The effect of zinc deficiency and iron overload on endocrine and exocrine pancreatic function in children with transfusion-dependent thalassemia: a cross-sectional study

Background Children with transfusion-dependent thalassemia (TDT) suffer from secondary hemosiderosis and the delirious effects this iron overload has on their different body organs, including the pancreas. They are also more prone to develop zinc deficiency than the general pediatric population. This study aimed to determine the effect of zinc deficiency and iron overload on the endocrine and exocrine pancreas in TDT children. Methods Eighty children, already diagnosed with TDT, were included in this study. We assessed the following in the participant children: serum ferritin, serum zinc, endocrine pancreatic function (oral glucose tolerance test (OGTT), fasting insulin level and from them, HOMA-IR was calculated), and exocrine pancreatic function (serum lipase and serum amylase). Results Forty-four TDT children had a subnormal zinc level, while 36 of them had a normal serum zinc level. TDT children with low serum zinc had significantly more impaired endocrine pancreatic function and an abnormally high serum lipase than children with normal serum zinc, p < 0.05 in all. Serum zinc was significantly lower in TDT children with serum ferritin above the ferritin threshold (≥2500 ng/ml) than those below (59.1 ± 20.2 vs. 77.5 ± 28.13), p = 0.02. TDT children, having a serum ferritin ≥2500 ng/ml, had significantly more frequently impaired endocrine pancreatic function and abnormally high serum lipase than TDT children below the ferritin threshold, p < 0.05 in all. Conclusion In children with transfusion-dependent thalassemia, zinc deficiency aggravates iron-induced pancreatic exocrine and endocrine dysfunction.

Recent Advances in Understanding the Complexity of Alcohol-Induced Pancreatic Dysfunction and Pancreatitis Development

Chronic excessive alcohol use is a well-recognized risk factor for pancreatic dysfunction and pancreatitis development. Evidence from in vivo and in vitro studies indicates that the detrimental effects of alcohol on the pancreas are from the direct toxic effects of metabolites and byproducts of ethanol metabolism such as reactive oxygen species. Pancreatic dysfunction and pancreatitis development are now increasingly thought to be multifactorial conditions, where alcohol, genetics, lifestyle, and infectious agents may determine the initiation and course of the disease. In this review, we first highlight the role of nonoxidative ethanol metabolism in the generation and accumulation of fatty acid ethyl esters (FAEEs) that cause multi-organellar dysfunction in the pancreas which ultimately leads to pancreatitis development. Further, we discuss how alcohol-mediated altered autophagy leads to the development of pancreatitis. We also provide insights into how alcohol interactions with other co-morbidities such as smoking or viral infections may negatively affect exocrine and endocrine pancreatic function. Finally, we present potential strategies to ameliorate organellar dysfunction which could attenuate pancreatic dysfunction and pancreatitis severity.

Efficiency of Shidnitsa mineral waters in complex rehabilitation of patients with chronic pancreatitis with concomitant diabetes mellitus

