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Long-Term Consequences of Adolescent Drug Use: Evidence from Pre-Clinical and Clinical Models

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455300 Year: Pages: 201 DOI: 10.3389/978-2-88945-530-0 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Medicine (General) --- Therapeutics --- Neurology --- Science (General)
Added to DOAB on : 2019-01-23 14:53:42
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Abstract

The purpose of this collection is to provide a forum to integrate pre-clinical and clinical investigations regarding the long-term consequences of adolescent exposure to drugs of abuse. Adolescence is characterized by numerous behavioral and biological changes, including substantial neurodevelopment. Behaviorally, adolescents are more likely to engage in risky activities and make impulsive decisions. As such, the majority of substance use begins in adolescence, and an earlier age of onset of use (<15 yr) is strongly associated with the risk for developing a substance use disorder later in life. Furthermore, adolescent drug use may negatively impact ongoing neurological development, which could lead to long-term cognitive and emotional deficits. A large number of clinical studies have investigated both the acute and long-term effects of adolescent drug use on functional outcomes. However, the clinical literature contains many conflicting findings, and is often hampered by the inability to know if functional differences existed prior to drug use. Moreover, in human populations it is often very difficult to control for the numerous types of drugs, doses, and combinations used, not to mention the many other environmental factors that may influence adult behavior. Therefore, an increase in the number of carefully controlled studies using relevant animal models has the potential to clarify which adolescent experiences, particularly what drugs used when, have long-term negative consequences. Despite the advantages of animal model systems in clarifying these issues, the majority of pre-clinical addiction research over the past 50+ years has been conducted in adult animals. Moreover, few addiction-related studies have investigated the long-term neurocognitive consequences of drug exposure at any age. In the past 10 years of so, however, the field of adolescent drug abuse research has burgeoned. To date, the majority of this research has focused on adolescent alcohol exposure using a variety of animal models. The results have given the field important insight into why adolescents are more likely to drink alcohol to excess relative to adults, and the danger of adolescent alcohol use (e.g., in leading to a persistence of excessive drinking in adulthood). More recently, research regarding the effects of adolescent exposure to other drugs of abuse, including nicotine, cocaine, and cannabinoids has expanded. Therefore, we are at unique point in time, when emerging results from carefully controlled pre-clinical studies can inform the sometimes confusing clinical literature. In addition, we expect an influx of prospective clinical studies in response to a cross-institute initiative at NIH, known as the ABCD grant. Several institutes are enrolling children prior to adolescence (and the initiation of drug use), in order to control for pre-existing neurobiological and neurobehavioral differences and to monitor the age of initiation and amount of drug used more carefully than is possible using retrospective designs.

Monitoring endogenous GPCRs: lessons for drug design

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196517 Year: Pages: 134 DOI: 10.3389/978-2-88919-651-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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G protein-coupled receptors (GPCRs) are integral membrane proteins forming the fourth largest superfamily in the human genome. Many of these receptors play key physiological roles and several pathologies have been associated with receptor functional abnormalities. GPCRs therefore represent important goals for drug design in pharmaceutical companies since they constitute the target of about one third of the drugs currently on the market. However, endogenous GPCRs are most often difficult to study because of a lack of tools to target them specifically and single out their response to physiological or drug-elicited stimulations. Hence, studies mostly focused on recombinant receptors expressed in a variety of cellular models that do not always closely reflect the receptor natural environment and often deal with levels of expression exceeding by far physiological ranges. Recent technological developments combining for example genetically modified animals and advanced imaging approaches have improved our ability to visualize endogenous GPCRs. To date, trailing receptor activation, subsequent intracellular redistribution, changes in signaling cascade up to integrated response to a drug-elicited stimulation is at hand though the impact of a physiological challenge on receptor dynamics remains a major issue. Data however suggest that the receptor may embrace a different fate depending on the type of stimulation in particular if sustained or repeated. This suggests that current drugs may only partially mimic the genuine response of the receptor and may explain, at least in part, their secondary effects. Commonalities and specificities between physiological and drug-induced activation can thus represent valuable guidelines for the design of future drugs.

