Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
1.
Mol Biol Rep ; 49(3): 2321-2324, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1664478

ABSTRACT

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/complications , Glucosides/therapeutic use , Renin-Angiotensin System/drug effects , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Angiotensin-Converting Enzyme 2/physiology , Clinical Trials, Phase III as Topic , Double-Blind Method , Drug Repositioning , Heart Diseases/prevention & control , Humans , Kidney Diseases/prevention & control , Mitochondria/drug effects , Multicenter Studies as Topic , Oxidative Stress/drug effects , Randomized Controlled Trials as Topic , Receptors, Virus/physiology , Respiratory Insufficiency/etiology , Sodium-Glucose Transporter 2/physiology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology
2.
FASEB J ; 35(9): e21870, 2021 09.
Article in English | MEDLINE | ID: covidwho-1373669

ABSTRACT

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium-induced intestinal inflammation in mice. It inhibited the production of pro-inflammatory cytokines IL-6 and TNFα, and promoted the expression of anti-inflammatory cytokine IL-10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS-stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half-life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down-regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal-specific KLHL5 deficiency, a CUL3-interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3-KLHL5 may function as an E3 for ATF2 degradation.


Subject(s)
Activating Transcription Factor 2/metabolism , Down-Regulation/drug effects , Drugs, Chinese Herbal/pharmacology , Flavanones/pharmacology , Glucosides/pharmacology , Inflammation/drug therapy , Proteolysis/drug effects , Ubiquitin Thiolesterase/deficiency , Animals , Cell Line , Colitis/chemically induced , Colitis/drug therapy , Cullin Proteins/metabolism , Cytokines/metabolism , Dextran Sulfate/pharmacology , Dextran Sulfate/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Flavanones/therapeutic use , Glucosides/therapeutic use , Inflammation/chemically induced , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Phosphorylation/drug effects , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Pyrroles/pharmacology , Pyrrolidines/pharmacology , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitination
3.
Lancet Diabetes Endocrinol ; 9(9): 550-551, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322420
4.
J Cardiovasc Pharmacol ; 78(1): e12-e19, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1232234

ABSTRACT

ABSTRACT: Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (coronavirus disease 2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Clinical Trials, Phase III as Topic , Comorbidity , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Disease Progression , Glucosides/adverse effects , Humans , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Treatment Outcome
5.
Diabet Med ; 38(2): e14458, 2021 02.
Article in English | MEDLINE | ID: covidwho-1214788

ABSTRACT

Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI ≥27 kg/m2 . Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration among other precipitating factors for diabetic ketoacidosis.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetic Ketoacidosis/epidemiology , Overweight/metabolism , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Drug Therapy, Combination , Glucosides/therapeutic use , Glycosides/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Overweight/complications , Practice Guidelines as Topic , United Kingdom
6.
Diabetes Obes Metab ; 23(4): 886-896, 2021 04.
Article in English | MEDLINE | ID: covidwho-1171152

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS: DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS: DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Cardiovascular Diseases/prevention & control , Glucosides/therapeutic use , Kidney Diseases/prevention & control , Mortality , Respiratory Insufficiency/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Atherosclerosis/epidemiology , COVID-19/complications , COVID-19/epidemiology , Cardiometabolic Risk Factors , Cardiovascular Diseases/etiology , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Double-Blind Method , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Kidney Diseases/etiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/epidemiology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Treatment Outcome
7.
Clin Nutr ESPEN ; 43: 197-199, 2021 06.
Article in English | MEDLINE | ID: covidwho-1135287

ABSTRACT

The COVID-19 pandemic as the largest global public health crisis is now considered as an emergency at the World Health Organization (WHO). As there is no specific therapy for SARS-CoV-2 infection at present and also because of the long time it takes to discover a new drug and the urgent need to respond urgently to a pandemic infection. Perhaps the best way right now is to find an FDA-approved drug to treat this infection. Oxidative stress and inflammation play a vital role in the progression of tissue injury in COVID-19 patients; furthermore, the G6PD activation is related to increased oxidative inflammation in acute pulmonary injury. In this regard, we propose a new insight that may be a good strategy for this urgency. Exploiting G6PD through inhibiting G6PD activity by modifying redox balance, metabolic switching and protein-protein interactions can be proposed as a new approach to improving patients in severe stage of COVID 19 through various mechanisms. Polydatin is isolated from many plants such as Polygonum, peanuts, grapes, red wines and many daily diets that can be used in severe stage of COVID-19 as a G6PD inhibitor. Furthermore, polydatin possesses various biological activities such as anti-inflammatory, antioxidant, immunoregulatory, nephroprotective, hepatoprotective, anti-arrhythmic and anti-tumor. Our hypothesis is that the consumption of antioxidants such as Polydatin (a glucoside of resveratrol) as a complementary therapeutic approach may be effective in reducing oxidative stress and inflammation in patients with COVID-19.


