Current pharmaceutical design
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Review
New tuberculostatic agents targeting nucleic acid biosynthesis: drug design using QSAR approaches.
Worldwide, tuberculosis (TB) is the leading cause of death among curable infectious diseases. The emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB is a growing global health concern and there is an urgent need for new anti-TB drugs. Enzymes involved in DNA and ATP biosynthesis are potential targets for tuberculostatic drug design, since these enzymes are essential for Mycobacterium tuberculosis growth. This review presents the current progress and applications of structure-activity relationship analysis for the discovery of innovative tuberculostatic agents as inhibitors of ribonucleotide reductase, DNA gyrase, ATP synthase, and thymidylate kinase enzymes, highlighting present challenges and new opportunities in TB drug design.
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General anesthesia-induced pharmacological protection of the central nervous system following injury has been under intense investigations during the past four decades. Indeed, if general anesthetics could provide therapeutic benefit in the event of hypoxia, ischemia or any other kinds of brain lesions, that would be of tremendous clinical importance. The potential for anesthesia-related brain protection, however, has been seriously challenged during the past 10 years. ⋯ The biological rational for anesthesia neurotoxicity will then be explored together with existing experimental and clinical evidence in favor of this possibility. Finally, insights into the increasing number of both experimental and clinical data suggesting that general anesthetics, especially ketamine, support the therapeutic value of these drugs in major depressive disorders. When taken together, these seemingly contradictory observations suggest the intriguing possibility that general anesthetics could stand as valuable context-dependent modulators of neural plasticity.
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P2Y12 inhibitors constitute an essential part of the antithrombotic treatment, with proven clinical benefit in acute coronary syndromes and after percutaneous coronary interventions. Substantial evidence has emerged that, apart from their primary antiplatelet action, P2Y12 receptor inhibitors exhibit several off-target effects. In this review, we present the supporting evidence of P2Y12 inhibitors' pleiotropic actions, discuss their clinical implications and underscore the necessity for further research on this issue.
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Aging is associated with arterial stiffening and subsequent acceleration of pulse wave movement. Traditional cardiovascular risk factors such as hypertension and dyslipidemia are associated with increased arterial stiffness, a 'premature' arterial aging. Antihypertensive drugs exhibit beneficial effects on arterial stiffness, both at the central and peripheral level, and these effects are mainly attributed to blood pressure reduction per se. ⋯ The effects of statins on arterial stiffness are not yet well established. Moreover, the effects of combining statins with antihypertensive drugs or other strategies to attenuate arterial aging are not adequately studied. The aim of the current review is to present the effects of available therapeutic strategies on arterial stiffness with special emphasis on hypolipidemic and antihypertensive drugs, critically evaluate available information and provide future perspectives in this field.
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Sexual addiction, which is also known as hypersexual disorder, has largely been ignored by psychiatrists, even though the condition causes serious psychosocial problems for many people. A lack of empirical evidence on sexual addiction is the result of the disease's complete absence from versions of the Diagnostic and Statistical Manual of Mental Disorders. However, people who were categorized as having a compulsive, impulsive, addictive sexual disorder or a hypersexual disorder reported having obsessive thoughts and behaviors as well as sexual fantasies. ⋯ As with other behavioral addictions, the appropriate treatment of sexual addiction should combine pharmacological and psychological approaches. Psychiatric and somatic comorbidities that frequently occur with sexual addiction should be integrated into the therapeutic process. Group-based treatments should also be attempted.