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1.
Parasit Vectors ; 17(1): 76, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378683

RESUMO

BACKGROUND: Sugar alcohols, such as erythritol, are low-impact candidates for attractive toxic sugar baits (ATSB) to kill mosquitoes. To determine whether erythritol has a viable future in ATSB formulations, a suite of assays was conducted to diagnose toxicity mechanisms and starvation effects on mortality in Aedes aegypti (L.) as a model system. METHODS: We measured general carbohydrate load, glucosidase levels, and free glucose in intoxicated adult mosquitoes to observe whether sugar digestion was impaired. We assayed the effects of sugar combinations with erythritol on larvae and adults. To measure erythritol effects when mosquitoes were not resource-deprived, additional assays manipulated the prior starvation status. RESULTS: Up to 50,000 ppm of erythritol in water had no effect on larvae within 72 h, but an ammonia spike indicated diuresis in larvae as early as 4 h (F8,44 = 22.50, P < 0.0001) after sucrose/erythritol combinations were added. Adult consumption of erythritol was diuretic regardless of the sugar pairing, while sucrose and erythritol together generated above 80% mortality (F2,273 = 33.30, P < 0.0001) alongside triple the normal excretion (F5,78 = 26.80, P < 0.0004). Glucose and fructose paired individually with erythritol had less mortality, but still double the fecal excretion. When ingesting erythritol-laced meals, less sugar was detected in mosquitoes as compared to after sucrose meals (χ2 = 12.54, df = 1, P = 0.0004). CONCLUSIONS: Data showed that erythritol is a linear competitive inhibitor of α-glucosidase, marking it as a novel class of insecticide in the current research climate. However, the efficacy on larvae was null and not persistent in adult mosquitoes when compared across various starvation levels. Despite significant diuresis, the combined effects from erythritol are not acute enough for vector control programs considering ATSB against mosquitoes.


Assuntos
Aedes , Inseticidas , Animais , Aedes/fisiologia , alfa-Glucosidases , Eritritol/farmacologia , Controle de Mosquitos , Mosquitos Vetores , Açúcares , Carboidratos , Sacarose/farmacologia , Inseticidas/farmacologia , Larva , Glucose , Diurese
2.
Circ Heart Fail ; 17(1): e011105, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38179728

RESUMO

BACKGROUND: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852). CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.


Assuntos
Diuréticos , Insuficiência Cardíaca , Humanos , Diuréticos/uso terapêutico , Natriurese , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Diurese , Sódio , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos
3.
Phytomedicine ; 124: 155260, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176264

RESUMO

BACKGROUND: Ji-Ming-Shan (JMS) is a traditional prescription used for patients with rheumatism, tendons swelling, relief of foot pain, athlete's foot, diuresis, gout. Although many studies have investigated the active compounds in each herb, the functional mechanism behind its therapeutic effect remains unclear. STUDY DESIGN: Metabolic cages for sample collection. The serum components obtained from the experimental animals were analyzed using LC-MS/MS. Furthermore, cross-analysis using the software MetaboAnalyst and Venn diagrams were used to investigate chronopharmacology of JMS in the animal models. PURPOSE: The aim of this study is to analyze the diuretic effects of JMS and to explore their chronopharmacology involved in organ regulation through four-quarter periods from serum samples of rat models. METHODS: Metabolic cages were used for collecting the urine samples and PocketChem UA PU-4010, Fuji DRI-CHEM 800 were used to examine the urine biochemical parameters. The serum components were identified through ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-Q-TOF) with a new developed method. Cross analysis, Venn diagram, MetaboAnalyst were used to investigate the key biomarker and major metabolism route with the oral administration of the drug. RESULT: JMS significantly changed the 6 h urine volume with no observed kidney toxicity. Urine pH value ranges from 7.0 to 7.5. The chronopharmacology of JMS diuresis activity were 0-6 and 6-12 groups. UPLC-Q-TOF analyses identified 243 metabolites which were determined in positive mode and negative mode respectively. With cross analysis in the Venn diagram, one key biomarker naringenin-7-O-glucoside has been identified. Major metabolic pathways such as 1: Glycerophospholipid metabolism, 2: Primary bile acid biosynthesis, 3: Sphingolipid metabolism, 4: Riboflavin metabolism, 5: Linoleic acid metabolism, 6: Butanoate metabolism. CONCLUSION: JMS significantly changed the urine output of animals in the 0-6 and 6-12 groups. No change in urine pH was observed and also kidney toxicity. A new UPLC-Q-TOF method was developed for the detection of the metabolites of JMS after oral administration. The cross analysis with Venn diagram and identified the key biomarker of JMS namely naringenin-7-O-glucoside. The results showed that six major pathways are involved in the gastrointestinal system and the liver. This study demonstrated the capability of JMS prescription in the regulation of diuresis and identified a key biomarker that is responsible for its therapeutic effect.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Ratos , Humanos , Animais , Espectrometria de Massas em Tandem/métodos , Ratos Sprague-Dawley , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Diurese , Biomarcadores , China
4.
Am J Physiol Regul Integr Comp Physiol ; 326(3): R230-R241, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38223938