Subject(s)
Antioxidants/therapeutic use , COVID-19/drug therapy , Glucosephosphate Dehydrogenase/antagonists & inhibitors , Glucosides/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Resveratrol/therapeutic use , Stilbenes/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , COVID-19/complications , COVID-19/metabolism , Glucosides/pharmacology , Humans , Inflammation/drug therapy , Inflammation/etiology , Inflammation/metabolism , Lung/drug effects , Magnoliopsida/chemistry , Oxidative Stress/drug effects , Pandemics , Plant Extracts/pharmacology , Resveratrol/pharmacology , SARS-CoV-2 , Stilbenes/pharmacology
8.
Circ Heart Fail ; 14(3): e007048, 2021 03.
Article in English | MEDLINE | ID: covidwho-1119347

ABSTRACT

BACKGROUND: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. METHODS: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. RESULTS: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (P=0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (P=0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (P=0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. CONCLUSIONS: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.


Subject(s)
Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Heart Failure/drug therapy , Hospitalization , Kidney/drug effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Aged , Aged, 80 and over , Benzhydryl Compounds/adverse effects , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19 , Creatinine/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/physiopathology , Early Termination of Clinical Trials , Female , Glucosides/adverse effects , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Japan , Kidney/physiopathology , Male , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Time Factors , Treatment Outcome
9.
Diabetes Obes Metab ; 23(4): 886-896, 2021 04.
Article in English | MEDLINE | ID: covidwho-1039811

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS: DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS: DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Cardiovascular Diseases/prevention & control , Glucosides/therapeutic use , Kidney Diseases/prevention & control , Mortality , Respiratory Insufficiency/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Atherosclerosis/epidemiology , COVID-19/complications , COVID-19/epidemiology , Cardiometabolic Risk Factors , Cardiovascular Diseases/etiology , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Double-Blind Method , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Kidney Diseases/etiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/epidemiology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Treatment Outcome
11.
Diabetes Metab Syndr ; 14(4): 405-406, 2020.
Article in English | MEDLINE | ID: covidwho-102280

ABSTRACT

It has been reported that frequent occurrence of COVID-19 infection in these patients is associated with low cytosolic pH. During virus infection, serum lactate dehydrogenase (LDH) level excessively rises. LDH is a cytosolic enzyme and the serum level increases as the cell break down. When anaerobic conditions develop, lactate formation increases from pyruvate. Cell pH is regulated by very complex mechanisms. When lactate increases in the extracellular area, this symporter carries lactate and H+ ion into the cell, and the intracellular pH quickly becomes acidic. Paradoxically, Na+/H+ exchanger activation takes place. While H+ ion is thrown out of the cell, Na+ and Ca+2 enter the cell. When Na+ and Ca+2 increase in the cell, the cells swell and die. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor. Dapagliflozin has been reported to reduce lactate levels by various mechanisms. Also, it reduces oxygen consumption in tissues and causes the use of glucose in the aerobic pathway, thereby reducing lactate production. A lactate decrease in the environment reduces the activation of lactate/H+ symporter. Thus, the H ion pumping into the cell by this symporter is reduced and the cytosolic pH is maintained. Dapagliflozin also directly inhibits NHE. Thus, Na+ and Ca+2 flow to the cell are inhibited. Dapagliflozin provides the continuation of the structure and functions of the cells. Dapagliflozin can prevent the severe course of COVID-19 infection by preventing the lowering of cytosolic pH and reducing the viral load.


Subject(s)
Benzhydryl Compounds/therapeutic use , Betacoronavirus , Coronavirus Infections/prevention & control , Diabetes Mellitus/drug therapy , Glucosides/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Dehydration/prevention & control , Diabetes Mellitus/epidemiology , Humans , Insulin/therapeutic use , Lactic Acid/metabolism , Oxygen Consumption/drug effects , Pneumonia, Viral/epidemiology , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL