- Catalase prevents myeloperoxidase self-destruction in response to oxidative stress. [Journal Article]
- JIJ Inorg Biochem 2019 May 04; 197:110706
- Catalase (CAT) and myeloperoxiase (MPO) are heme-containing enzymes that have attracted attention for their role in the etiology of numerous respiratory disorders such as cystic fibrosis, bronchial a…
Catalase (CAT) and myeloperoxiase (MPO) are heme-containing enzymes that have attracted attention for their role in the etiology of numerous respiratory disorders such as cystic fibrosis, bronchial asthma, and acute hypoxemic respiratory failure. However, information regarding the interrelationship and competition between the two enzymes, free iron accumulation, and decreased levels of non-enzymatic antioxidants at sites of inflammation is still lacking. Myeloperoxidase catalyzes the generation of hypochlorous acid (HOCl) from the reaction of hydrogen peroxide (H2O2) and chloride (Cl-). Self-generated HOCl has recently been proposed to auto-inhibit MPO through a mechanism that involves MPO heme destruction. Here, we investigate the interplay of MPO, HOCl, and CAT during catalysis, and explore the crucial role of MPO inhibitors and HOCl scavengers in protecting the catalytic site from protein modification of both enzymes against oxidative damage mediated by HOCl. We showed that CAT not only competes with MPO for H2O2 but also scavenges HOCl. The protective role provided by CAT versus the damaging effect provided by HOCl depends in part on the ratio between MPO/CAT and the affinity of the enzymes towards H2O2 versus HOCl. The severity of such damaging effects mainly depends on the ratio of HOCl to enzyme heme content. In addition to its effect in mediating protein modification and aggregation, HOCl oxidatively destroys the catalytic sites of the enzymes, which contain porphyrin rings and iron. Thus, modulation of MPO/CAT activities may be a fundamental feature of catalysis, and functions to down-regulate HOCl synthesis and prevent hemoprotein heme destruction and/or protein modification.
- Internally Quenched Fluorogenic substrates with unnatural amino acids for cathepsin G investigation. [Journal Article]
- BBiochimie 2019 May 16
- Cathepsin G is one of four members of the neutrophil serine protease family and constitutes an important biological target in various human inflammatory diseases, such as chronic obstructive pulmonar…
Cathepsin G is one of four members of the neutrophil serine protease family and constitutes an important biological target in various human inflammatory diseases, such as chronic obstructive pulmonary disease, acute respiratory distress syndrome and cystic fibrosis. Many studies have been focused on determining its biological roles, the latest ones concerning its involvement in acute myeloid leukemia, and as such, multiple chemical and biochemical tools were developed to investigate cathepsin G. Nevertheless, most of them lack selectivity or sensitivity and therefore cannot be used in complex systems. Here we present the development of an optimal cathepsin G Internally Quenched Fluorescence (IQF) substrate that incorporates unnatural amino acids causing the increase of its selectivity toward neutrophil elastase and potency in in vitro studies.
- Clustered randomized controlled trial of a clinic-based problem-solving intervention to improve adherence in adolescents with cystic fibrosis. [Journal Article]
- JCJ Cyst Fibros 2019 May 15
- CONCLUSIONS: The IMPACT intervention did not improve medication adherence or health outcomes over 12 months. Challenges to implementing the intervention as intended during busy clinic visits were identified.
- Fertility considerations and attitudes about family planning among women with cystic fibrosis. [Journal Article]
- CContraception 2019 May 15
- CONCLUSIONS: Women with cystic fibrosis described thoughtful considerations about desired pregnancies to be planned during times of optimal health. Gaps in knowledge may limit a woman's ability to make the most informed family planning decisions. Implications Having CF directly affects women's decisions around pregnancy and family planning. Understanding what motivates women with CF to use or not to use contraception can improve family planning care delivery to this population.
- Cystic Fibrosis Associated Liver Disease in Lung Transplant Recipients. [Journal Article]
- LTLiver Transpl 2019 May 18
- Cystic fibrosis (CF) is an autosomal recessive disease characterized by mutations in the gene that encodes for the CF transmembrane conductance regulator protein (CFTR). As the life expectancy of ind…
Cystic fibrosis (CF) is an autosomal recessive disease characterized by mutations in the gene that encodes for the CF transmembrane conductance regulator protein (CFTR). As the life expectancy of individuals with CF continues to increase through improved treatment protocols, the likelihood of multiple organ involvement, particularly liver comorbidities, also increases and requires continued interdisciplinary management. Liver related manifestations of CF include biliary strictures, hepatic steatosis, and cirrhosis, and non-cirrhotic portal hypertension. A better understanding of CF progression in adult patients, consistent diagnostic methodology and criteria for CF-related diseases, as well as subsequent surgical interventions and drug therapies, must be aligned for individualization of treatments across specialties to maximize survival and quality of life in this growing patient population This article is protected by copyright. All rights reserved.
- Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. [Journal Article]
- IInfection 2019 May 17
- CONCLUSIONS: Given the concern for MDR P. aeruginosa infections in CF patients, BT may offer a viable anti-infective adjunct to traditional antibiotic therapy.
- Antibody-Mediated Rejection in a Multiple Lung Transplant Patient: A Case Report. [Journal Article]
- TPTransplant Proc 2019; 51(4):1296-1298
- Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, w…
Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.
- Testicular Cancer in a Lung Transplant Patient With Cystic Fibrosis: A Case Report. [Journal Article]
- TPTransplant Proc 2019; 51(4):1293-1295
- Cystic fibrosis (CF) is one of the most common genetic disorders that develops from a mutation of the cystic fibrosis transmembrane regulator gene. Patients with CF are known to be at risk for malign…
Cystic fibrosis (CF) is one of the most common genetic disorders that develops from a mutation of the cystic fibrosis transmembrane regulator gene. Patients with CF are known to be at risk for malignancies, and lung transplantation-associated immunosuppression further increases this risk.
- Lung Transplantation in Hungary From Cardiac Surgeons' Perspective. [Journal Article]
- TPTransplant Proc 2019; 51(4):1263-1267
- Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of pr…
Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.
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- First 3 Years of the Hungarian Lung Transplantation Program. [Journal Article]
- TPTransplant Proc 2019; 51(4):1254-1257
- CONCLUSIONS: The number of cases rises steadily in the Hungarian Lung Transplantation Program, which is exceptional compared with the start of other centrums. The incidence of complications and mortality is comparable with those of other experienced centers around the world. Our future goal is to broaden our waiting list, thus increasing the number of lung transplants carried out.