This book succeeds Review of Medical Pharmacology , by Meyers, Jawetz, and Goldfien. Edited by B. G. Katzung, some of the important areas covered include drug receptors and pharmacodynamics, pharmacokinetics of absorption and biotransformation of drugs, autonomic pharmacology of cholinergic and adrenergic receptor stimulants and antagonists, antihypertensive agents, cardiac glycosides and other agents used in the treatment of congestive heart failure, therapeutic drugs for cardiac arrhythmias, diuretics, pharmacology of the CNS drugs such as anticonvulsants and anesthetics, antidepressants, narcotic analgesics, nonsteroidal anti-inflammatory agents, endocrine pharmacology, antimicrobial and antimycobacterial drugs, antiprotozoal and antihelmintic drugs, cancer chemotherapy, and drugs and the immune system. Written by several prominent researchers and scientists, each chapter begins with a section on the basic pharmacology, chemistry, pharmacokinetics, and pharmacodynamics of the agents under discussion. This is followed by a section on clinical pharmacology, which deals with relevant information regarding the clinical use of drugs on the various

Basic and Clinical Pharmacology

COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.202001807

Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.

N-acetylcysteine (NAC), a plant antioxidant naturally found in onion, is a precursor to glutathione. It has been used as a drug since the 1960s and is listed on the World Health Organization (WHO) Model List of Essential Medicines as an antidote in poisonings. There are numerous other uses or proposed uses in medicine that are still in preclinical and clinical investigations. NAC is also used in food supplements and cosmetics. Despite its abundant use, there are projections that the NAC global market will grow in the next five years; therefore, the purpose of this work is to provide a balanced view of further uses of NAC as a dietary supplement. Although NAC is considered a safe substance, the results among clinical trials are sometimes controversial or incomplete, like for many other antioxidants. More clinical trials are underway that will improve our understanding of NAC applicability.

/pdf/medical-and-dietary-uses-of-n-acetylcysteine-4zjgf3odgj.pdf

Medical and Dietary Uses of N-Acetylcysteine.

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

https://www.mdpi.com/2076-3921/10/6/967/pdf

N-Acetylcysteine (NAC): Impacts on Human Health

Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress of several neurodegenerative disorders. This review intends to summarize some of the findings that correlate the overproduction of reactive oxygen species with the pathophysiology of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Oxidative stress was also noted to modify the inflammatory response. Even though oxidative stress and neuroinflammation are two totally different pathological events, they are linked and affect one another. Nonetheless, there are still several mechanisms that need to be understood regarding the onset and the progress of neurodegenerative diseases in order to develop efficient therapies. As antioxidants are a means to alter oxidative stress and slow down the symptoms of these neurodegenerative diseases, the most common antioxidants, enzymatic as well as non-enzymatic, have been mentioned in this paper as therapeutic options for the discussed disorders.

/pdf/an-overview-of-oxidative-stress-neuroinflammation-and-e7744kdm.pdf

An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases

N-acetylcysteine (NAC), which is an acetylated cysteine compound, has aroused scientific interest for decades due to its important medical applications. It also represents a nutritional supplement in the human diet. NAC is a glutathione precursor and shows antioxidant and anti-inflammatory activities. In addition to the uses quoted in the literature, NAC may be considered helpful in therapies to counteract neurodegenerative and mental health diseases. Furthermore, this compound has been evaluated for its neuroprotective potential in the prevention of cognitive aging dementia. NAC is inexpensive, commercially available and no relevant side effects were observed after its administration. The purpose of this paper is to give an overview on the effects and applications of NAC in Parkinson’s and Alzheimer’s disorders and in neuropathic pain and stroke.

https://www.mdpi.com/1420-3049/23/12/3305/pdf

Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases.

Migraine is a disorder affecting an increasing number of subjects. Currently, this disorder is not entirely understood, and limited therapeutic solutions are available. Migraine manifests as a debilitating headache associated with an altered sensory perception that may compromise the quality of life. Animal models have been developed using chemical, physical or genetic modifications, to evoke migraine-like hallmarks for the identification of novel molecules for the treatment of migraine. In this context, experimental models based on the use of chemicals as nitroglycerin or inflammatory soup were extensively used to mimic the acute state and the chronicity of the disorder. This manuscript is aimed to provide an overview of murine models used to investigate migraine pathophysiology. Pharmacological targets as 5-HT and calcitonin gene-related peptide (CGRP) receptors were evaluated for their relevance in the development of migraine therapeutics. Drug delivery systems using nanoparticles may be helpful for the enhancement of the brain targeting and bioavailability of anti-migraine drugs as triptans. In conclusion, the progresses in migraine management have been reached with the development of emerging agonists of 5-HT receptors and novel antagonists of CGRP receptors. The nanoformulations may represent a future perspective in which already known anti-migraine drugs showed to better exert their therapeutic effects.

https://www.mdpi.com/1422-0067/20/12/2932/pdf

Migraine: Experimental Models and Novel Therapeutic Approaches.

