Cathepsin C role in inflammatory gastroenterological, renal, rheumatic, and pulmonary disorders

Cathepsin C (CatC, syn. Dipeptidyl peptidase I) is a lysosomal cysteine proteinase expressed in several tissues including inflammatory cells. This enzyme is important for maintaining multiple cellular functions and for processing immune cell-derived proteases. While mutations in the CatC gene were reported in Papillon-Lefèvre syndrome, a rare autosomal recessive disorder featuring hyperkeratosis and periodontitis, evidence from clinical and preclinical studies points toward pro-inflammatory effects of CatC in various disease processes that are mainly mediated by the activation of neutrophil serine proteinases. Moreover, tumor-promoting effects were ascribed to CatC. The aim of this review is to highlight current knowledge of the CatC as a potential therapeutic target in inflammatory disorders

Nutrition in Pancreatic Cancer: A Review

Background: Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. Summary: This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival. Key Message: Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data. Practical Implications: Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and L-carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer

Targeting cathepsin C ameliorates murine acetaminophen-induced liver injury

Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene expression during murine APAP-induced ALI by 3\u27mRNA sequencing (massive analysis of cDNA ends, MACE), we observed splenic mRNA accumulation encoding for the neutrophil serine proteases cathepsin G, neutrophil elastase, and proteinase-3 - all are hierarchically activated by cathepsin C (CtsC). This, along with increased serum levels of these proteases in diseased mice, concurs with the established phenomenon of myeloid cell mobilization during APAP intoxication

Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis

Acute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG(-/-) mice and corresponding controls acute experimental pancreatitis was induced by serial caerulein injections. Severity was assessed by histology, serum enzyme levels and zymogen activation. Neutrophil infiltration was quantified by chloro-acetate ersterase staining and myeloperoxidase measurement. CTSG was expessed in inflammatory cells but not in pancreatic acinar cells. CTSG had no effect on intra-acinar-cell trypsinogen activation. In CTSG(-/-) mice a transient decrease of neutrophil infiltration into the pancreas and lungs was found during acute pancreatitis while the disease severity remained largely unchanged. CTSG is involved in pancreatic neutrophil infiltration during pancreatitis, albeit to a lesser degree than the related neutrophil (PMN) elastase. Its absence therefore leaves pancreatitis severity essentially unaffected

Korruption: ein ungerechtfertigter Eingriff in internationale Menschenrechte? Chancen und Grenzen einer opferbezogenen Korruptionsperspektive

<p><b>Daily carbohydrate (A) and sugar (B) intake by groups and subgroups.</b> Carbohydrate (A) and sugar intake (B) as illustrated in percent. The boxes cover the first quartile on the bottom and the third quartile on the top. Whiskers reach from the minimum to the maximum value excluding outliers (illustrated by dots). Shift-working group and shift-working nursing-staff subgroup cover identical cohorts. NG, non-shift-working group; SG, shift-working group; SN, shift-working nursing-staff subgroup; NO, non-shift-working office-staff subgroup; NN, non-shift-working nursing-staff subgroup *p<0.05.</p

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass

Genetic Testing for Rare Diseases: A Systematic Review of Ethical Aspects

Genetic testing is associated with many ethical challenges on the individual, organizational and macro level of health care systems. The provision of genetic testing for rare diseases in particular requires a full understanding of the complexity and multiplicity of related ethical aspects. This systematic review presents a detailed overview of ethical aspects relevant to genetic testing for rare diseases as discussed in the literature. The electronic databases Pubmed, Science Direct and Web of Science were searched, resulting in 55 relevant publications. From the latter, a total of 93 different ethical aspects were identified. These ethical aspects were structured into three main categories (process of testing, consequences of the test outcome and contextual challenges) and 20 subcategories highlighting the diversity and complexity of ethical aspects relevant to genetic testing for rare diseases. This review can serve as a starting point for the further in-depth investigation of particular ethical issues, the education of healthcare professionals regarding this matter and for informing international policy development on genetic testing for rare diseases

Nutrition in Pancreatic Cancer: A Review

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. SUMMARY: This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival KEY MESSAGE: Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data PRACTICAL IMPLICATIONS: Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and l-carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer

Analysis of lifestyle factors in patients with concomitant chronic pancreatitis and liver cirrhosis

Background & objectives: Chronic pancreatitis (CP) and liver cirrhosis (LC) are common gastroentero-logical disorders but their co-incidence is considered to be rare. This study was designed to identify lifestyle factors that are associated with the development of concomitant LC in patients with CP. Methods: In a retrospective case-control study between 2000 and 2005 122 patients with both CP and LC and 223 matched control patients with CP and no known liver disease were identified in 11 European university medical centers. Another 24 patients and 48 CP controls were identified in the period between 2006 and 2012. Results: Alcoholism was most commonly regarded as aetiology for both CP (82.2%; 95% confidence interval (CI): 75.0-88.0%) and LC (79.5%; 95% CI: 72.0-85.7%) as compared to controls with CP only (68.6%; 95% CI: 62.7-74.1%). The preferred type of alcoholic beverage and pattern of alcohol intake were the only significant lifestyle factors in multivariate analysis. Frequency of alcohol intake (p = 0.105) and smoking status (p = 0.099) were not significant in bivariate analysis and dropped out of the multivariate model. Recurrent and chronic pancreatic pain was observed more often in patients with only CP, whereas gallstones were more common in individuals with both chronic disorders. Conclusions: These findings indicate that certain lifestyle factors might be important for the development of concomitant CP and LC. More studies will be needed to identify additional genetic and environmental factors underlying this association. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.Peer reviewe