RESUMO

Although body fluid volume control by the kidneys may be classified as a long-term arterial pressure (AP) control system, it does not necessarily follow that the urine flow (UF) response to changes in AP is slow. We quantified the dynamic characteristics of the UF response to short-term AP changes by changing mean AP between 60 mmHg and 100 mmHg every 10 s according to a binary white noise sequence in anesthetized rats (n = 8 animals). In a baro-on trial (the carotid sinus baroreflex was enabled), the UF response represented the combined synergistic effects of pressure diuresis (PD) and neurally mediated antidiuresis (NMA). In a baro-fix trial (the carotid sinus pressure was fixed at 100 mmHg), the UF response mainly reflected the effect of PD. The UF step response was quantified using the sum of two exponential decay functions. The fast and slow components had time constants of 6.5 ± 3.6 s and 102 ± 85 s (means ± SD), respectively, in the baro-on trial. Although the gain of the fast component did not differ between the two trials (0.49 ± 0.21 vs. 0.66 ± 0.22 µL·min-1·kg-1·mmHg-1), the gain of the slow component was greater in the baro-on than in the baro-fix trial (0.51 ± 0.14 vs. 0.09 ± 0.39 µL·min-1·kg-1·mmHg-1, P = 0.023). The magnitude of NMA relative to PD was calculated to be 32.2 ± 29.8%. In conclusion, NMA contributed to the slow component, and its magnitude was approximately one-third of that of the effect of PD.NEW & NOTEWORTHY We quantified short-term dynamic characteristics of the urine flow (UF) response to arterial pressure (AP) changes using white noise analysis. The UF step response approximated the sum of two exponential decay functions with time constants of ∼6.5 s and 102 s. The neurally mediated antidiuretic (NMA) effect contributed to the slow component of the UF step response, with the magnitude of approximately one-third of that of the pressure diuresis (PD) effect.


Assuntos
Pressão Arterial , Barorreflexo , Animais , Ratos , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Artérias Carótidas , Diurese
5.
CEN Case Rep ; 13(1): 9-13, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37074627

RESUMO

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been widely used. They inhibit proximal tubular glucose reabsorption, resulting in glycosuria. Herein, we report the case of a 65-year-old woman who presented with hypernatremia during the perioperative period of a subarachnoid hemorrhage. The patient continued to take dapagliflozin postoperatively and subsequently developed severe hypernatremia. Based on the urinalysis findings, we diagnosed osmotic diuresis due to glycosuria as contributing to hypernatremia. Hypernatremia improved with the discontinuation of dapagliflozin and the administration of a hypotonic infusion. In the perioperative period, physicians should discontinue SGLT2 inhibitors owing to concerns about the development of hypernatremia.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Glicosúria , Hipernatremia , Feminino , Humanos , Idoso , Hipernatremia/induzido quimicamente , Hipernatremia/diagnóstico , Glicosúria/complicações , Diurese , Glucose/uso terapêutico
7.
J Card Fail ; 30(1): 4-11, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37714260

