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The American Journal of Clinical... Dec 2004Vitamin D3 is a prohormone produced in skin through ultraviolet irradiation of 7-dehydrocholesterol. It is biologically inert and must be metabolized to... (Review)
Review
Vitamin D3 is a prohormone produced in skin through ultraviolet irradiation of 7-dehydrocholesterol. It is biologically inert and must be metabolized to 25-hydroxyvitamin D3 in the liver and then to 1alpha,25-dihydroxyvitamin D3 in the kidney before function. The hormonal form of vitamin D3, ie, 1alpha,25-dihydroxyvitamin D3, acts through a nuclear receptor to carry out its many functions, including calcium absorption, phosphate absorption in the intestine, calcium mobilization in bone, and calcium reabsorption in the kidney. It also has several noncalcemic functions in the body. This overview provides a brief description of the physiologic, endocrinologic, and molecular biologic characteristics of vitamin D. It also provides information on new selective analogs of 1alpha,25-dihydroyvitamin D3 for therapy.
Topics: Bone and Bones; Calcitriol; Calcium; Cholecalciferol; Humans; Intestinal Absorption; Kidney; Phosphates; Vitamin D; Vitamin D Deficiency
PubMed: 15585789
DOI: 10.1093/ajcn/80.6.1689S -
Nature Protocols Dec 2018In vitro models of the blood-brain barrier (BBB) are critical tools for the study of BBB transport and the development of drugs that can reach the CNS. Brain endothelial...
In vitro models of the blood-brain barrier (BBB) are critical tools for the study of BBB transport and the development of drugs that can reach the CNS. Brain endothelial cells grown in culture are often used to model the BBB; however, it is challenging to maintain reproducible BBB properties and function. 'BBB organoids' are obtained following coculture of endothelial cells, pericytes and astrocytes under low-adhesion conditions. These organoids reproduce many features of the BBB, including the expression of tight junctions, molecular transporters and drug efflux pumps, and hence can be used to model drug transport across the BBB. This protocol provides a comprehensive description of the techniques required to culture and maintain BBB organoids. We also describe two separate detection approaches that can be used to analyze drug penetration into the organoids: confocal fluorescence microscopy and mass spectrometry imaging. Using our protocol, BBB organoids can be established within 2-3 d. An additional day is required to analyze drug permeability. The BBB organoid platform represents an accurate, versatile and cost-effective in vitro tool. It can easily be scaled to a high-throughput format, offering a tool for BBB modeling that could accelerate therapeutic discovery for the treatment of various neuropathologies.
Topics: Astrocytes; Biological Transport; Blood-Brain Barrier; Cell Line; Coculture Techniques; Endothelial Cells; Humans; Microscopy, Confocal; Microscopy, Fluorescence; Optical Imaging; Organoids; Pericytes; Permeability; Pharmaceutical Preparations; Pharmacokinetics; Small Molecule Libraries; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 30382243
DOI: 10.1038/s41596-018-0066-x -
The AAPS Journal Jul 2014Immunogenicity is a significant concern for biologic drugs as it can affect both safety and efficacy. To date, the descriptions of product immunogenicity have varied not...
Immunogenicity is a significant concern for biologic drugs as it can affect both safety and efficacy. To date, the descriptions of product immunogenicity have varied not only due to different degrees of understanding of product immunogenicity at the time of licensing but also due to an evolving lexicon that has generated some confusion in the field. In recent years, there has been growing consensus regarding the data needed to assess product immunogenicity. Harmonization of the strategy for the elucidation of product immunogenicity by drug developers, as well as the use of defined common terminology, can benefit medical practitioners, health regulatory agencies, and ultimately the patients. Clearly, understanding the incidence, kinetics and magnitude of anti-drug antibody (ADA), its neutralizing ability, cross-reactivity with endogenous molecules or other marketed biologic drugs, and related clinical impact may enhance clinical management of patients treated with biologic drugs. To that end, the authors present terms and definitions for describing and analyzing clinical immunogenicity data and suggest approaches to data presentation, emphasizing associations of ADA development with pharmacokinetics, efficacy, and safety that are necessary to assess the clinical relevance of immunogenicity.
