Publications by authors named "Zoltan Rakonczay"
Heavy alcohol intake is one of the most common causes of acute pancreatitis (AP). We have previously shown that ethanol (EtOH) decreases the expression and activity of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a key role in alcohol-induced AP development. The prescription drug, Orkambi (a combination of ivacaftor and lumacaftor) can correct impaired CFTR function and expression in cystic fibrosis (CF) patients.
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- * Research showed that smokers, both with and without CP, have higher sweat chloride levels and lower CFTR expression, indicating impaired CFTR activity due to smoking.
- * Exposure to cigarette smoke and associated heavy metals like cadmium harms pancreatic function by reducing fluid and bicarbonate secretion and increasing intracellular calcium and ATP depletion.
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- Various organosulfur compounds, like dimethyl trisulfide (DMTS), have shown anti-inflammatory effects and were tested for their impact on acute pancreatitis in animal studies.
- DMTS treatment significantly reduced the severity of acute pancreatitis by decreasing leukocyte infiltration and cellular damage, while enhancing protective heat shock protein expression.
- Findings suggest that DMTS acts as a sulfur donor with antioxidant properties, indicating a need for more research on organosulfur compounds for potential therapeutic use in inflammatory diseases.
Background And Study Aims: Endoscopic biliary stent placement is a minimally invasive intervention for patients with biliary strictures. Stent patency and function time are crucial factors. Suprapapillary versus transpapillary stent positioning may contribute to stent function time, so a meta-analysis was performed in this comparison.
View Article and Find Full Text PDFHypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value.
View Article and Find Full Text PDFAlcoholic pancreatitis and hepatitis are frequent, potentially lethal diseases with limited treatment options. Our previous study reported that the expression of CFTR Cl channel is impaired by ethanol in pancreatic ductal cells leading to more severe alcohol-induced pancreatitis. In addition to determining epithelial ion secretion, CFTR has multiple interactions with other proteins, which may influence intracellular Ca signaling.
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- Noninvasive ventilation (NIV) shows promise in reducing mortality and intubation rates in adults with pneumonia-associated respiratory failure compared to not using NIV, although overall hospital mortality differences were not statistically significant.
- In intensive care settings, NIV significantly lowered mortality rates, demonstrating its effectiveness, especially among patients with overlapping conditions like COPD.
- The results suggest that NIV should be considered in treatment guidelines for pneumonia-related respiratory failure due to its substantial benefits in critical care outcomes.
Background: In severe acute pancreatitis (AP) the CNS is affected manifesting in neurological symptoms. Earlier research from our laboratory showed blood-brain barrier (BBB) permeability elevation in a taurocholate-induced AP model. Here we aimed to further explore BBB changes in AP using a different, non-invasive in vivo model induced by L-ornithine.
View Article and Find Full Text PDFOpioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats.
View Article and Find Full Text PDFThe pathophysiology of acute pancreatitis (AP) is not well understood, and the disease does not have specific therapy. Tryptophan metabolite L-kynurenic acid (KYNA) and its synthetic analogue SZR-72 are antagonists of the N-methyl-D-aspartate receptor (NMDAR) and have immune modulatory roles in several inflammatory diseases. Our aims were to investigate the effects of KYNA and SZR-72 on experimental AP and to reveal their possible mode of action.
View Article and Find Full Text PDFCystic fibrosis transmembrane conductance regulator (CFTR) has an essential role in maintaining pancreatic ductal function. Impaired CFTR function can trigger acute pancreatitis (AP) and exacerbate disease severity. We aimed to investigate the localization and expression of CFTR during AP, and determined the effects of a CFTR corrector (VX-661) and potentiator (VX-770) on disease severity.
View Article and Find Full Text PDFDisordered lysosomal/autophagy pathways initiate and drive pancreatitis, but the underlying mechanisms and links to disease pathology are poorly understood. Here, we show that the mannose-6-phosphate (M6P) pathway of hydrolase delivery to lysosomes critically regulates pancreatic acinar cell cholesterol metabolism. Ablation of the Gnptab gene encoding a key enzyme in the M6P pathway disrupted acinar cell cholesterol turnover, causing accumulation of nonesterified cholesterol in lysosomes/autolysosomes, its depletion in the plasma membrane, and upregulation of cholesterol synthesis and uptake.
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- Mutations in the CFTR gene are linked to cystic fibrosis (CF) and chronic pancreatitis, but patients with CFTR mutations usually retain some pancreatic function compared to those with CF.
- Researchers used transgenic mice with residual CFTR function to study the severity of pancreatitis and found that while pancreatic and lung injuries were worse, the activation of trypsin and necrosis did not differ from controls at certain time points.
- The study concluded that CFTR mutations that still allow some pancreatic function can worsen experimental pancreatitis primarily by impairing duct cell function and promoting inflammation, rather than making acinar cells more vulnerable to damage.
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- - The study conducted a systematic review and meta-analysis to assess how liver function tests and liver diseases at the time of admission impact the severity and outcomes of COVID-19, analyzing data from 50 studies registered on PROSPERO.
- - Key findings indicated that factors like acute liver failure, chronic liver disease, platelet counts, and liver enzyme levels (ALT, AST) were significant predictors for ICU admission, high severity cases, and in-hospital mortality rates in COVID-19 patients.
