bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpolymer Complexes Based on Carbopol<sup>®</sup> and Poly(2-ethyl-2-oxazoline) as Carriers for Buccal Delivery of Metformin
Authors: Viktorova A. S. , Elizarova E. S. , Romanova R. S. , Timergalieva V. R. , Khutoryanskiy V. V. , Moustafine R. I. 
Published: February 2021

Introduction. Buccal drug delivery has a number of advantages over oral administration: ease of application, good blood supply to the buccal mucosa, drug can enter the systemic circulation directly, avoiding the "first pass effect through the liver", and are not exposed to the acidic environment of the gastric juice and the destructive action of digestive enzymes. The use of interpolymer complexes (IPCs) makes it possible not only to ensure adhesion to the mucosal membranes of the oral cavity, but also to achieve a prolonged release of drugs.Aim. Development of carriers based on interpolymer complexes using Carbopol® 971 NF (C971) and poly(2-ethyl-2-oxazoline) (POZ) of different molecular weights for buccal delivery of metformin (MF).Materials and methods. The study of IPC adhesion was carried out using a TA.XTplus texture analyzer (Stable Micro Systems, UK); mucin compacts with a diameter of 13 mm were used as a substrate; these were prepared by compressing porcine gastric mucin powder using a manual hydraulic press for IR spectroscopy (PerkinElmer, USA) at a pressure of 2.45 MPa. The study of the swelling capacity was carried out by placing polymer matrices in an artificial saliva medium, with constant thermostating at a temperature of 37.0 ± 0.5 °C for 5 hours. The study of the release of MF from the matrices based on IPC was carried out using a DFZ II apparatus (Erweka, Germany) according to the Flow Through Cell method (USP IV) with cells for tablets (22.6 mm) and adaptors for ointments, creams and gels in a medium simulating saliva. The concentration of MF in the samples from the dissolution tests was determined with UV-spectrophotometry (Lambda, PerkinElmer, USA) at 232.8 nm.Results and discussion. In a comparative study of the mucoadhesive properties of polymer samples, IPC compacts showed a mucoadhesion capacity comparable to that of poly(2-ethyl-2-oxazoline); at the same time, compacts from physical mixtures (PM) and C971 are inferior in terms of the separation force to IPC samples, however, POZes dissolve in an artificial saliva medium, that is, they are not suitable as dosage forms for buccal delivery. For 5 hours of the experiment to assess the swelling capacity, the IPC matrices did not change significantly, which can ensure their comfortable use as carriers for buccal delivery. When evaluating the release of metformin from polymer matrices (with weight ratio MF/IPC 1: 0.5), the most complete release (more than 90 %) is observed from both IPC matrices compared to matrices of PM and individual polymers.Conclusion. Polycomplex matrix systems based on C971-POZ (50 kDa) and C971-POZ (500 kDa) are suitable for buccal delivery of metformin.
Ophthalmic Drug Delivery Systems (Review)
Authors: Bakhrushina E. O. , Anurova M. N. , Demina N. B. , Lapik I. V. , Turaeva A. R. , Krasnuk I. I. 
Published: February 2021

Introduction. Effective delivery of ophthalmic drugs is challenging. The eye has a number of protective systems and physiological barriers, which is why ophthalmic dosage forms have a low bioavailability, usually not exceeding 5 %. Topical drug administration is relatively easy to use and is most commonly prescribed by physicians for the treatment of ophthalmic diseases, especially the anterior segment of the eye. However, when using traditional delivery systems, a number of problems arise: patients' violation of the drug administration technique, and, as a consequence, a decrease in treatment compliance, restriction of drug delivery to the target eye tissues due to low epithelial permeability and rapid clearance after drug administration. Maintaining a constant therapeutic drug level is another challenge that traditional delivery systems often fail to cope with.Text. The article discusses the types of ophthalmic delivery systems. Traditional ones are represented by such dosage forms as eye drops, ointments, gels. Modern ophthalmic dosage forms are represented by: eye films, contact lenses and eye implants. The characteristics, advantages and disadvantages of each type of delivery systems and their promising directions of development, as well as modern developments in this area are given.Conclusion. Currently, most of the scientific research on the development of ophthalmic delivery systems is devoted to obtaining dosage forms capable of maintaining a constant concentration of the drug in the target tissue, providing the transport of active ingredients to them. This is achieved by using modern advances in nanotechnology and polymer chemistry. Receive liquid and soft dosage forms with micro-, nano- and micro-nano-carriers. Polymeric delivery systems such as films, lenses and implants are being actively developed and studied. The development of modern technological approaches opens up new possibilities for the treatment of a wide range of ophthalmic diseases by reducing the side effects often induced by the intrinsic toxicity of molecules, reducing the frequency of the administered dose and maintaining the pharmacological profile of the drug. Thus, the use of modern ophthalmic delivery systems can significantly limit the use of invasive treatments.
Use of Capillary Electrophoresis Method in Determination of Quantitative Content of Mangiferin in Grass of Species of Genus Hedysarum (Hedysarum Caucasicum M.Bieb., Hedysarum Grandiflorum Pall., Hedysarum Daghestanicum Rupr. ex Boiss) of flora of the North Caucasus
Authors: Imachueva D. R. , Serebryanaya F. K. 
Published: February 2021

