Long-Term Humoral Immune Response against SARS-CoV-2 after Natural Infection and Subsequent Vaccination According to WHO International Binding Antibody Units (BAU/mL)

The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination.

Challenges in Measuring AMH in the Clinical Setting

Serum anti-Mullerian hormone (AMH) is a widely used marker of functional ovarian reserve in the assessment and treatment of infertility. It is used to determine dosing of gonadotropins used for superovulation prior to in vitro fertilization, as well as to determine the degree of damage to ovarian reserve by cytotoxic treatments such as chemotherapy. AMH is also now used to predict proximity to menopause and potentially provides a sensitive and specific test for polycystic ovarian syndrome. Twenty one different AMH immunoassay platforms/methods are now commercially available. Of those compared, the random-access platforms are the most reliable. However, to date there has not been an agreed common international AMH reference preparation to standardize calibration between the various immunoassays. Recently, a purified human AMH preparation (code 16/190) has been investigated by the World Health Organization as a potential international reference preparation. However, this was only partially successful as commutability between it and serum samples was observed only in some but not all immunoassay methods. Development of a second generation reference preparation with wider commutability is proposed.

Autoantibodies in Rheumatoid Arthritis – Laboratory and Clinical Perspectives

Measurement of two groups of autoantibodies, rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) have gained increasing significance in the diagnosis and classification of rheumatoid arthritis (RA) over the last 65 years. Despite this rising importance of autoimmune serology in RA, there is a palpable lack of harmonization between different commercial RF and ACPA tests. While a minimal diagnostic specificity has been defined for RF tests, which almost always are related to an international reference preparation, neither of this applies to ACPA. Especially assays with low diagnostic specificity are associated with very low positive predictive values or post-test probabilities in real world settings. In this review we focus on issues of practical bearing for the clinical physician diagnosing patients who potentially have RA, or treating patients diagnosed with RA. We advocate that all clinically used assays for RF and ACPA should be aligned to a common diagnostic specificity of 98-99% compared to healthy controls. This high and rather narrow interval corresponds to the diagnostic specificity seen for many commercial ACPA tests, and represents a specificity that is higher than what is customary for most RF assays. Data on antibody occurrence harmonized in this way should be accompanied by test result-specific likelihood ratios for the target diagnosis RA on an ordinal or interval scale, which will provide the clinical physician with more granular and richer information than merely relating numerical values to a single cut-off point. As many physicians today are used to evaluate autoantibodies as positive or negative on a nominal scale, the introduction of test result-specific likelihood ratios will require a change in clinical mindset. We also discuss the use of autoantibodies to prognosticate future arthritis development in at-risk patients as well as predict severe disease course and outcome of pharmacological treatment.

Novel therapeutic modalities for children with spasticity

Background: early treatment using botulinum toxin type A (BTA) postpones or even prevents contractures and osteoarticular deformations and, therefore, surgical interventions in children with cerebral palsy (CP). Expansion of age groups and conditions to prescribe BTA is the primary trend of current studies. Aim: to assess the safety and efficacy of Relatox® in children aged 2–6 years with spastic CP. Patients and Methods: this simple blind randomized comparative study (2018–2019) enrolled 100 children aged 2–6 years with spastic CP. According to the study protocol, Relatox® (n=51) or reference preparation (n=49) was injected into spastic muscles. Each group included two subgroups (predominant involvement of the muscles of the upper or lower extremities). Topical and systemic reactions were evaluated immediately after injection. Over the follow-up (after 2, 4, 8, and 12 weeks after injections), muscle tonus using Modified Ashworth Scale (MAS) and pain severity using a 10-point visual analogue scale were assessed. Results: maximum total doses of botulinum toxin per injection session for both preparations were 60 to 200 units. The efficacy of both preparations was similar (p>0.05). Single self-limited mild and moderate topical and systemic adverse reactions typical for botulinum toxin were reported in both groups. Conclusions: the safety and efficacy of Relatox® are similar to these of reference preparation. Antispastic effect for muscles of the upper extremities was demonstrated, thereby allowing for expanding indications for Relatox®. Inclusion of the maximum number of spastic muscles in the protocol of injection session provided a full motor habilitation/rehabilitation of children. KEYWORDS: botulinum toxin type A, cerebral palsy, spasticity, efficacy, safety. FOR CITATION: Krasavina D.A., Ivanov Yu.I. Novel therapeutic modalities for children with spasticity. Russian Medical Inquiry. 2021;5(10):630–635 (in Russ.). DOI: 10.32364/2587-6821-2021-5-10-630-635.

