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Nutrients May 2020Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans...
Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans and different animal species through a systematic review following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In humans, dietary histidine may be associated with factors that improve metabolic syndrome and has an effect on ion absorption. In rats, histidine supplementation increases food intake. It also provides neuroprotection at an early stage and could protect against epileptic seizures. In chickens, histidine is particularly important as a limiting factor for carnosine synthesis, which has strong anti-oxidant effects. In fish, dietary histidine may be one of the most important factors in preventing cataracts. In ruminants, histidine is a limiting factor for milk protein synthesis and could be the first limiting AA for growth. In excess, histidine supplementation can be responsible for eating and memory disorders in humans and can induce growth retardation and metabolic dysfunction in most species. To conclude, the requirements for histidine, like for other EAA, have been derived from growth and AA composition in tissues and also have specific metabolic roles depending on species and dietary levels.
Topics: Animals; Chickens; Dietary Supplements; Eating; Fishes; Gastrointestinal Absorption; Histidine; Humans; Rats; Ruminants
PubMed: 32423010
DOI: 10.3390/nu12051414 -
Alimentary Pharmacology & Therapeutics Nov 2003Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic... (Review)
Review
BACKGROUND
Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking.
AIM
As experimental data suggest a role of bile acids in the regulation of hepatic drug metabolism at both the transcriptional and post-transcriptional level, the literature was screened for adverse drug reactions and drug interactions related to ursodeoxycholic acid.
METHODS
A systematic review of the literature was performed using a refined search strategy to evaluate the adverse effects of ursodeoxycholic acid and its interactions with other drugs.
RESULTS
Ursodeoxycholic acid caused diarrhoea in a small proportion of patients. Rare skin reactions were due to drug adjuvants rather than the active substance. Decompensation of liver cirrhosis was reported after the administration of ursodeoxycholic acid in single cases of end-stage primary biliary cirrhosis. Recurrent right upper quadrant abdominal pain was incidentally observed. The absorption of ursodeoxycholic acid was impaired by colestyramine, colestimide, colestipol, aluminium hydroxide and smectite. Metabolic drug interactions were reported for the cytochrome P4503A substrates, ciclosporin, nitrendipine and dapsone.
CONCLUSIONS
Ursodeoxycholic acid is generally well tolerated. Drug absorption interactions with anion exchange resins deserve consideration. Metabolic interactions with compounds metabolized by cytochrome P4503A are to be expected.
Topics: Cholagogues and Choleretics; Chronic Disease; Drug Interactions; Female; Humans; Liver Diseases; Pregnancy; Pregnancy Complications; Ursodeoxycholic Acid
PubMed: 14616161
DOI: 10.1046/j.1365-2036.2003.01792.x -
Phytotherapy Research : PTR Nov 2023Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid... (Review)
Review
Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid metabolism are crucial contributors in the development of cardiovascular diseases. The abnormal cardiac fatty acid metabolism usually leads to energy deficit, oxidative stress, excessive apoptosis, and inflammation. Targeting fatty acid metabolism has been regarded as a novel approach to the treatment of cardiovascular diseases. However, there are currently no specific drugs that regulate fatty acid metabolism to treat cardiovascular diseases. Many traditional Chinese medicines have been widely used to treat cardiovascular diseases in clinics. And modern studies have shown that they exert a cardioprotective effect by regulating the expression of key proteins involved in fatty acid metabolism, such as peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase 1. Hence, we systematically reviewed the relationship between fatty acid metabolism disorders and four types of cardiovascular diseases including heart failure, coronary artery disease, cardiac hypertrophy, and diabetic cardiomyopathy. In addition, 18 extracts and eight monomer components from traditional Chinese medicines showed cardioprotective effects by restoring cardiac fatty acid metabolism. This work aims to provide a reference for the finding of novel cardioprotective agents targeting fatty acid metabolism.
