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European Journal of Drug Metabolism and... Jul 2021Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a...
BACKGROUND AND OBJECTIVES
Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a loss of absorptive surfaces, the absorption of orally administered drugs is also often affected. The purpose of this study was to systematically review the published literature and examine the effects of short bowel syndrome on drug pharmacokinetics and clinical outcomes.
METHODS
Studies were identified through searches of databases MEDLINE, EMBASE, Web of Science, and SCOPUS, in addition to hand searches of studies' reference lists. Two reviewers independently assessed studies for inclusion, yielding 50 studies involving 37 different drugs in patients with short bowel syndrome.
RESULTS
Evidence of decreased drug absorption was observed in 29 out of 37 drugs, 6 of which lost therapeutic effect, and 14 of which continued to demonstrate clinical benefit through drug monitoring.
CONCLUSIONS
The influence of short bowel syndrome on drug absorption appears to be drug-specific and dependent on the location and extent of resection. The presence of a colon in continuity may also influence drug bioavailability as it can contribute significantly to the absorption of drugs (e.g., metoprolol); likewise, drugs that have a wide absorption window or are known to be absorbed in the colon are least likely to be malabsorbed. Individualized dosing may be necessary to achieve therapeutic efficacy, and therapeutic drug monitoring, where available, should be considered in short bowel syndrome patients, especially for drugs with narrow therapeutic indices.
Topics: Administration, Oral; Biological Availability; Humans; Intestinal Absorption; Pharmaceutical Preparations; Pharmacokinetics; Short Bowel Syndrome
PubMed: 34196913
DOI: 10.1007/s13318-021-00696-y -
Biomedicine & Pharmacotherapy =... Jan 2021Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines...
Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines (TCMs) have shown considerable effects in the treatment of metabolic disorders by regulating the gut microbiota. However, the underlying mechanisms are unclear. Studies have shown that TCMs significantly affect glucose and lipid metabolism by modulating the gut microbiota, particularly mucin-degrading bacteria, bacteria with anti-inflammatory properties, lipopolysaccharide- and short-chain fatty acid (SCFA)-producing bacteria, and bacteria with bile-salt hydrolase activity. In this review, we explored potential mechanisms by which TCM improved metabolic disorders via regulating gut microbiota composition and functional structure. In particular, we focused on the protection of the intestinal barrier function, modulation of metabolic endotoxemia and inflammatory responses, regulation of the effects of SCFAs, modulation of the gut-brain axis, and regulation of bile acid metabolism and tryptophan metabolism as therapeutic mechanisms of TCMs in metabolic diseases.
Topics: Animals; Bacteria; Blood Glucose; Drugs, Chinese Herbal; Dysbiosis; Energy Metabolism; Gastrointestinal Microbiome; Humans; Intestines; Lipid Metabolism; Medicine, Chinese Traditional; Metabolic Diseases; Treatment Outcome
PubMed: 33197760
DOI: 10.1016/j.biopha.2020.110857 -
Nutrients Oct 2020The Mediterranean diet (MD) may provide metabolic benefits but no systematic review to date has examined its effect on a multitude of outcomes related to metabolic... (Meta-Analysis)
Meta-Analysis
The Mediterranean diet (MD) may provide metabolic benefits but no systematic review to date has examined its effect on a multitude of outcomes related to metabolic health. This systematic review with meta-analysis (International Prospective Register of Systematic Reviews, PROSPERO; number CRD42019141459) aimed to examine the MD's effect on metabolic syndrome (MetSyn) incidence, components and risk factors (primary outcomes), and incidence and/or mortality from MetSyn-related comorbidities and receipt of pharmacologic treatment for MetSyn components and comorbidities (secondary outcomes). We searched Pubmed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science for controlled trials published until June 2019, comparing the MD with no treatment, usual care, or different diets in adults. Studies not published in English and not promoting the whole MD were excluded. Two authors independently extracted data and assessed risk of bias using the Cochrane Collaboration's and Risk of Bias in non-randomised studies (ROBINS-I) tools. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects meta-analyses, subgroup analyses and meta-regressions were performed, and heterogeneity was quantified using the I statistic. We identified 2654 reports and included 84 articles reporting 57 trials ( = 36,983). In random effects meta-analyses, the MD resulted in greater beneficial changes in 18 of 28 MetSyn components and risk factors (body weight, body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) index, total-, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, triglycerides, alanine transaminase, hepatic fat mass, C-reactive protein, interleukin-6, tumour necrosis factor-a, and flow-mediated dilatation) and lower risk of cardiovascular disease incidence (risk ratio (RR) = 0.61, 95% confidence intervals (CI) 0.42-0.80; I = 0%), and stroke (RR = 0.67, 95% CI 0.35-0.98; I = 0%). Only six studies reported effects on pharmacotherapy use, and pooled analysis indicated no differences between diet groups. Lack of consistency in comparator groups and other study characteristics across studies resulted in high heterogeneity for some outcomes, which could not be considerably explained by meta-regressions. However, a consistent direction of beneficial effect of the MD was observed for the vast majority of outcomes examined. Findings support MD's beneficial effect on all components and most risk factors of the MetSyn, in addition to cardiovascular disease and stroke incidence. More studies are needed to establish effects on other clinical outcomes and use of pharmacotherapy for MetSyn components and comorbidities. Despite the high levels of heterogeneity for some outcomes, this meta-analysis enabled the comparison of findings across studies and the examination of consistency of effects. The consistent direction of effect, suggesting the MD's benefits on metabolic health, supports the need to promote this dietary pattern to adult populations.
