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Panminerva Medica Dec 2021Physiologically guided revascularization, using fractional flow reserve (FFR) or instantaneous wave free ratio (iFR) has been demonstrated to be associated with better... (Review)
Review
Physiologically guided revascularization, using fractional flow reserve (FFR) or instantaneous wave free ratio (iFR) has been demonstrated to be associated with better long-term outcomes compared to an angiographically-guided strategy, mainly avoiding inappropriate coronary stenting and its associated adverse events. On the contrary, the role of invasive physiological assessment after percutaneous coronary intervention (PCI) is much less well established. However, a large body of evidence suggests that a relevant proportion of patients undergoing PCI with a satisfying angiographic result show instead a suboptimal functional product with a potentially negative prognostic impact. For this reason, many efforts have been focused to identify interventional strategies to physiologically optimize PCI. Measuring the functional result after as PCI, especially when performed after a physiological assessment, implies that the operator is ready to accept the hard truth of an unsatisfactory physiological result despite angiographically optimal and, consequently, to optimize the product with some additional effort. The aim of this review was to bridge this gap in knowledge by better defining the paradigm shift of invasive physiological assessment, from a simple tool for deciding whether an epicardial stenosis must be treated, to a thoroughly physiological approach to PCI with the suggestion of a practical flow chart.
Topics: Fractional Flow Reserve, Myocardial; Humans; Percutaneous Coronary Intervention; Stents
PubMed: 34486363
DOI: 10.23736/S0031-0808.21.04363-9 -
Seminars in Cell & Developmental Biology Jun 2015Tight Junctions (TJs) are multi-molecular complexes in epithelial tissues that regulate paracellular permeability. Within the TJ complex, claudins proteins span the... (Review)
Review
Tight Junctions (TJs) are multi-molecular complexes in epithelial tissues that regulate paracellular permeability. Within the TJ complex, claudins proteins span the paracellular space to form a seal between adjacent cells. This seal allows regulated passage of ions, fluids, and solutes, contingent upon the complement of claudins expressed. With as many as 27 claudins in the human genome, the TJ seal is complex indeed. This review focuses on changes in claudin expression within the epithelial cells of the gastrointestinal tract, where claudin differentiation results in several physiologically distinct TJs within the lifetime of the cell. We also review mechanistic studies revealing that TJs are highly dynamic, with the potential to undergo molecular remodeling while structurally intact. Therefore, physiologic Tight Junction plasticity involves both the adaptability of claudin expression and gene specific retention in the TJ; a process we term claudin switching.
Topics: Animals; Cell Differentiation; Claudins; Epithelial Cells; Gastrointestinal Tract; Gene Expression Regulation, Developmental; Humans; Permeability; Tight Junctions
PubMed: 25957515
DOI: 10.1016/j.semcdb.2015.04.003 -
The Western Journal of Emergency... Dec 2015Airway management in critically ill patients involves the identification and management of the potentially difficult airway in order to avoid untoward complications.... (Review)
Review
Airway management in critically ill patients involves the identification and management of the potentially difficult airway in order to avoid untoward complications. This focus on difficult airway management has traditionally referred to identifying anatomic characteristics of the patient that make either visualizing the glottic opening or placement of the tracheal tube through the vocal cords difficult. This paper will describe the physiologically difficult airway, in which physiologic derangements of the patient increase the risk of cardiovascular collapse from airway management. The four physiologically difficult airways described include hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure. The emergency physician should account for these physiologic derangements with airway management in critically ill patients regardless of the predicted anatomic difficulty of the intubation.
Topics: Acidosis; Airway Management; Critical Illness; Glottis; Heart Failure; Humans; Hypotension; Hypoxia; Intubation, Intratracheal; Risk Factors
PubMed: 26759664
DOI: 10.5811/westjem.2015.8.27467 -
Expert Opinion on Drug Metabolism &... Sep 2021: Physiological pH and chemical pKa are two sides of the same coin in defining the ionization of a drug in the human body. The Henderson-Hasselbalch equation and... (Review)
Review
Crosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicity.
