPs for targeting P-selectin-and cluster of differentiation (CD)44-expressing gastric tumors. The EGCG/DX-loaded NPs bound to GC cells and released bioactive combination drugs, demonstrating better anti-cancer effects than the EGCG/DX combination solution. In vivo assays in an orthotopic gastric tumor mouse model showed that the EGCG/DX-loaded NPs significantly increased the activity of gastric tumors without inducing organ injury. Overall, our EGCG/DX-NP system exerted a beneficial effect on GC treatment and may facilitate the development of nanomedicine-based combination chemotherapy against GC in the future.

Effectiveness of Periarticular Infiltration of the Knee during Total Knee Arthroplasty for Postoperative Pain Management

Background: Different treatment regimens of analgesia, nerve blocks and epidurals are used for pain relief in Total Knee Arthroplasty (TKA). Local infiltration analgesia (LIA) is one of the modalities in which a cocktail combination of different medicines is infiltrated locally into the capsule, surrounding tissues or intraarticular joint space. This study aims to analyze the effectiveness of periarticular injection of combination drugs (Bupivacaine, Ketorolac and Morphine) during TKA for postoperative pain management. Methods: Total of 150 patients who underwent primary unilateral TKA were randomly categorized into 2 groups (75 each). Group A (control group) didn’t receive intraoperative periarticular injection but Group-B received the intraoperative injection of combined local analgesics and anaesthetics (Bupivacaine, Ketorolac and Morphine). Pain following surgery at 0, 1, and 2 postoperative days were recorded with visual analogue scale (VAS) whereas Knee Society Score was used to evaluate the pain and function pre-operative and 3 months’ post-operative. Statistical analysis was done using SPSS software. Results: Patients receiving periarticular infiltration of combination drugs intraoperatively had lower VAS for postoperative pain (p < 0.001) and this group also showed reduced need of analgesia postoperatively. Conclusions: Periarticular infiltration of knee during Total Knee Arthroplasty is effective in management of postoperative pain Keywords: Periarticular; Total Knee Arthroplasty; combination drugs; postoperative pain

A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection

In the present study, we have described how by using molecular docking and molecular dynamics (MD) simulation studies the combination drug of ivermectin and doxycycline can be used as a potential inhibitor for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) virus. In lieu of unavailability of specific cure of coronavirus disease of 2019 (COVID-19) till now various possibilities for individual and combination drugs have been explored by the medical practitioners/scientists for the remedial purpose of CoV-2 infections. 3C-like protease (3CLpro) is the main protease of SARS-CoV-2 virus which plays an essential role in mediating viral replication in the human body. 3CLpro protein can serve as an attractive drug target. In this work, we have studied drug: 3CLpro interactions by in-silico molecular docking and MD simulation approaches. Common and easily available antiviral drugs ivermectin, doxycycline and their combination can regulate 3CLpro protein's function due to its easy inhibition.

Probing Synergistic Targets by Natural Compounds for Hepatocellular Carcinoma

BackgroundDesigning combination drugs for malignant cancers has been restricted due to the scarcity of synergy-medicated targets, while some natural compounds have demonstrated potential to enhance anticancer effects.MethodsWe here explored the feasibility of probing synergy-mediated targets by Berberine (BER) and Evodiamine (EVO) in hepatocellular carcinoma (HCC). Using the genomics-derived HCC signaling networks of compound treatment, NF-κB and c-JUN were inferred as key responding elements with transcriptional activity coinhibited during the synergistic cytotoxicity induction in BEL-7402 cells. Then, selective coinhibitors of NF-κB and c-JUN were tested demonstrating similar synergistic antiproliferation activity.ResultsConsistent with in vivo experiments of zebrafish, coinhibitors were found to significantly reduce tumor growth by 79% and metastasis by 96% compared to blank control, accompanied by anti-angiogenic activity. In an analysis of 365 HCC individuals, the low expression group showed significantly lower malignancies and better prognosis, with the median survival time increased from 67 to 213%, compared to the rest of the groups.ConclusionTogether, NF-κB and c-JUN were identified as promising synergistic inducers in developing anti-HCC therapies. Also, our method may provide a feasible strategy to explore new targeting space from natural compounds, opening opportunities for the rational design of combinational formulations in combatting malignant cancers.

Combination of Antiviral Drugs to Inhibit SARS-CoV-2 Polymerase and Exonuclease as Potential COVID-19 Therapeutics

SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment.

Gastroprotective effect of fluvoxamine and ondansetron on stress-induced gastric ulcers in mice

Objectives The association between stress and gastric ulcers has been well reported. This study is divided into two parts: the first part of this study is consisted of analyzing the effect of fluvoxamine administration by intracerebroventricular (ICV) and intraperitoneal (IP) injections on stress-induced gastric ulcers. The second part investigates the effect of ondansetron in influencing the protection of the gastric mucous by giving fluvoxamine to the mice before being induced with stress. Methods Water immersion restraint stress (WIRS) was used to induce stress. Fluvoxamine 50 and 100 mg/kg by IP injection, fluvoxamine 9.3 µg, and 18.6 µg by ICV injection 30 min before the induction of stress. Meanwhile, single drug and in combination administered to the mice, ondansetron 3 mg/kg was given by IP at 60 min, and fluvoxamine 50, 100 mg/kg orally at 30 min before stress induction. Results The obtained results show fluvoxamine 50 and 100 mg/kg by IP, and fluvoxamine 18.6 µg by ICV had significantly reduced ulcer index with p<0.005, p<0.001, and p<0.005 while fluvoxamine 9.3 µg showed the insignificant result. Fluvoxamine 50 mg/kg, fluvoxamine 100 mg/kg, and ondansetron 3 mg/kg monotherapy have a significant reduction in ulcers with p<0.005, p<0.001, and p<0.05, while the combination drugs showed an insignificant reduction in ulcers. Conclusions Fluvoxamine with different administration routes and ondansetron monotherapy before stress reduce the occurrence of gastric ulcers, while the combination drugs did not increase the protective effect of the gastric mucosa.