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Journal of the American Board of Family... 2024Consider IV Acetazolamide in addition to standard IV loop diuretic therapy in patients hospitalized for acute decompensated heart failure..
Consider IV Acetazolamide in addition to standard IV loop diuretic therapy in patients hospitalized for acute decompensated heart failure..
Topics: Humans; Acetazolamide; Heart Failure; Acute Disease; Sodium Potassium Chloride Symporter Inhibitors; Diuretics; Carbonic Anhydrase Inhibitors
PubMed: 38740482
DOI: 10.3122/jabfm.2023.230379R0 -
JACC. Heart Failure Apr 2024Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients.
BACKGROUND
Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients.
OBJECTIVE
To compare the potency and safety of commonly used diuretic regimens in CHF patients.
METHODS
A prospective, randomized, open-label, crossover study conducted in NYHA class II-IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250mg; IV furosemide 250mg plus oral metolazone 5mg; and IV furosemide 250mg plus IV acetazolamide 500mg. Treatments were administered once a week, in one of six randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation.
RESULTS
A total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4691 mg (95% CI: 4153-5229) compared to furosemide alone 3835 mg (95% CI: 3279-4392), P=0.015 and to furosemide plus acetazolamide 3584 mg (95% CI: 3020-4148), P=0.001. Furosemide plus metolazone resulted in 1.84 liters of urine (95% CI: 1.63-2.05), compared to 1.58 liters (95% CI: 1.37-1.8) P=0.039 collected following administration of furosemide plus acetazolamide and 1.71 liters (95% CI 1.49-1.93) following furosemide alone. The incidence of worsening renal function (WRF) was significantly higher when adding metolazone (41%) to furosemide compared to furosemide alone (17%) and to furosemide plus acetazolamide (2.6%), P<0.001.
CONCLUSIONS
In ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared to IV furosemide alone or furosemide plus acetazolamide.
PubMed: 38739124
DOI: 10.1016/j.jchf.2024.04.014 -
ACS Omega May 2024The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and...
The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are linked with various disorders including Alzheimer's disease. In this study, six new nicotinic hydrazide derivatives (-) were designed and synthesized for the first time, and their inhibitory profiles against hCA I, hCA II, AChE, and BChE were investigated by assays and studies. The structures of novel molecules were elucidated by using spectroscopic techniques and elemental analysis. These molecules showed inhibitory activities against hCA I and II with IC values ranging from 7.12 to 45.12 nM. Compared to reference drug acetazolamide (AZA), compound was the most active inhibitor against hCA I and II. On the other hand, it was determined that IC values of the tested molecules ranged between 21.45 and 61.37 nM for AChE and between 18.42 and 54.74 nM for BChE. Among them, compound was the most potent inhibitor of AChE and BChE, with IC values of 21.45 and 18.42 nM, respectively. In order to better understand the mode of action of these new compounds, state-of-the-art molecular modeling techniques were also conducted.
PubMed: 38737075
DOI: 10.1021/acsomega.3c10182 -
International Journal of Molecular... Apr 2024In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is...
In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca entry triggers a transepithelial Ca flux to regulate proximal tubular (PT) luminal [Ca], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca entry compared to the WT counterparts because of significant inhibition by the store-operated Ca entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca entry) inhibitors (Pyr10), Ca entry by WTT cells was moderately inhibited, suggesting that the Ca and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.
Topics: Animals; Hypercalciuria; Hydrogen-Ion Concentration; Mice; Mice, Knockout; Calcium Oxalate; Kidney Calculi; Calcium Phosphates; Nephrolithiasis; Calcium; TRPC Cation Channels; Kidney Tubules, Proximal; Male; Disease Models, Animal; Mice, Inbred C57BL; Acetazolamide
PubMed: 38732005
DOI: 10.3390/ijms25094787 -
Mikrochimica Acta May 2024The first electrochemical sensor application in the literature is described for the sensitive and selective determination of the selective Janus kinase (JAK)-1...
