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Respiratory
Published in Kristen Davies, Shadaba Ahmed, Core Conditions for Medical and Surgical Finals, 2020
The vast majority of pneumonias are caused by a bacterial infection (Table 2.3.1). Occasionally, pneumonia may occur secondary to viral or fungal infection. The two most common organisms causing CAP are Streptococcus pneumoniae and Haemophilus influenzae. Bacterial organisms causing CAP can be further subdivided into typical and atypical organisms. Atypical organisms include Mycoplasma pneumoniae and Legionella pneumophila, which manifest in a number of systemic features.
Severe Community-Acquired Pneumonia in the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
The clinical spectrum of S. pneumoniae CAP ranges from mild in ambulatory adults to fulminating/overwhelming sepsis in asplenics. Because of severe lung disease, even low-virulence organisms, e.g., M. catarrhalis, may decrease borderline respiratory function. Microbial virulence and host factors are the important determinants of severe CAP clinical presentation (Table 13.1).
Hymenoptera allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Rafael I. Monsalve, Te Piao King, Miles Guralnick
Several venom allergens have partial sequence identity with other proteins from diverse sources, and this is summarized in Table 18.4. As an example, the sequence identities of three vespid antigen 5s, fire ant antigen 5, human and mouse testis proteins, human glioma protein, and proteins from tomato, nematode, and lizard, in their C-terminal 50-residue region are given in Figure 18.2. These proteins together belong to a protein superfamily known as CAP, the naming due to its main constituents: cysteine-rich secretory proteins, antigen 5, and pathogenesis-related proteins [25].
Design, synthesis and biological evaluation of novel histone deacetylase (HDAC) inhibitors derived from β-elemene scaffold
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Yuan Gao, Jilong Duan, Xiawen Dang, Yinghui Yuan, Yu Wang, Xingrui He, Renren Bai, Xiang-Yang Ye, Tian Xie
Generally, the pharmacophores of HDACi are divided into three key components: the cap group (acts as a surface binding, Cap), the linker, and the pharmacophore (zinc-binding group, ZBG) (2, Figure 2). The cap portion, which accounts for the affinity gain through hydrophobic interaction with protein, can be large or small in size and can tolerate diverse structures. We envisioned that the lipophilic antitumor β-elemene scaffold should be well tolerated as a cap portion and might potentially provide some beneficial effects to achieve better anticancer activity through “hybrid” drug concept (Figure 2). The linker is typically linear and hydrophobic as well (e.g. straight carbon chain, trans- di-substituted olefin or di-substituted phenyl or heteroaryl are often used as the linker). In this study, the different carbon atoms “alkyl linker” and “aromatic linker” was used as the “Linker” to connect the β-elemene derivatives and the “ZBG” portion. The “ZBG” group (also known as pharmacophore or warhead) of many HDACi is hydroxamic acid, and those of few HDACi can also be acyl aniline, cyclic tetrapeptides, thiol, and aliphatic carboxylic acids, or their isosteric replacements. In this work, we examined three common pharmacophores as “ZBG”: hydroxamic acid, acyl aniline and acyl pyridine. As a result, six series of HDACi derived from β-elemene scaffold were designed and synthesised, and their biological activities were evaluated.
Ceftobiprole medocaril for the treatment of pneumonia
Published in Expert Review of Anti-infective Therapy, 2023
Wan-Hsuan Hsu, Chi-Kuei Hsu, Chih-Cheng Lai
Pneumonia is one of the most common types of infection and is associated with high morbidity and mortality [1]. Clinically, it can be classified into community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP) [2,3]. Even during the COVID-19 pandemic, bacteria remain the most common causative pathogens of pneumonia. However, the pathogens causing CAP and HAP differ significantly. The major bacterial pathogens causing CAP include Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Legionella pneumophila [4–8]. In contrast, the most frequent microorganisms found in HAP are Staphylococcus aureus, Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp [9–12]. Unfortunately, antibiotic-resistance bacteria, such as penicillin-resistant S. pneumoniae (PRSP) and methicillin-resistant S. aureus (MRSA), are emerging and have been frequently reported as causative pathogens of pneumonia [1,13]. The presence of these multi-drug organisms (MDROs) has not only greatly limited the choice of appropriate antibiotics but also worsened clinical outcomes with inexpedient empirical antibiotic use [14–18]. Given the widespread prevalence of antibiotic resistance, a novel antibiotic with broad-spectrum and potent activity is needed for managing pneumonia caused by MDROs [19].
Discovery and SAR analysis of 5-chloro-4-((substituted phenyl)amino)pyrimidine bearing histone deacetylase inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Lin Zhang, Yiming Chen, Fahui Li, Lihui Zhang, Jinhong Feng, Lei Zhang
Molecular docking was performed to predict the binding pattern of molecule L20 in the active site of HDAC3 using the FDA-approved SAHA, PXD101 and LBH589 as the control. The results showed that the linker and ZBG of L20 get into the narrow tunnel in the active site (Figure 4(a)). The cap moiety binds to the opening of the catalytic site. Unlike the caps of control molecules (SAHA, PXD101 and LBH589) which locate to a small pocket in the opening of the active site, the cap of the HDAC3 selective molecule L20 binds to the hydrophobic region in the surface of the catalytic site. The hydroxamic acid group which chelates to the zinc ion in the end of the binding pocket can also form hydrogen bond interactions with surrounding residues, such as Gly142, Asp258 and Tyr297 (Figure 4(b)). Hydrophobic interactions formed between the linker part of molecule L20 and key residues (Phe143, His171, Phe199 and Leu265) plays a significant role in the ligand-receptor binding. The cap region of L20 also makes contributions to the hydrophobic interactions by binding to hydrophobic residues, such as Phe198. The docking result provides structural information for further derivatisation of molecule L20.