bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factores de riesgo del pie diabético en adulta mayor: caso clínico
Authors: Huerta Chimborazo Veronica , Mesa Cano Isabel Cristina 
Published: February 2023

Introducción. El pie diabético se define como la infección, ulceración o destrucción de los tejidos profundos del pie que puede estar asociado a diferentes factores. Objetivo. Efectuar un análisis bibliográfico y tratamiento de la enfermedad para determinar los factores de riesgo del pie diabético en adulta mayor mediante un caso clínico del Centro geriátrico FUNPRA de la ciudad de Cañar – Ecuador. Metodología. Paciente de 80 años de edad, sexo femenino, viuda, procedente de la ciudad de Azogues y residente en Cañar-Ecuador FUNPRA (Asilo de ancianos), con ninguna instrucción. Es atendida por pie diabético grado I herida superficial en el pie derecho, no involucra tendón cápsula o hueso, en proceso de cicatrización se observa tejido de granulación. Resultados. Tratamiento y evolución: Se le administró dieta general, actividad física previa curaciones, insulina en la mañana 14 UI/dL y en la tarde 6 UI/dL por día al final curar y vendar. Con 3 años evolución DMT tipo II, 3 meses de evolución de pie diabético. Sin antecedentes patológicos, quirúrgicos y familiares. Se observa mejoría de la paciente después de las curaciones realizadas, control de la glicemia y la administración de la medicación adecuadamente. Conclusión. Se trató a una paciente con diabetes mellitus tipo II, se asocia su pie diabético a la obesidad, al inadecuado cuidado y mala higiene.
Standardization of Requirements for Culture Media Used to Assess the Quality of Drugs (Review)
Authors: Sukhanova S. M. 
Published: February 2023

Introduction. A reliable assessment of the quality and safety of medical products (MP) by biological indicators is directly related to the use of culture media (CM) that meet the established requirements. However, when conducting trial, it is necessary to take into account the peculiarities of culture media due to the presence in their composition of components of biological origin. In particular, a high degree of variability and unstable stability of raw materials, as well as possible mistakes in producing and storage of media, create the prerequisites for deviations. The use of industrial culture media also does not guarantee their suitability for the appropriate test. Therefore to obtain reliable results, the compliance of each batch CM with the specified criteria be confirmed must be confirmed by standard methods using the full range of meaningful indicators. The current lack of a state standard in the Russian Federation regulating the requirements for the use of culture media when confirming the quality of medical products makes it much more difficult to assess the suitability, comparability and reliability of the analysis results, both themselves CM and drugs.Text. The article discusses the draft General Pharmacopoeia Article (GPM) "Culture media", which presents the general requirements for of culture media when used in pharmacopoeia analysis. The standard is intended for specialists involved in the development, improvement and application of methods and / or techniques necessary for confirming the properties of medical products for the purpose of registration, entry into civil circulation, as well as in their production. The document was drawn up taking into account modern domestic and international approaches of good pharmaceutical practices to the assessment of the drugs that involve the use of culture media. The project identifies the key factors that most affect the quality of culture media. Based on the principle of continuity, compiled and described in detail a set of standardized control methods, including tests on physical-chemical and biological indicators. For exploring of specific properties, there are requirements for test cultures have been established. Governs special requirements for culture media used to obtain biological medical products are regulated. The procedure for storage and disposal of culture media unsuitable for use is described.Conclusion. The introduction of the GPM "Culture media" into the practice of domestic pharmacopoeic analysis will increase the reliability of the results of the evaluation of the effectiveness and safety of drugs, and as a result will lead to a reduction in production risks and risks of harm to health patients during in pharmacotherapy and immunoprophylaxis. The proposed approaches can also be used in other branches of science and industry.
Dissolution Profile Study and Uniformity of Dosage Units Test for Various Manufacturers of "Captopril" Drugs from the Russian Market
Authors: Grebenkin D. Yu. , Ryabova A. V. , Kuramshina A. M. , Kislyakov I. V. , Zhukova E. D. 
Published: February 2023

