Can platelet activation markers predict preeclampsia and/or its severity?

OBJECTIVE: This study aimed to evaluate the value of platelet activation markers in predicting preeclampsia and its severity. Preeclampsia is a serious pregnancy complication that affects 3-5% of pregnancies and can lead to significant morbidity and mortality for both the mother and the fetus. METHODS: The study included 99 patients diagnosed with preeclampsia and 60 healthy pregnant women as a control group. Platelet activation markers such as mean platelet volume (MPV), platelet distribution width (PDW), platelet count, and plateletcrit were evaluated along with other clinical parameters. RESULTS: The results of the study showed that platelet activation markers, particularly PDW and MPV, are valuable in the diagnosis and follow-up of preeclampsia. However, they are not sufficient to predict the severity of the disease. CONCLUSION: The study suggests that platelet activation markers could aid in predicting, diagnosing, and managing preeclampsia. However, further research is needed to determine the role of these markers in predicting the severity of the disease. The findings of this study could contribute to the development of more effective strategies for the prevention and management of preeclampsia, which could ultimately improve maternal and fetal outcomes.

OBJETIVO: El estudio tuvo como objetivo determinar el valor de los marcadores de activación plaquetaria en la predicción de la preeclampsia y su gravedad. MÉTODO: Se incluyeron 99 pacientes diagnosticadas con preeclampsia, incluyendo 36 casos graves, y un grupo control de 60 mujeres embarazadas sanas. Se evaluaron diversas variables, como el volumen plaquetario medio, el recuento de plaquetas, el hematocrito plaquetario y la amplitud de distribución plaquetaria. RESULTADOS: Los resultados mostraron que el volumen plaquetario medio y la amplitud de distribución plaquetaria son parámetros valiosos en el diagnóstico y seguimiento de la preeclampsia, aunque no son suficientes para predecir su gravedad. El análisis estadístico reveló que la edad, el volumen plaquetario medio, la amplitud de distribución plaquetaria, la semana de gestación y los puntajes de Apgar al primer y quinto minuto fueron significativamente diferentes en el grupo de preeclampsia en comparación con el grupo control. CONCLUSIONES: En conclusión, estos resultados sugieren que los marcadores de activación plaquetaria pueden ser útiles para el diagnóstico y seguimiento de la preeclampsia, y que el volumen plaquetario medio y la amplitud de distribución plaquetaria, por ser parámetros económicos y accesibles, podrían ayudar a predecir, diagnosticar y manejar esta complicación durante el embarazo.

Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial.

BACKGROUND: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect. METHODS: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. FINDINGS: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01). INTERPRETATION: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.

Surface chemistry modification of silica nanoparticles alters the activation of monocytes.

Aim: Nanoparticles (NPs) interaction with immune system is a growing topic of study. Materials & methods: Bare and amine grafted silica NPs effects on monocytes/macrophages cells were analyzed by flow cytometry, MTT test and LIVE/DEAD® viability/cytotoxicity assay. Results: Bare silica NPs inhibited proliferation and induced monocyte/macrophages activation (increasing CD40/CD80 expression besides pro-inflammatory cytokines and nitrite secretion). Furthermore, silica NPs increased cell membrane damage and reduced the number of living cells. In contrast, amine grafted silica NPs did not alter these parameters. Conclusion: Cell activation properties of bare silica NPs could be hindered after grafting with amine moieties. This strategy is useful to tune the immune system stimulation by NPs or to design NPs suitable to transport therapeutic molecules.

Deep Infiltrating Endometriosis and Activation and Memory Surface Markers and Cytokine Expression in Isolated Treg Cells.

It is not yet clear whether regulatory T (Treg) cells are active, and whether they play a favorable or adverse effect on endometrial foci implantation. Our aim was to evaluate activation and memory surface markers in Treg isolated from peritoneal fluid (PF) and peripheral blood (PB) of women with deep endometriosis and to assess its cytokine mRNA expression. This case-control study included 49 women with deep infiltrating endometriosis and 20 healthy controls. It was analyzed PF and PB of both groups. Cell surface markers GITR, TNFRII, HLA-DR, ICOS, CTLA-4, CD45RA, and CD45RO were evaluated in Treg (CD3+CD4+CD25+CD127lowFoxp3+) cells by flow cytometry. Additionally, Foxp3, TGF-beta, IL-10, IL-6, and TNF-alpha mRNA expression was assessed by real-time PCR in Treg cells (CD4+CD25+CD127dim/-) isolated using magnetic microbeads. Women with endometriosis had higher percentages of TNFRII+ Treg and CTLA-4+ Treg in their PB, and lower percentages of ICOS+ Treg and CD45RO+ Treg in their PF. The groups displayed no differences in mRNA expression. Regardless of the group, in PF, the percentage of Treg cells overall and of CD45RA+ Treg cells were significantly lower, whereas the percentage of TNFRII+ Treg and CD45RO+ Treg were significantly higher than in PB. Foxp3 and TGF-beta mRNA expression were also higher in PF than in PB. Our results indicated that Treg cells in women with endometriosis have a distinct profile of activation and memory markers, but similar cytokine expression. Moreover, we could observe clearly that Treg cells have distinct profile regarding their origin site.

