Гастропатии у пациентов с хронической обструктивной болезнью легких

Catedra Medicină internă nr. 6, USMF „Nicolae Testemiţanu”, Conferinţa Ştiinţifico-Practică „Medicina modernă, actualităţi şi perspective”, consacrată aniversării de 40 de ani ai Spitalului Clinic al Ministerului Sănătăţii, 27-28 mai, 2010, Chişinău, Republica MoldovaChronic obstructive pulmonary disease is the fourth leading cause of death in the age group of 45 years and older, and it is a unique disease for which the death rate indicator continues to increase steadily. The inclusion of ozonotherapy in the complex treatment of acute erosion and peptic ulcers of gastroduodenal zones with a background of chronic obstructive pulmonary disease reduces length of ulcer erosions epithelization, reduces activity of inflammatory process in the mucous membrane of a stomach and promotes improvement of immune homeostasis indicators.Хроническая обструктивная болезнь легких (ХОБЛ) занимает четвертое место в мире, как причина смерти лиц старше 45 лет и является единственным заболеванием, смертность от которого постоянно растет. Включение озонированного физиологического раствора в комплексное лечение острых эрозий и пептических язв гастродуоденальной зоны, ассоциированных с ХОБЛ, уменьшает продолжительность болевого и диспептического синдромов и эпителизации эрозивно-язвенных дефектов, снижает активность воспалительного процесса и ведет к нормализации показателей иммунного гомеостаза

Recent Upgrades of the Gas Handling System for the Cryogenic Stopping Cell of the FRS Ion Catcher

In this paper, the major upgrades and technical improvements of the buffer gas handling system for the cryogenic stopping cell of the FRS Ion Catcher at GSI/FAIR (in Darmstadt, Germany) are described. The upgrades include implementation of new gas lines and gas purifiers to achieve a higher buffer gas cleanliness for a more efficient extraction of reactive ions as well as suppression of the molecular background ionized in the stopping cell. Furthermore, additional techniques have been implemented for improved monitoring and quantification of the purity of the helium buffer gas

C-Terminus Glycans with Critical Functional Role in the Maturation of Secretory Glycoproteins

The N-glycans of membrane glycoproteins are mainly exposed to the extracellular space. Human tyrosinase is a transmembrane glycoprotein with six or seven bulky N-glycans exposed towards the lumen of subcellular organelles. The central active site region of human tyrosinase is modeled here within less than 2.5 Å accuracy starting from Streptomyces castaneoglobisporus tyrosinase. The model accounts for the last five C-terminus glycosylation sites of which four are occupied and indicates that these cluster in two pairs - one in close vicinity to the active site and the other on the opposite side. We have analyzed and compared the roles of all tyrosinase N-glycans during tyrosinase processing with a special focus on the proximal to the active site N-glycans, s6:N337 and s7:N371, versus s3:N161 and s4:N230 which decorate the opposite side of the domain. To this end, we have constructed mutants of human tyrosinase in which its seven N-glycosylation sites were deleted. Ablation of the s6:N337 and s7:N371 sites arrests the post-translational productive folding process resulting in terminally misfolded mutants subjected to degradation through the mannosidase driven ERAD pathway. In contrast, single mutants of the other five N-glycans located either opposite to the active site or into the N-terminus Cys1 extension of tyrosinase are temperature-sensitive mutants and recover enzymatic activity at the permissive temperature of 31°C. Sites s3 and s4 display selective calreticulin binding properties. The C-terminus sites s7 and s6 are critical for the endoplasmic reticulum retention and intracellular disposal. Results herein suggest that individual N-glycan location is critical for the stability, regional folding control and secretion of human tyrosinase and explains some tyrosinase gene missense mutations associated with oculocutaneous albinism type I

Mass measurements of As, Se and Br nuclei and their implication on the proton-neutron interaction strength towards the N=Z line

