Probe-based confocal laser endomicroscopy in diagnosis of diffuse cystic lung disease in Sjögren’s syndrome

Sjögren’s syndrome is systemic autoimmune disease characterized by lymphocytic infiltration of various organs with wide frequency of pulmonary involvement. Diffuse cystic lung disease in Sjögren’s syndrome is a rare condition and requires differential diagnosis with other cystic pathologies such as lymphangioleyomiomatosis or Langerhans cell histiocytosis. Probe-based confocal laser endomicroscopy (pCLE) is a method of in vivo investigation of airways and lung tissue on microscopic level during bronchoscopy. We used this method in diffuse cystic lung disease caused by Sjögren’s syndrome. The pCLE image showed a large number of fluorescent cells presumably lymphocytes in bronchioles, dilated alveolar spaces with fluid and thin alveolar walls. We think that the presence of the bronchiolar cells pattern can be used to differentiate between the pulmonary manifestations of Sjögren's disease and other cystic lung diseases

ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ПОКАЗАТЕЛЕЙ АНГИОГЕНЕЗА ПРИ РАКЕ ПОЧКИ

The results of research in 130 patients with space-occupying lesions of kidneys treated in MCH n.a. S.R. Mirotvorcev were analysed. The diagnostic significance of metabolic tumor marker TuM2Pk, matrix metalloproteinases ММР-9, ММP-3, vascular endothelial growth factor (VEGF) and angiogenic cytokines (TNF-α, IL-8, IL-12) was evaluated. It was determined that VEGF detection in blood serum has the most important diagnostic value in differential diagnosis between renal tumor and renal cyst and in TNM staging.Проведен анализ результатов исследования 130 пациентов с объемными образованиями почек, получавших лечение в ГКБ им. С.Р. Миротворцева. Выполнена оценка диагностической значимости метаболического онкомаркера TuM2Pk, матриксных металлопротеиназ (ММР) — ММР-9, ММP-3, фактора роста эндотелия сосудов (ФРЭС) и ангиогенных цитокинов — фактора некроза опухоли α, интерлейкинов (ИЛ) — ИЛ-8, ИЛ-12. Установлено, что наибольшее диагностическое значение при дифференциальной диагностике между опухолью почки и кистами почек, а также при стадировании опухолевого процесса по ТNМ имеет определение содержания в сыворотке крови ФРЭС

Photo-affinity labelling and biochemical analyses identify the target of trypanocidal simplified natural product analogues

This work was supported by the Leverhulme Trust (Grant number RL2012-025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Current drugs to treat African sleeping sickness are inadequate and new therapies are urgently required. As part of a medicinal chemistry programme based upon the simplification of acetogenin-type ether scaffolds, we previously reported the promising trypanocidal activity of compound 1 , a bis-tetrahydropyran 1,4-triazole (B-THP-T) inhibitor. This study aims to identify the protein target(s) of this class of compound in Trypanosoma brucei to understand its mode of action and aid further structural optimisation. We used compound 3 , a diazirine- and alkyne-containing bi-functional photo-affinity probe analogue of our lead B-THP-T, compound 1 , to identify potential targets of our lead compound in the procyclic form T. brucei. Bi-functional compound 3 was UV cross-linked to its target(s) in vivo and biotin affinity or Cy5.5 reporter tags were subsequently appended by Cu(II)-catalysed azide-alkyne cycloaddition. The biotinylated protein adducts were isolated with streptavidin affinity beads and subsequent LC-MSMS identified the FoF1-ATP synthase (mitochondrial complex V) as a potential target. This target identification was confirmed using various different approaches. We show that (i) compound 1 decreases cellular ATP levels (ii) by inhibiting oxidative phosphorylation (iii) at the FoF1-ATP synthase. Furthermore, the use of GFP-PTP-tagged subunits of the FoF1-ATP synthase, shows that our compounds bind specifically to both the α- and β-subunits of the ATP synthase. The FoF1-ATP synthase is a target of our simplified acetogenin-type analogues. This mitochondrial complex is essential in both procyclic and bloodstream forms of T. brucei and its identification as our target will enable further inhibitor optimisation towards future drug discovery. Furthermore, the photo-affinity labeling technique described here can be readily applied to other drugs of unknown targets to identify their modes of action and facilitate more broadly therapeutic drug design in any pathogen or disease model.Publisher PDFPeer reviewe

Kinetik und Thermodynamik des Elektronentransfers in photochemischen Reaktionen von Farbstoffen

Der Mechanismus des photochemischen Elektronentransfers bei der Reaktion von organischen Farbstoffen mit Metallionen wird auf der Grundlage der Modelle von Marcus, Marcus-Satin und Weller diskutiert. Untersucht wird die Abhängigkeit der Geschwindigkeitskonstanten sowohl der Triplettlöschung von Xanthenfarbstoffen als auch der Bildung von Radikalionen von der freien Reaktionsenergie. Die beste Übereinstimmung zwischen Experiment und Theorie ergibt das Weller-Modell. Außerdem werden die freie Aktivierungsenergie von Selbstaustauschreaktionen von Metallionen und die Quantenausbeute der Radikalionenbildung beim photochemischen Elektronentransfer bestimmt. Die Einflüsse des Frequenzfaktors, des Transmissionskoeffizienten, des spin-statistischen Faktors und der Radikalionen-Paarbildung auf die Kinetik des photochemischen Elektronentransfers werden aufgezeigt. Offensichtlich wird bei der Rekombination von Radikalionenpaaren, die aus Xanthen- oder Cynaninfarbstoffen mit Übergangsmetallkomplexen bestehen, das Spinverbot für den ISC-Prozess aufgehoben

DNA sequence analysis of the long terminal repeat of the C subtype of human immunodeficiency virus type 1 from southern Africa reveals a dichotomy between B subtype and African subtypes on the basis of upstream NF-IL6 motif

[No abstract available]Articl

The problem of «medical inertia» in the practice of an ophthalmologist

The authors study the problem of inertia in the medical practice of ophthalmology, which implies the absence of any modification of the treatment in the presence of objective necessity or clinical indications. The treatment of multifactorial diseases, including primary glaucoma is particularly critical. An anonymous survey of 147 ophthalmologists from different regions of Western Siberia — Altai Territory, Kemerovo Region and the Republic of Khakassia, has been conducted. Most of the surveyed doctors believed that their treatment was successful in 40‑80 % of patients. According to literature data, ithe target value of IOP level is achieved in practice in under half of the patients receiving regular therapy. Another reason of medical inertia was the fear of polypragmasy. Almost 54 % of doctors said they are afraid to prescribe several medications, which limits their desire to intensify therapy. The results of our study suggest that the cost of glaucoma treatment, i.e. the fear to prescribe an expensive treatment for patients does not significantly determine the doctors’activity. Doctors often exaggerate the fear of patients for the treatment, believing that a particular medical drugwill not be taken by the patient, without trying to figure out the patient’s intention. The economic barrier has become an essential factor for our doctors, as 35 % ophthalmologists believe that 300‑500 Rubles for the therapy per month is expencive for a patient. Over 30 % respondents discussed with the patient the prescribed treatment with cost about 700‑900 Rubles. This could potentially lead to the fact, that the second and third medical drugs would be less likely prescribed due to the increased cost of treatment. Thus, we have set up the structure of the causes of medical inertia — a psychological unwillingness to achieve target values of IOP, overestimation of the therapy success. Less important reasons were the lack of doctor’s awareness and the economic barrier forthe decision making