The first electrochemical sensor application in the literature is described for the sensitive and selective determination of the selective Janus kinase (JAK)-1 inhibitor abrocitinib (ABR). ABR is approved by the U.S. Food and Drug Administration (FDA) for the treatment of atopic dermatitis. The molecularly imprinted polymer (MIP)-based sensor was designed to incorporate zinc nanoflower (ZnNFs)-graphene oxide (GO) conjugate (ZnNFs@GO), synthesized from the root methanolic extract (RME) of the species Alkanna cappadocica Boiss. et Bal. to improve the porosity and effective surface area of the glassy carbon electrode (GCE). Furthermore, the MIP structure was prepared using ABR as a template molecule, 4-aminobenzoic acid (4-ABA) as a functional monomer, and other additional components. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the surface and structure of the synthesized nanomaterial and MIP-based surface. Among the electrochemical methods, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were preferred for detailed electrochemical characterization, and differential pulse voltammetry (DPV) was preferred for all other electrochemical measurements using 5.0 mM [Fe(CN)] solution as the redox probe. The MIP-based sensor, which was the result of a detailed optimization phase, gave a linear response in the 1.0 × 10 - 1.0 × 10 M range in standard solution and serum sample. The obtained limit of detection (LOD) and limit of quantification (LOQ) values and recovery studies demonstrated the sensitivity, accuracy, and applicability of the sensor. Selectivity, the most important feature of the MIP-based sensor, was verified by imprinting factor calculations using ibrutinib, ruxolitinib, tofacitinib, zonisamide, and acetazolamide.
Topics: Molecularly Imprinted Polymers; Electrochemical Techniques; Limit of Detection; Zinc; Graphite; Humans; Aminoimidazole Carboxamide; Nanostructures; Electrodes
PubMed: 38730044
DOI: 10.1007/s00604-024-06404-2 -
American Journal of Otolaryngology 2024Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical...
Evaluation of clinical predictors of postoperative outcomes in tegmen defect patients with and without concurrent superior semicircular canal dehiscence and cerebrospinal fluid leak.
OBJECTIVES
Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical utility of intraoperative intracranial pressure measurements has yet to be tested. This report aims to use intraoperative opening pressure and concurrent superior semicircular canal dehiscence (SSCD) to analyze factors influencing disease course and clinical outcomes in patients with tegmen dehiscence.
METHODS
A retrospective analysis of 61 patients who underwent tegmen defect repair was performed. Multiple variables of interest including body mass index (BMI), presence of SSCD, presence of dural venous sinus stenosis, opening pressure, and acetazolamide therapy use were recorded. The cohort was divided into those with or without concurrent SSCD and those presenting with or without cerebrospinal fluid (CSF) leak for analysis.
RESULTS
A linear relationship between opening pressure and BMI (p = 0.009) was noted; however, intraoperative opening pressure was not associated with disease outcome. Concurrent SSCD was present in 25 % of patients, while 62 % presented with CSF leak. The concurrent SSCD group exhibited higher opening pressure, higher likelihood of having dural sinus stenosis, and higher likelihood of being discharged on acetazolamide. The CSF leak group had higher likelihood of obstructive sleep apnea and persistent symptoms.
CONCLUSIONS
In patients undergoing tegmen defect repair, concurrent SSCD suggests increased disease severity. The presence of preoperative CSF leak predicts persistent symptoms following repair. BMI is linearly correlated with intracranial pressure in these patients.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Cerebrospinal Fluid Leak; Semicircular Canals; Semicircular Canal Dehiscence; Treatment Outcome; Adult; Body Mass Index; Aged; Intracranial Pressure; Postoperative Complications; Acetazolamide
PubMed: 38729011
DOI: 10.1016/j.amjoto.2024.104317 -
Wilderness & Environmental Medicine May 2024Prophylactic use of acetazolamide (ACZ) to prevent acute mountain sickness (AMS) is a common practice among high altitude travelers and mountaineers. With its use comes...
