Emese Tóth

Analysis of research activity in gastroenterology: Pancreatitis is in real danger

Objective Biomedical investment trends in 2015 show a huge decrease of investment in gastroenterology. Since academic research usually provides the basis for industrial research and development (R&D), our aim was to understand research trends in the field of gastroenterology over the last 50 years and identify the most endangered areas. Methods We searched for PubMed hits for gastrointestinal (GI) diseases for the 1965–2015 period. Overall, 1,554,325 articles were analyzed. Since pancreatology was identified as the most endangered field of research within gastroenterology, we carried out a detailed evaluation of research activity in pancreatology. Results In 1965, among the major benign GI disorders, 51.9% of the research was performed on hepatitis, 25.7% on pancreatitis, 21.7% on upper GI diseases and only 0.7% on the lower GI disorders. Half a century later, in 2015, research on hepatitis and upper GI diseases had not changed significantly; however, studies on pancreatitis had dropped to 10.7%, while work on the lower GI disorders had risen to 23.4%. With regard to the malignant disorders (including liver, gastric, colon, pancreatic and oesophageal cancer), no such large-scale changes were observed in the last 50 years. Detailed analyses revealed that besides the drop in research activity in pancreatitis, there are serious problems with the quality of the studies as well. Only 6.8% of clinical trials on pancreatitis were registered and only 5.5% of these registered trials were multicentre and multinational (more than five centres and nations), i.e., the kind that provides the highest level of impact and evidence level. Conclusions There has been a clear drop in research activity in pancreatitis. New international networks and far more academic R&D activities should be established in order to find the first therapy specifically for acute pancreatitis.

Bidirectional Relationship Between Reduced Blood pH and Acute Pancreatitis: A Translational Study of Their Noxious Combination

Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P < 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, pre-existing MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP.

Detection of biomolecules and bioconjugates by monitoring rotated grating-coupled surface plasmon resonance

Plasmonic biosensing chips were prepared by fabricating wavelength-scaled dielectric-metal interfacial gratings on thin polycarbonate films covered bimetal layers via two-beam interference laser lithography. Lysozyme (LYZ) biomolecules and gold nanoparticle (AuNP-LYZ) bioconjugates with 1:5 mass ratio were seeded onto the biochip surfaces. Surface plasmon resonance spectroscopy was performed before and after biomolecule seeding in a modified Kretschmann-arrangement by varying the azimuthal and polar angles to optimize the conditions for rotated grating-coupling. The shift of secondary and primary resonance peaks originating from rotated grating-coupling phenomenon was monitored to detect the biomolecule and bioconjugate adherence. Numerical calculations were performed to reproduce the measured reflectance spectra and the resonance peak shifts caused by different biocoverings. Comparison of measurements and calculations proved that monitoring the narrower secondary peaks under optimal rotated-grating coupling condition makes it possible to achieve enhanced sensitivity in biodetection. The sensitivity is further increased in case of bioconjugates due to coupled localized resonances on Au NPs. The enlarged resonance peak shift is resulted by the two-fold antisymmetric long-range plamonic modes propagating at the edge of the valleys and hills, which originate from Bragg scattered surface plasmon polaritons. Optimal configuration of ideal chips supporting rotated grating-coupled long-range plasmonic modes are proposed for biosensing.