Introduction. The species of the genus Hedysarum L. of the Fabaceae family are of significant interest in connection with the accumulation of a group of biologically active substances with antibacterial and antiviral activity against DNA-containing viruses.Aim. The purpose of the work is to develop a method for the quantitative determination of mangiferin in the aboveground part of species of the genus Hedysarum L., Hedysarum caucasicum M.Bieb., Hedysarum grandiflorum Pall., Hedysarum daghestanicum Rupr. ex. Boiss. collected in the North Caucasus by zonal capillary electrophoresis.Materials and methods. The objects of the study were species of the genus Hedysarum L., namely Hedysarum caucasicum M.Bieb., Hedysarum grandiflorum Pall., Hedysarum daghestanicum Rupr. ex. Boiss. collected in the North Caucasus. Registration of electronic spectra was carried out on capillary electrophoresis "KAPEL'®-105m" (OJSC "Lumex-marketing", Russia) with quartz capillary Leff./Ltol. = 50/60 cm, ID = 75 μm. As a standard sample, mangiferin (substance-powder, mangiferin content ≥98 %, Sigma-Aldrich, Lot SLBP4044V) was used.Results and discussion. As a result of comprehensive pharmacognostic studies of species of the kopecki genus growing in the North Caucasus under natural conditions, as well as under the conditions of introduction on the territory of the Botanical Garden of the Pyatigorsk Medical and Pharmaceutical Institute and the Mountain Botanical Garden of the Dagestan Federal Research Center of the Russian Academy of Sciences, we developed a method for the isolation and quantitative determination of mangiferin by capillary electrophoresis.Conclusion. Studies show that the use of the zonal capillary electrophoresis method in the analysis of xanthones, including the determination of the quantitative content of mangiferin, is promising. The largest content of mangiferin (0.25 %) is distinguished by Hedysarum caucasicum M.Bieb., which confirms the assumption based on molecular genetic studies, since it is this species that belongs to the Obscura section, as well as the alpine penny used to produce mangiferin. Therefore, it is possible to provide this technique for analysis of mangiferin xanthone glycoside along with spectrophotometry and high performance liquid chromatography.
Integration of High Velocity Elastic Band for Hamstring Training in Pre-Season Routine of Football Players
Authors: Januševičius Donatas , Sniečkus Audrius , Mickevičius Mantas , Satkunskienė Danguolė , Muanjai Pornpimol , Kamandulis Sigitas 
Published: February 2021

Background. A need for other methods of hamstring strengthening are thus warranted with the main aim of reducing the risk of injury during the subsequent intense athletic activities. The study aimed to examine changes in hamstring strength in response to high velocity elastic band training when incorporated into regular training routine of football players.
Methods. Research participants were professional top level football players (age 23.1 ± 5.7 years; weight 77.2 ± 7.7 kg, training experience 14.1 ± 5.8 years). In the pre-season, in addition to their routine training, the experimental group performed hamstring curls at maximal intensity while lying prone three times per week for five weeks, while control group continued their routine training. Concentric knee torque at 60°/s and 180°/s angular velocities, countermovement jump height, 30m sprint running performance from standing and flying start, and knee flexion-extension movement frequency were measured before and after the 5 weeks of training.
Results. Hamstring curl frequency during lying prone increase by 10.5 % (p < .05) in the experimental group and did not change in the control group. Peak torque for knee flexion and knee extension, jump height and sprint running performance did not change significantly in any group (p > .05).
Conclusion. High velocity elastic band training incorporated into regular pre-season routine is beneficial for football players to increase their knee extension-flexion maximal movement frequency with no evident effects on strength, jump and sprint running performance. Results might be related with concurrent training during preparatory training phase of the pre-season when several physical capacities are being developed simultaneously.
Keywords: high speed movements; peak torque; sprint performance; prevention of hamstring injuries; knee flexion strength.
Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice
Authors: Wang Lingfang , Chen Tingtao , Wang Huan , Wu Xiaoli , Cao Qing , Wen Ke , Deng Ke-Yu , Xin Hongbo 
Published: February 2021

