Benefits on Hematological and Biochemical Parameters of a High-Intensity Interval Training Program for a Half-Marathon in Recreational Middle-Aged Women Runners

(1) Background: half-marathon races are popular among recreational runners, with increases in participation among middle-aged and women. We aimed to determine the effects of two half-marathon training programs on hematological and biochemical markers in middle-aged female recreational runners; (2) Methods: ten women (40 ± 7 years) followed moderate intensity continuous training (MICT), based on running volume below 80% V˙O2max, and another ten women followed high intensity interval training (HIIT) at 80%–100% V˙O2max, with less volume, and combined with eccentric loading exercise. Hematology, plasma osmolality, and plasma markers of metabolic status, muscle damage, inflammatory, and oxidative stress were measured before (S1) and after (S2) training and 24 h after the half-marathon (S3); (3) Results: both training programs had similar moderate effects at S2. However, the acute response at S3 induced different alterations. There was a greater decrease in cholesterol and triglyceride levels in MICT and reductions in markers of damage and inflammation in HIIT. Greater variability in some plasma markers at S3 in MICT suggests that there is inter-individual variability in the response to training; (4) Conclusions: HIIT led to better adaptation to the competition maybe because of the repeated exposure to higher oxygen consumption and eccentric loading exercise.

Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

Various pathologies (COVID-19 including) are associated with abnormalities in erythrocyte properties. Hypertension represents an unfavorable condition for erythrocyte quality and is the most prevalent risk factor in COVID-19 patients. ACE2 downregulation that is typical of these patients can further deteriorate cardiovascular health; however, its consequences on erythrocyte properties are not known yet. The aim was to investigate the effect of ACE2 inhibition and the potential beneficial effect of zofenopril on erythrocytes in spontaneously hypertensive rats. ACE2 inhibition induced by MLN-4760 (1 mg/kg/day for 2 weeks) led to deterioration of erythrocyte morphology and osmotic resistance, but plasma markers of oxidative stress, erythrocyte deformability, nitric oxide production and Na,K-ATPase activity were not significantly affected. Zofenopril administration (10 mg/kg/day, initiated after 4-day-lasting ACE2 inhibition) resulted in unexpected increase in angiotensin II plasma levels in both control and ACE-inhibited spontaneously hypertensive rats, but in normalization of osmotic resistance in ACE2-inhibited rats. The overall effect of zofenopril on erythrocyte qualities could be evaluated as beneficial.

Adverse Outcome in COVID-19 Is Associated With an Aggravating Hypo-Responsive Platelet Phenotype

Thromboembolic complications are frequently observed in Coronavirus disease 2019 (COVID-19). While COVID-19 is linked to platelet dysregulation, the association between disease outcome and platelet function is less clear. We prospectively monitored platelet activation and reactivity in 97 patients during the first week of hospitalization and determined plasma markers of platelet degranulation and inflammation. Adverse outcome in COVID-19 was associated with increased basal platelet activation and diminished platelet responses, which aggravated over time. Especially GPIIb/IIIa responses were abrogated, pointing toward impeded platelet aggregation. Moreover, platelet-leukocyte aggregate formation was diminished, pointing toward abrogated platelet-mediated immune responses in COVID-19. No general increase in plasma levels of platelet-derived granule components could be detected, arguing against platelet exhaustion. However, studies on platelets from healthy donors showed that plasma components in COVID-19 patients with unfavorable outcome were at least partly responsible for diminished platelet responses.Taken together this study shows that unfavorable outcome in COVID-19 is associated with a hypo-responsive platelet phenotype that aggravates with disease progression and may impact platelet-mediated immunoregulation.

Association between plasmatic oxidative stress and thrombosis in primary antiphospholipid syndrome

Antiphospholipid antibodies induce a pro-inflammatory and hypercoagulable state that lead to increased risk of thrombosis. Whether oxidative damage contributes thrombosis risk is a matter of debate. We evaluated the association between oxidative stress and thrombosis in primary antiphospholipid syndrome (t-PAPS). Plasma total antioxidant capacity and the levels of malondialdehyde (TBARs), carbonyl protein, and 8-isoprostane in plasma were determined in a group of patients with t-PAPS and in individuals without a history of thrombosis (controls) using commercial ELISA assays. The levels of these plasma markers of oxidative stress were compared between t-PAPS and controls using Mann–Whitney test. A total of 70 patients with t-PAPS and 74 controls were included. Overall, measurements of all plasma oxidative stress markers were similar between t-PAPS patients and controls. In a subgroup analysis, patients with t-PAPS and arterial thrombosis had a higher antioxidant capacity as compared to controls. Thrombotic PAPS was not associated with increased levels of oxidative stress markers, in comparison with individuals without thrombosis. Even though it is not possible to rule out that a mild oxidative damage, not detected by plasma markers, occurs in t-PAPS, our results suggest that measuring plasma oxidative stress markers has limited clinical relevance in t-PAPS.

Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.

Changing profile of platelet activity and turnover indices during treatment response of immune thrombocytopenia

Both platelet count and function change after treatment of immune thrombocytopenia (ITP). Platelet function can be measured by plasma markers, including platelet activity (e.g. soluble P-selectin [sP-selectin] and soluble CD40 ligand [sCD40L]) and platelet turnover markers (e.g. glycocalicin [GC]). Patients were classified into no response (NR, including new diagnosis), partial response (PR) and complete response (CR). One hundred and sixteen samples (29 CR, 32 PR, and 55 NR) from 79 patients were collected. Plasma markers (sP-selectin, sCD40L and GC) were measured by ELISA. Platelet counts and mean platelet volume (MPV) were obtained in the clinical laboratory using GenS System-2. The results showed that responsive patients (PR + CR) had higher levels of sP-selectin (P = 0.026) and sCD40L (P = 0.001). Although there was no difference in MPV (P = 0.077) or GC (P = 0.078), there was a marked decrease of GC index (P < 0.001) in responsive patients. Paired sample analysis showed no difference in sP-selectin, sCD40L, MPV or GC but significant difference in GC index (P = 0.017) between NR and PR. Another paired sample analysis showed no difference in sP-selectin, sCD40L, MPV or GC but significant difference in GC index (P = 0.029) between PR and CR. Patients with refractory and newly diagnosed disease had significant difference in GC (P = 0.020) and sCD40L (P = 0.001), despite similarly low platelet counts. In conclusion, platelet activity markers (sP-selectin and sCD40L) and GC indices change in parallel with treatment response. Plasma levels of GC and sCD40L may be predictors of treatment response.

DOES HEPARIN HAVE AN ESSENTIAL ROLE IN THE TREATMENT OF THE COVID-19 PANDEMIC? A REVIEW

Coronavirus 2019 (COVID-19), is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first reported in December 2019. The plasma markers of coagulation, like D-dimers and elevated prothrombin time (PT) are higher in patients with COVID-19. The administration of anticoagulant is beneficial in those patients. Heparins have many therapeutic functions that are important for the controlling of COVID-19-associated clinical manifestations like, neutralization of inflammatory mediators and neutralization of extracellular cytotoxic histones. Many observational studies in different countries have been done and large number of clinical trials have been designed and registered to evaluate efficacy and safety of heparin for patients with COVID-19. The aim of this narrative review is to summarize all available data from previously published studies concerning the use of heparin in treatment of the COVID-19 pandemic.