Topics: Humans; Cardiovascular Diseases; Heart; Medicine, Chinese Traditional; PPAR alpha; Fatty Acids; Energy Metabolism
PubMed: 37533230
DOI: 10.1002/ptr.7965 -
International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
Drug Metabolism Reviews Feb 2014Exogenous cannabinoids are structurally and pharmacologically diverse compounds that are widely used. The purpose of this systematic review is to summarize the data... (Review)
Review
Exogenous cannabinoids are structurally and pharmacologically diverse compounds that are widely used. The purpose of this systematic review is to summarize the data characterizing the potential for these compounds to act as substrates, inhibitors, or inducers of human drug metabolizing enzymes, with the aim of clarifying the significance of these properties in clinical care and drug interactions. In vitro data were identified that characterize cytochrome P-450 (CYP-450) enzymes as potential significant contributors to the primary metabolism of several exogenous cannabinoids: tetrahydrocannabinol (THC; CYPs 2C9, 3A4); cannabidiol (CBD; CYPs 2C19, 3A4); cannabinol (CBN; CYPs 2C9, 3A4); JWH-018 (CYPs 1A2, 2C9); and AM2201 (CYPs 1A2, 2C9). CYP-450 enzymes may also contribute to the secondary metabolism of THC, and UDP-glucuronosyltransferases have been identified as capable of catalyzing both primary (CBD, CBN) and secondary (THC, JWH-018, JWH-073) cannabinoid metabolism. Clinical pharmacogenetic data further support CYP2C9 as a significant contributor to THC metabolism, and a pharmacokinetic interaction study using ketoconazole with oromucosal cannabis extract further supports CYP3A4 as a significant metabolic pathway for THC and CBD. However, the absence of interaction between CBD from oromucosal cannabis extract with omeprazole suggests a less significant role of CYP2C19 in CBD metabolism. Studies of THC, CBD, and CBN inhibition and induction of major human CYP-450 isoforms generally reflect a low risk of clinically significant drug interactions with most use, but specific human data are lacking. Smoked cannabis herb (marijuana) likely induces CYP1A2 mediated theophylline metabolism, although the role of cannabinoids specifically in eliciting this effect is questionable.
Topics: Cannabinol; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Inactivation, Metabolic
PubMed: 24160757
DOI: 10.3109/03602532.2013.849268 -
Expert Review of Clinical Pharmacology Sep 2017This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is... (Review)
Review
This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is available on two formulations (RBP-7000 and in Situ Microparticle), but 20 TDM articles on the microsphere formulation were found. Risperidone TDM includes the serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9-hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a normal value around 7 in oral risperidone). The weighted mean R/9-OH-R ratio was 0.48 (approximately twice that of oral risperidone TDM) in a combined analysis from 329 patients in 6 risperidone LAI studies without major confounders. The total C/D ratios from 297 patients in 6 risperidone LAI studies ranged from 7.4 to 9.7 ng/ml/mg/day with a weighted mean of 8.8 ng/ml/mg/day. Expert commentary: Clinicians using TDM for risperidone LAI microsphere formulation need to: 1) consider steady state to be reached ≥ 6 weeks after the first injection, 2) pay attention to a) co-medications with inducers/inhibitors, b) severe inflammations/infections, and c) hepatic/renal impairment, and 3) use Castberg's recommendation to calculate risperidone dosing.
Topics: Administration, Oral; Animals; Antipsychotic Agents; Delayed-Action Preparations; Drug Monitoring; Humans; Injections; Microspheres; Paliperidone Palmitate; Risperidone
PubMed: 28699847
DOI: 10.1080/17512433.2017.1345623 -
A systematic review and empirical analysis of the relation between dose and duration of drug action.Journal of Clinical Pharmacology Jan 2010There is a log-linear relation between the dose and duration of action of drugs with single-compartment pharmacokinetics and direct, reversible mechanisms of action.... (Review)
Review
There is a log-linear relation between the dose and duration of action of drugs with single-compartment pharmacokinetics and direct, reversible mechanisms of action. However, it has been suggested that this relation does not extend to drugs whose metabolites are active or slowly eliminated, drugs with saturable kinetics, and drugs with hit-and-run effects. The purpose of this study is to test this hypothesis and to quantify the relationship by way of a systematic review coupled to an empirical analysis. All issues of 4 clinical pharmacology journals from 1980 to 2005 are hand-searched for articles that present pharmacodynamic response versus time curves for 4 or more different doses. Data on duration of action, dose, and area under the plasma concentration versus time curve from zero to infinity (AUC) are abstracted and analyzed by panel data regression modeling, with within-study fixed effects. Duration of drug action is defined as the time during which a pharmacodynamic effect (or response) exceeds a nominal threshold. The generalized models of all observations from 33 publications, with duration of action as the dependent variable and the logarithm of the dose (or AUC) as the explanatory variable, yield significant log-linear relationships. The regressions for individual studies are correctly specified in 27 cases; there are insufficient data for analysis in 10 studies, and a log-linear specification is deemed inappropriate in 6. Analysis of published dose-ranging studies shows that the duration of action of a drug is directly proportional to the logarithm of dose across a wide range of different drugs, extending a result that was previously documented for very few compounds.
