Disbalanced lymphocyte subpopulations are early markers of mortality in our series of 701 SARS‐CoV‐2 infected patients, when severe lymphopenia has yet to develop. If available, the study of ...lymphocyte subsets by flow cytometry is recommended to identify high‐risk COVID‐19 patients at hospital admission.
Summary
The role of lymphocytes and their main subsets as prognostic factors of death in SARS‐CoV‐2‐infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)‐confirmed consecutive patients by lysed–no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3‐month follow‐up. The 112 patients who died were older and had significantly higher frequencies of known co‐morbidities than survivor COVID‐19 patients. A significant reduction in total lymphocytes, CD3+, CD4+, CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P < 0·001), while the percentage of CD56+/CD16+ natural killer (NK) cells was significantly higher (P < 0·001). Multivariate logistic regression analysis showed a significantly increased risk of in‐hospital death associated to age odds ratio (OR) = 2·36, 95% confidence interval (CI) = 1·9–3·0 P < 0·001; CD4+ T counts ≤ 500 cells/μl, (OR = 2·79, 95% CI = 1·1–6·7, P = 0·021); CD8+ T counts ≤ 100 cells/μl, (OR = 1·98, 95% CI = 1·2–3·3) P = 0·009) and CD56+/CD16+ NK ≥ 30%, (OR = 1·97, 95% CI = 1·1–3·1, P = 0·002) at admission, independent of total lymphocyte numbers and co‐morbidities, with area under the curve 0·85 (95% CI = 0·81–0·88). Reduced counts of CD4+ and CD8+ T cells with proportional expansion of NK lymphocytes at admission were prognostic factors of death in this Spanish series. In COVID‐19 patients with normal levels of lymphocytes or mild lymphopenia, imbalanced lymphocyte subpopulations were early markers of in‐hospital mortality.
•Melatonin is synthesised by non-Saccharomyces strains.•Red Fruit strain produces more melatonin than others included in this study.•Non-Saccharomyces synthesised Tryptophan ethyl ester during the ...fermentation process.•Melatonin synthesis took place at end of the exponential growth phase.•Saccharomyces strains consumed Tryptophan faster than non-Saccharomyces.
Melatonin is a neurohormone involved in the regulation of circadian rhythms in humans. Evidence has recently been found of its occurrence in wines and its role in the winemaking process. The yeast Saccharomyces cerevisiae is consequently thought to be important in Melatonin synthesis, but limited data and reference texts are available on this synthetic pathway.
This paper aims to elucidate whether the synthetic pathway of Melatonin in Saccharomyces and non-Saccharomyces strains involves these intermediates. To this end, seven commercial strains comprising Saccharomyces cerevisiae (Red Fruit, ES488, Lalvin QA23, Uvaferm BC, and Lalvin ICV GRE) and non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) were monitored, under controlled fermentation conditions, in synthetic must, for seven days. Samples were analysed using a UHPLC—HRMS system (Qexactive).
Five out of the seven strains formed Melatonin during the fermentation process: three S. cerevisiae strains and the two non-Saccharomyces. Additionally, other compounds derived from l-tryptophan occurred during fermentation.
•Hydroxytyrosol has been detected and quantified in intracellular media of yeast.•Strain of yeast is a crucial factor that influences the production of Hydroxytyrosol in wines.•The more efficient ...producer of Hydroxytyrosol was Saccharomyces cerevisiae strain QA23.•Sequential fermentations involving T. delbruekii strain, adversely affect the content of HT.•Sauvignon Blanc and Vigiriega grapes were the higher producers of HT of the studied varieties.
Hydroxytyrosol (HT) is a phenolic compound of recognized bioactivity that has been described in wines but little is known about its origin. This work demonstrates that yeast involved in wine making, i.e. Saccharomyces cerevisiae strains and the non-Saccharomyces Torulaspora delbrueckii, can synthesise HT, as this compound was identified in the intracellular media of three strains by means of a developed and validated UHPLC–HRMS method with LOQ and LOD of 0.108 and 0.035ngmL−1 respectively. Controlled fermentations were performed with different varieties of grapes (Corredera, Moscatel, Chardonnay, Palomino fino, Sauvignon Blanc, Vijiriega, and Tempranillo) and synthetic must. The Saccharomyces cerevisiae strain QA23 was the most efficient producer of HT from tested yeasts. On the other hand, the grape variety influences HT wine concentrations. Furthermore, the maximum concentration of HT is reached between the fourth and sixth day of fermentation. This work reveals that yeasts have a great potential for the production of HT.