Different aspects of platelet evaluation in dengue: Measurement of circulating mediators, ability to interact with the virus, the degree of activation and quantification of intraplatelet protein content.

Platelets play a role in hemostasis, coagulation, angiogenesis, inflammation and immune response is one of the most affected cells in dengue. Here we describe some aspects of platelets by observing their specific circulating mediators, the ability to interact with the virus and morphological consequences of this interaction, activation markers and intraplatelet protein contents in dengue. We conducted this study using dengue-patients as well as healthy donors. Immunoenzymatic assay, flow cytometry, transmission electron microscopy and intraplatelet proteins expression assays were carried out. Briefly, we found an increase in sCD62L, NO or TBX2 ratio in platelet count, mostly in patients with the worse clinical outcome. After in vitro DENV infection or during natural infection, platelets underwent morphological alteration with increased expression of platelet activation markers, particularly in natural infections. Analysis of intraplatelet protein contents revealed different angiogenic and inflammatory profiles, maintaining or not extracellular matrix integrity between DF and DFWS patients. Thus, platelets are frequently affected by dengue, either by altering their own functionality, as "carrier" of the virus, or as an antiviral and mediator-secreting effector cell. Thus, strategies aimed at recovering platelet amounts in dengue seem to be essential for a better clinical outcome of the patients.

Chronic activation profile of circulating CD8+ T cells in Sézary syndrome.

Sézary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sézary cells have been studied extensively, studies on adaptive immunity regarding CD8+T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Rα axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum. Although the SS patients of our cohort had reduced numbers of CD8+ T cells, they exhibited higher percentages of CD8+CD38+ T cells, mainly effector/memory CD8+ T cells, than the control group. In contrast, down-regulated expression of the activation markers CD127/IL-7R and CD26 was found in the CD8+ T cells of SS patients. High serum levels of sCD38 and sCD127 and scarce serum levels of IL-7 were detected, emphasizing the immune activation status of SS patients. Moreover, CD8+ T cells from SS patients exhibited IL-7 unresponsiveness to STAT5 phosphorylation and Bcl-2 expression, and IL-7 priming partially restored IFNγ production. Our findings showed a chronic activation profile of CD8+ T cells, as an attenuated cytotoxic profile and impaired IL-7 responsiveness was observed, suggesting chronic activation status of CD8+ T cells in SS patients.

Evidence of size-dependent effect of silica micro- and nano-particles on basal and specialized monocyte functions.

AIM: To analyze the effect of silica particles on monocyte/macrophage functions. MATERIALS & METHODS: Silica micro- and nanoparticles were obtained by the Stöber method. Their effect on monocyte/macrophage proliferation, activation, membrane integrity and metabolic activity were determined. RESULTS: Silica particles inhibit cell proliferation while 10 nm nanoparticles (NPs) did not affect it. Similarly, silica particles induced strong cell activation. However, 10 nm NPs do not alter IL-12 or nitrite levels. Furthermore, bigger NPs and microparticles increase cell membrane damage and reduce the number of living cells but smallest NPs (10 and 240 nm) did not. CONCLUSION: Cell activation properties of silica particles could be useful tools for immune stimulation therapy, while 10 nm NPs would be suitable for molecule transportation.

Impaired CD8(+) T cell responses upon Toll-like receptor activation in common variable immunodeficiency.

BACKGROUND: Infections caused by bacteria or viruses are frequent in common variable immunodeficiency (CVID) patients due to antibody deficiencies, which may be associated with altered T cell function. CVID patients are frequently in contact with pathogen-associated molecular patterns (PAMPs), leading to the activation of innate immunity through Toll-like receptors (TLR) affecting T cell activation. We evaluated the effect of TLR activation on T cells in CVID patients undergoing intravenous immunoglobulin (IVIg) replacement using synthetic ligands. METHODS: Expression of exhaustion, activation and maturation markers on T cells from peripheral blood as well as regulatory T cells and follicular T cells in peripheral blood mononuclear cells (PBMCs) from CVID and healthy individuals were evaluated by flow cytometry. PBMCs cultured with TLR agonists were assessed for intracellular IFN-γ, TNF, IL-10, IL-17a or IL-22 secretion as monofunctional or polyfunctional T cells (simultaneous cytokine secretion) by flow cytometry. RESULTS: We found increased expression of the exhaustion marker PD-1 on effector memory CD4(+) T cells (CD45RA(-)CCR7(-)) in the peripheral blood and increased expression of CD38 in terminally differentiated CD8(+) T cells (CD45RA(+)CCR7(-)). Furthermore, a decreased frequency of naïve regulatory T cells (CD45RA(+)Foxp3(low)), but not of activated regulatory T cells (CD45RA(-)Foxp3(high)) was detected in CVID patients with splenomegaly, the non-infectious manifestation in this CVID cohort (43.7 %). Moreover, the frequency of peripheral blood follicular helper T cells (CD3(+)CD4(+)CXCR5(+)PD-1(+)ICOS(+)) was similar between the CVID and control groups. Upon in vitro TLR3 activation, a decreased frequency of CD8(+) T cells secreting IFN-γ, IL-17a or IL-22 was detected in the CVID group compared to the control group. However, a TLR7/TLR8 agonist and staphylococcal enterotoxin B induced an increased Th22/Tc22 (IL-22(+), IFN-γ(-), IL-17a(-)) response in CVID patients. Both TLR2 and TLR7/8/CL097 activation induced an increased response of CD4(+) T cells secreting three cytokines (IL-17a, IL-22 and TNF)in CVID patients, whereas CD8(+) T cells were unresponsive to these stimuli. CONCLUSION: The data show that despite the unresponsive profile of CD8(+) T cells to TLR activation, CD4(+) T cells and Tc22/Th22 cells are responsive, suggesting that activation of innate immunity by TLRs could be a strategy to stimulate CD4(+) T cells in CVID.

