Stannites – a new promising class of durable electrocatalysts for efficient water oxidation

The oxygen evolution reaction (OER) through water oxidation is a key process for multiple energy storage technologies required for a sustainable energy economy such as the formation of the fuel hydrogen from water and electricity, or metal‐air batteries. Herein, we investigate the suitability of Cu2FeSnS4 for the OER and demonstrate its superiority over iron sulfide, iron (oxy)hydroxides and benchmark noble‐metal catalysts in alkaline media. Electrodeposited Cu2FeSnS4 yields the current densities of 10 and 1000 mA/cm2 at overpotentials of merely 228 and 330 mV, respectively. State‐of‐the‐art analytical methods are applied before and after electrocatalysis to uncover the fate of the Cu2FeSnS4 precatalyst under OER conditions and to deduce structure‐activity relationships. Cu2FeSnS4 is the first compound reported for OER among the broad class of stannite structure type materials containing multiple members with highly active earth‐abundant transition‐metals for OER.DFG, 390540038, EXC 2008: Cluster of Excellence UniSysCatTU Berlin, Open-Access-Mittel - 201

Animal models for investigating chronic pancreatitis

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed

Development of Pancreatic Cancer: Targets for Early Detection and Treatment

Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death worldwide and compared to other malignancies its share in cancer mortality is expected to rise further. This is due to a lack of sensitive diagnostic tools that would permit earlier detection in a potentially curable stage and the very slow progress in finding effective drug treatments for pancreatic cancer. Key Messages: Aside from genetic predispositions and environmental agents, chronic pancreatitis is by far the greatest risk factor for PDAC. It also shares several etiological factors with pancreatic cancer and represents its most challenging differential diagnosis. Biomarkers that can distinguish between chronic pancreatitis and PDAC may therefore be suitable for the latter's early detection. Moreover, targeting the natural history of chronic pancreatitis would be one approach to prevent PDAC. Targeting tumor-cell signaling directly by interfering with receptor tyrosine kinases has shown some efficacy, although the results in clinical trials were less encouraging than for other cancers. Other compounds developed have targeted the formation of extracellular matrix around the tumor, the proteolytic activity in the tumor environment, histone deacetylases, hedgehog signaling and heat shock proteins, but none has yet found its way into routine patient care. Attempts to individualize treatment according to the tumor's somatic mutation profile are novel but so far impractical. Conclusions: Progress in the treatment of pancreatic cancer has been exceedingly slow and mostly dependent on improved pharmaceutical preparations or combinations of established chemotherapeutic agents. The promise of major breakthroughs implied in targeting tumor signal transduction events has so far not materialized

Comprehensive metabolic profiling of chronic low-grade inflammation among generally healthy individuals.

BACKGROUND: Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers. METHODS: Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis. RESULTS: HsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3'-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83). CONCLUSIONS: Comprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders

Clinical results of the Metha short hip stem: a perspective for younger patients?

In recent years, various uncemented proximal metaphyseal hip stems were introduced for younger patients as a bone preserving strategy. Initial osteodensitometric analyses of the surrounding bone of short stems indicate an increase of bone mass with secondary bone ingrowth fixation as a predictor of long-term survival of these types of implants. We report the outcome of 151 modular Metha short hip stem implants in 148 patients between March 2005 and October 2007. The mean follow-up was 5.8±0.7 years and the mean age of the patients was 55.7±9.8 years. Along with demographic data and co-morbidities, the Harris Hip Score (HHS), the Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and also the results of a patient-administered questionnaire were recorded pre-operatively and at follow-up. The mean HHS increased from 46±17 pre-operatively to 90±5 the HOOS improved from 55±16 pre-operatively to 89±10 at the final follow-up. A total of three patients have been revised, two for subsidence with femoral revision and one for infection without femoral revision (Kaplan Meier survival estimate 98%). The radiological findings showed no radiolucent lines in any of the patients. The modular Metha short hip stem was implanted in younger patients, who reported an overall high level of satisfaction. The clinical and radiographic results give support to the principle of using short stems with metaphyseal anchorage. However, long-term results are necessary to confirm the success of this concept in the years to come

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

Synthesis and Properties of Vinylogous 6-(Cyclopentadienyl)pentafulvenes

The application of the principle of kinetic stabilization on vinylogous 6-(cyclopentadienyl)pentafulvenes 1 led to the synthesis of the di- and tetra-tert-butyl derivatives 7a – e and 8a - c. Their reactions with bases and acids form charged, heteroatom-free cyanine-type carbanionic 9a - e, 10a – e and carbocationic 11a – e, 12a – c species which were characterized with NMR and UV/Vis spectroscopy. Conclusions on the ion pair structures of the alkali metal salts 9a - e and 10a – c are drawn from the spectroscopic data. Additionally, in one case the behavior of the alkali metal salt 10b towards oxidants was studied by cyclic voltammetry and the structure of the corresponding hydrocarbon 8b was proved by X-ray structural analysis

Environmental Risk Factors for Chronic Pancreatitis and Pancreatic Cancer

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke

Helicobacter pylori infection associates with fecal microbiota composition and diversity

Helicobacter (H.) pylori is the most important cause for peptic ulcer disease and a risk factor for gastric carcinoma. How colonization with H. pylori affects the intestinal microbiota composition in humans is unknown. We investigated the association of H. pylori infection with intestinal microbiota composition in the population-based cohort Study-of-Health-in-Pomerania (SHIP)-TREND. Anti-H. pylori serology and H. pylori stool antigen tests were used to determine the H. pylori infection status. The fecal microbiota composition of 212 H. pylori positive subjects and 212 matched negative control individuals was assessed using 16S rRNA gene sequencing. H. pylori infection was found to be significantly associated with fecal microbiota alterations and a general increase in fecal microbial diversity. In infected individuals, the H. pylori stool antigen load determined a larger portion of the microbial variation than age or sex. The highest H. pylori stool antigen loads were associated with a putatively harmful microbiota composition. This study demonstrates profound alterations in human fecal microbiota of H. pylori infected individuals. While the increased microbiota diversity associated with H. pylori infection as well as changes in abundance of specific genera could be considered to be beneficial, others may be associated with adverse health effects, reflecting the complex relationship between H. pylori and its human host