Atypical Goodpasture’s disease: a clinical case report and literature review

Goodpasture’s disease (anti-GBM disease) is a rare small vessels vasculitis characterized by the presence of autoantibodies directed against the glomerular basement membrane (GBM) and alveolar basement membrane. Common feature of anti-GBM disease is a combination of rapidly progressive glomerulonephritis and alveolar hemorrhage (pulmonary-renal syndrome). We present a case of atypical disease course in a young male patient who developed alveolar hemorrhage without renal failure. The only symptom of renal involvement was isolated hematuria. Plasmapheresis combined with immunosuppression (cyclophosphamide and corticosteroids) was effective. We present a review of state-of-art data on the pathogenesis and disease course of anti-GBM disease

DIFFERENTIAL DIAGNOSIS OF RADICULOPATHY IN LYME BORRELIOSISAND DYSTROPHIC LESIONS OF THE VERTEBRAL COLUMN

Subjects and methods. Thirty patients, including 9 (30.0%) men and 21 (70.0%) women, with signs of radiculopathy (RP) in late-stages Lyme borreliosis (LB) were examined. A control group comprised 30 patients with vertebrogenic RP in the presence of dystrophic changes in the vertebral column. Results. 56.7% of the patients with LB were observed to have its primary chronic course in the absence of the acute period of LB. The latter with the signs of RP showed a topic association between the pain location and the tick bite site in 43.3% of the patients. A gradual disease development was more frequently (63.3%) observed in LB while the periods of remission and exacerbation were more typical (56.7%) in vertebrogenic RP. In the patients with LB, pain syndrome depended on posture and physical exercise less frequently (30.0%) than in those with vertebrogenic RP (96.7%). Bilateral pain irradiation was more characteristic of RP in LB than in dystrophic lesions of the vertebral column. The symptoms of tonic muscle tension and limited movement volume in the afflicted part of the vertebral column were significantly less common in the patients with LB than in those with vertebrogenic RP. LB was marked by a concomitance of radicular and polyneuritic disorders (83.3%) and vertebrogenic RP was characterized by a preponderance of the radicular-type of sensitivity disorder (100%). Systemic inflammatory syndrome and polysystemacy of manifestations were more characteristic of LB. The benefits of nonsteriodal antiinflammatory drugs in LB patients with RP were significantly worse than in those with vertebrogenic RP; regression of symptoms in LB was seen only after a course of specific antibiotic therapy

МЕТОДОЛОГИЧЕСКИЙ ПОДХОД К ПЛАНИРОВАНИЮ ЭКСПЕРИМЕНТА ПРИ ВЫБОРЕ КАЧЕСТВЕННЫХ РЕАКЦИЙ ДЛЯ ПОДТВЕРЖДЕНИЯ ПОДЛИННОСТИ КОМПОНЕНТОВ ЛЕКАРСТВЕННОГО СРЕДСТВА (НА ПРИМЕРЕ АСКОРБИНОВОЙ КИСЛОТЫ)