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome.

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (-1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (-1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.

Efecto in vitro de una solución de Zingiber officinale Rosc. (jengibre) sobre la respuesta de linfocitos humanos de donantes sanos y enfermos con inmunodeficiencia celular / In vitro effect of a solution of Zingiber officinale Rosc. (Ginger) on the response of human lymphocytes from healthy donors and patients with cellular immunodeficiency

El Zingiber officinale Rosc. (jengibre) es una especie que se ha utilizado por el hombre con diversos fines. Se estudió el efecto in vitro de una solución acuosa del rizoma de esta planta sobre los linfocitos de 30 donantes voluntarios de sangre y de 30 enfermos con diagnóstico de inmunodeficiencia celular, mediante la prueba de transformación linfoblástica, con el empleo de timidina tritiada, la técnica de formación de roseta activa y el ultramicrométodo inmunocitoquímico (UMICIQ). No se hallaron diferencias estadísticamente significativas entre las condiciones experimentales sin jengibre y con jengibre, con diluciones de este desde 1:2 hasta 1:2048 en la prueba de transformación linfoblástica. En la roseta activa y en los marcadores de activación HLA-DR y CD25 no se observaron diferencias estadísticamente significativas entre los linfocitos sin jengibre y los cultivados con la dilución 1:128, tanto en los donantes sanos como los enfermos(AU)

The Zingiber officinale Rosc (ginger) is a species used by man to different purposes. The in vitro effect of a aqueous solution from the rhizome of this plant on the lymphocytes of 30 volunteer blood donors and of 30 patients diagnosed with cellular immunodeficiency was studied by the lymphoblastic transformation test using tritiated thymidine, the technique of the rosette active formation and the immunocytochemical ultramicromethod (UMICIQ). There were not statistically significant differences among the experimental conditions with and without ginger with dilutions from 1:2 to 1:128 in the lymphoblastic transformation test. In the active rosette and in markers of the HLA-DR and CD25 activation there weren't statistically significant differences among lymphocytes without ginger and those cultured with a dilution 1:128 for healthy donors and for the patients(AU)

Efecto in vitro de una solución de Zingiber officinale Rosc. (jengibre) sobre la respuesta de linfocitos humanos de donantes sanos y enfermos con inmunodeficiencia celular / In vitro effect of a solution of Zingiber officinale Rosc. (Ginger) on the response of human lymphocytes from healthy donors and patients with cellular immunodeficiency

El Zingiber officinale Rosc. (jengibre) es una especie que se ha utilizado por el hombre con diversos fines. Se estudió el efecto in vitro de una solución acuosa del rizoma de esta planta sobre los linfocitos de 30 donantes voluntarios de sangre y de 30 enfermos con diagnóstico de inmunodeficiencia celular, mediante la prueba de transformación linfoblástica, con el empleo de timidina tritiada, la técnica de formación de roseta activa y el ultramicrométodo inmunocitoquímico (UMICIQ). No se hallaron diferencias estadísticamente significativas entre las condiciones experimentales sin jengibre y con jengibre, con diluciones de este desde 1:2 hasta 1:2048 en la prueba de transformación linfoblástica. En la roseta activa y en los marcadores de activación HLA-DR y CD25 no se observaron diferencias estadísticamente significativas entre los linfocitos sin jengibre y los cultivados con la dilución 1:128, tanto en los donantes sanos como los enfermos

The Zingiber officinale Rosc (ginger) is a species used by man to different purposes. The in vitro effect of a aqueous solution from the rhizome of this plant on the lymphocytes of 30 volunteer blood donors and of 30 patients diagnosed with cellular immunodeficiency was studied by the lymphoblastic transformation test using tritiated thymidine, the technique of the rosette active formation and the immunocytochemical ultramicromethod (UMICIQ). There were not statistically significant differences among the experimental conditions with and without ginger with dilutions from 1:2 to 1:128 in the lymphoblastic transformation test. In the active rosette and in markers of the HLA-DR and CD25 activation there weren't statistically significant differences among lymphocytes without ginger and those cultured with a dilution 1:128 for healthy donors and for the patients