BackgroundAlthough gut hormone glucagon-like peptide 1 (GLP-1) has been widely used for treating diabetes, the extremely short half-life greatly limits its application. The purpose of this study is to explore the effects of an engineered bacteria with expression of GLP-1 on obese mice induced by high fat diet (HFD).MethodsThe engineered strain of MG1363-pMG36e-GLP-1 (M-GLP-1) was constructed and its anti-obesity effects were evaluated in vivo. The bodyweight, the morphology of adipose and liver tissue, and liver function were examined. Quantitative RT-PCR and Western blot were used to measure the expressions of the genes involved in fatty acid oxidation synthesis. The intestinal microbial diversity was detected with high-throughput sequencing analysis.ResultsThe engineered bacteria could produce GLP-1. It also significantly decreased the bodyweight and improved the glucose intolerance in the obese mice induced by HFD. Moreover, the strain also reduced the triglyceride (TG) in serum, protected liver, as well as decreased the intracellular TG in liver tissues of the obese mice. Furthermore, our results showed that the expressions of the genes including peroxisome proliferator-activated receptors α (PPARα) and its target genes were enhanced in liver tissues when mice treated with M-GLP-1. Finally, we found that the engineered strain markedly increased intestinal microbial diversity.ConclusionOur results suggested the genetically engineered bacteria that constitutively secreted GLP-1 could improve obesity and the mechanism may be related to promoting fatty acid oxidation and increasing intestinal microbial diversity of the obese mice.
Development and Evaluation of the Rapid and Sensitive RPA Assays for Specific Detection of Salmonella spp. in Food Samples
Authors: Zhao Liwei , Wang Jianchang , Sun Xiao Xia , Wang Jinfeng , Chen Zhimin , Xu Xiangdong , Dong Mengyuan , Guo Ya-nan , Wang Yuanyuan , Chen Pingping , Gao Weijuan , Geng Yunyun 
Published: February 2021

Salmonella spp. is among the main foodborne pathogens which cause serious foodborne diseases. An isothermal real-time recombinase polymerase amplification (RPA) and lateral flow strip detection (LFS RPA) were used to detect Salmonella spp. targeting the conserved sequence of invasion protein A (invA). The Real-time RPA was performed in a portable florescence scanner at 39°C for 20 min. The LFS RPA was performed in an incubator block at 39°C for 15 min, under the same condition that the amplifications could be inspected by the naked eyes on the LFS within 5 min. The detection limit of Salmonella spp. DNA using real-time RPA was 1.1 × 101 fg, which was the same with real-time PCR but 10 times higher than that of LFS RPA assay. Moreover, the practicality of discovering Salmonella spp. was validated with artificially contaminated lamb, chicken, and broccoli samples. The analyzing time dropped from 60 min to proximately 5–12 min on the basis of the real-time and LFS RPA assays compared with the real-time PCR assay. Real-time and LFS RPA assays’ results were equally reliable. There was no cross-reactivity with other pathogens in both assays. In addition, the assays had good stability. All of these helped to show that the developed RPA assays were simple, rapid, sensitive, credible, and could be a potential point-of-need (PON) test required mere resources.
Early Detection of Checkpoint Inhibitor-Associated Myocarditis Using 68Ga-FAPI PET/CT
Authors: Finke Daniel , Heckmann Markus B. , Herpel Esther , Katus Hugo A. , Haberkorn Uwe , Leuschner Florian , Lehmann Lorenz H. 
Published: February 2021

Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis.Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells.Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)].Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.
The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial
Authors: Pilmark Nanna Skytt , Petersen-Bønding Christina , Holm Nielse Frederich Rose , Johansen Mette Yun , Pedersen Bente Klarlund , Hansen Katrine Bagge , Karstoft Kristian 
Published: February 2021