Introduction. As part of a comparative assessment of drugs quality available on the Russian market a dissolution profile studies and uniformity of dosage units test was conducted for various manufacturers of "Captopril" drugs. Drug release studies in three dissolution media (0.1 M hydrochloric acid, acetate buffer pH 4.5, phosphate buffer pH 6.8) with sampling at 0, 5, 10, 15, 20, 30 min and analysis using UV/Vis spectrophotometer at 212 nm were conducted. Dissolution kinetics was compared based on calculation of the similarity factor f2 and the values of relative standard deviations. Uniformity of dosage units test of scored tablets were evaluated based on HPLC-UV analysis and AV factor calculation.Aim. The purpose of this study was a comparative evaluation of "Captopril" drugs from various manufacturers on the Russian market based on dissolution profile studies and uniformity of dosage units test of scored tablets in order to assess the quality of the tablets.Materials and methods. To prove the dissolution profile studies DT 827/1000 tester (ERWEKA GmbH, Germany) was applied. Each drug in three dissolution media in 12 replicates for each dissolution medium was analyzed. The selected samples were analyzed on a UV 1800 UV spectrophotometer (Shimadzu, Japan) at a of 212 nm. In uniformity of dosage units test of scored tablets each tablet was divided according to the applied mark. Sample preparation was carried out in accordance with a validated method and samples were analyzed by HPLC-UV using Agilent 1260 (Agilent Technologies, США).Results and discussion. Based on the results of dissolution profile studies and calculations of the similarity factors and values of the relative standard deviation it can be concluded that the dissolution kinetics for drug no. 4, drug no. 5, drug no. 6 are not equivalent in comparison with the reference drug. During the uniformity of dosage units test of scored tablets, no deviations were found in accordance with the requirements of the RF Pharmacopoeia OFS.1.4.2.0008.18 "Uniformity of dosing" and the EAEU Pharmacopoeia OFS.2.1.9.14 "Uniformity of Dosed Units".Conclusion. The conducted dissolution profile studies and uniformity of dosage for scored tablets of Captopril drugs show the example of possibility to identify potential problems with drugs quality presented on the Russian market and as a result improve and maintain quality assurance of drugs for the national healthcare system.
Pharmacokinetic and Bioequivalence Study of the Two-component Drug Product "Ezetimibe + rosuvastatin" (JSC "Sanofi-aventis group", Russia): Resuts and Experience with the Use of Enzymatic Hydrolysis in the Analysis of Samples
Authors: Khokhlov A. L. , Grebenkin D. Yu. , Faeva E. K. , Kazey V. I. , Khokhlov A. A. , Miroshnikov A. E. , Lebedeva O. V. 
Published: February 2023

Introduction. As a part of the registration of the drug product a bioequivalence study of the fixed-dose combination "Ezetimibe + rosuvastatin" (JSC "Sanofi-aventis group", Russia) compared with coadministered Ezetrol® (ezetimibe) and Crestor® (rosuvastatin) was conducted with 76 healthy volunteers. Enzymatic hydrolysis was used to evaluate the pharmacokinetics of total ezetimibe. This was the reason for the inclusion of the additional monitored parameters in the validation and analysis.Aim. The purpose of the bioequivalence trial was a comparative study of the pharmacokinetics and evidence of the bioequivalence of the fixed-dose combination "Ezetimibe + rosuvastatin" (ezetimibe + rosuvastatin,tablets, 10 + 40 mg, JSC "Sanofi-aventis group", Russia) compared with coadministrated monocomponent drugs ezetimibe and rosuvastatin in fasting healthy volunteers after a single administration using the described additional parameters for controlling the enzymatic hydrolysis of ezetimibe-glucuronide during the analysis of samples.Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover two-period clinical trial was conducted. During the study, blood plasma samples were taken from volunteers, the concentrations of ezetimibe (unconjugated) and total ezetimibe (ezetimibe + ezetimibe-glucuronide) and rosuvastatin in plasma samples were determined by validated HPLC-MS/MS methods. Based on the received data pharmacokinetic and statistical analysis was performed and confidence intervals (CI) for the pharmacokinetic parameters Cmax and AUC0-72 were calculated.Results and discussion. It can be concluded that the studied formulations are bioequivalent in terms of pharmacokinetic parameters of ezetimibe (free) and rosuvastatin. Pharmacokinetic parameters of total ezetimibe were considered as secondary and were not required for the conclusion on bioequivalence. While HPLC-MS/MS analysis of incurred samples, additional control parameters for the enzymatic hydrolysis of ezetimibe-glucuronide made it possible to legitimately reject the results of inaccurate analytical batches.Conclusion. Thus, according to the criteria used in the study, the drugs are proved to be bioequivalent. The described additional parameters for controlling the enzymatic hydrolysis of ezetimibe-glucuronide have been shown to be effective.
Antitumor Activity of Species of the Genus <i>Artemisia</i> L.: Current State and Prospects (Review)
Authors: Romanteeva Yu. V. , Berezutsky M. A. , Kurchatova M. N. 
Published: February 2023