RESUMO

BACKGROUND: Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association among HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations and cost. METHODS: Using 100% Medicare inpatient, outpatient and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified. Encounters were sorted into mutually exclusive settings: (1) inpatient; (2) observation; (3) ED; or (4) outpatient IV diuretic clinic. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day hospitalization and total 30-day costs. Multivariable logistic and linear regression were used to examine the association between treatment location and the primary and secondary outcomes. RESULTS: Patients treated in observation and outpatient settings had lower 30-day mortality rates (observation OR 0.67, 95% CI 0.66-0.69; P < 0.001; outpatient OR 0.53, 95% CI 0.51-0.55; P < 0.001) compared to those treated in inpatient settings. Observation and outpatient treatment were also associated with decreased 30-day total cost compared to inpatient treatment. Observation relative cost -$5528.77, 95% CI -$5613.63 to -$5443.92; outpatient relative cost -$7005.95; 95% CI -$7103.94 to -$6907.96). Patients treated in the emergency department and discharged had increased mortality rates (OR 1.15, 95% CI 1.13-1.17; P < 0.001) and increased rates of hospitalization (OR 1.72, 95% CI 1.70-1.73; P < 0.001) compared to patients treated as inpatients. CONCLUSIONS: Medicare beneficiaries who received IV diuresis for acute HF in the outpatient and observation settings had lower mortality rates and decreased costs of care compared to patients treated as inpatients. Outpatient and observation management of acute decompensated HF, when available, is a safe and cost-effective strategy in certain populations of patients with HF.


Assuntos
Insuficiência Cardíaca , Medicare , Humanos , Idoso , Estados Unidos/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Hospitalização , Alta do Paciente , Diuréticos , Diurese
8.
Am J Physiol Renal Physiol ; 326(2): F278-F284, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38059298

RESUMO

The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule.NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria.


Assuntos
Anemia Falciforme , Diabetes Insípido Nefrogênico , Diabetes Insípido , Diabetes Mellitus , Humanos , Poliúria , Diurese , Concentração Osmolar , Antidiuréticos , Água
9.
Pediatr Nephrol ; 39(2): 505-511, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37656311

RESUMO

BACKGROUND: The management of posterior urethral valve (PUV) in neonates requires close monitoring in the intensive care unit because of the risk of post-obstructive diuresis (POD). Our aim was to describe the incidence and factors associated with POD in newborns treated for PUV. METHODS: Retrospective analysis of the medical records of all neonates who underwent surgical intervention for PUV in our neonatal intensive care unit between January 2014 and April 2021. RESULTS: Of the 40 patients included, 15 (37.5%) had POD defined by urine output > 6 ml.kg-1.h-1 during the first 24 h following urinary tract obstruction relief. At prenatal ultrasound examinations, oligohydramnios was more common in the group with POD than in the group without (53.3% vs. 8%, p = 0.002). Preterm birth was more frequent in neonates with POD (66.7% vs. 8%; p < 0.001). Median serum creatinine (212 [137-246] vs. 95 [77-125] µmol.l-1; p < 0.001) and urea (8.5 [5.2-12.2] vs. 4.1 [3.5-4.7] mmol.l-1; p < 0.001) concentrations on the day of obstruction relief were significantly higher in the group with POD than in the group without. After adjustment for prematurity, logistic regression models confirmed correlation between the occurrence of POD and the severity of the consequences of urethral obstruction (i.e., oligohydramnios and serum creatinine levels; ß = 2.90 [0.88; 5.36], p = 0.013 and ß = 0.014 [0.003; 0.031], p = 0.034, respectively). CONCLUSIONS: In neonates, POD is common after the relief of PUV-related obstruction. Our findings may help to identify patients at highest risk. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Oligo-Hidrâmnio , Nascimento Prematuro , Obstrução Uretral , Sistema Urinário , Gravidez , Feminino , Humanos , Recém-Nascido , Estudos Retrospectivos , Creatinina , Obstrução Uretral/etiologia , Obstrução Uretral/cirurgia , Diurese , Uretra/cirurgia
10.
J Vet Med Sci ; 85(12): 1314-1318, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-37853639

