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    • Identification of the drug to be used as first

    2019-11-04

    Identification of the drug to be used as first-step antihypertensive treatment has always been, and remains, a matter of debate. The decision wihich drug (or drug combination) to choose as first-line therapy depend on many variables such as coexisting metabolic disorders, obesity, presence of subclinical organ damage and cardiovascular disease [28]. The general criteria on wihich to Sotrastaurin a rational selection of a given drug can be summarized as follows. First, in a patient with a history of anti-hypertensive treatment previous favorable or unfavorable effects in terms of efficacy and tolerability of a given drug class should be taken into account. A second important issue refers to the effect of drugs on cardiovascular risk factors in relation to the cardiovascular risk profile of the individual patient. Third, the presence of subclinical organ damage, renal disease, cerebrovascular disease or diabetes should direct the doctor to the choice of drugs which have been reported to be more effective than others in these specific conditions. Fourth, particular attention should be paid to the presence of coexisting non cardiovascular diseases, because their treatment may interfere with anti-hypertensive drugs. Finally, it should be noted that the cost of drugs may represent an important variable that could compromise therapeutic compliance of the patients.
    Perspectives on new guidelines Cardiovascular prevention in the hypertensive setting needs to be greatly improved through tight control of BP with appropriate lifestyle measures and anti-hypertensive therapy. To achieve this ambitious but feasible goal, many topics of uncertainty need to be investigated and resolved with reliable scientific evidence. Some issues that need answers are briefly summarized from these questions: 1) what are the optimal office and out-office systolic and diastolic BP values to reach by treatment? this topic is particularly relevant in the light of the findings of some recent trials [55], [56]; 2) should elderly subjects with a systolic BP between 140 and 160 mmHg be given BP lowering drugs? 3) should drug treatment be given to subjects with pre-hypertension and WCH? and if so, in which patients? Results from many recent clinical trials and analyses–most notably from the Systolic Blood Pressure Intervention Trial (SPRINT) [55] are expected to form the basis of these new guidelines, which should address, as mentioned above, new hypertension treatment goals and new approaches to the treatment of the elderly, among other recommendations. It is hard to point out in this regard that the SPRINT Research Group randomly assigned 9361 persons with a systolic BP of 130mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic BP target of less than 120mm Hg (intensive treatment) or a target of less than 140mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, ordeath from cardiovascular causes. What will impact the results of the Sprint study in defining optimal BP targets by the new guidelines is still unclear. This is because 1) noteworthy patient populations were excluded from the trial (including those under the age of 50 years, those with diabetes, and those who had previously had a stroke); 2) major correction factors need to be applied to the unattended automatic office BP values to make them confrontable with those measured in all other randomized trials upon which guidelines have based their target BP recommendations [57].
    Introduction Amyotrophic lateral sclerosis (ALS), the most common and severe form of motor neuron diseases (MNDs), causes progressive muscle weakness and leads to death within several years. Vast amounts of findings concerning ALS have been reported, but the key mechanisms responsible for the disease are still not fully understood, hampering treatment. Consequently, the only FDA-approved drug, riluzole, was reported to prolong patient lifespan by just a few months. The establishment of induced pluripotent stem cells (iPSCs) offers a new approach to the study of MNDs and the discovery of new drugs.2, 3 In 2008, the first ALS patient iPSC-derived motor neurons (MNs) were generated. Since then, many ALS iPSC studies have been reported,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and this technology is leading to new findings and therapeutic candidates for ALS.