Pathogenic triad in COPD: oxidative stress, protease–antiprotease imbalance, and inflammation

Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction. COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma. Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression. Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology. Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease–antiprotease imbalance, and oxidative stress. Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients. For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status

Different expressions of trypsin and chymotrypsin in relation to growth in Atlantic salmon (Salmo salar L.)

The expressions of trypsin and chymotrypsin in the pyloric caeca of Atlantic salmon (Salmo salar L.) were studied in three experiments. Two internal (trypsin phenotypes, life stages) and three common external factors (starvation, feeding, temperatures) influencing growth rates were varied. Growth was stimulated by increased temperature and higher feeding rate, and it was depressed during starvation. The interaction between trypsin phenotype and start-feeding temperature affected specific activity of trypsin, but not of chymotrypsin. Trypsin specific activity and the activity ratio of trypsin to chymotrypsin (T/C ratio) increased when growth was promoted. Chymotrypsin specific activity, on the other hand, increased when there was a reduction in growth rate whereas fish with higher growth had higher chymotrypsin specific activity resulting in lower T/C ratio value. During a rapid growth phase, trypsin specific activity did not correlate with chymotrypsin specific activity. On the other hand, a relationship between specific activities of trypsin and chymotrypsin could be observed when growth declined, such as during food deprivation. Trypsin is the sensitive key protease under conditions favouring growth and genetically and environmentally affected, while chymotrypsin plays a major role when growth is limited or depressed. Trypsin specific activity and the T/C ratio value are shown to be important factors in the digestion process affecting growth rate, and could be applicable as indicators for growth studies of fish in captive cultures and in the wild, especially when food consumption rate cannot be measured

Polyethylenimine catalysts containing an isolated apolar binding site: Solovolysis of p -nitrophenyl esters

The preparation dodecane-block-poly[ethylenimine-graft-4(5)-methylimidazole] copolymers and related model compounds has been described and such polymers have been described and such polymers have been demonstrated to be efficient catalysts for the hydrolysis of activated phenyl esters in aqueous solutions. Polymeric catalysts that contain isolated apolar blocks exhibited enhanced catalytic activity for the hydrolysis of the p -nitrophenyl esters of acetate and butyrate compared with polymer model compounds. This rate enhancement was atributed to the apolar binding of substrate within the apolar polymer regime. Twenty-to 100-fold increases in the second-order rate constants were observed for the hydrolysis of the longer-chain p -nitrophenyl esters. This is indicative of a significant hydrophobic interaction. The contribution of the apolar block to the hydrophobic interaction was masked in the hydrolysis of the p -nitrophenyl caproate and p -nitrophenyl laurate substrates. In both instances the dominant contribution to the hydrophobic interactions was ascribed to a substrate-imidazole intermediate rather than the apolar block of the catalyst. The pH-rate profiles for the hydrolysis of p -nitrophenyl esters by the various catalysts indicated an absence of any cooperative interactions between imidazole residues or amine groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38694/1/170190704_ftp.pd

Solvolysis of 4-acyloxy-3-nitrobenzoic acid substrates catalyzed by polyethylenimine derivatives

The solvolytic reactions of anionic activated esters (S n − ) catalyzed by dodecane-block-poly[ethylenimine-graft-4(5)-methylimidazole] and related model compounds were investigated. Hydrolysis of 4-acetyl-3-nitrobenzoic acid (S 2 − ) as a function of pH suggested that electrostatic interactions are operative only in the higher molecular weight polymers. Apolar interactions were evident from the greater catalytic rates observed for the hydrolysis of a series of 4-acetoxy-3-nitrobenzoic acid substrates (S n − ). The largest rate enhancements were reflected by catalysts that make effective use of the electrostatic interaction and also provide an apolar binding site. Dodecane-block-poly[ethylenimine-graft-4(5)-methylimidazole], with a DP = 85, catalyzed hydrolysis of S n − (n = 2, 4, and 7), in excess substrate, exhibited saturation kinetics and followed a simple Michaelis-Menten-type mechanism. Inhibition of the catalyst in the hydrolysis of S 12 − was observed and can be rationalized by analogy to certain multisite enzymatic reactions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38695/1/170190715_ftp.pd

Pulmonary blastomycosis presenting as primary lung cancer

Abstract Background Blastomycosis is an endemic mycosis in North America that is caused by the dimorphic fungus Blastomyces dermatitidis. The illness is a systemic disease with a wide variety of pulmonary and extra-pulmonary manifestations. The initial presentation of blastomycosis may easily be mistaken for other infectious or non-infectious etiologies. Case presentation We present the case of a 52-year-old African-American male and former smoker that presented to his primary care provider with a 2-week history of non-productive cough, night sweats and weight loss. Initially diagnosed with primary lung malignancy, the patient was subsequently found to have pulmonary blastomycosis mimicking lung cancer. The patient underwent a successful course of treatment with posaconazole. Conclusions Chronic blastomycosis can present with clinical and radiographic features indistinguishable from thoracic malignancies. There is no clinical syndrome specific for blastomycosis, thus a high degree of suspicion is required for early diagnosis. In this case report, we review recent evidence in radiographic features, diagnostic considerations and treatment of the disease