RESUMO

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a protein kinase that inactivates eEF2, a protein that mediates a peptidyl-tRNA translocation during an elongation step of protein synthesis. We have previously shown that eEF2K was involved in pathogenesis of essential and pulmonary hypertension. A484954 (7-amino-1-cyclopropyl-3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-6-carboxamide), a selective eEF2K inhibitor, is a membrane permeable small molecule. We have previously shown that A484954 lowered blood pressure and induced diuretic effects in spontaneously hypertensive rats (SHR) due to an increase in renal blood flow. Here we aimed to reveal mechanisms underlying the diuretic effects of A484954 in SHR. A484954-induced diuresis and increase in urinary Na+ excretion were inhibited by N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor. A484954 increased mRNA expression of angiotensin type 2 receptor (AT2R) and nuclear factor-erythroid 2-related factor 2 (Nrf2). In summary, we for the first time revealed that A484954 induces diuresis in SHR at least partly via the activation of NO/Nrf2/AT2R pathway.


Assuntos
Quinase do Fator 2 de Elongação , Óxido Nítrico , Animais , Ratos , Pressão Sanguínea , Diurese , Diuréticos/farmacologia , Quinase do Fator 2 de Elongação/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Pirimidinas/farmacologia , Ratos Endogâmicos SHR
12.
Nucl Med Commun ; 44(12): 1135-1143, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37799105

RESUMO

OBJECTIVE: We compared diagnostic quality of 68 Ga-PSMA PET/CT imaging focused on the pelvic structures using two furosemide protocols in two different groups of patients. MATERIAL AND METHODS: A total of 55 patients with prostate cancer were retrospectively enrolled in the study. Out of 55, 31 patients were in group 1 (median age: 66 years, Range 44-78 years) in which furosemide injection was given after completion of whole-body 68 Ga-PSMA PET/CT scan and 24 patients were in group 2 (median age: 63.5 years, range: 50-82 years) in which it was given along with the 68 Ga-PSMA injection. In both groups, an initial time point scan (T0 scan) and a delayed time point scan (T1scan) were done. The images were analyzed qualitatively as well as quantitatively. RESULTS: Quantitatively there was no statistically significant difference between the SUVmax and T:B of prostatic lesion and seminal vesicle invasion (SVI) in both the groups at two time points ( P  > 0.05). Early furosemide injection caused a washout of the urinary bladder radiotracer concentration in significantly higher number of patients in group 2 (62.5% vs. 6.45% patients, P  < 0.001). There was significant clearance of radiotracer activity from the ureters in group 2 (SUVmax: 9.28 vs. 3.09, P  = 0.002). CONCLUSION: The simultaneous furosemide and 68 Ga-PSMA injection can reduce the urinary excretion of the tracer and improve the diagnostic confidence of prostatic lesion, SVI and lymph nodal metastasis, along with reducing the scanning time and radiation burden, making this protocol an effective alternative to the present protocol of delayed furosemide injection.