IntroductionIn general, patients with type 2 diabetes have lower cardiorespiratory fitness levels and perform exercise at lower intensities compared to healthy controls. Since metformin (MET) has been shown to increase the rate of perceived exertion (RPE) during exercise with a fixed intensity, MET per se may reduce self-selected exercise intensity. The aim of this study was to assess the effect of MET on self-selected exercise intensity.MethodsHealthy males were eligible for this crossover, counterbalanced study with two treatment periods: MET and placebo (PLA), each lasting 17 days. Treatment dose was gradually increased and reached 2 g/day on treatment day 9, and continued at that level for the rest of the treatment period. The two periods were performed in randomized order. Two experimental days (A+B) were conducted on Day 15 (A) and Day 17 (B) of each period, respectively. Day A consisted of an exercise bout with self-selected exercise intensity (equal to RPE = 14–15 on the Borg Scale). Day B consisted of an exercise bout with fixed intensity (70% of VO2peak). Oxygen consumption rate was assessed continuously during both exercise bouts.ResultsFifteen males (age 23.7 ± 0.6 years, BMI 22.3 ± 2.0, VO2peak 3.5 ± 0.6 L/min) were included in the study. On Day B, RPE was higher in MET compared to PLA (14.8 ± 0.4 vs. 14.0 ± 0.3, P = 0.045). On Day A, no difference in self-selected exercise intensity measured by oxygen consumption rate (PLA 2.33 ± 0.09 L O2/min, MET 2.42 ± 0.10 L O2/min, P = 0.09) was seen between treatment periods.ConclusionsSelf-selected exercise intensity was not reduced by MET in healthy males, despite the fact that MET increased RPE during an exercise bout with fixed intensity.
Clinical Characteristics of Primary Hyperparathyroidism: 15-Year Experience of 457 Patients in a Single Center in China
Authors: Lin Xiaoyun , Fan Youben , Zhang Zhenlin , Yue Hua 
Published: February 2021

ObjectivePrimary hyperparathyroidism (PHPT) is a common endocrine disorder of calcium metabolism. However, data concerning a large cohort of PHPT patients in the Chinese population are scarce. Thus, the objective of this study was to determine the general clinical signatures of 457 Chinese PHPT patients and explore the clinical characteristic differences between benign and malignant PHPT.MethodsA single-center retrospective study was designed. Medical records between preoperation and postoperative follow-up, were assessed and statistical analysis of the clinical data was performed.ResultsPatients with PHPT aged 12–87 years, with a mean onset age of 56.16 ± 14.60 years, were included. Most patients (68.7%) in our center had symptomatic patterns described as bone pain (74.8%), urolithiasis (25.5%), fatigue (17.5%), and pathological fracture (13.1%), but an increasing tendency has been established in the proportion of patients with asymptomatic forms. Correlation analysis revealed that patients with higher serum levels of parathyroid hormone (PTH) and calcium presented higher serum levels of bone turnover markers (BTMs) and lower 25-hydroxy-vitamin D (25OHD) values (P&lt;0.001). Gains in bone mineral density (BMD) at L1–4, the femoral neck and the total hip were observed 1–2 years after parathyroidectomy (9.6, 5.9, and 6.8%). Parathyroid carcinoma patients presented prominently higher serum PTH and calcium levels and BTMs and lower BMD at femoral neck and total hip than benign PHPT patients (P&lt;0.05), while no significant differences in age, sex, and serum 25OHD concentration were observed between benign and malignant PHPT patients.ConclusionsPHPT should be paid attention to in the patients with bone pain. While, BMD and BTMs can differentiate parathyroid carcinoma from parathyroid adenoma and hyperplasia to some extent. In addition, anti-osteoporosis drugs could be used when necessary to avoid hip fractures in patients with parathyroid carcinoma.
Vitamin D Association With Macrophage-Derived Cytokines in Polycystic Ovary Syndrome: An Enhanced Risk of COVID-19 Infection?
Authors: Moin Abu Saleh Md , Sathyapalan Thozhukat , Butler Alexandra E. , Atkin Stephen L. 
Published: February 2021

BackgroundWomen with polycystic ovary syndrome (PCOS) often have vitamin D deficiency, a known risk factor for severe COVID-19 disease. Alveolar macrophage-derived cytokines contribute to the inflammation underlying pulmonary disease in COVID-19. We sought to determine if basal macrophage activation, as a risk factor for COVID-19 infection, was present in PCOS and, if so, was further enhanced by vitamin D deficiency.MethodsA cross-sectional study in 99 PCOS and 68 control women who presented sequentially. Plasma levels of a macrophage-derived cytokine panel were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Vitamin D was measured by tandem mass spectroscopy.ResultsVitamin D was lower in PCOS women (p&lt;0.0001) and correlated negatively with body mass index (BMI) in PCOS (r=0.28, p=0.0046). Basal macrophage activation markers CXCL5, CD163 and MMP9 were elevated, whilst protective CD200 was decreased (p&lt;0.05); changes in these variables were related to, and fully accounted for, by BMI. PCOS and control women were then stratified according to vitamin D concentration. Vitamin D deficiency was associated with decreased CD80 and IFN-γ in PCOS and IL-12 in both groups (p&lt;0.05). These factors, important in initiating and maintaining the immune response, were again accounted for by BMI.ConclusionBasal macrophage activation was higher in PCOS with macrophage changes related with increased infection risk associating with vitamin D; all changes were BMI dependent, suggesting that obese PCOS with vitamin D deficiency may be at greater risk of more severe COVID-19 infection, but that it is obesity-related rather than an independent PCOS factor.