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Frontiers in Veterinary Science 2023A 7-year-old castrated male Munchkin cat was presented with anorexia. This cat had been diagnosed with chronic kidney disease due to polycystic kidney disease....
A 7-year-old castrated male Munchkin cat was presented with anorexia. This cat had been diagnosed with chronic kidney disease due to polycystic kidney disease. Tachycardia with a systolic murmur (grade III/VI) was auscultated and for further diagnosis, echocardiography was performed. Based on echocardiography, persistent left cranial vena cava (PLCVC) was suspected due to enlargement of the coronary sinus and confirmed by saline contrast echocardiography. The dilated coronary sinus compressed the left atrium, and left ventricular hypertrophy with the systolic anterior motion of the mitral valve, aortic regurgitation, and mitral regurgitation were identified. After medical management using atenolol, left atrial function and other hemodynamics of the heart were improved, including the disappearance of regurgitation and normalization of left ventricular wall thickness. This case report describes the echocardiographic characteristics, diagnostic procedures, and disease progression in a cat with PLCVC after medical management using atenolol. Additionally, this is the first report of a cat with PLCVC, coexisting with polycystic kidney disease.
PubMed: 37869489
DOI: 10.3389/fvets.2023.1268493 -
Frontiers in Immunology 2023Severe inflammation via innate immune system activation causes organ dysfunction. Among these, the central nervous system (CNS) is particularly affected by...
Severe inflammation via innate immune system activation causes organ dysfunction. Among these, the central nervous system (CNS) is particularly affected by encephalopathies. These symptoms are associated with the activation of microglia and a potential infiltration of leukocytes. These immune cells have recently been discovered to have the ability to produce extracellular traps (ETs). While these components capture and destroy pathogens, deleterious effects occur such as reduced neuronal excitability correlated with excessive ETs production. In this study, the objectives were to determine (1) whether immune cells form ETs in the CNS during acute inflammation (2) whether ETs produce neuromuscular disorders and (3) whether an immunomodulatory treatment such as β1-adrenergic blockers limits these effects. We observed an infiltration of neutrophils in the CNS, an activation of microglia and a production of ETs following lipopolysaccharide (LPS) administration. Atenolol, a β1-adrenergic blocker, significantly decreased the production of ETs in both microglia and neutrophils. This treatment also preserved the gastrocnemius motoneuron excitability. Similar results were observed when the production of ETs was prevented by sivelestat, an inhibitor of ET formation. In conclusion, our results demonstrate that LPS administration increases neutrophils infiltration into the CNS, activates immune cells and produces ETs that directly impair neuromuscular function. Prevention of ETs formation by β1-adrenergic blockers partly restores this function and could be a good target in order to reduce adverse effects in severe inflammation such as sepsis but also in other motor related pathologies linked to ETs production.
Topics: Mice; Animals; Extracellular Traps; Lipopolysaccharides; Neutrophils; Inflammation; Leukocytes
PubMed: 37809074
DOI: 10.3389/fimmu.2023.1228374 -
The Lancet. Global Health Oct 2023A cardiovascular polypill containing generic drugs might facilitate sustained implementation of and adherence to evidence-based treatments, especially in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A cardiovascular polypill containing generic drugs might facilitate sustained implementation of and adherence to evidence-based treatments, especially in resource-limited settings. However, the impact of a cardiovascular polypill in mitigating atherosclerotic risk among stroke survivors has not been assessed. We aimed to compare a polypill regimen with usual care on carotid intima-media thickness (CIMT) regression after ischaemic stroke.
METHODS
In SMAART, a phase 2 parallel, open-label, assessor-masked, randomised clinical trial, we randomly allocated individuals (aged ≥18 years) who had an ischaemic stroke within the previous 2 months, using a computer-generated randomisation sequence (1:1), to either a polypill or usual care group at a tertiary centre in Ghana. The polypill regimen was a fixed-dose pill containing 5 mg ramipril, 50 mg atenolol, 12·5 mg hydrochlorothiazide, 20 mg simvastatin, and 100 mg aspirin administered as two capsules once per day for 12 months. Usual care was tailored guideline-recommended secondary prevention medications. The primary outcome was the change in CIMT over 12 months with adjustment for baseline values, compared using ANCOVA in all participants with complete data at month 12. Safety was analysed in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, NCT03329599, and is completed.
FINDINGS
Between Feb 12, 2019, and Dec 4, 2020, we randomly assigned 148 participants (74 to the usual care group and 74 to the polypill group), 74 (50%) of whom were male and 74 (50%) female. CIMT was assessed in 62 (84%) of 74 participants in the usual care group and 59 (80%) of 74 participants in the polypill group; the main reason for loss to follow-up was participants not completing the study. The mean CIMT change at month 12 was -0·092 mm (95% CI -0·130 to -0·051) in the usual care group versus -0·017 mm (-0·067 to 0·034) in the polypill group, with an adjusted mean difference of 0·049 (-0·008 to 0·109; p=0·11). Serious adverse events occurred among two (3%) participants in the usual care group, and eight (11%) participants in the polypill group (p=0·049).