The need for identification  testing of active substances or excipients in multi-component medicinal products,  including the use of qualitative tests, calls for research substantiating the choice of tests and test conditions  with due regard to interference  effects caused by other components  of medicinal products and the amount of the sample used. The aim of the study was to develop a methodological approach to designing experiments while selecting qualitative reactions for identification testing of a medicinal product component based on the results of studies investigating the possibility of using known qualitative tests (as illustrated by ascorbic acid in a multi-component product — 0.4 mg of ascorbic acid per 100 mg of the vial contents)  with due regard to interference on the part of other medicinal product components and the amount of the sample used. Material and methods: the study focused on a multi-component medicinal product — lyophilisate for solution for intravenous and intramuscular  injections containing an antiinflammatory active substance and ascorbic acid as a stabilizing agent (antioxidant). The analysis of literature sources helped to determine qualitative tests that were assessed for potential use for identification testing of ascorbic acid as a component of the analysed medicinal product. The study involved experimental testing of the qualitative reactions based on acidic and reducing properties of ascorbic acid. Results: it was demonstrated that several well-known qualitative tests could be used for identification  testing of ascorbic acid as a component of the analysed medicinal product,  namely, the reaction of ferrous ascorbate formation  and the reaction of silver nitrate reduction to metallic silver after preliminary separation of ascorbic acid from the other medicinal product components, as well as the reaction of Prussian blue formation,  iodine test and reaction with a potassium permanganate solution, which do not require additional sample preparation.  It is not practicable to use the reaction with a methylene blue solution and the Fehling’s reagent reaction for this particular medicinal product,  since their results are feeble. Conclusions: the analysis of the multi-component medicinal product helped to develop a methodological  approach to choosing qualitative reactions for identification testing of one of the medicinal product’s components  (e.g., ascorbic acid). The suggested algorithm includes the choice of reactions, determination of their sensitivity and applicability for a particular medicinal product, analysis of the other components’ effects on the results of the chemical reaction,  and the need for additional sample preparation.  The whole complex of the studies performed helped to determine qualitative reactions and optimal conditions for identification testing of the analysed substance.Необходимость подтверждения подлинности  действующих  или  вспомогательных веществ  многокомпонентных лекарственных средств,  в том числе с использованием качественных  реакций, влечет за собой  необходимость  проведения исследований по выбору реакций  и условий их проведения с учетом мешающего  влияния других компонентов лекарственного средства  и количества  используемого образца.  Цель работы: разработка  методологического подхода к планированию эксперимента при выборе  качественных  реакций  для подтверждения подлинности определяемого компонента лекарственного средства на основании результатов исследований возможности использования известных качественных  реакций  (на примере  аскорбиновой кислоты  в многокомпонентном лекарственном средстве — 0,4 мг аскорбиновой кислоты / 100 мг содержимого  флакона) с учетом мешающего влияния других компонентов лекарственного средства и количества  используемого образца.  Материалы и методы: в качестве  объекта исследования было выбрано  многокомпонентное лекарственное средство  — лиофилизат для приготовления раствора  для внутривенного и внутримышечного введения  с лекарственным веществом,  обладающим  противовоспалительным действием,  в состав которого  входит аскорбиновая кислота  в качестве  стабилизатора (антиоксиданта). В результате анализа  данных литературы  выбраны  качественные реакции  для проведения исследований возможности их использования для подтверждения  подлинности аскорбиновой кислоты  в изучаемом  лекарственном средстве.  Проведена  экспериментальная проверка  реакций, основанных на кислотных  и восстановительных свойствах аскорбиновой кислоты.  Результаты: установлено, что в изучаемом многокомпонентном лекарственном средстве для подтверждения подлинности аскорбиновой кислоты могут быть применимы несколько известных качественных реакций: реакции образования аскорбината железа и восстановления нитрата серебра до металлического серебра после предварительного отделения аскорбиновой кислоты  от других компонентов лекарственного средства,  а также реакция  образования берлинской лазури,  йодная проба и реакция  с раствором  перманганата калия,  не требующие  дополнительной пробоподготовки. Использование реакций  с раствором  метиленового  синего и реактивом  Фелинга  применительно к данному лекарственному средству нецелесообразно, так как результат указанных реакций  слабо выражен. Выводы: на примере многокомпонентного лекарственного средства разработан  методологический подход к выбору качественных  реакций  для подтверждения подлинности одного  из компонентов лекарственного средства  (например, аскорбиновой кислоты).  Алгоритм действий включает в себя выбор реакций, определение их чувствительности и целесообразности применения для конкретного лекарственного средства,  изучение  влияния других его компонентов на результат химической реакции, а также необходимость  или отсутствие дополнительной пробоподготовки. Совокупность проведенных  исследований позволяет сделать выбор качественных  реакций  и оптимальных  условий  их проведения для достижения поставленной цели — подтверждения подлинности определяемого вещества

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Micro-Raman study of crichtonite group minerals enclosed into mantle garnet