Assuntos
Carcinoma , Neoplasias da Próstata , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Furosemida , Estudos Retrospectivos , Radioisótopos de Gálio , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Diurese , Ácido Edético
13.
Insect Biochem Mol Biol ; 162: 104025, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37813200

RESUMO

Diuretic hormones (DHs) bind to G protein-coupled receptors (GPCRs), regulating water and ion balance to maintain homeostasis in animals. Two distinct DHs are known in insects: calcitonin (CT)-like DH31 and corticotropin-releasing factor (CRF)-like DH44. In this study, we identified and characterized DH31 and two DH31 GPCR variants, DH31-Ra and DH31-Rb, from spotted-wing drosophila, Drosophila suzukii, a globally prevalent vinegar fly causing severe damage to small fruits. Both GPCRs are active, but DH31-Ra is the dominant receptor based on gene expression analyses and DH31 peptide binding affinities. A notable difference between the two variants lies in 1) the GPCR structures of their C-termini and 2) the utilization of second messengers, and the amino acid sequences of the two variants are identical. DH31-Ra contains 12 additional amino acids, providing different intracellular C-terminal configurations. DH31-Ra utilizes both cAMP and Ca2+ as second messengers, whereas DH31-Rb utilizes only cAMP; this is the first time reported for an insect CT-like DH31 peptide. DH31 stimulated fluid secretion in D. suzukii adults, and secretion increased in a dose-dependent manner. However, when the fly was injected with a mixture of DH31 and CAPA, an anti-diuretic hormone, fluid secretion was suppressed. Here, we discuss the structures of the DH31 receptors and the differential signaling pathways, including second messengers, involved in fly diuresis. These findings provide fundamental insights into the characterization of D. suzukii DH31 and DH31-Rs, and facilitate the identification of potential biological targets for D. suzukii management.


Assuntos
Drosophila , Neuropeptídeos , Animais , Drosophila/metabolismo , Diuréticos/metabolismo , Sistemas do Segundo Mensageiro , Receptores Acoplados a Proteínas G/metabolismo , Neuropeptídeos/metabolismo , Diurese , Hormônios/metabolismo
15.
PLoS One ; 18(8): e0290319, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37651353

RESUMO

Urinary flow measurement and colorimetry are vital medical indicators for critically ill patients in intensive care units. However, there is a clinical need for low-cost, continuous urinary flow monitoring devices that can automatically and in real-time measure urine flow. This need led to the development of a non-invasive device that is easy to use and does not require proprietary disposables. The device operates by detecting urine flow using an infrared barrier that returns an unequivocal pattern, and it is capable of measuring the volume of liquid in real-time, storing the history with a precise date, and returning alarms to detect critical trends. The device also has the ability to detect the color of urine, allowing for extended data and detecting problems in catheterized patients such as hematuria. The device is proposed as an automated clinical decision support system that utilizes the concept of the Internet of Medical Things. It works by using a LoRa communication method with the LoRaWAN protocol to maximize the distance to access points, reducing infrastructure costs in massive deployments. The device can send data wirelessly for remote monitoring and allows for the collection of data on a dashboard in a pseudonymous way. Tests conducted on the device using a gold standard medical grade infusion pump and fluid densities within the 1.005 g/ml to 1.030 g/ml urine density range showed that droplets were satisfactorily captured in the range of flows from less than 1 ml/h to 500 ml/h, which are acceptable ranges for urinary flow. Errors ranged below 15%, when compared to the values obtained by the hospital infusion pump used as gold standard. Such values are clinically adequate to detect changes in diuresis patterns, specially at low urine output ranges, related to renal disfunction. Additionally, tests carried out with different color patterns indicate that it detects different colors of urine with a precision in detecting RGB values <5%. In conclusion, the results suggest that the device can be useful in automatically monitoring diuresis and colorimetry in real-time, which can facilitate the work of nursing and provide automatic decision-making support to intensive care physicians.