INTERPRETATION
The polypill regimen resulted in similar regression in subclinical atherosclerosis and many secondary and tertiary outcome measures as the tailored drug regimen, but with more serious adverse events. Larger, longer-term, event-based studies, including patients with stroke in primary care settings, are warranted.
FUNDING
US National Institutes of Health.
TRANSLATION
For the Akan (Twi) translation of the abstract see Supplementary Materials section.
Topics: United States; Humans; Female; Male; Adolescent; Adult; Stroke; Secondary Prevention; Ghana; Brain Ischemia; Carotid Intima-Media Thickness; Ischemic Stroke
PubMed: 37734804
DOI: 10.1016/S2214-109X(23)00347-9 -
Therapeutic Hypothermia and Temperature... Dec 2023A 50-year-old man was admitted to our hospital with hypotension and bradycardia after receiving high doses of atenolol, amlodipine, and etizolam. He had a drug-induced J...
A 50-year-old man was admitted to our hospital with hypotension and bradycardia after receiving high doses of atenolol, amlodipine, and etizolam. He had a drug-induced J wave on electrocardiography and subsequently underwent cardiac arrest. The patient was successfully rescued by venoarterial extracorporeal membrane oxygenation (VA-ECMO) and a good neurological outcome was achieved with therapeutic hypothermia (TH). In patients with J waves, TH is thought to increase the J waves and cause fatal arrhythmias, but in this case, rapid cooling with VA-ECMO allowed the patient to successfully complete TH.
Topics: Humans; Male; Middle Aged; Cardiopulmonary Resuscitation; Cold Temperature; Extracorporeal Membrane Oxygenation; Heart Arrest; Hypothermia, Induced; Treatment Outcome
PubMed: 37722017
DOI: 10.1089/ther.2023.0041 -
Critical Care Explorations Sep 2023We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the...
Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.
OBJECTIVES
We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury.
DESIGN
Retrospective cohort study.
SETTING
ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study.
PATIENTS
Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI.
INTERVENTIONS
None.
MEASUREMENTS
Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction.
MAIN RESULTS
Of the 450 eligible participants, 57 (13%) received early beta blockers (BB group). The BB group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB group and BB group (odds ratio = 0.86; 95% CI, 0.48-1.53). There was no association between BB exposure and secondary outcomes.
CONCLUSIONS
About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limited by overall low total doses administered compared with prior studies.
PubMed: 37693305
DOI: 10.1097/CCE.0000000000000958 -
Molecular Pharmaceutics Oct 2023In vitro intestinal models are used to study biological processes, drug and food absorption, or cytotoxicity, minimizing the use of animals in the laboratory. They...
In vitro intestinal models are used to study biological processes, drug and food absorption, or cytotoxicity, minimizing the use of animals in the laboratory. They usually consist of enterocytes and mucus-producing cells cultured for 3 weeks, e.g., on Transwells, to obtain a fully differentiated cell layer simulating the human epithelium. Other important components are the extracellular matrix (ECM) and strong vascularization. The former serves as structural support for cells and promotes cellular processes such as differentiation, migration, and growth. The latter includes endothelial cells, which coordinate vascularization and immune cell migration and facilitate the transport of ingested substances or drugs to the liver. In most cases, animal-derived hydrogels such as Matrigel or collagen are used as ECM in in vitro intestinal models, and endothelial cells are only partially considered, if at all. However, it is well-known that animal-derived products can lead to altered cell behavior and incorrect results. To circumvent these limitations, synthetic and modifiable hydrogels (Peptigel and Vitrogel) were studied here to mimic xenofree ECM, and the data were compared with Matrigel. Careful rheological characterization was performed, and the effect on cell proliferation was investigated. The results showed that Vitrogel exhibited shear-thinning behavior with an internal structure recovery of 78.9 ± 11.2%, providing the best properties among the gels investigated. Therefore, a coculture of Caco-2 and HT29-MTX cells (ratio 7:3) was grown on Vitrogel, while simultaneously endothelial cells were cultured on the basolateral side by inverse cultivation. The model was characterized in terms of cell proliferation, differentiation, and drug permeability. It was found that the cells cultured on Vitrogel induced a 1.7-fold increase in cell proliferation and facilitated the formation of microvilli and tight junctions after 2 weeks of cultivation. At the same time, the coculture showed full differentiation indicated by high alkaline phosphatase release of Caco-2 cells (95.0 ± 15.9%) and a mucus layer produced by HT29-MTX cells. Drug tests led to ex vivo comparable permeability coefficients () (i.e., ; antipyrine = (33.64 ± 5.13) × 10 cm/s, ; atenolol = (0.59 ± 0.16) × 10 cm/s). These results indicate that the newly developed intestinal model can be used for rapid and efficient assessment of drug permeability, excluding unexpected results due to animal-derived materials.
