Thin chip microsprayer system coupled to quadrupole time-of-flight mass spectrometer for glycoconjugate analysis

A thin chip polymer-based microsprayer has been coupled to a hybrid quadrupole time-of-flight mass spectrometer (QTOF MS) and introduced in carbohydrate research. The feasibility of the approach is demonstrated for mapping, sequencing and structural elucidation of glycoconjugates originating from human body fluids and tissues such as a glycopeptide mixture from normal human urine and an isolated and purified GT1 ganglioside fraction from normal adult human brain. The optimization procedure required by each glycoconjugate category is described and the advantages of the system in terms of flexibility and adaptability to QTOF MS, stability of the ESI MS signal, carbohydrate ionization and sequencing, sensitivity, speed of analysis and sample consumption are discussed

A history of heart failure is an independent risk factor for death in patients admitted with coronavirus 19 disease

Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. Methods and Results: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. Conclusions: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19

Increased blood pressure in adult offspring of families with Balkan Endemic Nephropathy: a prospective study

BACKGROUND: Previous studies have linked smaller kidney dimensions to increased blood pressure. However, patients with Balkan Endemic Nephropathy (BEN), whose kidneys shrink during the course of the disease, do not manifest increased blood pressure. The authors evaluated the relationship between kidney cortex width, kidney length, and blood pressure in the offspring of BEN patients and controls. METHODS: 102 offspring of BEN patients and 99 control offspring of non-BEN hospital patients in the Vratza District, Bulgaria, were enrolled in a prospective study and examined twice (2003/04 and 2004/05). Kidney dimensions were determined using ultrasound, blood pressure was measured, and medical information was collected. The parental disease of BEN was categorized into three groups: mother, father, or both parents. Repeated measurements were analyzed with mixed regression models. RESULTS: In all participants, a decrease in minimal kidney cortex width of 1 mm was related to an increase in systolic blood pressure of 1.4 mm Hg (p = 0.005). There was no association between kidney length and blood pressure. A maternal history of BEN was associated with an increase in systolic blood pressure of 6.7 mm Hg (p = 0.03); paternal BEN, +3.2 mm Hg (p = 0.35); or both parents affected, +9.9 mm Hg (p = 0.002). There was a similar relation of kidney cortex width and parental history of BEN with pulse pressure; however, no association with diastolic blood pressure was found. CONCLUSION: In BEN and control offspring, a smaller kidney cortex width predisposed to higher blood pressure. Unexpectedly, a maternal history of BEN was associated with average increased systolic blood pressure in offspring

Metals and kidney markers in adult offspring of endemic nephropathy patients and controls: a two-year follow-up study

Abstract Background The etiology of Balkan Endemic Nephropathy, (BEN), a tubulointerstitial kidney disease, is unknown. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, similar manifestations are reported to occur in other regions, for instance Tunisia and Sri Lanka. A number of explanations have been stated including lignites, aristolochic acid, ochratoxin A, metals, and metalloids. Etiologic claims are often based on one or a few studies without sound scientific evidence. In this systematic study, we tested whether exposures to metals (cadmium and lead) and metalloids (arsenic and selenium) are related to Balkan Endemic Nephropathy. Methods In 2003/04 we recruited 102 adults whose parents had BEN and who resided in one of three communities (Vratza, Bistretz, or Beli Izvor, Bulgaria). A control group comprised of 99 adults having non-BEN hospitalized parents was enrolled in the study during the same time. We conducted face-to-face interviews, ultrasound kidney measurements, and determined kidney function in two consecutive investigations (2003/04 and 2004/05). Metals and metalloids were measured in urine and blood samples. To assess the agreement between these consecutive measurements, we calculated intraclass correlation coefficients. Repeated measurement data were analyzed using mixed models. Results We found that cadmium and arsenic were associated with neither kidney size nor function. Lead had a significant but negligible effect on creatinine clearance. Selenium showed a weak but significant negative association with two of the four kidney parameters, namely creatinine clearance and β2-microglobulin. It was positively related to kidney length. These associations were not restricted to the offspring of BEN patients. Adding credence to these findings are reports showing comparable kidney effects in animals exposed to selenium. Conclusion The findings of this 2-year follow-up study indicate that metals and metalloids do not play a role in the etiology of Balkan Endemic Nephropathy. Against the assumption in the literature, selenium was not protective but a risk factor. Since comparable associations were observed in animals, future studies are needed to explore whether selenium may have adverse renal effects in humans.</p