Assuntos
Líquidos Corporais , Fluxômetros , Humanos , Anônimos e Pseudônimos , Colorimetria , Diurese
16.
Eur Heart J ; 44(37): 3672-3682, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37623428

RESUMO

BACKGROUND AND AIMS: In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent across the entire range of renal function remains unclear. METHODS: This is a pre-specified analysis of the ADVOR trial that randomized 519 patients with ADHF to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The main endpoints of decongestion, diuresis, natriuresis, and clinical outcomes are assessed according to baseline renal function. Changes in renal function are evaluated between treatment arms. RESULTS: On admission, median estimated glomerular filtration rate (eGFR) was 40 (30-52) mL/min/1.73 m². Acetazolamide consistently increased the likelihood of decongestion across the entire spectrum of eGFR (P-interaction = .977). Overall, natriuresis and diuresis were higher with acetazolamide, with a higher treatment effect for patients with low eGFR (both P-interaction < .007). Acetazolamide was associated with a higher incidence of worsening renal function (WRF; rise in creatinine ≥ 0.3 mg/dL) during the treatment period (40.5% vs. 18.9%; P < .001), but there was no difference in creatinine after 3 months (P = .565). This was not associated with a higher incidence of heart failure hospitalizations and mortality (P-interaction = .467). However, decongestion at discharge was associated with a lower incidence of adverse clinical outcomes irrespective of the onset of WRF (P-interaction = .805). CONCLUSIONS: Acetazolamide is associated with a higher rate of successful decongestion across the entire range of renal function with more pronounced effects regarding natriuresis and diuresis in patients with a lower eGFR. While WRF occurred more frequently with acetazolamide, this was not associated with adverse clinical outcomes. CLINICALTRIALS.GOV IDENTIFIER: NCT03505788.


Assuntos
Acetazolamida , Insuficiência Cardíaca , Humanos , Acetazolamida/uso terapêutico , Acetazolamida/farmacologia , Creatinina , Diurese , Rim/fisiologia , Doença Aguda
17.
Future Cardiol ; 19(8): 385-396, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37609913

RESUMO

Aim: Compare heart failure (HF) costs of Furoscix use at home compared with inpatient intravenous (IV) diuresis. Patients & methods: Prospective, case control study of chronic HF patients presenting to emergency department (ED) with worsening congestion discharged to receive Furoscix 80 mg/10 ml 5-h subcutaneous infusion for ≤7 days. 30-day HF-related costs in Furoscix group derived from commercial claims database compared with matched historical patients hospitalized for <72 h. Results: Of 24 Furoscix patients, 1 (4.2%) was hospitalized in 30-day period. 66 control patients identified and were well-matched for age, sex, ejection fraction (EF), renal function and other comorbidities. Furoscix patients had reduced mean per patient HF-related healthcare cost of $16,995 (p < 0.001). Conclusion: Furoscix use was associated with significant reductions in 30-day HF-related healthcare costs versus matched hospitalized controls.


What is this article about? In heart failure (HF), the heart cannot pump as well as it should. This causes blood to back up in the vessels that return blood to the heart. Fluid leaks from these vessels and collects in vital organs such as the lungs. This fluid build-up is called congestion. Congestion causes symptoms such as shortness of breath, tiredness and leg swelling. Furoscix is a prescription medicine, a diuretic, that treats congestion. Diuretics help get rid of extra fluid by increasing urination. Congestion is usually managed with oral diuretics, but sometimes congestion cannot be controlled by oral diuretics and patients may have to spend several days at a clinic or hospital to receive diuretics given through a vein (intravenous or iv.). Furoscix is a new formulation of furosemide, a common diuretic, and is delivered into the skin (subcutaneous) by a self-administered pump instead of through an iv. Our investigation aimed to answer two questions Can Furoscix be given to patients at home instead of in the hospital with iv. diuretics? Is there a cost savings to using Furoscix? Instead of being admitted to the hospital for iv. diuretics, HF patients with worsening congestion who came to the emergency department were sent home to receive Furoscix 80 mg/10 ml 5-h subcutaneous infusion for ≤7 days. 30-day costs related to HF in these patients were compared with costs from similar group of patients previously hospitalized for iv. diuretics. What were the results & what do they mean? In patients who needed to be admitted to the hospital for iv. diuretics, Furoscix given at home instead reduced congestion and resulted in significant cost savings. Patients with heart failure, who are not getting relief with oral diuretics, can be treated with Furoscix at home without having to be admitted to the hospital for iv. diuretics. Use of Furoscix instead of iv. furosemide can save money to the healthcare system.