Introduction. Recently, the anticancer activity of representatives of the genus Artemisia L. has been actively studied, and most studies are devoted to Artemisia annua L., which has been used since ancient times in the folk medicine of several countries as an antimalarial and anticancer agent. The similarity of the chemical composition predetermines the study of the anticancer activity of other species of the genus Artemisia L. The information about this is still not fully presented in scientific publications, is very diverse and sometimes even contradictory. Review of modern studies of anticancer activity of species of the genus Artemisia L., generalization of available data and providing information for future research is relevant.Text. The article presents a review of experimental data on the study of anticancer activity of representatives of the genus Artemisia L. It is noted that the main mechanism of such activity is apoptosis. Apoptosis is triggered by the increase of reactive oxygen species (ROS) inside cancer cells, reduction of mitochondrial membrane potential, activation of pro-apoptotic and, on the contrary, inhibition of anti-apoptotic proteins, as well as by formation of membrane bubbles, cell compression and by activation caspase.Conclusion. In the presented review, about 30 species of the genus Artemisia L. With the presented degree of study of this area, a number of questions remain unresolved. The most studied with respect to cytotoxic activity are Artemisia absinthium L. and Artemisia vulgaris L. In this aspect, the study of other closely related species of the genus Artemisia L. Also relevant is the study of cytotoxicity of representatives of the genus Artemisia L. on normal cell cultures and in comparison with positive control. In addition, a detailed study of the pool of secondary metabolites of different species of the genus Artemisia L. remains significant in order to reliably determine the components responsible for the manifestation of anticancer action. The pronounced effectiveness against cancer cells and, at the same time, a weak effect on healthy cells of the body of representatives of the genus Artemisia L. opens up the prospect of their use as sources of partner drugs with a synergistic effect and means of augmentation of antitumor therapy.
Methodology of the Development of a Topical Transdermal Fucoidan Delivery System
Authors: Obluchinskaya E. D. , Shikov A. N. , Pozharitskaya O. N. 
Published: February 2023

Introduction. Marine-derived polysaccharides are promising candidates for the development of innovative drugs. One of such compounds is the polysaccharide fucoidan from brown seaweeds, which shows anticoagulant and anti-inflammatory activity. The development of topical transdermal formulation for the treatment of chronic venous diseases is of particular interest, because with targeted delivery, the active compound in high concentration comes directly to the site where the drug is required, while the risk of side effects is minimal.Aim. Experimental and theoretical justification of the methodological scheme for the development of a transdermal delivery system with fucoidan for local therapy using the Quality by Design (QbD) approach.Materials and methods. Fucoidan was isolated from the thalli of Fucus vesiculosus L. from the Barents Sea according to the original technology of the MMBI RAS. All excipients were approved for medical use. The experiments for rational selection of the excipients for the transdermal delivery system (TSD) were planned using the Greek-Latin square 4 × 4 with repeated observations. The colloidal and thermal stability and pH were evaluated as physicochemical parameters of TSD Structural and mechanical properties of TSD were deter-mined with rotational viscometer. The dissolution rate of fucoidan in vitro was evaluated using the paddle-over-disk method at a temperature of 32 ± 0.5 °C.Results and discussion. The composition and technology of topical TSD цwith fucoidan were developed using the QbD concept. The composition and technology of topical TSD with 15 % of fucoidan as active ingredient were developed. TSD has thermo- and colloidal stability, and has a pH value close to the pH of human skin. Poloxamer 407 was used as a gel base; olive oil was used as a hydrophobic phase. It was found that the ratio of poloxamer 407 to the aqueous phase should be no less than 0.1 and no more than 0.37; the ratio of water to the aqueous phase should not be less than 0.56 and not more than 0.69; and the ratio of polyoxyl 40 hydrogenated castor oil to the oil phase must be at least 0.34. It was found that 9 % poloxamer 407 provides the necessary structural and mechanical properties of TSD. It has been established that the developed TSD of fucoidan with poloxamer 407 belongs to non-Newtonian flow types with plastic properties and has thixotropy.Conclusion. The complex of studies based on QbD approach led to the experimental and theoretical justification of the methodological scheme for the development of a transdermal delivery system with marine polysaccharide fucoidan. The methodological scheme takes into account the physicochemical and technological features of fucoidan and allows you to create a high-quality TSD that ensures stability and complete release of the active substance.
Double Proteolysis for N- and O-glycan Analysis of Fc-fusion Protein Etanercept
Authors: Varzieva V. G. , Mesonzhnik N. V. , Belushenko A. О. , Bochkareva N. L. , Appolonova S. А. 
Published: February 2023

