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Kidney360 Mar 2022Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) affect levels of serum electrolytes, especially magnesium. This study... (Meta-Analysis)
Meta-Analysis
Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Serum Electrolyte Levels in Patients with Type 2 Diabetes: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) affect levels of serum electrolytes, especially magnesium. This study aimed to integrate direct and indirect trial evidence to maximize statistical power to clarify their overall and comparative effects in patients with type 2 diabetes (T2D).
METHODS
We systematically searched PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov up to January 2021 to identify eligible randomized controlled trials (RCTs) of SGLT2is that reported mean changes in serum electrolytes, including magnesium, sodium, potassium, phosphate, and calcium. We performed both random-effects pairwise and network meta-analyses to calculate the weighted mean difference (WMD) and 95% confidence intervals (CI).
RESULTS
In total, we included 25 RCTs involving 28,269 patients with T2D and 6 SGLT2is. Compared with placebo, SGLT2is were significantly associated with elevations in serum magnesium by 0.07 mmol/L (95% CI, 0.06 to 0.08 mmol/L) and serum phosphate by 0.03 mmol/L (95% CI, 0.02 to 0.04 mmol/L). Our network meta-analysis showed no evidence of significantly superior efficacy of any specific SGLT2 inhibitor over the others, although dapagliflozin was associated with a larger increment in serum magnesium (WMD=0.16 mmol/L) compared with other SGLT2is. Similarly, no statistically detectable differences among the effects of SGLT2is on serum levels of other electrolytes were detected.
CONCLUSIONS
SGLT2is significantly increased serum magnesium and phosphate levels, consistent with a class effect of SGLT2 inhibition. However, further investigations of long-term efficacy and safety in patients with T2D with different clinical phenotypes are needed.
Topics: Diabetes Mellitus, Type 2; Electrolytes; Glucose; Humans; Hypoglycemic Agents; Magnesium; Network Meta-Analysis; Phosphates; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35582188
DOI: 10.34067/KID.0006672021 -
Frontiers in Pharmacology 2022Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for... (Review)
Review
Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (K), and small (SK) and large (BK) conductance calcium-activated K channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K channels can facilitate drug development for the treatment of various K channel-related disorders.
PubMed: 35273505
DOI: 10.3389/fphar.2022.831963 -
Journal of Periodontal Research Jan 2022The present systematic review examined the available evidence on distinctive salivary ion profile in periodontitis compared to periodontal health and provided a... (Review)
Review
OBJECTIVES
The present systematic review examined the available evidence on distinctive salivary ion profile in periodontitis compared to periodontal health and provided a qualitative assessment of the literature.
BACKGROUND
Macro and trace elements are essential for cellular physiology, and their changes in biological fluids can be revelatory of an underlying pathological status.
METHODS
Data from relevant studies identified from PubMed, Embase, and Scopus databases were retrieved to answer the following PECO question: "In systemically healthy individuals, are there any differences in any salivary macro or trace element concentration between periodontally healthy subjects (H) and patients with periodontitis (P)?" Quality of included studies was rated using a modified version of the QUADOMICS tool. A consistency analysis was performed to identify significantly discriminant chemical elements.
RESULTS
After the screening of 873 titles, 13 studies were included reporting data on 22 different elements. Among them, levels of sodium and potassium were consistently and significantly higher in P compared to H. Conflicting results were found for all the other elements, despite concentration of calcium, copper, and manganese mostly increased in saliva of P. Levels of magnesium were found higher in P than in H in 2 studies but lower in 3. Zinc resulted significantly increased in saliva from H compared to P individuals in 2 studies, but one study reported opposite results. Four studies were considered as high quality, while reporting of operative protocols and statistical analysis was a major limitation for the others. Due to high methodologic heterogeneity, meta-analysis was not performed.
CONCLUSIONS
Levels of macro or trace elements were differentially identified in saliva across diverse periodontal conditions, having a major potential for investigation of oral homeostasis and for high-resolution periodontal diagnosis. Products of inflammatory physiologic cellular impairment, such as sodium and potassium, were the most consistently associated with periodontitis (PROSPERO CRD42021235744).
Topics: Biomarkers; Humans; Periodontal Diseases; Periodontitis; Saliva; Trace Elements
PubMed: 34837226
DOI: 10.1111/jre.12956 -
International Journal of Molecular... Oct 2021The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide...