: Physiological pH and chemical pKa are two sides of the same coin in defining the ionization of a drug in the human body. The Henderson-Hasselbalch equation and pH-partition hypothesis form the theoretical base to define the impact of pH-pKa crosstalk on drug ionization and thence its absorption, distribution, metabolism, excretion, and toxicity (ADMET).: Human physiological pH is not constant, but a diverse, dynamic state regulated by various biological mechanisms, while the chemical pKa is generally a constant defining the acidic dissociation of the drug at various environmental pH. Works on pH-pKa crosstalk are scattered in the literature, despite its significant contributions to drug pharmacokinetics, pharmacodynamics, safety, and toxicity. In particular, its impacts on drug ADMET have not been effectively linked to the physiologically based pharmacokinetic (PBPK) modeling and simulation, a powerful tool increasingly used in model-informed drug development (MIDD). Lacking a full consideration of the interactions of physiological pH and chemical pKa in a PBPK model limits scientists' capability in mechanistically describing the drug ADMET. This mini-review compiled literature knowledge on pH-pKa crosstalk and its impacts on drug ADMET, from the viewpoint of PBPK modeling, to pave the way to a systematic incorporation of pH-pKa crosstalk into PBPK modeling and simulation.
Topics: Animals; Computer Simulation; Drug Development; Drug-Related Side Effects and Adverse Reactions; Humans; Hydrogen-Ion Concentration; Models, Biological; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 34253134
DOI: 10.1080/17425255.2021.1951223 -
Physiological Measurement May 2018Physiological, behavioral, and psychological changes associated with neuropsychiatric illness are reflected in several related signals, including actigraphy, location,... (Review)
Review
Physiological, behavioral, and psychological changes associated with neuropsychiatric illness are reflected in several related signals, including actigraphy, location, word sentiment, voice tone, social activity, heart rate, and responses to standardized questionnaires. These signals can be passively monitored using sensors in smartphones, wearable accelerometers, Holter monitors, and multimodal sensing approaches that fuse multiple data types. Connection of these devices to the internet has made large scale studies feasible and is enabling a revolution in neuropsychiatric monitoring. Currently, evaluation and diagnosis of neuropsychiatric disorders relies on clinical visits, which are infrequent and out of the context of a patient's home environment. Moreover, the demand for clinical care far exceeds the supply of providers. The growing prevalence of context-aware and physiologically relevant digital sensors in consumer technology could help address these challenges, enable objective indexing of patient severity, and inform rapid adjustment of treatment in real-time. Here we review recent studies utilizing such sensors in the context of neuropsychiatric illnesses including stress and depression, bipolar disorder, schizophrenia, post traumatic stress disorder, Alzheimer's disease, and Parkinson's disease.
Topics: Behavior; Electrocardiography, Ambulatory; Humans; Mental Disorders; Monitoring, Physiologic; Smartphone; Wearable Electronic Devices
PubMed: 29671754
DOI: 10.1088/1361-6579/aabf64 -
Molecular Pharmaceutics Oct 2010Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic... (Review)
Review
Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that match drug and dosage form properties with practical dissolution media and apparatus may be appropriate. However, where in vitro-in vivo correlations are desired, it is logical to consider and utilize knowledge of the in vivo condition. This publication critically reviews the literature that is relevant to oral human drug delivery. Physiologically relevant information must serve as a basis for the design of dissolution test methods and systems that are more representative of the human condition. As in vitro methods advance in their physiological relevance, better in vitro-in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bioperformance.
Topics: Administration, Oral; Biological Availability; Body Fluids; Chemistry, Pharmaceutical; Dosage Forms; Drug Delivery Systems; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Solubility
PubMed: 20822152
DOI: 10.1021/mp100149j -
Current Opinion in Anaesthesiology Apr 2022The physiologically difficult airway is one in which physiologic alterations in the patient increase the risk for cardiorespiratory and other complications during... (Review)
Review
PURPOSE OF REVIEW
The physiologically difficult airway is one in which physiologic alterations in the patient increase the risk for cardiorespiratory and other complications during tracheal intubation and transition to positive pressure ventilation. This review will summarize the recent literature around the emerging concept of the physiologically difficult airway, describe its relevance and various patient types in which this entity is observed.
RECENT FINDINGS
Physiologic derangements during airway management occur due acute illness, pre-existing disease, effects of anesthetic agents, and positive pressure ventilation. These derangements are especially recognized in critically ill patients, but can also occur in otherwise healthy patients including obese, pregnant and pediatric patients who have certain physiological alterations. Critically ill patients may have a physiologically difficult airway due to the presence of acute respiratory failure, hypoxemia, hypotension, severe metabolic acidosis, right ventricular failure, intracranial hypertension, and risk of aspiration of gastric contents during tracheal intubation.
SUMMARY
Understanding the physiological alterations and the risks involved in patients with a physiologically difficult airway is necessary to optimize the physiology and adopt strategies to avoid complications during tracheal intubation. Further research will help us better understand the optimal strategies to improve outcomes in these patients.
