Severe form of COVID 19 has been linked to the phenomenon of dysregulated inflammation with excessive cytokine release and elevated interleukin 6 (IL6) levels. Suppressive agents enabling specific inhibition of cytokines, notably monoclonal antibodies to IL6 and its receptors, have been applied as a rescue therapy in COVID 19 despite the underexplored clinical scope for these biologic medications. This study aimed to evaluate the clinical utility of IL6 receptor antagonist tocilizumab in moderate symptomatic COVID 19 prone to aggravation. The retrospective cohort study enrolled two groups of hospitalized patients (a total of n = 72) diagnosed with moderate COVID-19. The main group received a single 400 mg dose of tocilizumab (TCZ) on top of standard therapy. The comparative analysis included statistical evaluation for a number of clinical and laboratory parameters at reference time points and disease outcomes with regard to treatment strategy. Overall, TCZ administration provided no advantages in terms of oxygen supplementation status, disease progression, or survival. Lethal cases constituted 19.2% (10 pts) and 5% (1 pt) in TCZ and comparison groups, respectively. The results indicate that administration of monoclonal antibody drugs in hospital patients with COVID-19 must follow differential schemes with regard to the disease severity and comorbidities, as well as proper commencement schedules.
VIEWS 2173
Skin wound healing mechanisms and new ways of improving their efficiency represent an important focus in medicine. In this regard, regulatory peptides, which exhibit physiological polyfunctionality and modulate cell growth and differentiation, are of special interest. This study evaluates the effects of Gly-His-Lys (GHK) and Gly-His-Lys-D-Ala (GHK-D-Ala) peptides in the infected skin wound healing. The wounds were modeled in rats (n=150) by full-thickness dorsal skin defects. The peptides were administered intracutaneously at daily doses of 0.5 or 1.5 µg/kg. The healing was assessed on days 3, 7, and 10 by histomorphometric examination of the wounds with adjacent intact skin. GHK-D-Ala administered at daily doses of 0.5 µg/kg had pronounced positive effect on regeneration processes in the wound, as indicated by significantly reduced numbers of granulocytes and lymphocytes with increased representation of fibroblastic lineages and macrophages, and the resulting higher cellular index (p < 0.05–0.001). At higher doses of GHK-D-Ala (1.5 µg/kg), the beneficial effects were less pronounced. According to the comparative morphological examination, the highest positive effect was achieved with 0.5 µg/kg of GHK-D-Ala. Thus, local administration of the GHK peptide with extra D-alanine at carboxy-terminus significantly mitigated the inflammatory reaction and facilitated the healing of infected skin wounds in rat model.
VIEWS 2435
Simultaneous pancreas and kidney transplantation (SPK) provides effective treatment in patients with type 1 diabetes mellitus (T1DM) and end-stage renal failure (ESRF), mitigating the hyperglycemia and uremic syndrome. The study aimed at the assessment of morphofunctional status of the macula and macular hemodynamics in patients with T1DM after SPK. The study enrolled 45 patients subdivided into three groups: Group A — patients with T1DM after SPK; Group B — patients with T1DM and ESRF, maintained on programmed hemodialysis (PH), on waiting list for SPK; and Group C — individuals without ophthalmic or systemic pathologies. All patients were subject to the standard ophthalmological examination complemented by measurements of the central retinal thickness (CRT) and the average perfusion density (PD) in four vascular layers: superficial capillary plexus of the retina (SCP), deep capillary plexus of the retina (DCP), choriocapillaris, and choroid. The patients after SPK had significantly lower CRT (241 ± 33 µm in Group A, 309±10 µm in Group B; p < 0.05) and significantly higher PD of the macular region in both the retina (Group A: SCP — 19.0 ± 1.6%, DCP — 10.7 ± 1.3%; Group B: SCP — 11.7 ± 0.8%, DCP — 4.8 ± 0.8%; p < 0.05) and the choroid (Group A: choriocapillaris — 28.1 ± 1.8%, choroid — 31.3 ± 1.6%; Group B: choriocapillaris — 20.4 ± 1.6%, choroid — 21.8 ± 1.3%; p < 0.05), as well as significantly higher visual acuity (Group A: 0.7 ± 0.1; Group B: 0.5 ± 0.1; p < 0.05) and macular light threshold (Group A: 25.9 ± 1.4 dB; Group B: 22.3 ± 1.1 dB; p < 0.05) compared with the patients on PH. Thus, the normalization of carbohydrate metabolism and the mitigation of uremic syndrome in patients with T1DM and ESRF after SPK favorably affect the functional condition of the macular area, as indicated by the improvement in macular blood flow and visual functions.