Topics: Antibody Formation; Guidelines as Topic; Humans; Peptides; Proteins; Terminology as Topic
PubMed: 24764037
DOI: 10.1208/s12248-014-9599-2 -
Journal of Pharmacokinetics and... Dec 2010Malcolm Rowland has greatly facilitated an understanding of drug structure-pharmacokinetic relationships using a physiological perspective. His view points, covering a... (Review)
Review
Malcolm Rowland has greatly facilitated an understanding of drug structure-pharmacokinetic relationships using a physiological perspective. His view points, covering a wide range of activities, have impacted on my own work and on my appreciation and understanding of our science. This overview summarises some of our parallel activities, beginning with Malcolm's work on the pH control of amphetamine excretion, his work on the disposition of aspirin and on the application of clearance concepts in describing the disposition of lidocaine. Malcolm also spent a considerable amount of time developing principles that define solute structure and transport/pharmacokinetic relationships using in situ organ studies, which he then extended to involve the whole body. Together, we developed a physiological approach to studying hepatic clearance, introducing the convection-dispersion model in which there was a spread in blood transit times through the liver accompanied by permeation into hepatocytes and removal by metabolism or excretion into the bile. With a range of colleagues, we then further developed the model and applied it to various organs in the body. One of Malcolm's special interests was in being able to apply this knowledge, together with an understanding of physiological differences in scaling up pharmacokinetics from animals to man. The description of his many other activities, such as the development of clearance concepts, application of pharmacokinetics to the clinical situation and using pharmacokinetics to develop new compounds and delivery systems, has been left to others.
Topics: Absorption; Animals; Biological Transport; Humans; Liver; Metabolic Clearance Rate; Permeability; Pharmaceutical Preparations; Pharmacokinetics; Pharmacology, Clinical; Technology Transfer; Tissue Distribution
PubMed: 21107662
DOI: 10.1007/s10928-010-9174-0 -
Current Osteoporosis Reports Apr 2021Voltage-sensitive calcium channels (VSCCs) are ubiquitous multimeric protein complexes that are necessary for the regulation of numerous physiological processes. VSCCs... (Review)
Review
Voltage-sensitive calcium channels (VSCCs) are ubiquitous multimeric protein complexes that are necessary for the regulation of numerous physiological processes. VSCCs regulate calcium influx and various intracellular processes including muscle contraction, neurotransmission, hormone secretion, and gene transcription, with function specificity defined by the channel's subunits and tissue location. The functions of VSCCs in bone are often overlooked since bone is not considered an electrically excitable tissue. However, skeletal homeostasis and adaptation relies heavily on VSCCs. Inhibition or deletion of VSCCs decreases osteogenesis, impairs skeletal structure, and impedes anabolic responses to mechanical loading. RECENT FINDINGS: While the functions of VSCCs in osteoclasts are less clear, VSCCs have distinct but complementary functions in osteoblasts and osteocytes. PURPOSE OF REVIEW: This review details the structure, function, and nomenclature of VSCCs, followed by a comprehensive description of the known functions of VSCCs in bone cells and their regulation of bone development, bone formation, and mechanotransduction.
Topics: Animals; Bone and Bones; Calcium Channels; Humans; Tissue Distribution
PubMed: 33721180
DOI: 10.1007/s11914-020-00647-7 -
Experimental Dermatology Sep 2022The analytical technology of Raman spectroscopy has an almost 100-year history. During this period, many modifications and developments happened in the method like... (Review)
Review
The analytical technology of Raman spectroscopy has an almost 100-year history. During this period, many modifications and developments happened in the method like discovery of laser, improvements in optical elements and sensitivity of spectrometer and also more advanced light detection systems. Many types of the innovative techniques appeared (e.g. Transmittance Raman spectroscopy, Coherent Raman Scattering microscopy, Surface-Enhanced Raman scattering and Confocal Raman spectroscopy/microscopy). This review article gives a short description about these different Raman techniques and their possible applications. Then, a short statistical part is coming about the appearance of Raman spectroscopy in the scientific literature from the beginnings to these days. The third part of the paper shows the main application options of the technique (especially confocal Raman spectroscopy) in skin research, including skin composition analysis, drug penetration monitoring and analysis, diagnostic utilizations in dermatology and cosmeto-scientific applications. At the end, the possible role of artificial intelligence in Raman data analysis and the regulatory aspect of these techniques in dermatology are briefly summarized. For the future of Raman Spectroscopy, increasing clinical relevance and in vivo applications can be predicted with spreading of non-destructive methods and appearance with the most advanced instruments with rapid analysis time.
Topics: Artificial Intelligence; Microscopy, Confocal; Skin; Skin Absorption; Spectrum Analysis, Raman
PubMed: 35837832
DOI: 10.1111/exd.14645 -
Biomedicine & Pharmacotherapy =... Feb 2022The emergence of many new viruses in recent times has resulted in a significant scientific challenge for discovering drugs and vaccines that effectively treat and... (Review)
Review
The emergence of many new viruses in recent times has resulted in a significant scientific challenge for discovering drugs and vaccines that effectively treat and prevent viral diseases. Nanotechnology has opened doors to prevent the spread of several diseases, including those caused by viruses. Polymer-hybrid nanodevices are a class of nanotechnology platforms for biomedical applications that present synergistic properties among their components, with improved performance compared to conventional forms of therapy. Considering the growing interest in this emerging field and the promising technological advantages of polymer-hybrid nanodevices, this work presents the current status of these systems in the context of prevention and treatment of viral diseases. A brief description of the different types of polymer-hybrid nanodevices highlighting some peculiar characteristics such as their composition, biodistribution, delivery of antigens, and overall immune responses in systemic tissues are discussed. Finally, the work presents the future trends for new nanotechnological hybrid materials based on polymers and perspectives for clinical use.