Relevance. Rehabilitation of patients with chronic pancreatitis (CP) combined with diabetes mellitus (DM) requires a complex systemic and personified approach, since such comorbidity is characterized by complicated interactions of these nosology items, with more lesions of pancreas as the main organ involved in the formation and depth pathological manifestations of each patient, as well as the involvement of adjacent organs of the gastrointestinal tract, other organs and systems. Process of integrated rehabilitation, which purpose is to maximally restore the lost functions of the above organs, especially the pancreas, should include, in addition to standard protocol approaches, the adjuvant effective techniques that showed their practical effectiveness but require research and scientific substantiation. Such techniques include the use of therapeutic mineral water (MW) both in resorts and in outpatient practice according to the place of residence of patients. The aim of the study is to investigate the effectiveness of rehabilitation of patients with CP and concomitant DM with the use of the drug ademetionin in the sublingual form (Agepta) and the course of treatment with drinking MW of the Shidnitsa deposit. Material and methods of research. 77 patients with CP and concomitant DM were examined. According to treatment programs, patients were divided into 3 groups: Group 1 (protocol treatment (PT) — 26 patients) — received enzyme preparation of pure pancreatin, proton pump inhibitor (pantoprazole 40 mg), anesthetics (mebeverin) and/or prokinetic (motilium), metformin 1000 mg twice a day); Group 2 (PT + ademetionin — 26 patients) — in addition to PT received a drug ademetionin (sublingual tablets Agepta 400 mg) 1 tablet 2 times per day 30–60 min before eating, holding under tongue at least 15–20 min — until complete dissolution, 1 month course; Group 3 — in addition to PT and Agepta in the above-mentioned scheme, they took the course of treatment by drinking MW of the Shidnitsa deposit according to the proposed scheme. Results. Positive dynamics in all groups of comparison was revealed, but its intensity differed in those groups. Improvement of exocrine and endocrine pancreatic function was found: level of fecal α-elastase increased by 58.5% in Group 1, by 82.6% in Group 2, by 93.4% in Group 3; level of blood glucose decreased by 9.2% in Group 1, by 13.3% in Group 2, by 19.5% in Group 3; level of HbA1c — by 4.9% in Group 1, by 9.2% in Group 2, by 12.2% in Group 3; changes in the coprogram — by 24.5% in Group 1, by 38.6% in Group 2, by 55.2% in Group 3. Discussion. There was a statistically significant improvement in the results of Group 2 as compared to Group 1 (p<0.05), which indicates the effectiveness of use of ademetionin (Agepta sublingual tablets) in a comprehensive correction program for patients with CP and DM. However, the most evident dynamics of indicators of exocrine and endocrine pancreatic function was found in Group 3 as compared to Groups 2 and 1, respectively, indicating the expediency of the additional appointment of the therapeutic course of drinking MW of the Shidnitsa deposit according to the proposed scheme. Conclusion. The effectiveness of inclusion of ademetionin in complex standard protocol program of treatment of patients with CP with concomitant DM in sublingual tablets (Agepta) with 400 mg twice a day during 1 month and 14-day course of treatment with drinking MW of the Shidnitsa deposit according to the proposed scheme was proved by statistically significant improvement of the indices of exocrine and endocrine pancreatic function (p<0.05).

Cystic Fibrosis–Related Diabetes: Pathophysiology and Therapeutic Challenges

Cystic fibrosis–related diabetes (CFRD) is among the most common extrapulmonary co-morbidity associated with cystic fibrosis (CF), affecting an estimated 50% of adults with the condition. Cystic fibrosis is prevalent in 1 in every 2500 Caucasian live births and is caused by a mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene. Mutated CFTR leads to dehydrated epithelial surfaces and a build-up of mucus in a variety of tissues including the lungs and pancreas. The leading cause of mortality in CF is repeated respiratory bacterial infections, which prompts a decline in lung function. Co-morbid diabetes promotes bacterial colonisation of the airways and exacerbates the deterioration in respiratory health. Cystic fibrosis–related diabetes is associated with a 6-fold higher mortality rate compared with those with CF alone. The management of CFRD adds a further burden for the patient and creates new therapeutic challenges for the clinical team. Several proposed hypotheses on how CFRD develops have emerged, including exocrine-driven fibrosis and destruction of the entire pancreas and contrasting theories on the direct or indirect impact of CFTR mutation on islet function. The current review outlines recent data on the impact of CFTR on endocrine pancreatic function and discusses the use of conventional diabetic therapies and new CFTR-correcting drugs on the treatment of CFRD.

Mini-Review on the Glucose Metabolism Modifications after Pancreatic Resection

Pancreatic cancer is one of the most severe malignant disease, with an extreme degree of lethality, considering that the survival rate at 5 years is up to 4%. In addition, a major disadvantage of this disease is the fact that the diagnosis is determined very late in the evolution of the disorder, despite the development of new technologies. In this way, the main symptoms are occurring later on, when the tumour is already locally advanced and unresectable. Up to now surgery is the only modality that can provide a greater chance of survival, but unfortunately the pancreatic resection has many unknowns and controversies around it. Moreover, the studies on endocrine pancreatic function after resection are very few and somehow controversial. In this way, in the present mini-review we will describe the most relevant experimental data regarding the post-resection pancreatogenic diabetes, the pancreatic polypeptide PP and the pancreatic glucose metabolism after resection or the glucose metabolism after partial or total pancreatectomy.

Middle Segment-Preserving Pancreatectomy for Recurrent Metastasis of Renal Cell Carcinoma after Pancreatoduodenectomy: A Case Report

Many cases of surgical resection of metastatic pancreatic tumors originating from renal cell carcinoma have been reported; however, cases of reresection of recurrent pancreatic metastasis of renal cell carcinoma in the remnant pancreas are rare. We performed a second resection for recurrent pancreatic metastasis of renal cell carcinoma six years after pancreatoduodenectomy with pancreaticogastrostomy reconstruction. By performing middle segment-preserving pancreatectomy, we were able to successfully spare the exocrine and endocrine pancreatic function compared to that observed after total pancreatectomy, with no signs of recurrence for two years after the surgery.