VIEWS 2176
Alterations in intracellular signaling pathways affecting immune cell activation, proliferation and differentiation of keratinocytes in psoriasis could explain the complex pathogenesis of the disease. NF-κB is one of the intracellular signaling pathways, which is involved in regulation of numerous pro-inflammatory genes, and affects the synthesis of pro-inflammatory cytokines directly involved in the development of psoriasis. The study was aimed to assess the number of cells with NF-κB translocation in lymphocyte populations of children with psoriasis depending in the disease severity and therapy. A total of 130 children with psoriasis vulgaris were examined. The comparison group included 30 healthy children. The study was conducted using the imaging flow cytometry Amnis ImageStreamX system. It was found that there were significant differences in the number of cells with NF-κB translocation in the lymphocyte populations of both children with psoriasis and comparison group. Children with psoriasis had a higher number of cells with NF-κB translocation in the populations of T helper cells, Tact, Treg, and Th17 compared to healthy children (p < 0.05). The number of cells with NF-κB translocation in children with psoriasis correlated with the disease severity PASI (Rmul = 0.32) and BSA (Rmul = 0.31) scores, as well as with the disease duration (p < 0.05). NF-κB determination could be considered an additional criterion for the disease severity assessment in children with psoriasis. The differences in the degree of reduction of the number of cells with NF-κB translocation 24 h after administration of biologics (adalimumab, etanercept, ustekinumab) have been shown. Studying NF-κB in cell populations offers the prospect of understanding pathogenetic mechanisms of inflammation and developing new therapeutic methods for psoriasis.
VIEWS 2438
Optimization of the educational process, including distance learning, requires orderly arrangement of the information presented, which translates into the need to factor in oculomotor reactions accompanying the search for solutions to simple cognitive tasks. This need supports the relevance of the present study, which aimed to investigate the age-dependent parameters of the oculomotor reactions occurring in solving a simple cognitive task. The sample included 97 persons, 47 males and 50 females, ages 21 to 36. For the purpose of rating the oculomotor reactions, the sample was divided into age groups: 21–26 years (n = 34); 27–32 years (n = 29); 33–36 years (n = 34). The methodology that governed the rating procedures was developed by the authors of the study and relied on the Tobii EyeX eye tracking hardware and software solution (GazeControl software). The study revealed a significant correlation between orientation of the image (presentation angle) and distribution of the visual fixations: regardless of the image presentation angle and its properties (schematic monochrome or full color image), the fixations tend to fall predominantly into the top and left parts of the image (the first quadrant). Other findings include a) a significant dependence of the capability to solve simple cognitive tasks and recognize the contents of the image on the spatial orientation of the presented stimuli, and b) the number of errors made in image contents recognition increasing with age, this dependence being significant and observed for both the schematic monochrome image (p1 = 0.014; p2 = 0.016; p3 = 0.014) and the full-color image (p1 = 0.015; p2 = 0.015; p3 = 0.017). The researchers have also identified the significant angles of rotation of the presented face images that stably caused recognition errors.
VIEWS 2153
Development of highly sensitive methods for drug analysis is an ongoing challenge posed by modern bioanalytical and pharmaceutical chemistry. Drug analysis is essential to monitor the quality and purity of pharmaceuticals, study the delivery vehicles for therapeutic agents, to assess the effectiveness of the substance incorporation into the drug delivery system, to estimate the kinetic parameters of reactions, catalyzed by enzymes involved in xenobiotic metabolism, and to study the mechanisms of the drug-DNA interactions from the perspective of pharmacogenomics. The study was aimed to develop an electrochemical technique for detection of a number of drugs. The method is based on electrochemical oxidation of organic molecules at positive potentials between +(0÷1.6) V. The commercially available three-contact electrodes obtained by screen printing with unmodified graphite working electrode were used for analysis. It is shown that electrochemical technique allows for simultaneous detection of several compounds at various working electrode potentials, and for detection of drugs over a wide range of the clinically meaningful drug concentrations (50 µM – 10 mМ), which could be used when working with biological fluids (blood plasma, blood serum, blood, urine), as well as when performing drug monitoring and drug–drug interaction analysis.
VIEWS 2259
Adherence to treatment is one of the major challenges posed by modern medicine. Today, cataract is the leading cause of reversible blindness and visual disability. The study was aimed to assess adherence to timely surgical treatment in individuals with cataract. The data of the cross-sectional, population-based Ural Eye and Medical Study were assessed. Among 546 participants, there were 46.3% men and 53.7% women, 59.6% urban resudents, 40.4% rural residents. Their average age was 66.36 ± 9.47 years (40–88 years). Statistical data analysis was performed using the IBM SPSS Statistic software package. The findings showed that the lack of awareness of the disorder and low interest in surgery were the main factors, affecting the patients' motivation for cataract treatment. At the same time, the frequency of ophtalmology visits was inversely related to the patients' age (OR 1.24; 95% CI 1.04–1.49) and the duration of vision loss (OR 1.08; 95% CI 0.81–1.43), and directly related to the cataract diagnosis age (OR 1.20; 95% CI 1.04–1.38), the presence of ophthalmologist in the community clinic (OR 1.71; 95% CI 1.29–2.26), trust in the doctor (OR 3.62; 95% CI 3.02–4.35), ophthalmologist's explanation of the cataract complications and advanced treatment methods (OR 1.62; 95% CI 1.34–1.97). Understanding the main factors, contributing to low treatment adherence in patients with cataracts, would make it possible to optimize the measures to improve healthcare delivery to such patients, associated with the increased coverage of surgical treatment.
VIEWS 2535