Topics: Adult; Biomarkers; Blood Pressure; Comorbidity; Controlled Clinical Trials as Topic; Diet, Mediterranean; Health; Humans; Incidence; Insulin Resistance; Metabolic Syndrome; Metabolism; Oxidative Stress; Risk Factors
PubMed: 33143083
DOI: 10.3390/nu12113342 -
Nutrients May 2020Nitric oxide related ergogenic aids such as arginine (Arg) have shown to impact positively on sport performance through several physiological and metabolic mechanisms.... (Meta-Analysis)
Meta-Analysis
Nitric oxide related ergogenic aids such as arginine (Arg) have shown to impact positively on sport performance through several physiological and metabolic mechanisms. However, research results have shown to be controversial. The great differences regarding required metabolic pathways and physiological demands between aerobic and anaerobic sport disciplines could be the reasons. The aim of this systematic review and meta-analysis was to evaluate the effects of Arg supplementation on aerobic (≤VOmax) and anaerobic (>VOmax) performance. Likewise, to show the effective dose and timing of this supplementation. A structured search was carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and PICOS guidelines in PubMed/MEDLINE, Web of Science (WOS), and Scopus databases from inception to January 2020. Eighteen studies were included which compare Arg supplementation with placebo in an identical situation and testing its effects on aerobic and anaerobic performance tests. Trials analyzing supplementation with other supplements were removed and there was not athlete's level, gender, ethnicity, or age filters. The performed meta-analysis included 15 studies and random effects model and pooled standardized mean differences (SMD) were used according to Hedges' g. Results revealed that Arg supplementation could improve aerobic (SMD, 0.84; 95% CI, 0.12 to 1.56; magnitude of SMD (MSMD), large; I2, 89%; = 0.02) and anaerobic (SMD, 0.24; 95% CI, 0.05 to 0.43; MSMD, small; I2, 0%; = 0.01) performance tests. In conclusion, acute Arg supplementation protocols to improve aerobic and anaerobic performance should be adjusted to 0.15 g/kg of body weight ingested between 60-90 min before. Moreover, chronic Arg supplementation should include 1.5-2 g/day for 4-7 weeks in order to improve aerobic performance, and 10-12 g/day for 8 weeks to enhance anaerobic performance.
Topics: Aerobiosis; Anaerobiosis; Arginine; Athletic Performance; Body Weight; Dietary Supplements; Energy Metabolism; Female; Humans; Male; Nitric Oxide; Performance-Enhancing Substances
PubMed: 32370176
DOI: 10.3390/nu12051300 -
British Journal of Sports Medicine Aug 2021We systemically reviewed the literature to assess how long-term testosterone suppressing gender-affirming hormone therapy influenced lean body mass (LBM), muscular area,...
How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation.
OBJECTIVES
We systemically reviewed the literature to assess how long-term testosterone suppressing gender-affirming hormone therapy influenced lean body mass (LBM), muscular area, muscular strength and haemoglobin (Hgb)/haematocrit (HCT).
DESIGN
Systematic review.
DATA SOURCES
Four databases (BioMed Central, PubMed, Scopus and Web of Science) were searched in April 2020 for papers from 1999 to 2020.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Eligible studies were those that measured at least one of the variables of interest, included transwomen and were written in English.
RESULTS
Twenty-four studies were identified and reviewed. Transwomen experienced significant decreases in all parameters measured, with different time courses noted. After 4 months of hormone therapy, transwomen have Hgb/HCT levels equivalent to those of cisgender women. After 12 months of hormone therapy, significant decreases in measures of strength, LBM and muscle area are observed. The effects of longer duration therapy (36 months) in eliciting further decrements in these measures are unclear due to paucity of data. Notwithstanding, values for strength, LBM and muscle area in transwomen remain above those of cisgender women, even after 36 months of hormone therapy.
CONCLUSION
In transwomen, hormone therapy rapidly reduces Hgb to levels seen in cisgender women. In contrast, hormone therapy decreases strength, LBM and muscle area, yet values remain above that observed in cisgender women, even after 36 months. These findings suggest that strength may be well preserved in transwomen during the first 3 years of hormone therapy.
