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1.
Autoimmun Rev ; 21(12): 103205, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36195246

RESUMO

OBJECTIVES: To evaluate the outcomes of hospitalized patients in two intensive care units (ICU) treated with intravenous immunoglobulin (IVIg) added to standard-of-care therapy. The indications for IVIg therapy were sepsis or autoimmune disease. METHODS: We conducted a retrospective study involving adult patients with sepsis and autoimmune diseases, who received IVIg in the ICU at Wolfson and Sheba Medical Centers. A predefined chart was compiled on Excel to include a complete demographic collection, patient comorbidities, chronic medication use, disease severity scores (Charlson Comorbidity Index; SOFA and APACHE II index scores), indication and dosage of IVIg administration, duration of hospitalization and mortality rates. RESULTS: Patients (n - 111) were divided into 2 groups: patients with sepsis only (n-67) and patients with autoimmune disease only (n-44). Septic patients had a shorter ICU stay, received IVIg early, and had reduced mortality if treated with high dose IVIg. Patients with autoimmune diseases did not have a favorable outcome despite IVIg treatment. In this group, IVIg was administered later than in the sepsis group. CONCLUSIONS: IVIg therapy improved the outcomes for ICU patients with sepsis.


Assuntos
Doenças Autoimunes , Sepse , Adulto , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , Sepse/tratamento farmacológico , Unidades de Terapia Intensiva , Doenças Autoimunes/tratamento farmacológico
2.
mBio ; 8(4)2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28851852

RESUMO

Telomeres, the ends of the eukaryotic chromosomes, help to maintain the genome's integrity and thus play important roles in aging and cancer. Telomere length is strictly controlled in all organisms. In humans, telomeres shorten with age, and it has been proposed that telomere shortening may play a causal role in aging. We took advantage of the availability of yeast strains with genetically or physiologically generated differences in telomere length to measure the effect that telomere length may have on cellular growth. By comparing the growth rates affecting telomere length of various yeast mutants we show that there is no correlation between their telomere length and cellular fitness. We also show that wild-type yeast cells carrying extremely long telomeres (~5 times longer than the average) showed no signs of mitotic or meiotic defects, and competition experiments found no differences in growth between strains with normal telomeres and strains with long telomeres. No advantage or disadvantage of cells with long telomeres was detected under stress conditions either. Finally, telomere length had no effect in a chronological life span assay, which measures survival of post-mitotic-stage cells. We conclude that extreme telomere length has no effects (positive or negative) on the fitness of yeast cells.IMPORTANCE Telomeres protect the chromosomal ends from fusion, degradation, and unwanted repair. Therefore, telomeres preserve genome stability and cell viability. In humans, telomeres shorten with each cell duplication event and with age. It has thus been proposed that telomere shortening may be responsible for human aging and that elongation of telomeres may be a way to rejuvenate cells and to combat aging. However, it is difficult to prove this hypothesis in human cells. Yeasts are easy to manipulate and have telomeres whose length is strictly maintained. Here we show that yeast cells manipulated to have extremely long telomeres (~5-fold those of normal cells) did not show any improvement or reduction in fitness compared to otherwise identical cells with telomeres of normal length under all the conditions tested. Moreover, an assay that measures cell aging showed no effect of the presence of extremely long telomeres. We thus conclude that extreme telomere length, at least in yeast cells, does not affect cellular fitness, aging, or senescence.


Assuntos
Aptidão Genética , Saccharomyces cerevisiae/genética , Encurtamento do Telômero , Telômero/genética , Mutação , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/fisiologia , Telômero/fisiologia
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