Rational use of raw capers growing in Uzbekistan

This article presents data on the export of raw materials and the results of pharmacological studies of caper buds for use in the pharmaceutical industry. For this, the volumes of export products for the last 2 years were studied and preclinical studies of the aqueous-alcoholic extract obtained from local plant materials were carried out in comparison with reference preparations. As a result, the aqueous-alcoholic extract obtained from local plant materials has reliable hypoglycemic activity comparable to the reference preparation “Gluqueir” capsule, but inferior to the synthetic preparation “Diabeton MR” 60 mg tablets with modified release. The range of effective doses (ED30, ED50 and ED100) was also established and the most effective dose was found.

Biodestructors efficiency against sweet cherry (Cerasus avium Moench.) Coccomyces hiemalis Higg.

Spraying of the sweet cherry plantations with the biodestructor Ekostern and preparation Urea against Coccomyces hiemalis Higg. was carried out in the autumn 2016-2018. The highest technical efficiency (79.5 %) was achieved when applying Ekostern – 2.0 l/ha. The leaves affection was spot was the least – 6.9 % with the disease development intensity 1.1%. The larger amount of the affectioned leaves was detected in the variants with the combined use of Ekostern (1.0 l/ha) and Urea (25.0 kg/ha) (8.3 and 1.5 % respectively) as well as Urea – 50.0 kg/ha (11.8 and 2.8%). Owing to the fallen leaves mineralization the mass of the substrate on which the Coccomyces hiemalis Higg causative agent hibernated appeared to reduce as a result of which the resource of the primary infection sources and the disease spread intensity were limited in the springtime period. The researched preparation Ekostern concerning the sweet cherry leaves destruction activity exceeded the reference preparation Urea by 1.4 times. Under the combined application of Ekostern and Urea with half standards of cost these means technical efficiency decreased by 1.2 times as compared to the Ekostern separate application and in comparison with the full hectare Urea standard was higher by 1.2 times. As a result of the leaves treatment with Ekostern this mean inhibitory influence on the pathogene reproductive function displayed itself that expressed itself in limiting the fruiting bodies (apothecia) formation. Their number was less as compared to the control in all the variants. Urea in concentration of 5 % displayed the lowest effectivity, the preparations Ekostern (2.0 l/ha) without adding Urea and in the combination with it with the half standards of costs did the highest effectivity (83.3 %). Their efficiency was 1.5-1.7 times higher in comparison with the reference.

Immune histochemical study of KI-67 level and ribonucleic acid in the process of healing of burn wounds after treatment with drugs containing dexpanthenol and ceramide

Ceramides are structural components of the stratum corneum that regulate cell proliferation and differentiation. The study of the effect of the cream containing dexpanthenol and ceramide on the proliferation processes and regeneration of burn wounds in rats. Experimental rats with III-A degree thermal burn were treated separately with the following preparations: cream with ceramides, cream with dexpanthenol and ceramides and cream "Bepanten". The proliferative-regenerative activity of the drugs was investigated by studying the content of the Ki-67 producing cells and the content of ribonucleic acid (RNA) in the cytoplasm of the granulation tissue fibroblasts. Ceramides contributed to wounds healing, increasing the content of Ki-67 antigenpositive cells, accelerating the formation of scar in the wound. The therapeutic effect of creams with ceramides exceeds the efficacy of the reference preparation “Bepanten” cream. The addition of ceramides to dexpanthenol increases the quality and reduces the wound healing time.

A WHO Reference Reagent for lupus (anti-dsDNA) antibodies: international collaborative study to evaluate a candidate preparation

IntroductionAntibodies against double-stranded DNA (anti-dsDNA) are a specific biomarker for systemic lupus erythematosus (SLE). The first WHO International Standard (IS) for anti-dsDNA (established in 1985), which was used to assign units to diagnostic tests, was exhausted over a decade ago.MethodsPlasma from a patient with SLE was first evaluated in 42 European laboratories. The plasma was thereafter used by the National Institute for Biological Standards and Control to prepare a candidate WHO reference preparation for lupus (anti-dsDNA) antibodies. That preparation, coded 15/174, was subjected to an international collaborative study, including 36 laboratories from 17 countries.ResultsThe plasma mainly contained anti-dsDNA, other anti-chromatin antibodies and anti-Ku. The international collaborative study showed that the field would benefit from 15/174 as a common reference reagent improving differences in performance between different assays. However, no statistically meaningful overall potency or assay parallelism and commutability could be shown.Conclusion15/174 cannot be considered equivalent to the first IS for anti-dsDNA (Wo/80) and was established as a WHO Reference Reagent for lupus (oligo-specific) anti-dsDNA antibodies with a nominal value of 100 units/ampoule. This preparation is intended to be used to align test methods quantifying levels of anti-dsDNA antibodies.

