Dynamics of findings of non-specific resistance in the mouth cavity in children with lesions of the mucous membrane epithelium of the mouth cavity against acute lymphoblastic leukemia in the treatment process.

There was con­ducted study of dynamics of findings of non-specific resistance in the mouth cavity in children with lesions of the mucous membrane epithelium of the mouth cavity against acute lymphoblastic leukemia  in the treatment process by authors-developed methods. It is known that in children with leukemia immunodeficiency states develop immunological disorders resulted from treatment with cytotoxic drugs. Moreover, not only general, but also the local immunity of the mouth cavity suffers, which is accompanied by development of infectious processes in the tissues that perform the barrier function, which include mucous membrane epithelium of the mouth cavity. A key role in the system of antimicrobial protection of the mouth cavity is performed by mucolytic enzyme lisocyme and α-defensins (HNP 1-3). 76 children with acute lymphoblastic leukemia  aged from 2 to 18 years suffering  from such dental diseases as generalized chronic catarrhal gingivitis, erosive-ulcerative and candidal stomatitis took part in the clinical study. All children under clinical study were divided into 2 groups - the main and comparison. Standard protocol treatment was used in the comparison group. Developed treatment-and-prophylactic complex was used in the main group. The children of the main group were prescribed developed treatment-and-prophylactic complex depending on the period of the disease: the first version of local treatment was used in the acute period and the relapse of the disease, the second - in the period of remission. The results of research have shown a stimulating effect of therapeutic and prophylactic measures on the natural antimicrobial system of mouth cavity protection, both in children of the main groups under study and in the comparison groups. Such a phenomenon should be considered as a positive process that contributes to the increase of resistance in periodontal tissues and mucous membrane epithelium of the mouth cavity

Correction of retinal ischemia/reperfusion by 3-(1H-benzimidazol-2-il)-1,2,2-trimethyl cyclopentancarbonic acid in experiment

Results of ocular fundus studies revealed the most pronounced protective effects of 3-(1Hbenzimidazol-2-il)-1,2,2-trimethyl cyclopentancarbonic acid in a dose 50 mg/kg on the model of retinal ischemiareperfusion in Wistar rats, which is reflected in the restoration of the optic disc. Correction of retinal ischemiareperfusion by 3-(1H-benzimidazol-2-il)-1,2,2-trimethyl cyclopentancarbonic acid in a dose 50 mg/kg leads to higher values of the coefficient b/a of electroretinography after 72 hours of reperfusion compared to the group with pathology correction by the same drug in a dose 10 mg/kg, which indicates the restoration of the electrophysiological state of the retin

Good Pharmacovigilance Practice in the United States and the European Union

The article presents the results of a comparative analysis of Goodpharmacovigilance practices (GVP), developed by experts of the regulatory bodiesof the European Union (EU) and the United States. It is shown that the EU GVP cover almost all possible aspects of pharmacovigilance. It is noted that the disadvantages of EU GVP are difficulties in the correct understanding and interpretation of certain definitions and processes, as well as the complexity of the implementation in practice of a number of provisions, mainly related to the organization of the quality management system, including audit and inspection. As the basis for development of the Russian Rules GVP is recommended to use the GVP E

Comparative evaluation of recommendations for preclinical studies of transporter-mediated drug–drug interactions

Scientific relevance. Sound recommendations for preclinical studies of transporter- mediated pharmacokinetic interactions of medicinal products can help increase the likelihood of identifying potentially nephrotoxic and hepatotoxic medicinal products at the development and authorisation stages. However, overly strict requirements for the number of studies to be performed may lead to a significant increase in the cost of finished medicinal products.Aim. The aim was to compare regulatory documents on studying transporter-mediated drug–drug interactions (DDIs).Discussion. This review examines changes in regulatory requirements for studying DDIs in chronological order from the first guidelines that appeared in 1997. As exemplified in this article, the multiplicity of transporters and the lack of specific inhibitors pose significant challenges in assessing the role of a particular transporter in drug distribution and drug–drug interactions. This comparative review shows that extrapolating from in vitro transporter inhibition studies to in vivo pharmacokinetics can be misleading.Conclusions. A unified approach to studying transporter-mediated DDIs will increase the likelihood of identifying potentially toxic agents at the stage of new molecule screening. At the same time, it is advisable to limit the number of in vitro and in vivo transporter studies and recommend conducting these studies only for medicinal products with a narrow therapeutic index

Susceptibility of HEK293 and RPTEC Cell Lines to Nephrotoxic Effects of Cefuroxime and Cefepime: A Comparative Study