Topics: Animals; Antiviral Agents; Drug Delivery Systems; Humans; Immunity, Cellular; Nanoparticles; Nanotechnology; Polymers; Tissue Distribution; Virus Diseases
PubMed: 34972632
DOI: 10.1016/j.biopha.2021.112249 -
Comprehensive Physiology Mar 2018The Slc9 family of Na /H exchangers (NHEs) plays a critical role in electroneutral exchange of Na and H in the mammalian intestine as well as other absorptive and... (Review)
Review
The Slc9 family of Na /H exchangers (NHEs) plays a critical role in electroneutral exchange of Na and H in the mammalian intestine as well as other absorptive and secretory epithelia of digestive organs. These transport proteins contribute to the transepithelial Na and water absorption, intracellular pH and cellular volume regulation as well as the electrolyte, acid-base, and fluid volume homeostasis at the systemic level. They also influence the function of other membrane transport mechanisms, affect cellular proliferation and apoptosis as well as cell migration, adherence to the extracellular matrix, and tissue repair. Additionally, they modulate the extracellular milieu to facilitate other nutrient absorption and to regulate the intestinal microbial microenvironment. Na /H exchange is inhibited in selected gastrointestinal diseases, either by intrinsic factors (e.g., bile acids, inflammatory mediators) or infectious agents and associated bacterial toxins. Disrupted NHE activity may contribute not only to local and systemic electrolyte imbalance but also to the disease severity via multiple mechanisms. In this review, we describe the cation proton antiporter superfamily of Na /H exchangers with a particular emphasis on the eight SLC9A isoforms found in the digestive tract, followed by a more integrative description in their roles in each of the digestive organs. We discuss regulatory mechanisms that determine the function of Na /H exchangers as pertinent to the digestive tract, their regulation in pathological states of the digestive organs, and reciprocally, the contribution of dysregulated Na /H exchange to the disease pathogenesis and progression. © 2018 American Physiological Society. Compr Physiol 8:555-583, 2018.
Topics: Animals; Digestive System; Gastrointestinal Diseases; Gene Expression Regulation; Humans; Intestinal Absorption; Salivary Glands; Sodium-Hydrogen Exchangers
PubMed: 29687889
DOI: 10.1002/cphy.c170027 -
International Journal of Environmental... Apr 2022The emergence of new psychoactive substances has earned a great deal of attention, and several reports of acute poisoning and deaths have been issued involving, for... (Review)
Review
The emergence of new psychoactive substances has earned a great deal of attention, and several reports of acute poisoning and deaths have been issued involving, for instance, synthetic opiates. In recent years, there have been profound alterations in the legislation concerning consumption, marketing, and synthesis of these compounds; rapid alert systems have also been subject to changes, and new substances and new markets, mainly through the internet, have appeared. Their effects and how they originate in consumers are still mostly unknown, primarily in what concerns chronic toxicity. This review intends to provide a detailed description of these substances from the point of view of consumption, toxicokinetics, and health consequences, including case reports on intoxications in order to help researchers and public health agents working daily in this area.
Topics: Analgesics, Opioid; Illicit Drugs; Marketing; Psychotropic Drugs; Public Health
PubMed: 35457736
DOI: 10.3390/ijerph19084869 -
Nutrients May 2019Understanding how the gut responds to food has always been limited by the available investigatory techniques. Previous methods involving intubation and aspiration are... (Review)
Review
Understanding how the gut responds to food has always been limited by the available investigatory techniques. Previous methods involving intubation and aspiration are largely limited to liquid-only meals. The aim of this review is to describe how MRI has allowed analysis of the processing of complex multiphase meals. This has demonstrated the role of physical factors such as viscosity, fat and fibre content in controlling gastric secretion and motility. It has also allowed the description of changes induced in small bowel water content and the role of osmotic effects of poorly absorbed carbohydrates such as fructose, sorbitol and mannitol. Intestinal secretions can be shown to be stimulated by a range of fruit and vegetables and the effect of this on colonic water content can also be measured. This has been used to demonstrate the mode of action of commonly used laxatives including bran and psyllium. The wealth of data which can be obtained together with its non-invasive nature and safety makes the technique ideal for the serial evaluation of the impact of different nutrients and drugs in both health and disease.
Topics: Animals; Diet; Eating; Gastrointestinal Absorption; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Intestines; Magnetic Resonance Imaging; Nutritional Status; Nutritive Value; Predictive Value of Tests; Stomach
PubMed: 31126027
DOI: 10.3390/nu11051147