The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.
Topics: Amiloride; Animals; Epithelial Sodium Channels; Humans; Ion Transport; Lithium; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Structure, Quaternary; Sodium
PubMed: 34681656
DOI: 10.3390/ijms222010998 -
Archives of Biochemistry and Biophysics Oct 2021Mechanical environments were associated with alterations in bone metabolism. Ion channels present on bone cells are indispensable for bone metabolism and can be directly...
Mechanical environments were associated with alterations in bone metabolism. Ion channels present on bone cells are indispensable for bone metabolism and can be directly or indirectly activated by mechanical stimulation. This review aimed to discuss the literature reporting the mechanical regulatory effects of ion channels on bone cells and bone tissue. An electronic search was conducted in PubMed, Embase and Web of Science. Studies about mechanically induced alteration of bone cells and bone tissue by ion channels were included. Ion channels including TRP family channels, Ca release-activated Ca channels (CRACs), Piezo1/2 channels, purinergic receptors, NMDA receptors, voltage-sensitive calcium channels (VSCCs), TREK2 potassium channels, calcium- and voltage-dependent big conductance potassium (BK) channels, small conductance, calcium-activated potassium (SK) channels and epithelial sodium channels (ENaCs) present on bone cells and bone tissue participate in the mechanical regulation of bone development in addition to contributing to direct or indirect mechanotransduction such as altered membrane potential and ionic flux. Physiological (beneficial) mechanical stimulation could induce the anabolism of bone cells and bone tissue through ion channels, but abnormal (harmful) mechanical stimulation could also induce the catabolism of bone cells and bone tissue through ion channels. Functional expression of ion channels is vital for the mechanotransduction of bone cells. Mechanical activation (opening) of ion channels triggers ion influx and induces the activation of intracellular modulators that can influence bone metabolism. Therefore, mechanosensitive ion channels provide new insights into therapeutic targets for the treatment of bone-related diseases such as osteopenia and aseptic implant loosening.
Topics: Animals; Bone and Bones; Cell Line; Humans; Ion Channels; Mechanotransduction, Cellular; Receptors, Purinergic
PubMed: 34461086
DOI: 10.1016/j.abb.2021.109020 -
Clinical Oral Investigations Jul 2021To conduct a systematic review and meta-analysis to evaluate the risk and intensity of tooth sensitivity (TS) after topical application of desensitizers containing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To conduct a systematic review and meta-analysis to evaluate the risk and intensity of tooth sensitivity (TS) after topical application of desensitizers containing potassium nitrate before dental bleaching.
METHODS
We searched PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and SIGLE. We also surveyed gray literature without restrictions. We meta-analyzed the data using the random-effects model to compare potassium nitrate and placebo in terms of risk and intensity of TS and color change (∆SGU or ∆E). The quality of the evidence was rated using the GRADE approach. The risk of bias (RoB) of the included studies was analyzed using the Cochrane RoB tool.
RESULTS
After the database screening, 24 articles remained. A significant 12% lower risk for the groups where desensitizing agents were applied (p = 0.02), with a risk ratio of 0.88 (95% CI 0.78 to 0.98). About the intensity of TS, a significant average mean difference of - 0.77 units of VAS units (95%CI - 1.34 to - 0.19; p = 0.01) in favor of the desensitizer group. In the NRS scale, a significant average mean difference of - 0.36 (95% CI - 0.61 to - 0.12; p value = 0.004) in favor of the desensitizer group. No significant difference was observed in color change (p > 0.28) in ∆SGU and ∆E.
CONCLUSIONS
Although a significant reduction in the risk and intensity of TS was observed in groups treated with a potassium nitrate at some point during the bleaching, the clinical significance of this reduction is subtle and clinically questionable. Color change is not affected by the use of agents.
CLINICAL RELEVANCE
The reduction in the risk and intensity of TS with the topical application of potassium nitrate-based desensitizing agents in dental bleaching is subtle and maybe clinically questionable.