Patients with Autism Spectrum Disorder (ASD) need to be provided with behavioral, psychological, educational, or skill-building interventions as early as possible. Cognitive Behavior Therapy has proven useful to manage such problems. There is also growing evidence on the usefulness of Virtual Reality Therapy (VRT) in treating various functional deficits in ASD. This exploratory study is aimed at assessing the changes in cognitive functions in children with ASD, and the putative subtending neurophysiological mechanisms, following the provision of rehab training using an innovative VRT system. Twenty patients with ASD, aged 6–15 years, were provided with 24 sessions of VRT by using the pediatric module of the BTS NIRVANA System. Neuropsychological and EEG evaluations were carried out before and at the end of the training. After VRT, all patients showed a significant improvement in their cognitive-behavioral problems concerning attention processes, visuospatial cognition, and anxiety. These findings were paralleled by an evident reshape of frontoparietal connectivity in the alpha and theta frequency range. Our study suggests that VRT could be a useful and promising tool to improve ASD neurorehabilitation outcomes. This improvement is likely to occur through changes in frontoparietal network connectivity following VRT.

Improvement of brain functional connectivity in autism spectrum disorder: an exploratory study on the potential use of virtual reality

Moringin [4-(α-L-rhamnosyloxy) benzyl isothiocyanate] is an isothiocyanate extracted from Moringa oleifera seeds. It is an antioxidant known for several biological properties useful in the treatment of neurodegenerative diseases. Several neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases are linked to dysfunctional mitochondria due to the resulting increase of Reactive Oxygen Species (ROS). Stem cell-based therapeutic treatments in neurodegenerative diseases provide an alternative strategy aimed to replace the impaired tissue. In this study were investigated the deregulated genes involved in mitophagy in the human periodontal ligament stem cells pretreated with moringin. The RNA-seq study reveals the downregulation of PINK1, with a fold change (FC) of −0.56, such as the genes involved in the phagophore formation (MAP1LC3B FC: −0.73, GABARAP FC: −0.52, GABARAPL1 FC: −0.70, GABARAPL2 FC: −0.39). The moringin pretreatment downregulates the pro−apoptotic gene BAX (−0.66) and upregulates the anti-apoptotic genes BCL2L12 (FC: 1.35) and MCL1 (FC: 0.36). The downregulation of the most of the caspases (CASP1 FC: −1.43, CASP4 FC: −0.18, CASP6 FC: −1.34, CASP7 FC: −0.46, CASP8 FC: −0.65) implies the inactivation of the apoptotic process. Our results suggest that mitochondrial dysfunctions induced by oxidative stress can be inhibited by moringin pretreatment in human periodontal ligament stem cells (hPDLSCs).

Moringin Pretreatment Inhibits the Expression of Genes Involved in Mitophagy in the Stem Cell of the Human Periodontal Ligament.

The Sicilian black pig (SB) (Nero Siciliano), also known as the Nero dei Nebrodi, Nero delle Madonie, or Nero dell'Etna pig ecotype, is an autochthonous Italian breed. The origins of this breed date back to Greek and Carthaginian dominations. In ancient times, its breeding was fairly common throughout Sicily, registering only a temporary reduction during the Arab domination. This breed is known primarily for its distinctive black coat, although some individuals display wattles and a partially or wholly white face. The SB pig has a birth rate with an average per sow of 7.6 piglets, each of 1.4 kg live body weight, showing an average daily gain (ADG) of 346 g/day during the fattening period. Slaughter generally takes place at an average age of 390 days, with an average live weight of 95 kg. This breed also appears to withstand adverse climatic conditions and resist disease. The purpose of this manuscript is to offer a general overview regarding the Sicilian Black pig and to consider the recent findings related to genome investigation. The recent application of Next Generation Sequencing (NGS) technologies in the study of the genome of autochthonous breeds showed that polymorphisms of some candidate genes for production performance and phenotypic traits represent important information for selection processes. The protection of autochthonous breeds, intended as sources of genomic diversity for the further improvements of pigs for commercial use, constitutes a valuable opportunity to create new sustainable pig chains.

Giuseppe Tardiolo

Papers

Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases.

Migraine: Experimental Models and Novel Therapeutic Approaches.

Improvement of brain functional connectivity in autism spectrum disorder: an exploratory study on the potential use of virtual reality

Moringin Pretreatment Inhibits the Expression of Genes Involved in Mitophagy in the Stem Cell of the Human Periodontal Ligament.

Sicilian Black Pig: An Overview