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Indian Journal of Ophthalmology Jul 2024
Comparative Study
Topics: Humans; Intravitreal Injections; Administration, Oral; Rifampin; Central Serous Chorioretinopathy; Vascular Endothelial Growth Factor A; Propranolol; Angiogenesis Inhibitors; Adrenergic beta-Antagonists
PubMed: 38905466
DOI: 10.4103/IJO.IJO_2774_23 -
Circulation Research Jun 2024GPCRs (G protein-coupled receptors), also known as 7 transmembrane domain receptors, are the largest receptor family in the human genome, with ≈800 members. GPCRs... (Review)
Review
GPCRs (G protein-coupled receptors), also known as 7 transmembrane domain receptors, are the largest receptor family in the human genome, with ≈800 members. GPCRs regulate nearly every aspect of human physiology and disease, thus serving as important drug targets in cardiovascular disease. Sharing a conserved structure comprised of 7 transmembrane α-helices, GPCRs couple to heterotrimeric G-proteins, GPCR kinases, and β-arrestins, promoting downstream signaling through second messengers and other intracellular signaling pathways. GPCR drug development has led to important cardiovascular therapies, such as antagonists of β-adrenergic and angiotensin II receptors for heart failure and hypertension, and agonists of the glucagon-like peptide-1 receptor for reducing adverse cardiovascular events and other emerging indications. There continues to be a major interest in GPCR drug development in cardiovascular and cardiometabolic disease, driven by advances in GPCR mechanistic studies and structure-based drug design. This review recounts the rich history of GPCR research, including the current state of clinically used GPCR drugs, and highlights newly discovered aspects of GPCR biology and promising directions for future investigation. As additional mechanisms for regulating GPCR signaling are uncovered, new strategies for targeting these ubiquitous receptors hold tremendous promise for the field of cardiovascular medicine.
Topics: Humans; Receptors, G-Protein-Coupled; Animals; Cardiovascular Diseases; Signal Transduction; Drug Discovery; History, 21st Century; History, 20th Century
PubMed: 38900852
DOI: 10.1161/CIRCRESAHA.124.323067 -
International Journal of Molecular... May 2024Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement... (Review)
Review
Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.
Topics: Humans; Liver Cirrhosis; Cardiomyopathies; Animals; Adrenergic beta-Antagonists; Antioxidants
PubMed: 38892040
DOI: 10.3390/ijms25115849 -
Scientific Reports Jun 2024Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and...
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
Topics: Animals; Female; Binge Drinking; Male; Rats; Disease Models, Animal; Rats, Wistar; Ethanol; Adrenergic Antagonists; Naltrexone; Propranolol; Sex Factors; Alcohol Drinking
PubMed: 38890353
DOI: 10.1038/s41598-024-64565-9 -
Annals of Noninvasive Electrocardiology... Jul 2024This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta-blocker therapy (BB) and...
OBJECTIVES
This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta-blocker therapy (BB) and compare it to healthy controls.
METHODS
Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age-groups and four heart rate (HR) ranges.
RESULTS
In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age-groups compared to controls at HR 120-140 bpm (1-15 years: p < .01; 15-18 years: p = .03). At HR 80-100, LQT1 patients aged 1-10 years had lower HF than LQT2 patients (1-5 years: p = .05; 5-10 years: p = .02), and LQT2 patients aged 15-18 years had lower HF than LQT1 patients (p < .01). Symptomatic patients aged 10-15 years had lower PTOT at HR 100-120 bpm than asymptomatic patients (p = .04). LQT1 girls aged 10-15 and 15-18 years had a lower PTOT (10-15 years: p = .04; 15-18 years: p = .02) than boys.
CONCLUSION
This study shows a correlation between HR and changes in HRV parameters. At higher HRs, LQTS patients generally had lower HRV values than controls, suggesting an abnormal autonomic response. These results may strengthen the link between physical activity and arrhythmias in LQTS.
Topics: Humans; Adolescent; Female; Child; Male; Heart Rate; Electrocardiography, Ambulatory; Long QT Syndrome; Retrospective Studies; Child, Preschool; Infant; Case-Control Studies; Adrenergic beta-Antagonists
PubMed: 38888254
DOI: 10.1111/anec.13132 -
Vascular Health and Risk Management 2024Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the... (Review)
Review
Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the literature remains limited. We reported about a 1-year-old boy diagnosed with superficial KHE who received oral propranolol in combination with topical sirolimus and reviewed relevant reports and treatment of superficial KHE.
Topics: Humans; Infant; Male; Administration, Oral; Biopsy; Hemangioendothelioma; Propranolol; Sarcoma, Kaposi; Sirolimus; Treatment Outcome
PubMed: 38883398
DOI: 10.2147/VHRM.S461505 -
The American Journal of the Medical... Jun 2024Incomplete decongestion is the main cause of readmission in the early post-discharge period of a hospitalization for acute heart failure. Recent heart failure guidelines... (Review)
Review
Incomplete decongestion is the main cause of readmission in the early post-discharge period of a hospitalization for acute heart failure. Recent heart failure guidelines have highlighted initiation and rapid up-titration of quadruple therapy with angiotensin receptor neprilysin inhibitor, beta adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor to prevent hospitalizations for heart failure with reduced ejection fraction. However, full decongestion remains the foremost therapeutic goal of hospitalization for heart failure. While early addition of sodium glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists may be helpful, the value of the other therapeutics comes after decongestion is complete.
