Background: Many patients who have been suffering by Covid-19 suffer of long-Covid syndrome, with symptoms of fatigue and muscular weakness that characterize post-acute sequelae SARS-CoV-2 infection (PASC). However, there is limited knowledge about the molecular pathophysiology, and about the serum profile of these patients.Methods: We studied the blood serum profile of 75 selected patients, with previous confirmed Covid-19, 2 months after hospital discharge, who reported new-onset fatigue, muscle weakness and/or dyspnea not present prior to the virus infection and independently from concomitant diseases and/or clinical conditions.Results: All patients had very high serum concentrations of ferritin and D-Dimer. 87 and 72% of patients had clinically significant low levels of hemoglobin and albumin, respectively. Seventy three percentage had elevations in erythrocyte sedimentation rate and CRP. Twenty seven percentage had elevations in LDH.Conclusions: The co-existence of patient symptoms along with blood markers of coagulation, protein disarrangement and inflammation suggests ongoing alterations in the metabolism, promoting an inflammatory/hypercatabolic state which maintains a vicious circles implicated in the persistence of PASC. The persistence of altered D-Dimer levels raises the possibility of long-term risks of thromboembolic disease. All these markers levels should be accurately evaluated in the long-term follow-up, with individualized consideration for prophylactic nutritional, anti-inflammatory and/or anticoagulant therapy if indicated.
The present study demonstrates that CHF, but not compensatory hypertrophy, is a specific stimulus for chronic HSP72 induction in the heart and liver. On the contrary, CHF does not affect HSP in lungs and peripheral muscles. HSP 72 induction represents an intracellular marker of stress reaction which can persist chronically.
The spleen is a lymphoid organ with multiple functions including blood filtration and immune activity.Aging changes the spleen's anatomy for both immune and stromal cells and can lead to immunesenescence, contributing to the increased rates of mortality and morbidity commonly observed in the elderly. Much evidence indicates that the combination of food quantity and quality can influence chronic inflammatory states in the spleen. Quantitative amino-acids (AA) adequacy is pivotal to maintain cell integrity in mammals. Aged mice feed with balanced essential-AA (EAA) formulation improved mitochondrial biogenesis and morphological and molecular changes in many organs, as well as increased lifespan. Here, we evaluated the inflammatory state of the spleen in aged male mice (fifteen months old) chronically fed for twelve months with a particular EAA-rich diet compared to a standard laboratory diet. This study found that chronic consumption of an EAA-rich diet decreased inflammation and modulated reticular and mitochondrial chaperones, mitochondrial function and cells survival, maintaining the correct architecture of the spleen. These changes could also be beneficial for immune system integrity, providing a possible theoretical-speculative basis for the role of EAA improving the quality of life of the elderly by probably slowing immune-senescence.
This research was a controlled open-label trial. Research protocol was approved by the Ethics Committee of Spedali Civili di Brescia, and performed in accordance with the Declaration of Helsinki. We selected non-smokers 15 males patients with mean age of 69±1.3 years with a controlled diet of 7949kJ (1900
CommentaryHuman and experimental data show that nutritional supplementation with a specific mixture of essential amino (EAA) improves both mitochondrial function and biogenesis and reduces either ROS formation or apoptotic drive in myocytes . Supplementation with EAA is also effective in humans when tested in patients with cardiac dysfunction . Doxorubicin (Doxo), an effective cancer chemotherapy agent, causes severe cardio-toxicity due to mitochondria damage, production of reactive oxygen species (ROS) and cell apoptosis with myofibrillar disarrangement, which in turn induces chronic heart failure. Pathogenesis of toxicity, as reported by Zhang et al.  is connected to the binding of Doxo to topoisomeraseIIb , which triggers a complex cascade of events, altering the DNA response and apoptosis pathways and triggering a marked alteration in the transcriptome, that selectively affects oxidative phosphorylation and mitochondrial biogenesis in cardiomyocytes. As a result, Doxoinduced cardiotoxicity limits optimal drug-dose use, reducing its potential therapeutic effects in cancer patients .Consequently, we hypothesized that supplementation with EAA would