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Danish Medical Journal Jun 2024Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute...
INTRODUCTION
Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs.
METHODS
This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward. Remote dielectric sensing (ReDS) will directly measure lung fluid content, and cardiac filling pressures will be assessed by echocardiography with Doppler and strain analysis.
CONCLUSIONS
This study will examine if furosemide leads to a hyperacute reduction in pulmonary congestion assessed by ReDS independent of diuretic effects in patients with AHF. We hypothesise that the haemodynamic effect of furosemide shown on pulmonary congestion may explain the subjective instant relief in patients with AHF receiving furosemide.
FUNDING
Dr. Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by the Danish Heart Foundation.
TRIAL REGISTRATION
This protocol was approved by the Scientific Ethical Committee, H-23029822, and the Danish Data Protection Agency P-2013-14703. The protocol was registered with ClinicalTrial.org on 29 August 2023 (Identifier: NCT06024889).
Topics: Furosemide; Humans; Heart Failure; Prospective Studies; Pulmonary Edema; Diuretics; Acute Disease; Remote Sensing Technology; Female; Male; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 38903022
DOI: 10.61409/A11230697 -
BMC Gastroenterology Jun 2024In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently...
BACKGROUND
In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework.
METHODS
The study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ.
RESULTS
The analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of 'economic consequences of intervention' showed the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'.
CONCLUSION
Employing the EVIDEM framework, VPZ's value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.
Topics: Sulfonamides; Pyrroles; Humans; Proton Pump Inhibitors; China; Gastroesophageal Reflux; Decision Support Techniques; Cost-Benefit Analysis
PubMed: 38902604
DOI: 10.1186/s12876-024-03297-6 -
Bioresource Technology Jun 2024Limited information is available on the removal of per- and polyfluoroalkyl substances (PFAS) in anaerobic digestion (AD). Τhe fate of six PFAS was studied in...
Limited information is available on the removal of per- and polyfluoroalkyl substances (PFAS) in anaerobic digestion (AD). Τhe fate of six PFAS was studied in thermophilic bioreactors in the presence of granular activated carbon (GAC) and voltage application. Reactors with GAC exhibited lower concentrations of volatile fatty acids and higher methane production compared to those with and without the application of voltage. Analysis of PFAS in dissolved and solid phase showed that their distribution was dependent on perfluorocarbon chain length and functional group. Mass balances showed that PFAS were not removed during conventional AD or after applying voltage; however, significant removal (up to 61 ± 8 %) was observed in bioreactors with GAC for perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS). Biomass characterization showed that in these bioreactors, the relative abundance of Acinetobacter and Pseudomonas was higher, indicating their potential role in PFAS biotransformation.
PubMed: 38901748
DOI: 10.1016/j.biortech.2024.131013 -
Journal of Materials Science. Materials... Jun 2024Tissue engineering holds promise for developing therapeutic applications using viscous materials e.g. hydrogels. However, assessing the cytotoxicity of such materials... (Comparative Study)
Comparative Study
Tissue engineering holds promise for developing therapeutic applications using viscous materials e.g. hydrogels. However, assessing the cytotoxicity of such materials with conventional assays can be challenging due to non-specific interactions. To address this, we optimized a live/dead staining method for quantitative evaluation and compared it with the conventional CCK8 assay. Our MicroDrop method involved seeding droplets containing 5000 cells in 10 µl medium on 12-well plates. After allowing them to adhere for 4 h, various viscous samples were applied to the cells and measurements were conducted using a fluorescence microscope immediately and at daily intervals up to 72 h. A sodium dodecyl sulfate (SDS) dilution series compared the MicroDrop with the CCK8 assay. The findings revealed a cell-type specific pattern for 10 mg/ml hyaluronic acid (HA), wherein MC3T3-E1 cells maintained 95% viability until 72 h, while L929 cells experienced a gradual decline to 17%. 2 mg/ml HA exhibited consistent viability above 90% across all time points and cell lines. Similarly, fibrin demonstrated 90% viability across dilutions and time points, except for undiluted samples showing a decrease from 85% to 20%. Gelatin-methacrylol sustained viability above 70% across all time points at both 5% and 10% concentrations. The comparison of the SDS dilution series between viability (MicroDrop) and metabolic activity (CCK8) assay showed a correlation coefficient of 0.95. The study validates the feasibility of the established assay, providing researchers with an efficient tool for assessing cytotoxicity in viscous materials. Additionally, it holds the potential to yield more precise data on well-known hydrogels.