•The efficiency of three methods of intracellular extraction was evaluated.•Two UHPLC/MS methods were validated to measure metabolites related to tryptophan–tyrosine.•Removing phospholipids and ...proteins enabling obtain good values for matrix effects.•Higher temperatures of the extraction methods produce overestimating of extracted amino acids.•Extractions at low temperatures had a better efficiency and satisfactory repeatability values.
Yeast nitrogen metabolism produces metabolites, whose origin in wines has scarcely been studied, with an important biological and organoleptic role. The present work focuses on comparing three intracellular extraction methods in order to elucidate efficiency of extraction while measuring the effect of temperature upon the integrity of the compounds related to the metabolism of tryptophan and tyrosine by yeast.
Two UHPLC/HRMS methods to measure 16 metabolites were developed and validated. The validation provided optimum values of LOD (7.4·10−6 to 0.1 μg L−1), of LOQ (2·10−5 to 0.02 μg L−1) of precision (11–0.5% RSD) and repeatability (12–0.5% RSD). The removal of interfering molecules enabled matrix effects to be kept at low levels.
The results pointed out that the low-temperature methods were more effective, providing better precision for 16 metabolites. The high-temperature extraction method may yield false enhanced compounds concentrations since they originate in cell wall macromolecules degradation.
Background and Aims
Tryptophan is involved in the formation of bioactive compounds, such as melatonin (MEL) and 3‐indoleacetic acid (3‐IAA), by yeast. Melatonin is a neurohormone whose occurrence in ...wine has been widely reported in recent years. The occurrence, however, of MEL and other indolic compounds related to tryptophan metabolism by wine yeast strains has been scarcely reported in grape musts. This work examined the occurrence of these compounds during the alcoholic fermentation (AF) of musts from seven grape cultivars, Corredera, Chardonnay, Moscatel, Palomino Fino, Sauvignon Blanc, Tempranillo and Vijiriega.
Methods and Results
Must was fermented with three Saccharomyces cerevisiae strains and then in two cases an additional sequential inoculation with the non‐Saccharomyces yeast Torulaspora delbrueckii was carried out. Fermented must samples were analysed by UHPLC/HRMS to determine the concentration of: l‐tryptophan, 5‐hydroxytryptophan, 5‐hydroxytryptamine, N‐acetyl‐5‐hydroxytryptamine, MEL, 3‐IAA, tryptamine, tryptophol and l‐tryptophan ethyl ester. The profile of indolic compounds during AF with the Aroma White strain depended on the cultivar. The yeast strain did not influence the profile of indolic compounds; instead, fermentation time was found to be a more influential factor.
Conclusions
The production of indolic compounds during the AF depends largely on the cultivar used and the day of fermentation on natural grape musts.
Significance of the Study
This is the first study that quantifies 5‐hydroxytryptophan and N‐acetyl‐5‐hydroxytryptamine during the AF of grape must. The occurrence of compounds with bioactive potential, for example 3‐IAA and ML, during fermentation with commercial yeast strains is also described.
Abstract Evaluation of specific antibody (Ab) response to polysaccharide antigens is essential for diagnosis of primary immunodeficiencies. We assessed the specific Ab responses to the ...pneumococcal-polysaccharide (PPV) and to Salmonella typhi-polysaccharide (TyphimVi) vaccines in a prospective study (EMPATHY) in patients with common variable immunodeficiency (CVID-Group, n = 22), hypogammaglobulinemia (HYPOG-Group; n = 27) and healthy controls (HC-Group; n = 16). Specific Ab concentrations in response to PPV and to TyphimVi vaccines were measured by ELISA (The Binding Site, UK), defining 3-fold increase as normal response (Ratio:3 ×). The RatioTyphimVi:3 × was significantly greater in HC than in CVID-Group ( p < 0.0001), but not than HYPOG-Group ( p = 0.138). However, the RatioPPV:3 × showed no significant differences among the three groups. By ROC analysis, TyphimVi better differentiated HC from CVID (AUC:0.893, IC95%: 0.791–0.996, p < 0.0001) than PPV. Our results suggest that the use of specific Ab response to TyphimVi could represent a complementary assay for the diagnosis of anti -polysaccharide Ab production deficiency in patients with CVID.
