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

Increased Prevalence of G1P[4] Genotype among Children with Rotavirus-Associated Gastroenteritis in Metropolitan Detroit

The G and P genotypes of rotavirus stool isolates from 100 children were determined by reverse transcription-PCR and nucleotide sequencing. G1P[4] was the most prevalent genotype(41%), followed by G1P[8] (16%) and G4P[4] (14%). The G genoypes detected were G1 (73%), G4 (17.4%), G9 (6.3%), and G2 (2.8%). The P genotypes were P[4] (71%) and P[8] (29%). Coinfection with more than one G genotype occurred in 12 patients, and coinfection with more than one P genotype occurred in 11 patients

DIAGNOSTIC VALUE OF ANGIOGENESIS RATES IN RENAL-CELL CARCINOMA

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

PUBERTAL DEVELOPMENT IN BOYS WITH UNILATERAL CRYPTORCHIDISM

The results of a prospective study of 32 boys 11-15 years, underwent orchiopexy about unilateral cryptorchidism are presented in article. The evaluation of pubertal development, testicular ultrasound and doppler, prostate investigation and the tests of serum reproductive hormones were performed. The examination were found the reduced gonads volume side orhiopexy determined at the initiation of puberty and expanded as it progresses, degenerative changes of the prostate gland . There were not significant changes in serum gonadotropins and testosterone