blunt Doxo cardio-toxicity, but we also tested if this would happen without interfering with the Doxo therapeutic effects on cancer cells. We used C57BL/6 mice fed on a normal diet and i.p. injected with a single saline or Doxo-HCl (15 mg/kg, from SigmaAldrich) injection to induce cardiomyopathy , with or without oral supplementation of EAA (1.5 g/kg). After 14 days, the heart was collected and morphologically evaluated by optical and electron microscopy. In addition, to test whether EAA supplementation negatively interferes with the Doxo anticancer action, we treated different cancer cell lines (3 × 10 5 cells/well in DMEM medium of HCT116 colon carcinoma; MCF7 mammary gland carcinoma; M14 melanoma), with Doxo (0.7 microg/ml) and with or without EAA (1% w/v). Untreated cancer cell lines (cultured in DMEM only) were used as controls. The osmolarity of the culture medium was the same for all groups. After 24 hours the cells were counted with the Trypan blue dye exclusion assay to distinguish live from dead cells.The in vivo experiments showed that Doxo significantly lowered body weight (22.59 ± 1.33 g vs 30.12 ± 1.4 g. p<0.05) and heart weight (0.12 ± 0.01 g vs 0.17 ± 0.01 g. p<0.05) compared to the control group. Furthermore, Doxo induced morphological alteration of cardiomyocytes with giant and irregularly shaped nuclei with condensed chromatin (Figure 1a A-C). In addition, Doxo impaired cellular distribution, morphology and the number of mitochondria (24 ± 2.8 vs 31.62 ± 5.5 Nmit/100µ2. p<0.05). Interestingly, EAA supplementation of Doxo-treated animals protected normal heart weight (0.16 ± 0.01 g vs 0.12 ± 0.01 g. p<0.05) and preserved cardiomyocytes architecture, mitochondrial morphology and number (28 ± 2.8 vs 24 ± 2.8 Nmit/100µ2. p<0.05) (Figure 1a The in vivo findings were partially surprising because previous studies had shown that EAA nu...
Malnutrition in patients with chronic heart failure (CHF) is not always as severe as muscle wasting in the same patients. Our data showed that 24% of patients with CHF had malnutrition (serum albumin < 3.5 g/dl) while 68% had muscle atrophy. This apparent discrepancy can be explained by considering the metabolic role of the striate muscle. The striate muscle maintains body metabolic performance by continuous exchange of fuel (amino acids) with other organs such as the liver. This happens when the subject is suffering from malnutrition or is starving, and it is regulated by the ratio of catabolic to anabolic molecules such as hormones or cytokines. Glucose is produced when amino acids are metabolized in the liver by gluconeogenesis. Malnutrition, muscle wasting and the frequent progression to cachexia can be reduced by the use of specific therapeutic agents such as cytokines and/or catabolic hormone antagonists. This is because cytokines and catabolic hormones, with consequent insulin resistance (IR), can cause muscle wasting. An alternative and/or complementary therapy may be exogenous supplementation with amino acids. Amino acids: are rapidly absorbed independent of pancreatic activity, reduce IR, induce production in the liver of anabolic molecules such as growth hormone and insulin-like growth factor, and modulate catabolic hormone-mediated effects on adipocytes. Research on the most suitable qualitative and quantitative amino acid composition for an alternative and/or complementary therapy is being undertaken in different research centres. Keywords Heart Failure · Cachexia · Malnutrition The problemMalnutrition, muscle wasting and cachexia are often present in patients with chronic heart failure (CHF) [1,2]. Malnutrition is caused by reduced caloric intake, i.e. intake of amino acids (AA), carbohydrates and lipids. Malnutrition can be estimated from the serum albumin concentration. A serum albumin level < 3.5 g/dl is an important marker of poor nutritional status, because it can predict morbidity and mortality during cardiovascular surgery  and in several pathological conditions such as stroke . However, it is interesting to note that malnutrition in patients with CHF is not always as severe as muscle wasting, and protein synthesis is often conserved. In a recent survey, skeletal muscle atrophy (documented by magnetic resonance spectroscopy) was found in 68% of patients studied, although up to 24% of patients had serum albumin levels < 3.5 g/dl .This apparent discrepancy can be explained by considering the metabolic role of the AA of striate muscles. Striate muscles comprise about 45% of the body weight of an average human adult. Taken together, they are the pivotal organ that maintains body metabolic performance Mediterr J Nutr Metab (2008) 1:95-98
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