PubMed: 38880301
DOI: 10.1016/j.amjms.2024.06.002 -
Therapeutic Advances in Respiratory... 2024Some systematic reviews (SRs) on triple therapy (consisting of long-acting β-agonist, long-acting muscarinic antagonist, and inhaled corticosteroid, LABA/LAMA/ICS) for...
BACKGROUND
Some systematic reviews (SRs) on triple therapy (consisting of long-acting β-agonist, long-acting muscarinic antagonist, and inhaled corticosteroid, LABA/LAMA/ICS) for chronic obstructive pulmonary disease (COPD) have reported conflicting results. As the number of syntheses increases, the task of identifying and interpreting evidence becomes increasingly complex and demanding.
OBJECTIVES
To provide a comprehensive overview of the efficacy and safety of triple therapy for COPD.
DESIGN
Overview of SRs.
METHODS
Two independent reviewers conducted comprehensive searches in PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant SRs that compared triple therapy with any non-triple therapy for COPD, from the inception of these databases until 1 June 2023. The AMSTAR 2 and GRADE tools were utilized to assess the quality of the included studies and the evidence for each outcome.
RESULTS
Eighteen SRs encompassing 30 original studies and involving 47,340 participants were analyzed. The overall AMSTAR 2 rating revealed that 3 SRs were of low quality, 13 SRs were of critically low quality, and 2 SRs were of high quality. No high-certainty evidence revealed a significant advantage of triple therapy in improving lung function or reducing acute exacerbations. However, all evidence, including one high certainty, supported the benefits of improving quality of life. Regarding all-cause mortality, no significant difference was found when compared to LAMA or ICS/LABA; however, high-certainty evidence confirmed its effectiveness when compared with LABA/LAMA. Notably, high-certainty evidence indicated that triple therapy was associated with a significant increase in the risk of pneumonia compared to LABA/LAMA.
CONCLUSION
Triple therapy demonstrated notable benefits in improving lung function, reducing exacerbations, improving quality of life, and reducing all-cause mortality. However, it is important to note that it may also significantly increase the risk of pneumonia.
TRIAL REGISTRATION
This overview protocol was prospectively registered with PROSPERO (No. CRD42023431548).
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Systematic Reviews as Topic; Drug Therapy, Combination; Muscarinic Antagonists; Treatment Outcome; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenal Cortex Hormones; Bronchodilator Agents; Lung; Quality of Life
PubMed: 38877687
DOI: 10.1177/17534666241259634 -
Annals of Noninvasive Electrocardiology... Jul 2024The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF... (Comparative Study)
Comparative Study
BACKGROUND
The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF patients treated with BB have a similar HR response to 6MWT as the AF and sinus rhythm (SR) patients without BB treatment at the same resting HR level.
METHODS
The before-after study involving 74 AF patients was to evaluate the effect of BB treatment (pre-BB and with BB). The comparison study included 74 BB-treated AF patients (with BB), 74 matched AF patients without BB (no BB), and 74 SR patients. The percentage increase amplitude of HR (HR-PIA) in 6MWT was calculated: [(the exercise HR - the resting HR)/(the resting HR)] × 100%.
RESULTS
The before-after study showed that BB treatment decreased the resting and mean exercise HR (98.6 ± 15.2 vs. 85.5 ± 11.2 bpm and 121.3 ± 17.3 vs. 109.0 ± 16.7 bpm) during 6MWT. The comparison study demonstrated that against the SR, the AF with BB and no BB groups have higher mean exercise HR-PIA (28.2 ± 17.1% and 22.0 ± 9.6%, vs. 6.9 ± 3.7%) when their resting HR is similar. Moreover, the mean exercise HR-PIA was also significantly higher in the with BB group than in the no BB group.
CONCLUSION
In AF patients with relatively higher resting HR, BB treatment could decrease the resting and exercise HR during 6MWT. However, BB treatment could not effectively attenuate the exercise HR rise as compared with AF without BB treatment, even with similar resting HR levels.
Topics: Humans; Atrial Fibrillation; Heart Rate; Male; Female; Adrenergic beta-Antagonists; Aged; Middle Aged; Exercise Test; Walk Test; Walking; Treatment Outcome; Electrocardiography
PubMed: 38872457
DOI: 10.1111/anec.13128 -
Bioscience Reports Jun 2024High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the...
High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the major cause of morbidity and mortality in these patients. Current drug therapy to reduce portal pressure is mainly limited to β-adrenergic receptor blockade but about forty percent of patients do not respond. Our aim was to use microarray to measure the expression of ~20,800 genes in portal vein from patients with PH undergoing transplantation for liver cirrhosis (PH, n = 12) versus healthy vessels (control, n = 9) to identify potential drug targets to improve therapy. Expression of 9,964 genes above background was detected in portal vein samples. Comparing PH veins versus control (adjusted p value < 0.05, fold change > 1.5) identified 548 upregulated genes and 1,996 downregulated genes. The 2,544 differentially expressed genes were subjected to pathway analysis. We identified 49 significantly enriched pathways. The endothelin pathway was ranked the tenth most significant, the only vasoconstrictive pathway to be identified. ET-1 gene (EDN1) was significantly upregulated, consistent with elevated levels of ET-1 peptide previously measured in PH and cirrhosis. ETA receptor gene (EDNRA) was significantly downregulated, consistent with an adaptive response to increased peptide levels in the portal vein but there was no change in the ETB gene (EDNRB). The results provide further support for evaluating the efficacy of ETA receptor antagonists as a potential therapy in addition to β-blockers in patients with PH and cirrhosis.
PubMed: 38860875
DOI: 10.1042/BSR20240528