Topics: Hydrogels; Mice; Animals; Cell Survival; Hyaluronic Acid; Viscosity; Cell Line; Materials Testing; Biocompatible Materials; Tissue Engineering; Sodium Dodecyl Sulfate; Gelatin; Fibrin
PubMed: 38900233
DOI: 10.1007/s10856-024-06800-3 -
Oncology (Williston Park, N.Y.) Jun 2024The June Hot Topics focuses on the challenges venetoclax regimens have faced in multiple myeloma trials.
The June Hot Topics focuses on the challenges venetoclax regimens have faced in multiple myeloma trials.
Topics: Multiple Myeloma; Humans; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Chromosomes, Human, Pair 14; Antineoplastic Agents; Translocation, Genetic; Chromosomes, Human, Pair 11; Clinical Trials as Topic; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38899981
DOI: 10.46883/2024.25921023 -
The New England Journal of Medicine Jun 2024The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but...
BACKGROUND
The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown.
METHODS
We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs. A phase 2 expansion in patients with germinal-center B-cell (GCB) and non-GCB DLBCL was performed. ViPOR was administered every 21 days for six cycles.
RESULTS
In phase 1b of the study, involving 20 patients (10 with DLBCL), a single dose-limiting toxic effect of grade 3 intracranial hemorrhage occurred, a result that established venetoclax at a dose of 800 mg as the recommended phase 2 dose. Phase 2 included 40 patients with DLBCL. Toxic effects that were observed among all the patients included grade 3 or 4 neutropenia (in 24% of the cycles), thrombocytopenia (in 23%), anemia (in 7%), and febrile neutropenia (in 1%). Objective responses occurred in 54% of 48 evaluable patients with DLBCL, and complete responses occurred in 38%; complete responses were exclusively in patients with non-GCB DLBCL and high-grade B-cell lymphoma with rearrangements of and or (or both). Circulating tumor DNA was undetectable in 33% of the patients at the end of ViPOR therapy. With a median follow-up of 40 months, 2-year progression-free survival and overall survival were 34% (95% confidence interval [CI], 21 to 47) and 36% (95% CI, 23 to 49), respectively.
CONCLUSIONS
Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.).
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Female; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Sulfonamides; Aged; Male; Bridged Bicyclo Compounds, Heterocyclic; Lenalidomide; Piperidines; Adult; Antibodies, Monoclonal, Humanized; Prednisone; Adenine; Aged, 80 and over; Recurrence; Pyrazoles; Pyrimidines; Molecular Targeted Therapy; Progression-Free Survival
PubMed: 38899693
DOI: 10.1056/NEJMoa2401532 -
BioMed Research International 2024In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with...
MATERIALS AND METHODS
In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with MRSA. Various treatments were applied to the burn wounds daily, including Myrtus ointment, silver nanoparticles, silver nanoparticles-Myrtus ointment, silver sulfadiazine-Myrtus ointment, silver sulfadiazine 1%, mupirocin ointment, and a positive control. The study measured the antimicrobial effects, wound area, percentage of wound healing, antioxidant capacities, malondialdehyde, and nitric oxide concentrations in the serum of the rats. Data analysis was performed using GraphPad software, with one-way ANOVA and Tukey's tests used to determine the statistical significance of the results.
RESULTS
Rats treated with Myrtus ointment, silver nanoparticles-Myrtus ointment, and mupirocin had reduced bacterial growth compared to the positive control group, nanoparticle ointment, and silver sulfadiazine ( < 0.05). The wound area of the Myrtus ointment group decreased significantly on the seventh and fourteenth days, as well as the level of MDA and nitric oxide, compared to the other groups. In Myrtus and silver sulfadiazine-Myrtus ointment increased the thickness of the epidermis and dermis compared to the other groups.
CONCLUSION
Based on the anti-inflammatory, antimicrobial, and wound healing properties of Myrtus, with further studies, an ointment of this plant may be used as a main or complementary treatment for burn wound infections caused by MRSA.
Topics: Animals; Wound Healing; Methicillin-Resistant Staphylococcus aureus; Burns; Plant Extracts; Male; Ointments; Rats; Rats, Wistar; Anti-Inflammatory Agents; Plant Leaves; Myrtus; Anti-Infective Agents; Wound Infection; Staphylococcal Infections; Metal Nanoparticles; Silver Sulfadiazine
PubMed: 38899039
DOI: 10.1155/2024/6758817 -
Nature Communications Jun 2024Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their...
Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their synthesis using conventional methods presents significant challenges. In this study, we introduce a practical and efficient approach that harnesses hydrogen atom transfer photocatalysis to activate volatile alkanes, such as isobutane, butane, propane, ethane, and methane. Subsequently, these nucleophilic radicals react with SO to yield the corresponding sulfinates. These sulfinates then serve as versatile building blocks for the synthesis of diverse sulfur-containing organic compounds, including sulfones, sulfonamides, and sulfonate esters. Our use of flow technology offers a robust, safe and scalable platform for effectively activating these challenging gaseous alkanes, facilitating their transformation into valuable sulfinates.
PubMed: 38897988
DOI: 10.1038/s41467-024-49322-w -
Life Sciences Aug 2024Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in...
AIMS
Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study.
MAIN METHODS
PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid.
KEY FINDINGS
PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stage-dependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth.
SIGNIFICANCE
PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.
Topics: Connexins; Colonic Neoplasms; Animals; Humans; Mice; Mice, Inbred BALB C; Nerve Tissue Proteins; Disease Progression; Female; Mice, SCID; Mice, Inbred NOD; Male; Cell Proliferation; Cell Line, Tumor; Xenograft Model Antitumor Assays; Gene Expression Regulation, Neoplastic; Probenecid; HCT116 Cells; Biomarkers, Tumor; Cell Survival
PubMed: 38897345
DOI: 10.1016/j.lfs.2024.122851 -
International Journal of Hygiene and... Jul 2024Bisphenol A (BPA) is a well-known endocrine disrupter used in several consumer products. Restricted use of BPA has led to increased use of bisphenol F (BPF) and...
BACKGROUND
Bisphenol A (BPA) is a well-known endocrine disrupter used in several consumer products. Restricted use of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). While previous studies found no associations between prenatal BPA and BPF exposure and bone mineral density (BMD), two recent cohort studies found that prenatal BPS exposure was negatively associated with bone mineral density in the offspring.
AIM
To determine possible associations between maternal and child urinary bisphenol concentrations, BMD and bone mineral content (BMC) in 7-year-old healthy children.
METHODS
Pregnant women were recruited in 2010-2012 to participate in the Odense Child Cohort (OCC), Denmark. Maternal urine samples were collected in gestational week 28 and urinary BPA concentration was measured by isotope diluted LC-MS/MS. The children delivered a urine sample at age 7 years in which BPA, BPF and BPS were measured by an extended LS-MS/MS method based on the original method. At age 7 years DXA scans were performed and BMC and Z-score for BMD calculated. Associations between osmolality adjusted urinary maternal BPA and child BPA, BPF and BPS concentrations and BMC and BMD Z-score were examined by multiple linear regression analysis adjusted for potential confounders. Additionally, a combined effect of the bisphenols were evaluated by including the sum of child urinary BPA, BPF and BPS concentrations in the statistical analyses.
RESULTS
A total of 546 mothers and 453 children aged 7 years participated. BPA was detected in 84% and 96% of the maternal and child urine samples, respectively. We found no significant association between maternal urinary BPA concentration during pregnancy and BMC and BMD Z-score in 7-year-old children. In addition, no association between current bisphenol exposure in tertiles and bone density was found, interestingly, current BPA and summed bisphenol exposure in the highest 10% was associated with lower BMD Z-score at age 7-years, statistically significant for boys.
CONCLUSION
In these low exposed children we found no association between prenatal or current bisphenol exposure in tertiles and BMD in healthy children, however, the highest 10% exposed children had lower BMD, significant for boys, suggesting a negative impact with high bisphenol exposure. The short half-lives of bisphenols and the cross-sectional nature of the child exposure prompt more longitudinal studies to further clarify this topic.
Topics: Humans; Phenols; Child; Female; Benzhydryl Compounds; Bone Density; Male; Prenatal Exposure Delayed Effects; Pregnancy; Sulfones; Denmark; Cohort Studies; Endocrine Disruptors; Environmental Pollutants; Adult; Environmental Exposure; Maternal Exposure
PubMed: 38896984
DOI: 10.1016/j.ijheh.2024.114408