Topics: Adipose Tissue; Androgen Antagonists; Athletic Performance; Body Composition; Cyproterone Acetate; Estradiol; Female; Hematocrit; Hemoglobin A; Humans; Male; Muscle Strength; Muscle, Skeletal; Sports; Testosterone; Time Factors; Transgender Persons; Transsexualism
PubMed: 33648944
DOI: 10.1136/bjsports-2020-103106 -
European Journal of Pharmacology Sep 2022Gastrointestinal cation exchangers that can bind potassium in the gut, including sodium polystyrene sulfonate (SPS), calcium polystyrene sulfonate (CPS), patiromer and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gastrointestinal cation exchangers that can bind potassium in the gut, including sodium polystyrene sulfonate (SPS), calcium polystyrene sulfonate (CPS), patiromer and sodium zirconium cyclosilicate (SZC), are emerging medications for the treatment of hyperkalemia with chronic kidney disease (CKD). However, which might be the best alternative for patients with chronic kidney disease and hyperkalemia remains disputed.
METHODS
We performed this systematic review and network meta-analysis with the Bayesian approach to conduct direct and indirect comparisons among potassium binders regarding their efficacy and safety. The surface under the cumulative ranking curve analysis (SUCRA) was used to calculate the best intervention for each outcome.
RESULTS
All four potassium binders had a promising effect regarding potassium reduction. SPS had favorable efficacy and safety for short-term use (MD: -0.94; 95% CIs: -1.4 to -0.48; SUCRA = 94.69%), but long-term treatment required strict dose control and assessment of gastrointestinal conditions. CPS had a positive effect on reducing potassium, and could especially maintain the serum potassium concentration in patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi). Patiromer might reduce all-cause mortality in CKD patients with hyperkalemia and have a positive effect on potassium-lowering, though it had significant gastrointestinal adverse effects. SZC had a potassium-lowering effect in both the short-term and long-term, and can be a promising long-term treatment for the hyperkalemia in CKD patients, especially in combination with RAASi.
CONCLUSION
These four potassium binders had their own advantages and disadvantages, and the medication should be selected according to the clinical situation of the patient.
Topics: Bayes Theorem; Humans; Hyperkalemia; Potassium; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 35964658
DOI: 10.1016/j.ejphar.2022.175174 -
Nutrients Aug 2020Beta-alanine supplementation (BA) has a positive impact on physical performance. However, evidence showing a benefit of this amino acid in aerobic-anaerobic transition... (Meta-Analysis)
Meta-Analysis
Beta-alanine supplementation (BA) has a positive impact on physical performance. However, evidence showing a benefit of this amino acid in aerobic-anaerobic transition zones is scarce and the results controversial. The aim of this systematic review and meta-analysis is to analyze the effects of BA supplementation on physical performance in aerobic-anaerobic transition zones. At the same time, the effect of different dosages and durations of BA supplementation were identified. The search was designed in accordance with the PRISMA guidelines for systematic reviews and meta-analyses and performed in Web of Science (WOS), Scopus, SPORTDiscus, PubMed, and MEDLINE between 2010 and 2020. The methodological quality and risk of bias were evaluated with the Cochrane Collaboration tool. The main variables were the Time Trial Test (TTT) and Time to Exhaustion (TTE) tests, the latter separated into the Limited Time Test (LTT) and Limited Distance Test (LDT). The analysis was carried out with a pooled standardized mean difference (SMD) through Hedges' g test (95% CI). Nineteen studies were included in the systematic review and meta-analysis, revealing a small effect for time in the TTT (SMD, -0.36; 95% CI, -0.87-0.16; I = 59%; = 0.010), a small effect for LTT (SMD, 0.25; 95% CI, -0.01-0.51; I = 0%; = 0.53), and a large effect for LDT (SMD, 4.27; 95% CI, -0.25-8.79; I = 94%; = 0.00001). BA supplementation showed small effects on physical performance in aerobic-anaerobic transition zones. Evidence on acute supplementation is scarce (one study); therefore, exploration of acute supplementation with different dosages and formats on physical performance in aerobic-anaerobic transition zones is needed.
Topics: Aerobiosis; Anaerobiosis; Dietary Supplements; Humans; Physical Functional Performance; Sports Nutritional Physiological Phenomena; beta-Alanine
PubMed: 32824885
DOI: 10.3390/nu12092490 -
Lipids in Health and Disease Oct 2019Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions...
BACKGROUND
Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations.
METHODS
A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines.
RESULTS
Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes.
CONCLUSIONS
Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.
Topics: Animals; Cardiovascular Diseases; Chronic Disease; DNA Methylation; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Epigenesis, Genetic; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Gene-Environment Interaction; Humans; Insulin Resistance; Lipid Metabolism; Obesity; Trans Fatty Acids
PubMed: 31615571
DOI: 10.1186/s12944-019-1120-6 -
Therapeutic Drug Monitoring Feb 2020Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug...
Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.
Topics: Anti-Bacterial Agents; Bayes Theorem; Drug Dosage Calculations; Drug Interactions; Drug Monitoring; Half-Life; Humans; Linezolid; Liver Failure; Metabolic Clearance Rate; Microbial Sensitivity Tests; Models, Biological; Pediatrics; Renal Insufficiency; Renal Replacement Therapy; Tuberculosis
PubMed: 31652190
DOI: 10.1097/FTD.0000000000000710 -
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