Plant Natural Products for Human Health

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ISBN: 9783038977124 Year: Pages: 514 DOI: 10.3390/books978-3-03897-713-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics --- Medicine (General)
Added to DOAB on : 2019-04-05 10:34:31
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Plants have served mankind as an important source of foods and medicines. While we all consume plants and their products for nutritional support, a majority of the world population also rely on botanical remedies to meet their health needs, either as their own “traditional medicine” or as “complementary and alternative medicine”. From a pharmaceutical point of view, many compounds obtained from plant sources have long been known to possess bio/pharmacological activities, and historically, plants have yielded many important drugs for human use, from morphine discovered in the early nineteenth century to the more recent paclitaxel and artemisinin. Today, we are witnessing a global resurgence in interest and use of plant-based therapies and botanical products, and natural products remain an important and viable source of lead compounds in many drug discovery programs.This Special Issue on “Plant Natural Products for Human Health” compiles a series of scientific reports to demonstrate the medicinal potentials of plant natural products. It covers a range of disease targets, such as diabetes, inflammation, cancer, neurological disease, cardiovascular disease, liver damage, bacterial, and fungus infection and malarial. These papers provide important insights into the current state of research on drug discovery and new techniques. It is hoped that this Special Issue will serve as a timely reference for researchers and scholars who are interested in the discovery of potentially useful molecules from plant sources for health-related applications.

Keywords

heat-process --- onion --- calorie restriction --- Amadori rearrangement compounds --- hyperglycemia --- A549 cells --- hinokitiol --- MMPs --- p53/Bax --- antioxidant enzymes --- caspases --- migration --- cannabinoid type 1 receptor --- endoplasmic reticulum stress --- gluconeogenesis --- gomisin N --- lipogenesis --- insulin resistance --- garlic --- ischemia --- heme oxygenase --- reperfusion --- heart --- Keap1 --- Nrf2 --- Neuroprotective --- PC12 cells --- PhGs --- anti-malaria activity --- plants --- natural products --- ethnopharmacology --- Plasmodium parasites --- copaiba --- oleoresin --- essential oil --- sesquiterpenoids --- diterpenoids --- biological activity --- molecular targets --- Astragali Radix --- astragaloside IV --- genistein --- mitochondrial bioenergetics --- oxygen consumption rate --- natural products --- drug design and development --- innovation --- automation --- computational softwares --- bioinformatics --- precision medicine --- omics --- global health --- sweet orange --- bitter orange --- neroli --- orange petitgrain --- mandarin --- lemon --- lime --- grapefruit --- bergamot --- yuzu --- kumquat --- cannabigerol --- Cannabis sativa --- neuroinflammation --- oxidative stress --- phytocannabinoid --- iridoids --- nuclear factor-kappaB --- mitogen-activated protein kinase --- anti-inflammation --- Ziziphus jujuba --- triterpenic acids --- pharmacokinetic study --- acute liver injury --- A? --- AD --- lychee seed --- neuroinflammation --- catechin --- procyanidin A2 --- apoptosis --- cinnamamides --- antistaphylococcal activity --- time-kill assay --- biofilm --- antitubercular activity --- MTT assay --- antifungal activity --- PET inhibition --- toxicity --- structure–activity relationship --- bleeding time --- flavonoid --- morin hydrate --- OH· free radical --- platelet activation --- protein kinase --- thromboembolism --- Glycyrrhiza uralensis --- prenylated flavonoids --- antiproliferation --- differentiation --- melanoma cell --- adjuvant-induced arthritis --- arthritis --- celastrol --- curcumin --- dietary supplements --- EGCG --- green tea --- inflammation --- liposomes --- microbiome --- nanoparticles --- natural products --- resveratrol --- rheumatoid arthritis --- targeted delivery --- traditional medicine --- Tripterygium wilfordii --- triptolide --- Penthorum chinense Pursh --- NAFLD --- hepatic steatosis --- flavonoids --- SIRT1 --- AMPK --- dihydromyricetin --- myocardial hypertrophy --- oxidative stress --- sirtuin 3 --- ginseng --- human-hair-follicle dermal papilla cells --- WNT/?-catenin --- Shh/Gli --- TGF-? --- BMP/Smad --- mouse-hair growth --- Panax notoginseng saponins --- aspirin --- HepaRG cells --- herb–drug interactions --- P. eryngii --- glucans --- inflammation --- inflammatory bowel disease --- medicinal plants --- phytochemicals --- scoulerine --- bergapten --- immunomodulator --- adjuvant --- cytoxicity --- dendritic cells --- immune modulation --- APAP --- acetaminophen --- hepatotoxicity --- hpatoprotection --- paracetamol --- animals --- preclinical studies --- natural products --- small molecules --- phytochemicals --- plants --- fucoidan --- acetaminophen --- Nrf2 --- oxidative stress --- hepatotoxicity --- plant natural product --- drug discovery --- human health

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