Introduction. Highly glycosylated proteins are the most abundant class of modern biopharmaceuticals. A majority of such therapeuticals produced by Russian biopharmaceutical companies is biosimilars. The foundation of biosimilar manufacturing is analytical assessment of structure equivalence to an original molecule. Fc-fusions present a challenge due to their structural properties. The only biosimilar of this kind registered in Russia is etanercept – a fusion of tumor necrosis factor receptor α and Fc-fragment of IgG1. Existing approaches widely used in protein analysis do not allow accurate and reliable description of glycoylation of these proteins. Development of new approaches and principles of such analysis is necessary, as the changes in biosimilar’s molecular structure can seriously affect its efficacy and safety.Aim. Development of double proteolysis approaches for glycopeptide mapping of Fc-fusion protein etanercept using Arg-C protease.Materials and methods. Etanercept was subjected to enzymatic hydrolysis using trypsin in combination with Arg-C or Asp-N. The resulting peptides were analyzed using HPLC-MS system Xevo G2-XS QTOF (Waters Corporation, USA). The conformation of glycan structure was performed via analysis of fragment spectra of glycopeptides, acquired with high collision energy mode (MS E ). UNIFI (version 1.8) with biopharmasuetical assessment setting (Waters Corporation, USA) was used to analyze the peptide maps.Results and discussion. It was found that using the combination of trypsin with protease Arg-C leads to reliable results Using the developed approach we successfully determined the majority of O-glycosylation sites and types of O-glycans. It was shown that for an effective O-glycopeptide maping N-deglycosylation stage is required. Most abundant N-glycan structures were identified for each of three N-glycosylation sites (N149, N171, N317). It was determined, that the combination of trypsin with Arg-C allows identification of three-antenna forms despite the presence of O-glycosylation site on the analyzed peptide. General N-glycosylation profile shows comparability of results for both approaches.Conclusion. As a result of this research we developed glycopeptide mapping approaches in which a combination of proteases is used. Using these methods sites of N- and O-glycosilation and glycofoms of etanercept were accurately and reproducibly determined. Developed procedures can be applied to other types of Fc-fusion proteins, making it of broader appeal and benefit to the overall biopharmaceutical industry. These approaches provide comprehensive information useful for structure-function studies and of potential value for product comparability measurements and possibly even future manufacturing control strategies.
Phytofabrication and characterization of Alchornea cordifolia silver nanoparticles and evaluation of antiplasmodial, hemocompatibility and larvicidal potential
Authors: Kojom Foko Loick Pradel , Hawadak Joseph , Verma Vaishali , Belle Ebanda Kedi Philippe , Eboumbou Moukoko Carole Else , Kamaraju Raghavendra , Pande Veena , Singh Vineeta 
Published: February 2023