Recurrent respiratory tract infections (RRTIs) are common clinical conditions in individuals with alterations of the immune function. A prospective open pilot study in a cohort of patients with RRTIs ...has been performed to assess whether sublingual immunization with a polyvalent bacterial vaccine could exert an immunomodulatory effect on the antigen-specific immunological responses and have an impact on the clinical outcome. Seventeen patients with RRTIs were recruited. An oral polyvalent bacterial preparation (Bactek®) was administered to all patients daily for 6 months. Immunological assessment was performed at baseline and at the end of immunization. Immunological measurements included: T cell-specific proliferations of CD3⁺CD4⁺ and CD3⁺CD8⁺ to Bactek® antigens, total immunoglobulin levels, antibodies to pneumococcal polysaccharide and tetanus toxoid and B, T and natural killer (NK) cell subsets. There was a significant increase in the proliferative capacity of CD3⁺CD4⁺ T cells specific to Bactek® antigens at month 6 in comparison to baseline (P < 0·0001). A significant increase in total CD3⁺ T cells was also observed (P < 0·05). No significant differences were observed between baseline and month 6 in levels of total immunoglobulins, specific antibodies and B, T or NK cell subsets. A significant reduction in the patient's rate of RRTIs was observed compared with 1 year prior to initiation of therapy (P < 0·0001). The results demonstrate that long-term administration of a sublingual polyvalent bacterial preparation in patients with RRTIs exerts an immune stimulating effect on CD4⁺ T helper cell responses to bacterial antigens which could be associated with clinical benefit.
A new type of hereditary angioedema (type III) affecting mainly women with normal C1-inhibitor level and function has been described. Exposition to estrogens is an important precipitating factor. ...Recently, a missense mutation in the gene of the blood coagulation factor XII (Hageman factor) has been reported in a few families with this type of hereditary angioedema. To study a patient and her family with recurrent swelling attacks during pregnancy. Complement factors C3 and C4 as well as C1-inhibitor level and function were determined. Genomic DNA was isolated from venous blood samples and screened for mutations in the coagulation factor XII gene. C3 and C4 levels as well as C1-inhibitor level and function were normal. A missense mutation Thr309Lys was identified in factor XII gene with a heterozygotic pattern. This mutation was also identified in the mother of the patient, her daughter and her son. These results support that the mentioned mutation in factor XII gene causes hereditary angioedema type III.
Mechanisms of action of immune globulin Fernández‐Cruz, E.; Alecsandru, D.; Ramón, S. S.
Clinical and experimental immunology,
September 2009, Letnik:
157, Številka:
Supplement_1
Journal Article
Melatonin is a bioactive compound that is present in wines because of the metabolism of
l
-tryptophan by yeasts. Even though the complete pathway of synthesis is not well elucidated, certain related ...indolic compounds might be involved in it. Consequently, their determination is a matter of interest. On one hand, their formation during fermentation might be related to a specific role for yeasts metabolism, not known so far. On the other hand, the synthesis by yeasts of bioactive compounds with putative health benefits for consumers, such as melatonin or serotonin, is a relevant matter. This paper aims to develop and validate an analytical method by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC/HRMS) to monitor both melatonin and related indolic compounds, in order to decrease their detection limits and make it possible to assess their occurrence in culture medium and fermented products. In addition, the other objective is to evaluate the production of these compounds by a commercial
Saccharomyces cerevisiae
used to make white wines. Diminishing the limit of detection below 0.5 ng mL
−1
for all compounds under study is an achievement of this work. Furthermore, the strain under study (AROMA WHITE) has been found to synthesise melatonin and related compounds as serotonin. Additionally, the evolution of these compounds over time may contribute to understanding the role that they play in yeast metabolism.
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