Researchers need to identify the nephrotoxic properties of medicinal products both during preclinical development and when exploring options to optimise pharmacotherapy. The main challenge is to find an experimental model for assessing drug-induced nephrotoxicity that reflects in vivo conditions as closely as possible.The aim of the study was to compare the susceptibility of HEK293 and RPTEC cell lines used as experimental models for assessing the nephrotoxicity of cefuroxime and cefepime.Materials and methods. The study investigated HEK293 and RPTEC cell lines cultured on plates with 0.4 µm pore membrane inserts. The cell lines were incubated for 3 days with cefuroxime and cefepime (cephalosporins excreted primarily by the kidneys). The medicinal products were added to the basal part of the well at concentrations of 50 and 150 µg/mL (cefuroxime) or 30 and 120 µg/mL (cefepime) twice a day. After incubating the cells with cefuroxime and cefepime for 24, 48, and 72 hours, the authors determined the expression levels of the SLC22A6 and SLC22A8 genes encoding organic anion transporters by a reverse transcription polymerase chain reaction. The authors considered caspase 3 and caspase 7 activation indicative of the nephrotoxic effect of cephalosporins; they evaluated this indicator by a fluorometric assay after 24, 48, and 72 hours of incubation.Results. According to the study, the expression of the SLC22A6 and SLC22A8 genes decreased with cephalosporin transport in both cell lines. The decrease occurred in the RPTEC cell line earlier than in the HEK293 cell line. The authors observed caspase 3 and caspase 7 activation only in the RPTEC cell line after incubation with cefuroxime and cefepime at low concentrations (50 and 30 µg/mL, respectively) for 72 hours and at high concentrations (150 and 120 µg/mL, respectively) for 24 hours.Conclusions. The RPTEC cell line exhibits higher susceptibility to cefuroxime and cefepime toxic effects than the HEK293 cell line due to higher transporter gene expression. Higher cephalosporin concentrations accelerate caspase 3 and caspase 7 activation in the RPTEC cell line. The experimental model based on the RPTEC cell line is a promising tool for the analysis of the nephrotoxic properties of a wide range of medicinal products

THE INFLUENCE OF THE PREOPERATIVE PRELOAD WITH CARBOHYDRATES UPON METABOLIC, IMMUNE AND CYTOKINE STATUSES AFTER RECONSTRUCTIVE ESOPHAGEAL SURGICAL INTERVENTIONS

The aim of this prospective randomized clinical study was to investigate the role of preoperative carbohydrate admnistration in surgery-induced metabolic, immune and inflammatory reactions after thoracoabdominal operations. At the Surgical department I (B.V. Petrovsky National Research Center of Surgery), we investigated a modulatory role of carbohydrate preload upon surgical stress observed after major thoracoabdominal operations (thoracoscopic and open esophagectomy, retrosternal colonic esophagoplasty) followed by the enhanced recovery protocol. The study was performed in 2014-2017, it included 30 patients, divided into 2 groups. Group A patients (n = 16) received carbohydrates preload (12.5% maltodextrin solution per os or enterally). In patients with dysphagia, the 12.5% dextrose solution was used intravenously in equal volumes. Group B patients didn’t receive any additional preload with carbohydrates. The groups were age- and gendermatched, similar for disease and surgery types. Glucose and insulin levels (with HOMA insulin resistance index, HOMA-IR) were measured before surgery and on day +1, interleukin levels (IL-6, IL-10, IL-8) and index IL-8/IL-10 were assessed before surgery, and on days +1 and +5 after surgery. Cell-mediated immunity was investigated before surgery and on day +5.The stress-induced hyperglycemia (> 7.8 mmol/L) was detected more frequently in group B (50%), than in group A (6%), p = 0.012. Insulin resistance measured by HOMA-IR in group B was detected in 71% of patients and in 25% patients of group A only, p = 0.027. Individual analysis of immune response demonstrated that a trend for immune recovery was detected by the day +5 post-op in the group A. Postoperative levels of IL-6 and IL-10 were lower on day +1 and +5 in group A. Morbidity rates and the terms of hospitalization were similar in both groups. Local postsurgical infections in group A were developed in 6% of the patients vs 35.6% in group B (p = 0.072).In conclusion, a complex study of surgical stress, i.e., metabolic, immune and inflammatory reactions after esophageal surgery has shown that the carbohydrate preload decreased the incidence of postoperative insulin resistance and stress-induced hyperglycemia, being accompanied by lower release of proinflammatory cytokines and provides positive effects upon the patient’s immune system