Purpose: The recent emergence of Plasmodium falciparum (Pf) parasites resistant to current artemisinin-based combination therapies in Africa justifies the need to develop new strategies for successful malaria control. We synthesized, characterized and evaluated medical applications of optimized silver nanoparticles using Alchornea cordifolia (AC-AgNPs), a plant largely used in African and Asian traditional medicine.Methods: Fresh leaves of A. cordifolia were used to prepare aqueous crude extract, which was mixed with silver nitrate for AC-AgNPs synthesis and optimization. The optimized AC-AgNPs were characterized using several techniques including ultraviolet-visible spectrophotometry (UV-Vis), scanning/transmission electron microscopy (SEM/TEM), powder X-ray diffraction (PXRD), selected area electron diffraction (SAED), energy dispersive X-ray spectroscopy (EDX), Fourier transformed infrared spectroscopy (FTIR), dynamic light scattering (DLS) and Zeta potential. Thereafter, AC-AgNPs were evaluated for their hemocompatibility and antiplasmodial activity against Pf malaria strains 3D7 and RKL9. Finally, lethal activity of AC-AgNPs was assessed against mosquito larvae of Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti which are vectors of neglected diseases such as dengue, filariasis and chikungunya.Results: The AC-AgNPs were mostly spheroidal, polycrystalline (84.13%), stable and polydispersed with size of 11.77 ± 5.57 nm. FTIR revealed the presence of several peaks corresponding to functional chemical groups characteristics of alkanoids, terpenoids, flavonoids, phenols, steroids, anthraquonones and saponins. The AC-AgNPs had a high antiplasmodial activity, with IC50 of 8.05 μg/mL and 10.31 μg/mL against 3D7 and RKL9 Plasmodium falciparum strains. Likewise, high larvicidal activity of AC-AgNPs was found after 24 h- and 48 h-exposure: LC50 = 18.41 μg/mL and 8.97 μg/mL (Culex quinquefasciatus), LC50 = 16.71 μg/mL and 7.52 μg/mL (Aedes aegypti) and LC50 = 10.67 μg/mL and 5.85 μg/mL (Anopheles stephensi). The AC-AgNPs were highly hemocompatible (HC50 &gt; 500 μg/mL).Conclusion: In worrying context of resistance of parasite and mosquitoes, green nanotechnologies using plants could be a cutting-edge alternative for drug/insecticide discovery and development.
Rare earths stick to rare cyanobacteria: Future potential for bioremediation and recovery of rare earth elements
Authors: Paper Michael , Koch Max , Jung Patrick , Lakatos Michael , Nilges Tom , Brück Thomas B. 
Published: February 2023

Biosorption of metal ions by phototrophic microorganisms is regarded as a sustainable and alternative method for bioremediation and metal recovery. In this study, 12 cyanobacterial strains, including 7 terrestrial and 5 aquatic cyanobacteria, covering a broad phylogenetic diversity were investigated for their potential application in the enrichment of rare earth elements through biosorption. A screening for the maximum adsorption capacity of cerium, neodymium, terbium, and lanthanum was conducted in which Nostoc sp. 20.02 showed the highest adsorption capacity with 84.2–91.5 mg g-1. Additionally, Synechococcus elongatus UTEX 2973, Calothrix brevissima SAG 34.79, Desmonostoc muscorum 90.03, and Komarekiella sp. 89.12 were promising candidate strains, with maximum adsorption capacities of 69.5–83.4 mg g-1, 68.6–83.5 mg g-1, 44.7–70.6 mg g-1, and 47.2–67.1 mg g-1 respectively. Experiments with cerium on adsorption properties of the five highest metal adsorbing strains displayed fast adsorption kinetics and a strong influence of the pH value on metal uptake, with an optimum at pH 5 to 6. Studies on binding specificity with mixed-metal solutions strongly indicated an ion-exchange mechanism in which Na+, K+, Mg2+, and Ca2+ ions are replaced by other metal cations during the biosorption process. Depending on the cyanobacterial strain, FT-IR analysis indicated the involvement different functional groups like hydroxyl and carboxyl groups during the adsorption process. Overall, the application of cyanobacteria as biosorbent in bioremediation and recovery of rare earth elements is a promising method for the development of an industrial process and has to be further optimized and adjusted regarding metal-containing wastewater and adsorption efficiency by cyanobacterial biomass.