Determination of Cellular Lipids Bound to Human CD1d Molecules

CD1 molecules are glycoproteins that present lipid antigens at the cell surface for immunological recognition by specialized populations of T lymphocytes. Prior experimental data suggest a wide variety of lipid species can bind to CD1 molecules, but little is known about the characteristics of cellular ligands that are selected for presentation. Here we have molecularly characterized lipids bound to the human CD1d isoform. Ligands were eluted from secreted CD1d molecules and separated by normal phase HPLC, then characterized by mass spectroscopy. A total of 177 lipid species were molecularly identified, comprising glycerophospholipids and sphingolipids. The glycerophospholipids included common diacylglycerol species, reduced forms known as plasmalogens, lyso-phospholipids (monoacyl species), and cardiolipins (tetraacyl species). The sphingolipids included sphingomyelins and glycosylated forms, such as the ganglioside GM3. These results demonstrate that human CD1d molecules bind a surprising diversity of lipid structures within the secretory pathway, including compounds that have been reported to play roles in cancer, autoimmune diseases, lipid signaling, and cell death

An Introduction to Sphingolipid Metabolism and Analysis by New Technologies

Sphingolipids (SP) are a complex class of molecules found in essentially all eukaryotes and some prokaryotes and viruses where they influence membrane structure, intracellular signaling, and interactions with the extracellular environment. Because of the combinatorial nature of their biosynthesis, there are thousands of SP subspecies varying in the lipid backbones and complex phospho- and glycoheadgroups. Therefore, comprehensive or “sphingolipidomic” analyses (structure-specific, quantitative analyses of all SP, or at least all members of a critical subset) are needed to know which and how much of these subspecies are present in a system as a step toward understanding their functions. Mass spectrometry and related novel techniques are able to quantify a small fraction, but nonetheless a substantial number, of SP and are beginning to provide information about their localization. This review summarizes the basic metabolism of SP and state-of-art mass spectrometric techniques that are producing insights into SP structure, metabolism, functions, and some of the dysfunctions of relevance to neuromedicine

Floristic Composition as Parameter of Quality of ass. \u3cem\u3eAgrostietum Vulgaris\u3c/em\u3e

In hilly-mountainous region of Serbia, meadows and pastures are the main sourcees of roughage feeds and grazing for ruminants. On Stara Planina mountain, in SE Serbia, meadows and pastures with different plant associations and a wide range of species of differing nutritional value predominate. Until the 1930s, and even until now, only species of the grass family and leguminous plants were desired and all other plants were considered worthless or harmful Klapp (1986). The main criteria to evaluate whether a meadow plant species is a weed are: is it poisonous?; is it suitable for consumption by domestic animals as regards its morphology?; do animals eat it or not?; is it nutritious and digestible? This study aimed (1) to quantify the proportion of useful plants, other species and weeds based on the presence of certain plant species at 3 locations in ass. Agrostetum vulgaris and, (2) based on this data, to establish the quality potential for ruminant nutrition. Measures to improve the quality of grassland arise from the results obtained

Floristic Composition as a Parameter of the Quality of the Grassland Type \u3cem\u3eFestucetum Vallesacae\u3c/em\u3e in Thestara Planina Hilly-Mountainous Region of Serbia

With the increase of sea level and changes of climatic conditions, the possibilities for growing cultivated forages decreases. Therefore natural grasslands will become more important in relation to livestock nutrition. This will increase the importance of the nutritive value of these natural grasslands that have very diverse and dynamic floristic composition. The quality of the grassland depends on species categorised as grasses, legumes and other species. Other species were often regarded as harmful in regard to quality, however, they often contain many medicinal and stimulating substances that may have beneficial effects on animals and on the quality of animal products (Djordjevic-Milosevic, 1997). Conversely, there are also weed and harmful species among grasses and legumes. however, among species from other families there are also useful species. To provide nutrition of livestock from quality grasslands melioration measures are necessary. This paper reports on the composition of grasslands in Stara Planina and provides information on the proportion of useful species

Useful species as quality factors of meadow vegetation on Stara Planina Mountain

Meadows and pastures are significant natural source of animal feed and recently their importance is increasing because of the growing trend in the World regarding production of safe food. Therefore, the quality of the biomass obtained from grasslands with high quality plant species, and the possibilities for increasing their proportion in natural grasslands is extremely important. Investigations were carried out on Stara Planina Mountain of 700-800 m a.s.l. Two main plant associations wereas identified: the Agrostietum vulgaris with a total of 47 plant species and Festucetum vallesiacae with 77 plant species. High quality plant species present in these grasslands were classified into three categories: high quality grasses, high quality leguminous plants and useful or conditionally useful plant species belonging to other plant families. The association Agrostietum vulgaris had 11 useful grasses or 23.4%, 15 useful leguminous plants or 32% and 3 or 6.4% of useful and conditionally useful plants. The association Festucetum vallesiacae had 11 high quality grass species or 14.28%, 20 species of high quality leguminous plants or 26% and other useful and conditionally useful plants 11 or 14.28%