LIPID COMPOSITION AND MEMBRANOPROTECTIVE ACTION OF EXTRACT FROM MARINE GREEN ALGAE ULVA LACTUCA (L.)

The object of the present study was a water-alcohol extract obtained from the dried thallus of the marine green alga Ulva lactuca (L.) (syn.: Ulva fenestrate P. et R.) – ulva lettuce. Glycolipids (40.6%) and neutral lipids (34%) prevailed in the lipid fraction of the extract; phospholipids contained 13.4% of the total lipids. The content of polyunsaturated fatty acids (PUFA) was 50% of the total amount of fatty acids, among which PUFA of the n-3 family predominated (37.43%). On the model of toxic hepatitis induced by the introduction of carbon tetrachloride (CCl4) (50% solution in olive oil, subcutaneously 2 ml/kg for 4 days), we study the effect of the lipid fraction of U. lactuca extract and the commercial reference preparation Essentiale® on the physiological and biochemical characteristics of erythrocytes and lipid composition of erythrocyte membranes in rats. The introduction of the lipid fraction from the ulva (dose 80 mg of total lipids per kg of body weight) to the animals intragastrically for 7 days after withdrawal of CCl4 exerted a protective effect, which was manifested in the restoration of the erythrocyte size characteristics (average volume and diameter), their osmotic resistance to hemolysis, levels of malondialdehyde and reduced glutathione, as well as maintaining of the ratio of phospholipid fractions. Under the damaging effects of CCl4, the lipid fraction from the green alga U. lactuca was not inferior to the effectiveness of reference preparation Essentiale® in restoring of the physiological characteristics of erythrocytes and the phospholipid composition of its membranes.

SYNTHESIS AND HERBICID ACTIVITY OF ARYLOXYACETIC ACIDS AND AMIDES OF ARYLOXY ACETIC ACIDS CONTAINING CYCLOACETAL FRAGMENT

The herbicidal activity of esters and amides based on commercially available phenoxy chlorides and 2,4-dichlorophenoxyacetic acids was studied. Esters of 2,2-methyl-4-hydroxymethyl-1,3-dioxolane, 5-ethyl-5-hydroxymethyl-1,3-dioxane and 1,3-dioxolan-4-ylmethanol and 1,3-dioxane-5 -ol (glycerin formulas), as well as amides containing gem-dichlorocyclopropane and 1,3-dioxolane fragments were obtained. The acid chlorides, 1,3-dioxacycloalkanes and secondary amines were prepared according to standard basic methods. Esters and amides were synthesized from these starting compounds in a short time and with a quantitative yield (more than 90%). As a result of the synthesis of a mixture of 1,3-dioxolan-4-ylmethyl phenylacetate and 1,3-dioxan-5-yl phenylacetate, the content of the 5-ring cyclic derivative over the 6-chain structure was predominant, which is obviously associated with greater activity in the esterification reaction of primary alcohol than secondary. The screening results showed that the activity relative to wheat of the 1,3-dioxalane ester of 2,4-dichlorophenoxyacetic acid is superior to the Octagon-Extra standard. With respect to peas, derivatives of 2,4-dichlorophenoxyacetic acid and 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane are close to the standard for inhibition of shoot mass. The results of N-benzyl-N-[(2,2-dichlorocyclopropyl) methyl] -2-phenoxyacetamide and N-[(2,2-dichlorocyclopropyl) methyl]-N-(1,3-dioxolan-4-ylmethyl)-2-phenoxyacetamide with respect to peas and wheat also showed a marked herbicidal effect, close in value to the reference one. The test results of synthesized benzamides on wheat showed that, at a concentration of 100 mg/l, the compounds act approximately the same as the reference preparation at a dose of 50 mg/l. The obtained results prove the prospects of creating herbicidal preparations based on phenoxy- chlorides and 2,4-dichlorophenoxyacetic acids containing 1,3-dioxacycloalkane fragments. Therefore, these objects are very attractive for further study and synthesis of biologically active compounds containing the above pharmacophore groups.