Topics: Airway Management; Child; Critical Illness; Female; Humans; Hypotension; Hypoxia; Intubation, Intratracheal; Pregnancy
PubMed: 35165233
DOI: 10.1097/ACO.0000000000001102 -
Intensive Care Medicine Dec 2008A physiological review on renal replacement therapies (RRT) is a challenging task: there is nothing "physiologic" about RRT, since the most accurate, safe and perfectly... (Review)
Review
INTRODUCTION
A physiological review on renal replacement therapies (RRT) is a challenging task: there is nothing "physiologic" about RRT, since the most accurate, safe and perfectly delivered extracorporeal therapy would still be far from "physiologically" replacing the function of the native kidney.
METHODS
This review will address the issues of physiology of fluid and solute removal, acid base control and impact on mortality during intermittent and continuous therapies: different RRT modalities and relative prescriptions will provide different "physiological clinical effects" to critically ill patients with acute kidney injury (AKI), with the aim of restoring lost "renal homeostasis". On the other side, however, the "pathophysiology" of RRT, consists with unwanted clinical effects caused by the same treatments, generally under-recognized by current literature but often encountered in clinical practice. Physiology and pathophysiology of different RRT modalities have been reviewed.
CONCLUSION
Physiology and pathophysiology of RRT often coexist during dialysis sessions. Improvement in renal recovery and survival from AKI will be achieved from optimization of therapy and increased awareness of potential benefits and dangers deriving from different RRT modalities.
Topics: Acid-Base Equilibrium; Hemofiltration; Humans; Renal Dialysis; Renal Insufficiency; Water-Electrolyte Balance
PubMed: 18791697
DOI: 10.1007/s00134-008-1258-6 -
Nature Reviews. Cardiology Jan 2020Flowing blood generates a frictional force called shear stress that has major effects on vascular function. Branches and bends of arteries are exposed to complex blood... (Review)
Review
Flowing blood generates a frictional force called shear stress that has major effects on vascular function. Branches and bends of arteries are exposed to complex blood flow patterns that exert low or low oscillatory shear stress, a mechanical environment that promotes vascular dysfunction and atherosclerosis. Conversely, physiologically high shear stress is protective. Endothelial cells are critical sensors of shear stress but the mechanisms by which they decode complex shear stress environments to regulate physiological and pathophysiological responses remain incompletely understood. Several laboratories have advanced this field by integrating specialized shear-stress models with systems biology approaches, including transcriptome, methylome and proteome profiling and functional screening platforms, for unbiased identification of novel mechanosensitive signalling pathways in arteries. In this Review, we describe these studies, which reveal that shear stress regulates diverse processes and demonstrate that multiple pathways classically known to be involved in embryonic development, such as BMP-TGFβ, WNT, Notch, HIF1α, TWIST1 and HOX family genes, are regulated by shear stress in arteries in adults. We propose that mechanical activation of these pathways evolved to orchestrate vascular development but also drives atherosclerosis in low shear stress regions of adult arteries.
Topics: Animals; Atherosclerosis; Endothelium, Vascular; Gene Expression Regulation, Developmental; Genetic Predisposition to Disease; Humans; Mechanotransduction, Cellular; Neovascularization, Physiologic; Phenotype; Regional Blood Flow; Risk Factors; Stress, Mechanical; Vascular Remodeling
PubMed: 31366922
DOI: 10.1038/s41569-019-0239-5 -
European Journal of Pharmaceutics and... Mar 2017This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of... (Review)
Review
This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of oral drugs, and the various absorption models that are used to describe/predict oral drug absorption. The rate and extent of oral drug absorption is determined by a complex interaction between a drug's physicochemical properties, GI physiologic factors, and the nature of the formulation administered. GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability. Different regions of the GI tract have different drug absorptive properties. Thus, the transit time in each GI region and its variability between subjects may contribute to the variability in the rate and/or extent of drug absorption. Food-drug interactions can result in delayed, decreased, increased, and sometimes un-altered drug absorption. Food effects on oral absorption can be achieved by direct and indirect mechanisms. Various models have been proposed to describe oral absorption ranging from empirical models to the more sophisticated "mechanism-based" models. Through understanding of the physicochemical and physiological rate-limiting factors affecting oral absorption, modellers can implement simplified population-based modelling approaches that are less complex than whole-body physiologically-based models but still capture the essential elements in a physiological way and hence will be more suited for population modelling of large clinical data sets. It will also help formulation scientists to better predict formulation performance and to develop formulations that maximize oral bioavailability.
Topics: Administration, Oral; Aged; Biological Availability; Food-Drug Interactions; Gastrointestinal Tract; Humans; Hydrogen-Ion Concentration; Pharmacokinetics; Solubility
PubMed: 27914234
DOI: 10.1016/j.ejpb.2016.11.034