Mass measurements of the nuclides 69As, 70,71Se, and 71Br, produced via fragmentation of a 124Xe primary beam at the Fragment Separator (FRS) at GSI, have been performed with the multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS) of the FRS Ion Catcher with an unprecedented mass resolving power of almost 1000000. Such high resolving power is the only way to achieve accurate results and resolve overlapping peaks of short-lived exotic nuclei, whose total number of accumulated events is always limited. For the nuclide 69As, this is the first direct mass measurement. A mass uncertainty of 22 keV was achieved with only ten events. For the nuclide 70Se, a mass uncertainty of 2.6 keV was obtained, corresponding to a relative accuracy of δm/m=4.0×10−8, with less than 500 events. The masses of the nuclides 71Se and 71Br have been measured with an uncertainty of 23 and 16 keV, respectively. Our results for the nuclides 70,71Se and 71Br are in good agreement with the 2016 Atomic Mass Evaluation, and our result for the nuclide 69As resolves the discrepancy between the previous indirect measurements. We measured also the mass of the molecule 14N15N40Ar (A=69) with a relative accuracy of δm/m=1.7×10−8, the highest yet achieved with an MR-TOF-MS. Our results show that the measured restrengthening of the proton-neutron interaction (δVpn) for odd-odd nuclei along the N=Z line above Z=29 (recently extended to Z=37) is hardly evident at the N−Z=2 line, and not evident at the N−Z=4 line. Nevertheless, detailed structure of δVpn along the N−Z=2 and N−Z=4 lines, confirmed by our mass measurements, may provide a hint regarding the ongoing ≈500 keV discrepancy in the mass value of the nuclide 70Br, which prevents including it in the world average of Ft value for superallowed 0+→0+β decays. The reported work sets the stage for mass measurements with the FRS Ion Catcher of nuclei at and beyond the N=Z line in the same region of the nuclear chart, including the nuclide 70Br.peerReviewe

Insight into the Regulation of Glycan Synthesis in Drosophila Chaoptin Based on Mass Spectrometry

BACKGROUND: A variety of N-glycans attached to protein are known to involve in many important biological functions. Endoplasmic reticulum (ER) and Golgi localized enzymes are responsible to this template-independent glycan synthesis resulting glycoforms at each asparagine residues. The regulation mechanism such glycan synthesis remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate the relationship between glycan structure and protein conformation, we analyzed a glycoprotein of Drosophila melanogaster, chaoptin (Chp), which is localized in photoreceptor cells and is bound to the cell membrane via a glycosylphosphatidylinositol anchor. Detailed analysis based on mass spectrometry revealed the presence of 13 N-glycosylation sites and the composition of the glycoform at each site. The synthetic pathway of glycans was speculated from the observed glycan structures and the composition at each N-glycosylation site, where the presence of novel routes were suggested. The distribution of glycoforms on a Chp polypeptide suggested that various processing enzymes act on the exterior of Chp in the Golgi apparatus, although virtually no enzyme can gain access to the interior of the horseshoe-shaped scaffold, hence explaining the presence of longer glycans within the interior. Furthermore, analysis of Chp from a mutant (RNAi against dolichyl-phosphate alpha-d-mannosyltransferase), which affects N-glycan synthesis in the ER, revealed that truncated glycan structures were processed. As a result, the distribution of glycoforms was affected for the high-mannose-type glycans only, whereas other types of glycans remained similar to those observed in the control and wild-type. CONCLUSIONS/SIGNIFICANCE: These results indicate that glycan processing depends largely on the backbone structure of the parent polypeptide. The information we obtained can be applied to other members of the LRR family of proteins

Minimal in vivo efficacy of iminosugars in a lethal Ebola virus guinea pig model

The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated. A pilot study treating infected animals three times within an 8 hour period was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected guinea pigs were treated. On histopathological examination, animals treated with NB-DNJ had reduced lesion severity in liver and spleen. However, a second study, in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not confirm drug-associated benefits. Neither was any antiviral effect of iminosugars detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a lethal EBOV-infection at the dose levels and regimens tested. However, the one surviving animal and signs of improvements in three animals of the NB-DNJ treated cohort could indicate that NB-DNJ at these levels may have a marginal beneficial effect. Future work could be focused on the development of more potent iminosugars

Folding of Matrix Metalloproteinase-2 Prevents Endogenous Generation of MHC Class-I Restricted Epitope

BACKGROUND: We previously demonstrated that the matrix metalloproteinase-2 (MMP-2) contained an antigenic peptide recognized by a CD8 T cell clone in the HLA-A*0201 context. The presentation of this peptide on class I molecules by human melanoma cells required a cross-presentation mechanism. Surprisingly, the classical endogenous processing pathway did not process this MMP-2 epitope. METHODOLOGY/PRINCIPAL FINDINGS: By PCR directed mutagenesis we showed that disruption of a single disulfide bond induced MMP-2 epitope presentation. By Pulse-Chase experiment, we demonstrated that disulfide bonds stabilized MMP-2 and impeded its degradation. Finally, using drugs, we documented that mutated MMP-2 epitope presentation used the proteasome and retrotranslocation complex. CONCLUSIONS/SIGNIFICANCE: These data appear crucial to us since they established the existence of a new inhibitory mechanism for the generation of a T cell epitope. In spite of MMP-2 classified as a self-antigen, the fact that cross-presentation is the only way to present this MMP-2 epitope underlines the importance to target this type of antigen in immunotherapy protocols

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk