Author: Mesa, Alejandra Galeano ; dos Santos, Debora ; Raimondi, Alejandro ; Bavbek, Sevim ; Al-Lehebi, Riyad Omar ; Garcia, Elizabeth ; Mahboub, Bassam ; Noibi, Saeed ; Soares, Claudia ; Fernandez, Patricia ; Abreu, Gabriela ; Dos Santos, Debora ; Maturu, Venkata Nagarjuna ; Al Ahmad, Mona ; Levy, Gur ; Queiroz, Juliana ; Laucho-Contreras, Maria

INTRODUCTIONThe Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies.METHODSA multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation.PRIMARY ENDPOINTincident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores).RESULTSOverall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of - 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation.CONCLUSIONMepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.

01 Oct 2024·International Dental Journal

Impact of Brief Exposure to Lysozyme and Lactoferrin on Pathogenic Attributes of Oral Candida

Article

Author: Ellepola, Arjuna Nishantha Bandara ; Khan, Zia Uddin

INTRODUCTION AND AIMSAdhesion to buccal epithelial cells (BEC) and denture acrylic surfaces (DAS), germ tube (GT) formation, cell surface hydrophobicity (CSH), and haemolysin production are attributes associated with pathogenicity of Candida. Candida albicans and Candida dubliniensis are allied in causing oral candidosis. Lysozyme and lactoferrin exert antimicrobial activity on a range of oral microorganisms, including Candida. There is no information on the impact of brief exposure to lysozyme and lactoferrin on adhesion-related attributes and haemolysin production of aforementioned oral Candida isolates. Thus, we investigated the impact of lysozyme and lactoferrin on adhesion to BEC and DAS, GT formation, CSH, and haemolysin production of these isolates.METHODSAfter exposure to lysozyme and lactoferrin for 1 hour, susceptibility to lysozyme and lactoferrin of 20 isolates each of C albicans and C dubliniensis isolates was determined following a 48-hour period of incubation. Candida cell suspensions, obtained from colony-forming units after this period, were assessed for adhesion to BEC and DAS, GT formation, CSH, and haemolysin production using in vitro assays.RESULTSExposure to lysozyme and lactoferrin significantly suppressed the ability of C albicans and C dubliniensis isolates to adhere to BEC and DAS, GT formation, CSH, and haemolysin production (P < 0.01 for all virulent attributes tested).CONCLUSIONSThese data provide a tantalising glimpse into the possibility that exposure to either lysozyme or lactoferrin, even for a brief period, would induce a sustainable antifungal effect by suppressing adhesion-related attributes and haemolysin production of these oral Candida species in vitro. Resistance to conventional antifungal agents has been reported in clinical isolates of Candida. The presence of such resistance indicates the need for possible alternative therapies to facilitate the management of oral candidosis. Further research on the pharmacodynamics of lysozyme and lactoferrin and their effects on candidal pathogenic attributes should be fostered, with the vision of developing novel topical antifungal drugs.

01 Oct 2024·Lung

Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study

Article

Author: Hou, Hsin-Han ; Chen, Yen-Fu ; Chien, Jung-Yien ; Chen, Ying-Yin ; Wang, Hao-Chien ; Lu, Kai-Zen ; Chien, Ning ; Yu, Chong-Jen ; Hung, Zheng-Ci

AbstractPurposeBronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients.MethodsIn a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO.ResultsAmong 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence.ConclusionsOur study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

100 Deals associated with Aranidipine

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KEGG	Wiki	ATC	Drug Bank
D01562	Aranidipine	C08CA	DB09229

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Indication	Country/Location	Organization	Date
Angina Pectoris	JP	-	27 Apr 1997
Hypertension	-	-	01 Jan 1996

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