Assuntos
Custos de Cuidados de Saúde , Insuficiência Cardíaca , Humanos , Estudos de Casos e Controles , Estudos Prospectivos , Diurese , Insuficiência Cardíaca/tratamento farmacológico , Hospitais
18.
Endocrinology ; 164(8)2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37450603

RESUMO

Patients with secondary adrenal insufficiency can present with impaired free water excretion and hyponatremia, which is due to the enhanced secretion of vasopressin (AVP) despite increased total body water. AVP is produced in magnocellular neurons in the paraventricular nucleus of the hypothalamus (PVH) and supraoptic nucleus and in parvocellular corticotropin-releasing factor (CRF) neurons in the PVH. This study aimed to elucidate whether magnocellular AVP neurons or parvocellular CRF neurons coexpressing AVP are responsible for the pathogenesis of hyponatremia in secondary adrenal insufficiency. The number of CRF neurons expressing copeptin, an AVP gene product, was significantly higher in adrenalectomized AVP-floxed mice (AVPfl/fl) than in sham-operated controls. Adrenalectomized AVPfl/fl mice supplemented with aldosterone showed impaired water diuresis under ad libitum access to water or after acute water loading. They became hyponatremic after acute water loading, and it was revealed under such conditions that aquaporin-2 (AQP2) protein levels were increased in the kidney. Furthermore, translocation of AQP2 to the apical membrane was markedly enhanced in renal collecting duct epithelial cells. Remarkably, all these abnormalities observed in the mouse model for secondary adrenal insufficiency were ameliorated in CRF-AVP-/- mice that lacked AVP in CRF neurons. Our study demonstrates that CRF neurons in the PVH are responsible for the pathogenesis of impaired water excretion in secondary adrenal insufficiency.


Assuntos
Insuficiência Adrenal , Hiponatremia , Camundongos , Animais , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Hormônios Liberadores de Hormônios Hipofisários/metabolismo , Hiponatremia/metabolismo , Aquaporina 2/genética , Aquaporina 2/metabolismo , Arginina Vasopressina/metabolismo , Hipotálamo/metabolismo , Vasopressinas/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Neurônios/metabolismo , Diurese
19.
Curr Hypertens Rev ; 19(2): 79-92, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37309769

RESUMO

BACKGROUND: Medicinal plants have been found beneficial in the control and therapy of many ailments as they contain bioactive compounds, and many of them are used as precursors in the biosynthesis of natural medicines. Diuretics are used as a primary treatment in patients with edema associated with liver cirrhosis and kidney diseases, hyperkalemia, hypertension, heart failure, or renal failure. Furthermore, they are also used to increase the excretion of sodium and reduce blood volume. Due to various adverse events associated with synthetic diuretics, there is a need to investigate alternate plant-based bioactive components that have effective diuretic activity with minimal side effects. OBJECTIVE: This review compiled the reported bioactive compounds from different plant sources along with their mechanisms of diuretic activity. METHODS: Different sources were used to collect information regarding herbal plants with therapeutic value as diuretics. These included published peer-reviewed journal articles, scholarly articles from StatPearls, and search engines like Google Scholar, PubMed, Scopus, Springer, ScienceDirect, Wiley, etc. Results: In this review, it was found that flavonoids like rutin, acacetin, naringenin, etc. showed significant diuretic activity in experimental models by various mechanisms, but mostly by blocking the sodium-potassium-chloride co-transporter, while some bioactive compounds showed diuretic actions via other mechanisms as well. CONCLUSION: Research on clinical trials of these isolated bioactive compounds needs to be further conducted. Thus, this review provides an understanding of the potential diuretic bioactive compounds of plants for further research and pharmaceutical applications.


Assuntos
Hipertensão , Nefropatias , Humanos , Diuréticos/efeitos adversos , Diurese , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/induzido quimicamente , Sódio/uso terapêutico
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