Topics: Dentin Sensitivity; Humans; Hydrogen Peroxide; Nitrates; Potassium Compounds; Tooth Bleaching; Tooth Bleaching Agents
PubMed: 34075489
DOI: 10.1007/s00784-021-03994-6 -
The Journal of Dermatological Treatment May 2022Molluscum contagiosum (MC) is a self-limited cutaneous viral infection. Topical 10% potassium hydroxide (KOH) has been used for treating MC. However, it remains unclear... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Molluscum contagiosum (MC) is a self-limited cutaneous viral infection. Topical 10% potassium hydroxide (KOH) has been used for treating MC. However, it remains unclear whether it is beneficial or not to apply topical 10% KOH for treating MC.
METHODS
To confirm the efficacy and safety of topical 10% KOH compared with placebo as well as other treatments for MC, meta-analysis was used. Up to September 2020, we performed a comprehensive search of literature based on three databases with following keywords including 'molluscum contagiosum' and 'potassium hydroxide'.
RESULTS
Our meta-analyses demonstrated a significant difference between topical 10% KOH and placebo for complete clearance of MC (RR: 2.96, 95% CI: 1.69 - 5.17, = .0001), while there were no statistical differences between them in the number of patients with adverse events (RR: 1.73, 95% CI: 0.67 - 4.45, = .2562). Also, topical 10% KOH was as effective as mechanical treatments for MC (RR: 0.95, 95% CI: 0.84 - 1.07, = .3833).
CONCLUSION
We demonstrate that application of topical 10% KOH may be one of effective and appropriate methods for the treatment of MC compared with awaiting spontaneous resolution due to its safety and effectiveness.
Topics: Administration, Topical; Humans; Hydroxides; Molluscum Contagiosum; Potassium
PubMed: 33667150
DOI: 10.1080/09546634.2021.1898527 -
Cardiovascular Drugs and Therapy Oct 2021Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK) and maintaining a long-term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia.
METHOD
We searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included.
RESULTS
Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK (-0.42 mmol/L; 95% CI: -0.63 to -0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p < 0.05). The risk of edema (4.30, 1.17 to 15.84; p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups.
CONCLUSIONS
SZC effectively decreased the sK level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.
Topics: Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Hyperkalemia; Ion Exchange Resins; Potassium; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Renin-Angiotensin System; Silicates
PubMed: 33459923
DOI: 10.1007/s10557-020-07134-2 -
Clinical Neurology and Neurosurgery Jan 2021To conduct a systematic review of the available literature for primary research articles identifying potential gene mutations, polymorphisms and other molecular...
OBJECTIVE
To conduct a systematic review of the available literature for primary research articles identifying potential gene mutations, polymorphisms and other molecular regulatory mechanisms related to trigeminal neuralgia in order to identify the genetic and molecular models of primary trigeminal neuralgia currently being investigated.
METHODS
PubMed and Web of Science were systematically searched to identify primary research articles discussing genetic predictors of trigeminal neuralgia and neuropathic pain that were published prior to July 2020. This review was conducted according to PRISMA guidelines.
RESULTS
Out of the 333 articles originally identified, a total of 14 papers were selected for study inclusion. These articles included 5 human studies, 6 mouse studies and 3 rat studies. Four articles investigated sodium channels, 1 investigated a sodium channel and nerve growth factor receptor, 2 investigated potassium channels, 1 investigated calcium channels, 1 investigated the downstream regulatory element antagonist modulator protein, 1 investigated the dynorphin-kappa opioid receptor system, 1 investigated TRPA1, 1 investigated the Nrg1/ErbB3/ErbB2 signaling complex, 1 investigated a serotonin transporter and 1 investigated potassium channels, sodium channels, calcium channels, chloride channels, TRP channels and gap junctions.
CONCLUSION
Researchers have identified multiple genetic and molecular targets involved with potential pathophysiologies that have a relationship to the creation of trigeminal neuralgia. At this time, there does not seem to be clear causal frontrunner, demonstrating the possibility that genetic predisposition to trigeminal neuralgia may involve multiple genes and/or downstream products, such as ion channels.
Topics: Animals; Genetic Predisposition to Disease; Humans; Ion Channels; Neuralgia; Polymorphism, Genetic; Trigeminal Neuralgia
PubMed: 33338828
DOI: 10.1016/j.clineuro.2020.106397 -
Kidney International Jan 2021Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the...
Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment.
Topics: Adult; Child; Consensus; Cystine; Cystinuria; Humans; Kidney; Quality of Life
PubMed: 32918941
DOI: 10.1016/j.kint.2020.06.035