Topics: Area Under Curve; Dose-Response Relationship, Drug; Humans; Models, Statistical; Prescription Drugs; Time Factors
PubMed: 19797537
DOI: 10.1177/0091270008329555 -
Metabolites Dec 2022Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid... (Review)
Review
Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological roles in glioma and the identification of potential lipids biomarker. This systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extensive research articles search for the last 10 years, from 2011 to 2021, were conducted using four electronic databases, including PubMed, Web of Science, CINAHL and ScienceDirect. A total of 158 research articles were included in this study. All studies reported significant lipid alteration between glioma and control groups, impacting glioma cell growth, proliferation, drug resistance, patients' survival and metastasis. Different lipids demonstrated different biological roles, either beneficial or detrimental effects on glioma. Notably, prostaglandin (PGE2), triacylglycerol (TG), phosphatidylcholine (PC), and sphingosine-1-phosphate play significant roles in glioma development. Conversely, the most prominent anti-carcinogenic lipids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamin D3 have been reported to have detrimental effects on glioma cells. Furthermore, high lipid signals were detected at 0.9 and 1.3 ppm in high-grade glioma relative to low-grade glioma. This evidence shows that lipid metabolisms were significantly dysregulated in glioma. Concurrent with this knowledge, the discovery of specific lipid classes altered in glioma will accelerate the development of potential lipid biomarkers and enhance future glioma therapeutics.
PubMed: 36557318
DOI: 10.3390/metabo12121280 -
Journal of the American Nutrition... Aug 2022Goji berry has been used in China more than 2,000 years as a traditional medicinal herb and food supplement. Lycium barbarum polysaccharide (LBP), the chief active... (Meta-Analysis)
Meta-Analysis
Goji berry has been used in China more than 2,000 years as a traditional medicinal herb and food supplement. Lycium barbarum polysaccharide (LBP), the chief active component in goji berry, has been used to treat hypertension, atherosclerosis and other cardiovascular diseases in Chinese traditional medicine. However, the underlying effects of LBP- mediated activity in blood glucose and lipid metabolism remain poorly understood. The present study aims to apply the meta-analysis to explore the healthy effects of LBP. Eligible studies published up to November 15, 2020, were searched and identified from CNKI, Pubmed, Web of Science, Cocharane library detabases. A total of 315 publications were retrieved and 7 articles were included. The STATA (version 11.0) was applied to process the meta-analysis. The pooled estimate showed that daily consumption of LBP played significant effects on regulating serum triglyceride (TG), fasting blood glucose, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) concentrations ( < 0.05), while it was effect-free on the total cholesterol (TC). The present study provided a better understanding of current research status and suggested that LBP could play potential role in prevention and therapy for non-communicable chronic diseases, and more scientific evidence are required in the future.Key teaching pointsGoji berry and LBP, its main biologically active ingredient, have a wide range of health promotion effects.The supplement of LBP may played significant effects on regulating serum TG, HDL, LDL and FBG concentrations.Goji may serve as a potential drug to prevent and treat chronic non-communicable diseases in the future.Healthy dietary patterns containing goji berries will be a new choice for consumers in the future.
Topics: Blood Glucose; Drugs, Chinese Herbal; Glucose; Lipid Metabolism; Lycium
PubMed: 34213407
DOI: 10.1080/07315724.2021.1925996 -
Journal of Controlled Release :... Jul 2021Absorption, distribution, metabolism and excretion (ADME) studies represent a fundamental step in the early stages of drug discovery. In particular, the absorption of... (Review)
Review
Absorption, distribution, metabolism and excretion (ADME) studies represent a fundamental step in the early stages of drug discovery. In particular, the absorption of orally administered drugs, which occurs at the intestinal level, has gained attention since poor oral bioavailability often led to failures for new drug approval. In this context, several in vitro preclinical models have been recently developed and optimized to better resemble human physiology in the lab and serve as an animal alternative to accomplish the 3Rs principles. However, numerous models are ineffective in recapitulating the key features of the human small intestine epithelium and lack of prediction potential for drug absorption and metabolism during the preclinical stage. In this review, we provide an overview of in vitro models aimed at mimicking the intestinal barrier for pharmaceutical screening. After briefly describing how the human small intestine works, we present i) conventional 2D synthetic and cell-based systems, ii) 3D models replicating the main features of the intestinal architecture, iii) micro-physiological systems (MPSs) reproducing the dynamic stimuli to which cells are exposed in the native microenvironment. In this review, we will highlight the benefits and drawbacks of the leading intestinal models used for drug absorption and metabolism studies.
Topics: Animal Testing Alternatives; Animals; Biological Availability; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Models, Biological; Pharmaceutical Preparations
PubMed: 34033859
DOI: 10.1016/j.jconrel.2021.05.028