Topics: Animals; Humans; Caco-2 Cells; Intestinal Mucosa; Endothelial Cells; Intestinal Absorption; Extracellular Matrix; Endothelium; Hydrogels
PubMed: 37677739
DOI: 10.1021/acs.molpharmaceut.3c00532 -
Acta Dermato-venereologica Aug 2023Parents of infants treated with beta-blockers for infantile haemangioma are often concerned about the long-term aesthetic outcome. This cross-sectional study assessed...
Parents of infants treated with beta-blockers for infantile haemangioma are often concerned about the long-term aesthetic outcome. This cross-sectional study assessed the influence on the long-term aesthetic outcome of characteristics of the infantile haemangioma, the beta-blocker treatment, and the infant. The study included 103 children aged 6-12 years, treated with beta-blockers (propranolol or atenolol) for infantile haemangioma during infancy (age at treatment initiation ≤1 year) for ≥6 months. Dermatologists and parents scored the Patient Observer Scar Assessment Scale, and the child scored a visual analogue scale. Dermatologists identified whether telangiectasia, fibrofatty tissue, and atrophic scar tissue were present. The long-term aesthetic outcome of infantile haemangioma was judged more negatively by dermatologists and parents in case of a superficial component, ulceration, older age at treatment initiation, higher cumulative dose, and/or shorter follow-up time. According to children, infantile haemangioma located on the head had better aesthetic outcome than infantile haemangioma located elsewhere. Close monitoring, particularly of infantile haemangioma with a superficial component, is essential for early initiation of treatment, and to prevent or treat ulceration. These outcome data can support parental counselling and guide treatment strategy.
Topics: Child; Infant; Humans; Cicatrix; Cross-Sectional Studies; Prognosis; Hemangioma, Capillary; Adrenergic beta-Antagonists; Esthetics
PubMed: 37649330
DOI: 10.2340/actadv.v103.5286 -
European Journal of Internal Medicine Jan 2024Arterial hypertension is the most common cardiovascular comorbidity in atrial fibrillation (AF). Few studies investigated management strategies of hypertension in AF.
BACKGROUND
Arterial hypertension is the most common cardiovascular comorbidity in atrial fibrillation (AF). Few studies investigated management strategies of hypertension in AF.
MATERIALS AND METHODS
We included 5769 AF patients on oral anticoagulants from the nationwide ongoing Italian START registry. We investigated the prescription of antihypertensive drugs and mortality risk. Subgroup analyses according to sex and major cardiovascular comorbidities were performed.
RESULTS
Mean age was 80.8 years, 46.1% were women; 80.3% of patients were hypertensive. Furosemide (30.1%) was the most frequent diuretic followed by hydrochlorothiazide (15.4%) and potassium canrenoate (7.9%). 61.1% received β-blockers: 34.2% bisoprolol, 6.2% atenolol. Additionally, 36.9% were on angiotensin converting enzyme inhibitors (ACE-I): ramipril (20.9%), enalapril (5.3%) and perindopril (2.8%); 31.7% were on angiotensin receptors blockers (ARBs): valsartan (7.6%) and irbesartan (6.4%). Amlodipine and lercanidipine were prescribed in 14.0% and 2.3%, respectively. ACE-I (p < 0.001), α-blockers (p = 0.020) and Dihydropyridines calcium channel blockers (p = 0.004) were more common in men, while ARBs (p = 0.008), thiazide diuretics (p < 0.001) and β-blockers (p < 0.001) in women. During 22.61 ± 17.1 months, 512 patients died. Multivariable Cox regression analysis showed that ACE-I (Hazard ratio [HR] 0.758, 95% Confidence Interval [95%CI] 0.612-0.940, p = 0.012) and ARBs (HR 0.623, 95%CI 0.487-0.796, p < 0.001) inversely associated with mortality. ACE-I/ARBs inversely associated with mortality in both sexes and in patients with diabetes. This associastion was evident for ACE-I in patients with previous cardiovascular disease, and for ARBs in HF.
CONCLUSION
A lower mortality risk was found in AF patients on ACE-I/ARBs. Different prescription patterns of antihypertensive drugs between men and women do exist.
Topics: Male; Humans; Female; Aged; Aged, 80 and over; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System; Atrial Fibrillation; Angiotensin Receptor Antagonists; Hypertension; Adrenergic beta-Antagonists
PubMed: 37648584
DOI: 10.1016/j.ejim.2023.08.019 -
Membranes Aug 2023The present work investigates nanofiltration (NF) and ultrafiltration (UF) for the removal of three widely used pharmaceutically active compounds (PhACs), namely...
Ultrafiltration and Nanofiltration for the Removal of Pharmaceutically Active Compounds from Water: The Effect of Operating Pressure on Electrostatic Solute-Membrane Interactions.
The present work investigates nanofiltration (NF) and ultrafiltration (UF) for the removal of three widely used pharmaceutically active compounds (PhACs), namely atenolol, sulfamethoxazole, and rosuvastatin. Four membranes, two polyamide NF membranes (NF90 and NF270) and two polyethersulfone UF membranes (XT and ST), were evaluated in terms of productivity (permeate flux) and selectivity (rejection of PhACs) at pressures from 2 to 8 bar. Although the UF membranes have a much higher molecular weight cut-off (1000 and 10,000 Da), when compared to the molecular weight of the PhACs (253-482 Da), moderate rejections were observed. For UF, rejections were dependent on the molecular weight and charge of the PhACs, membrane molecular weight cut-off (MWCO), and operating pressure, demonstrating that electrostatic interactions play an important role in the removal of PhACs, especially at low operating pressures. On the other hand, both NF membranes displayed high rejections for all PhACs studied (75-98%). Hence, considering the optimal operating conditions, the NF270 membrane (MWCO = 400 Da) presented the best performance, achieving permeate fluxes of about 100 kg h m and rejections above 80% at a pressure of 8 bar, that is, a productivity of about twice that of the NF90 membrane (MWCO = 200 Da). Therefore, NF270 was the most suitable membrane for this application, although the tight UF membranes under low operating pressures displayed satisfactory results.
PubMed: 37623804
DOI: 10.3390/membranes13080743 -
BMC Chemistry Aug 2023Cardiovascular disorders are among the leading causes of death worldwide, especially hypertension, a silent killer syndrome requiring multiple drug therapy for...
Sustainable chromatographic quantitation of multi-antihypertensive medications: application on diverse combinations containing hydrochlorothiazide along with LC-MS/MS profiling of potential impurities: greenness and whiteness evaluation.
Cardiovascular disorders are among the leading causes of death worldwide, especially hypertension, a silent killer syndrome requiring multiple drug therapy for appropriate management. Hydrochlorothiazide is an extensively utilized thiazide diuretic that combines with several antihypertensive drugs for effective treatment of hypertension. In this study, sustainable, innovative and accurate high performance liquid chromatographic methods with diode array and tandem mass detectors (HPLC-DAD and LC-MS/MS) were developed, optimized and validated for the concurrent determination of Hydrochlorothiazide (HCT) along with five antihypertensive drugs, namely; Valsartan (VAL), Amlodipine besylate (AML), Atenolol (ATN), Amiloride hydrochloride (AMI), and Candesartan cilextil (CAN) in their diverse pharmaceutical dosage forms and in the presence of Chlorothiazide (CT) and Salamide (DSA) as HCT officially identified impurities. The HPLC-DAD separation was achieved utilizing Inertsil ODS-3 C column (250 × 4.6 mm, 5 μm) attached with photodiode array detection at 225.0 nm. Gradient elution was performed utilizing a mixture of solvent A (20.0 mM potassium dihydrogen phosphate, pH 3.0 ± 0.2, adjusted with phosphoric acid) and solvent B (acetonitrile) at ambient temperature. Linearity ranges were 0.1-100.0 µg/mL for HCT, VAL, AML and CAN, 0.05 -100.0 µg/mL for both ATN and AMI and 0.05-8.0 µg/mL for both CT and DSA. Additionally, this work describes the use of liquid chromatography-electrospray-tandem mass spectrometry for the accurate detection and quantification of the impurities; CT and DSA in the negative mode utilizing triple quadrupole mass spectrometry. The linearity ranges for those impurities were 1.0-200.0 ng/mL and 5.0-200.0 ng/mL for CT and DSA, respectively. Developed methods' validation was achieved in accordance with International Conference on Harmonization (ICH) guidelines. Upon applying liquid chromatographic techniques for the drug analysis, a green and sustainable assessment have to be handled due to the consumption of energy and many solvents. Through the use of the HEXAGON, Analytical Greenness (AGREE) and White Analytical Chemistry (WAC) tools, greenness and sustainability have been statistically assessed. The optimized HPLC-DAD and LC-MS/MS methods were fast, accurate, precise, and sensitive, and consequently could be applied for conventional analysis and quality control of the proposed drugs in their miscellaneous dosage forms for the purpose of reducing laboratory wastes, time of the analysis time, effort, and cost.
PubMed: 37598182
DOI: 10.1186/s13065-023-01015-z