We report the first comprehensive micro-Raman study of crichtonite group minerals (CGM) as inclusions in pyropic garnet grains from peridotite and pyroxenite mantle xenoliths of the Yakutian kimberlites as well as in garnet xenocrysts from the Aldan shield lamprophyres (Russia). The CGM form (i) morphologically oriented needles, lamellae, and short prisms and (ii) optically unoriented subhedral to euhedral grains, either single or intergrown with other minerals. We considered common mantle-derived CGM species (like loveringite, lindsleyite, and their analogues), with Ca, Ba, or Sr dominating in the dodecahedral A site and Zr or Fe in the octahedral B site. The Raman bands at the region of 600–830 cm−1 are indicative of CGM and their crystal-chemical distinction, although the intensity and shape of the bands appear to be dependent on laser beam power and wavelength. The factor-group analysis based on the loveringite crystal structure showed the octahedral and tetrahedral cation groups with 18f and 6c Wyckoff positions, namely, dominantly TiO6 and to a lower extent CrO6, MgO4, and FeO4 groups, to be the major contributors to the Raman spectral features. The ionic groups with dodecahedral (M0) and octahedral (M1) coordination are inactive for Raman scattering while active in infrared absorption. A number of observed Raman modes in the CGM spectra are several times lower than that predicted by the factor group analysis. The noticed broadening of modes in the CGM Raman spectra may result from a combining of bands at the narrow frequency shift regions. Solid solution behavior, luminescence, and partial metamictization of the CGM may exert additional influence on the Raman band shape. The Raman spectral features showed CGM to be accurately identified and distinguished from other Ti-, Fe-, Cr-, and Zr-containing oxides (e.g., ilmenite or those of spinel and magnetoplumbite groups) occurring as accessory mantle minerals. © 2020 The Authors. Journal of Raman Spectroscopy published by John Wiley & Sons LtdRussian Science Foundation, RSF: 18‐77‐10062Council on grants of the President of the Russian FederationThis study was supported by the Russian Science Foundation (Grant 18‐77‐10062). The equipment of the Ural Center for Shared Use «Modern Nanotechnology», Ural Federal University, and the Analytical Center for Multi‐elemental and Isotope Research, IGM, was used. Sampling was supported by the Russian Federation state assignment project of IGM. We are grateful to Nikolai V. Sobolev for Samples O‐173, O‐39, and O‐264. Vladimir N. Korolyuk, Elena N. Nigmatulina (IGM), and Allan Patchen (UT) are highly appreciated for the help with EMP analyses. We express our sincere thanks to F. Nestola and an anonymous reviewer for their thorough reviews and helpful suggestions, and to C. Marshall for regardful editorial handling of the manuscript on every stage of its revision

Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

Background: Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. the goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone.Methodology: We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-gamma ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-gamma, TNF-alpha, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-gamma responses and survived a lethal challenge given within the first 3 months following immunization. the addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro restimulation.Conclusion: Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.National Institutes of HealthFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Millennium Institute for Gene TherapySt Louis Univ, Dept Internal Med, St Louis, MO 63103 USAUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilSt Louis Univ, Dept Mol Microbiol, St Louis, MO 63103 USAUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilNational Institutes of Health: RO1 AI040196CNPq: 420067/2005-1Web of Scienc

An oribatid mite (Arachnida: Acari) from the Oxford Clay (Jurassic: Upper Callovian) of South Cave Station Quarry, Yorkshire, UK

A single specimen of a new species of oribatid mite belonging to the genus Jureremus Krivolutsky, in Krivolutsky and Krassilov 1977, previously described from the Upper Jurassic of the Russian Far East, is described as J. phippsi sp. nov. The mite is preserved by iron pyrite replacement, and was recovered by sieving from the Oxford Clay Formation (Jurassic: Upper Callovian) of South Cave, Yorkshire. It is the first record of a pre-Pleistocene mite, and the second species record of the family Cymbaeremaeidae, from the British Isles; also, it is only the third record of Acari from the Jurassic Period. The presence of a terrestrial mite in a sedimentary sequence of open marine origin is noteworthy, and suggestions for its mode of transport to the site of deposition are discussed