- - Overall, the research established that having pre-existing liver conditions or experiencing acute liver injury during COVID-19 significantly affects prognosis and can help in predicting patient outcomes.
The main causes of acute pancreatitis (AP) are biliary disease, alcohol consumption, hypertriglyceridaemia (HTG) and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this meta-analysis was to evaluate the effects of these aetiological factors on the severity and outcome of AP. Pubmed and Embase were searched between 01/01/2012 and 31/05/2020.
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- Inhaled sodium bicarbonate shows promise as a treatment for cystic fibrosis due to its ability to break down mucus and inhibit bacteria, but its direct effects on respiratory cells hadn't been explored before this study.
- Researchers created co-culture models using human CF bronchial epithelial cell lines—both with normal and mutant CFTR channels—and discovered that vascular endothelial cells improved the barrier function of CFBE cells.
- Sodium bicarbonate was well-tolerated by the cells, reduced the pH of mutant CFBE cells, and demonstrated potential therapeutic benefits for those with the deltaF508 mutation in the CFTR channel.
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- Chronic pancreatitis (CP) is a serious inflammatory condition that significantly impacts quality of life and leads to lasting pancreatic damage.
- An international group of 20 experts reviewed 14 key factors affecting CP risk, finding strong agreement that alcohol, smoking, and genetic factors increase risk significantly.
- Education on healthy lifestyle choices and genetic counseling may help lower the occurrence of CP, as both personal history and environmental factors play a crucial role in its development.
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- A systematic literature review was conducted to evaluate the effectiveness and best methods for palliative double stenting in cases of malignant duodenobiliary obstruction, comparing this technique with surgical double bypass.
- The review included 80 studies, revealing high technical (97%) and clinical success rates (92%) for double stenting, as well as showing that endoscopic biliary stenting had a higher clinical success than surgery (97% vs 86%).
- Despite having fewer adverse events (13% vs 28%), double stenting required more reinterventions (21% vs 10%) compared to surgical options, with ERCP being the best option for minimizing adverse events.
Key Points: Acute biliary pancreatitis is a significant clinical challenge as currently no specific pharmaceutical treatment exists. Intracellular Ca overload, increased reactive oxygen species (ROS) production, mitochondrial damage and intra-acinar digestive enzyme activation caused by bile acids are hallmarks of acute biliary pancreatitis. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca overload across different diseases.
View Article and Find Full Text PDFKey Points: •Bile acids, ethanol and fatty acids affect pancreatic ductal fluid and bicarbonate secretion via mitochondrial damage, ATP depletion and calcium overload. •Pancreatitis-inducing factors open the membrane transition pore (mPTP) channel via cyclophilin D activation in acinar cells, causing calcium overload and cell death; genetic or pharmacological inhibition of mPTP improves the outcome of acute pancreatitis in animal models. •Here we show that genetic and pharmacological inhibition of mPTP protects mitochondrial homeostasis and cell function evoked by pancreatitis-inducing factors in pancreatic ductal cells.
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- The study investigates the secretory processes of pancreatic epithelial cells, noting that primary cells are hard to study and pancreatic organoid cultures might offer a better model for research.
- Researchers compared gene expression, morphology, and functionality between primary isolated pancreatic ductal cells and organoids, finding significant similarities in ion channel and transporter expression between the two.
- The results indicate that pancreatic organoids mimic primary ductal cell activities, making them a promising model for studying pancreatic ion transport and developing treatments for conditions like cystic fibrosis and chronic pancreatitis.
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- - The study investigates how effective biological therapies, specifically anti-TNFα agents, are in preventing postoperative recurrence (POR) of Crohn's disease compared to conventional treatments.
- - A comprehensive search of research articles was conducted, revealing that anti-TNFα therapies demonstrated significantly better outcomes in preventing various types of POR, including clinical and endoscopic recurrence.
- - The findings suggest that anti-TNFα agents like infliximab and adalimumab are more effective than conventional therapies in preventing POR in Crohn's disease patients, indicating a favorable option for treatment post-surgery.
In cases of difficult biliary cannulation, transpancreatic sphincterotomy (TPS) can be an alternative approach of biliary access. However, its success and safety profile have not been studied in detail. A systematic review and meta-analysis were performed to study the overall cannulation success and adverse events of TPS.
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- - Acute pancreatitis (AP) is a major gastrointestinal issue leading to hospitalizations globally, with 10-20% of cases becoming severe, risking higher mortality; age is identified as a significant risk factor in various scoring systems.
- - A systematic review analyzed 33 studies involving 194,702 AP patients to examine how aging affects the severity and mortality of the disease, utilizing various analytical methods for data assessment.
- - Results showed that severe AP incidence increases with age, from 1.6% in patients under 30 to 9.6% in those aged 70, and mortality rates escalated dramatically, particularly after age 60, indicating that aging poses a considerable risk factor for worse outcomes in AP. *
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- Myofibroblasts (MFs) play a significant role in both healthy tissues and the tumor microenvironment, and this study compares MFs from gastrointestinal tumors and adjacent normal tissues to analyze their differences.
- The research found that tumor-derived MFs have a higher number and different morphology compared to normal MFs, along with distinct gene expression related to cancer progression and metastasis.
- While mutation frequency was similar in both types of MFs, specific epigenetic changes and increased activity in tumor-associated MFs contributed to their enhanced migratory abilities and altered functions compared to healthy tissue MFs.