| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T542 |
0-4 |
Sentence |
denotes |
8.4. |
| T543 |
5-33 |
Sentence |
denotes |
Safety and Efficacy Concerns |
| T544 |
34-418 |
Sentence |
denotes |
Unfortunately, diseases of different aetiologies may present similar final dysfunction/alterations (e.g., cardiac dysfunction/lung alterations/thrombosis are induced by excessive activation of either AT1R or MasR/AT2R pathways, see Figure 1), while diseases with same aetiologies may present different final dysfunction/alterations depending on patients (COVID-19 is a clear example). |
| T545 |
419-631 |
Sentence |
denotes |
This confounding aspect of diseases can lead to erroneous interpretations, and only defining the correct and early molecular origin of diseases is possible to reach a successful outcome if a therapy is available. |
| T546 |
632-824 |
Sentence |
denotes |
In order to decide who to treat, and when to start treatment, it is important to define the entity of dysfunctions, probability of treatment success and probability to develop adverse effects. |
| T547 |
825-938 |
Sentence |
denotes |
To promptly intervene in order to prevent severe forms of COVID-19, we need early markers of disease progression. |
| T548 |
939-1335 |
Sentence |
denotes |
To this regard, if plasma (free) Zn2+ (or total zinc/albumin molar ratio), albumin, IL-10, Ang (1–9), Ang (1–7), Ang (1–5) and/or bradykinin (1–7) will be proven to be reliable surrogate markers for ACE and/or ACE2 enzymatic activity in vivo, they could be exploited, together with circulating ACE and ACE2 activity evaluation, in order to decide who and when to start treating COVID-19 patients. |
| T549 |
1336-1434 |
Sentence |
denotes |
Alternatively, eosinopaenia and hypotension may be also exploited as signs of disease progression. |
| T550 |
1435-1861 |
Sentence |
denotes |
In any case, since the conditions of some patients can be critical, it is highly recommended to administer the minimal effective dose in order to reduce possible side effects, starting with low and increasing doses, while at the same time monitoring patient status and early signs of disease progression (e.g., blood pressure, eosinophil counts, molecular concentrations of the RAS peptides and other markers of inflammation). |
| T551 |
1862-2262 |
Sentence |
denotes |
The aim of the project was not necessarily to stop viral entry (the epithelial cells take already care of it shedding ACE2) but to block positive feedback loops that follow the cellular response to SARS-CoV-2 infection, which are likely the main cause of the severe symptoms associated with COVID-19, doing so, the disease might hopefully become like a simple flu, a spontaneously eradicable disease. |
| T552 |
2263-2393 |
Sentence |
denotes |
At the moment, I am alone in proposing these new and non-conventional therapeutic approaches that may or may not work on COVID-19. |
| T553 |
2394-2579 |
Sentence |
denotes |
In doing so, I have not only described a rationale/strategy to counter COVID-19, but also provided practical information to optimize the RAS inhibitors based on known experimental data. |
| T554 |
2580-2769 |
Sentence |
denotes |
Before any in vivo drug administration (e.g., ACE2 inhibitor), it has to be checked the biological activity (e.g., ACE2) that is affected by the drug, considering the possible side effects. |
| T555 |
2770-2948 |
Sentence |
denotes |
However, this is not always the case and, in some cases, patients are treated without a careful evaluation of the biological parameter that is modulated by the administered drug. |
| T556 |
2949-3161 |
Sentence |
denotes |
In this regard, I have tried to address all aspects of the RAS inhibition in detail because my main concern is that the use of these approaches in a wrong way may lead to a failure or even to deleterious effects. |
| T557 |
3162-3405 |
Sentence |
denotes |
That is why I have meticulously described all the steps before possible administration and provided the guideline suggestions and specific recommendations in order to increase the probability of success and to minimize the deleterious effects. |
| T558 |
3406-3506 |
Sentence |
denotes |
The readers are, however, expected and encouraged to debate and make their own optimized guidelines. |