Prophylactic use of acetazolamide (ACZ) to prevent acute mountain sickness (AMS) is a common practice among high altitude travelers and mountaineers. With its use comes a possible risk of acute kidney injury (AKI). We present a case in which a 56-year-old male hiker in Grand Canyon National Park developed acute exertional rhabdomyolysis and subsequent AKI while taking prophylactic ACZ to prevent AMS. This medication was prescribed despite the hiker encountering only moderate altitude at Grand Canyon with a planned descent within <24 h. The resulting AKI was determined to be the combined result of acute exertional rhabdomyolysis and dehydration/hypovolemia, with the ACZ, a diuretic, as a contributing factor. Medical providers need to recognize the risks/benefits with ACZ use for AMS prophylaxis and avoid prescribing it to individuals whose altitude exposure and activity fall outside the clinical practice guidelines recommended for use.
PubMed: 38725416
DOI: 10.1177/10806032241249452 -
Cureus Apr 2024The morning glory (MG) disc anomaly is a congenital excavation of the posterior globe involving the optic disc, with a distinct appearance reminiscent of the MG flower....
The morning glory (MG) disc anomaly is a congenital excavation of the posterior globe involving the optic disc, with a distinct appearance reminiscent of the MG flower. Various intracranial and ocular associations with MG have been documented. Conditions such as trans-sphenoidal encephalocele and hypoplasia of the intracranial vasculature have been observed in association with this anomaly. In this report, we present a case of MG optic disc anomaly accompanied by serous macular detachment.
PubMed: 38721220
DOI: 10.7759/cureus.57817 -
Acute Coronary Syndrome at Altitude: Diagnostic Dilemma on Aconcagua Using Point-of-Care Ultrasound.Wilderness & Environmental Medicine May 2024At the Plaza de Mulas medical tent, located at 4300 m (14,100 ft) along the Normal Route to the 6960 m (22,837 ft) summit of Aconcagua in Argentina, a Korean male in...
At the Plaza de Mulas medical tent, located at 4300 m (14,100 ft) along the Normal Route to the 6960 m (22,837 ft) summit of Aconcagua in Argentina, a Korean male in his 50s with no known medical conditions presented with lightheadedness and shortness of breath. He had taken sildenafil and acetazolamide that morning without improvement. Vital signs on arrival were notable for oxygen saturations in the high 60s with basilar crackles on lung auscultation, concerning for high altitude pulmonary edema. The patient was started on oxygen via nasal cannula and given dexamethasone. History was limited secondary to language barriers, but on review of systems the patient noted mild chest pressure. Bedside cardiac echocardiogram was performed, which revealed a septal wall motion abnormality. The patient was therefore given aspirin and clopidogrel and was flown to a lower trailhead, where he was met by local Emergency Medical Services. A 12-lead electrocardiogram revealed an anterior ST-elevation myocardial infarction, and the patient was taken emergently to the catheterization lab in Mendoza and underwent stent placement with a full recovery.
PubMed: 38720618
DOI: 10.1177/10806032241249128 -
ACG Case Reports Journal May 2024Cerebrospinal fluid (CSF) ascites is a rare cause of ascites that presents in patients with ventriculoperitoneal (VP) shunts, treated by conversion to a ventriculoatrial...
Cerebrospinal fluid (CSF) ascites is a rare cause of ascites that presents in patients with ventriculoperitoneal (VP) shunts, treated by conversion to a ventriculoatrial shunt. Our case describes a patient presenting with CSF ascites almost 40 years after VP shunt placement, with fluid analysis showing elevated serum ascites albumin gradient, and response to acetazolamide therapy. As shown in this case, CSF ascites can present with elevated serum ascites albumin gradient and should be kept a differential diagnosis. Acetazolamide can be considered as a potential alternative treatment in patients who are not candidates for a VP to ventriculoatrial shunt conversion.
PubMed: 38716358
DOI: 10.14309/crj.0000000000001361