Determination of the Degree of Unsaturation in Essential Oils

Being widely used, medicinal products based on vegetable oils require strict regulation and evaluation of quality attributes, determination of shelf-life periods, and monitoring of storage conditions. The most common testing method for unsaturated compounds in vegetable oils is the iodine value determination, which has a range     of limitations. An alternative method for determining the degree of unsaturation is based on epoxidation.The aim of the study was to evaluate the possibility of determining the degree of unsaturation of terpenoids and essential oils using peroxycarboxylic acids.Materials and methods. The authors performed epoxidation of linalool, myrcene, and lemon oil with peroxydecanoic and peroxyoctanoic acids, followed by iodometric titration of the excess acid.Results. The study demonstrated the possibility of measuring the degree of unsaturation of the selected essential oil and terpenoids using peracid epoxidation.   The authors developed a procedure for determining the iodine value of essential oils and calculated the iodine values of linalool, myrcene, and lemon oil. Epoxidation proceeded as a second-order reaction. The authors obtained the following reaction rate constants: 3.9 L×mol–1×min–1 for linalool (298 К), 1.76 L×mol–1×min–1 for myrcene converting to monoxide (298 К), 0.044 L×mol–1×min–1 for myrcene epoxide converting to diepoxide (298 К), and 3.9 L×mol–1×min–1 for lemon oil (297 К).Conclusions. The suggested procedure involving peracid titration for rapid and efficient determination of the degree of unsaturation (iodine value) provides a potential basis for developing a quantification method for total unsaturated bioactive compounds in essential oils

NMR Spectroscopy Study of the Effect of the Molecular Mass of Hypromellose Phthalate on Its Solubility

Scientific relevance. Hypromellose phthalate is used in enteric coatings for oral medicinal products. The proportion of phthalate groups in the polymer is standardised because it has a significant effect on solubility. Whereas, the molecular mass of hypromellose phthalate is not controlled, and its impact on solubility in media with different pH values is understudied.Aim. The study aimed to employ NMR spectroscopy to investigate the effect the molecular mass of hypromellose phthalate may have on the dissolution kinetics at the pH value declared by the polymer manufacturer.Materials and methods. The study analysed hypromellose phthalate isolated from proton-pump inhibitor enteric coatings and the hypromellose phthalate reference standard. The molecular mass of the polymer was estimated by diffusion-ordered NMR spectroscopy (DOSY) with polyethylene glycols of known molecular masses for calibration. The authors studied the dissolution profiles of hypromellose phthalates of different molecular masses using 1H NMR spectra.Results. The authors developed a procedure for estimating the average molecular mass of hypromellose phthalate by DOSY. The procedure showed variations in the molecular mass of the polymer in the test samples; the molecular mass scatter amounted to 10 kDa. The dissolution profile of the test samples in an aqueous buffer solution (pH 5.59) was described by a linear function during the first hour. The slope characterising the dissolution rate varied from 10° to 36°.Conclusions. The variation in the molecular mass of hypromellose phthalate significantly affects the dissolution rate of the test samples. The function of the dissolution rate against the molecular mass of hypromellose phthalate is non-linear. The article provides a compelling reason for further research to derive a correlation equation for the dissolution rate of hypromellose phthalate as a function of two variables (molecular mass and proportion of phthalate groups in the polymer)

Antibiotic Dosing in Chronic Kidney Disease

Infectious process is an important cause of morbidity and mortality among patients with chronic kidney disease. Prescription of antibacterial drugs should take into account the pharmacokinetic parameters of the medicine and the individual characteristics of the patient. Adequate antibiotic dosing is crucial for positive treatment outcome and minimisation of side effects. The aim of the study was to analyse scientific literature on factors affecting the dosing of antibacterials in patients with chronic kidney disease. Since most antibacterial medicines are eliminated by the kidneys, a decrease in glomerular filtration rate or kidney function should be followed by the dose adjustment in order to prevent the medicine accumulation and reduce the risk of side effects. Antibiotic dosing in such patients should be accompanied by kidney function assessment and be adjusted to ensure effective and safe treatment, as well as prevention of bacterial resistance. The review provides data on the dosing of some antibiotic groups (beta-lactams, aminoglycosides, fluoroquinolones) at different creatinine clearance rates. Extrarenal excretion of medicines does not usually require the dose adjustment in patients with chronic kidney disease

Qualitative methods of benefit / risk assessment

In this article authors describe some existing methods of benefit / risk assessment