Intramuscular islet allotransplantation in type 1 diabetes mellitus

OBJECTIVE: Alternative sites to the liver for islet transplantation have been studied for a long time. Intramuscular islet transplantation appears to be an alternative site to the liver because of the ease of access. First islet autotransplantations were reported in patients after total pancreatectomies. The transplanted islets showed a proper revascularization and their function was observed for up to 2 years after the implant. However, only a few cases of autotransplantation and no allotransplantation have been performed. The aim of this study was to verify the feasibility of islet allotransplantation into muscles.

PATIENTS AND METHODS: In four patients affected by type 1 diabetes mellitus in which liver islet allotransplantation was contraindicated, human islets were transplanted into patients' arm muscle with local anesthesia.

RESULTS: The surgery was minimally invasive, without complications. In one patient a moderate local inflammatory reaction was observed at the site of the implant, which resolved spontaneously within 4 days. Islet graft function was observed after transplantation in all patients, but it progressively disappeared in 3 out 4 patients within a short time.

CONCLUSIONS: In this first ever-reported intramuscular pancreatic islet allotransplantation, the procedure appears feasible but new strategies must be envisaged to significantly improve islet engraftment and the long-term graft function.

L'articolo Intramuscular islet allotransplantation in type 1 diabetes mellitus sembra essere il primo su European Review.

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Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men

OBJECTIVE: To investigate the relationship between bone metabolic indicators and non-alcoholic fatty liver disease (NAFLD) in healthy middle-aged men.

PATIENTS AND METHODS: The bone metabolic indicators of 232 healthy middle-age men with NAFLD (NAFLD group) and 308 healthy controls without fatty liver (Control group) were measured, including non-collagenous osteocalcin, the procollagen type 1 N-terminal propeptide (P1NP), beta-C-terminal telopeptide of type I collagen (β-CTX). The Student's t-test was used to analyze the differences in the bone metabolic indicators, age, clinical data, biochemical indicators, and the indicators of glucose and lipid metabolism between the two groups. The correlation of fatty liver-related indicators was detected using the logistic regression analysis.

RESULTS: The body mass index (BMI), diastolic blood pressure, and heart rate in NAFLD group were significantly higher than those in Control group. Among the indicators of glucose and lipid metabolism in NAFLD group, the levels of blood glucose [fasting plasma glucose, postprandial blood glucose and hemoglobin A1c (HbA1c)] were significantly higher than those in Control group. In addition, the insulin resistance and secretion indexes were also significantly higher than those in Control group. The levels of lipid metabolic indicators such as triglyceride were higher, but high-density lipoprotein cholesterol was lower than that in Control group. From logistic regression analysis, the BMI, Homeostasis model assessment (HOMA)-β, HOMA-IR, HbA1c and P1NP were positively associated with the occurrence of NAFLD.

CONCLUSIONS: The bone metabolic indicator P1NP might be a potential predicator for the diagnosis of NAFLD in clinical application.

L'articolo Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men sembra essere il primo su European Review.

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Islet transplantation 30 years after the first transplants

First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function.  Several strategies have been proposed to increase the success rate of pancreas digestion and islet purification or to facilitate islet engraftment by reducing islet hypoxia and the inflammatory reaction occurring in the site of transplantation. The co-transplantation of progenitors of beta cell together with the islets has expected to contribute to prolong graft function. Clinical trials are expected soon. Scientific advances, as well as economical efforts, are required to make this procedure a real therapeutical option for patients with type 1 diabetes mellitus.

L'articolo Islet transplantation 30 years after the first transplants sembra essere il primo su European Review.

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The role of adiponectin gene mediated by NF-κB signaling pathway in the pathogenesis of type 2 diabetes

OBJECTIVE: To investigate the role of adiponectin (ADPN) gene mediated by NF-κB signaling pathway in the pathogenesis of type 2 diabetes (T2DM).

PATIENTS AND METHODS: The levels of expression of ADPN were measured by fluorescence quantitative PCR technology, enzyme-linked immunosorbent assay, Western-blotting and immunohistochemistry in 78 patients with type 2 diabetes.

RESULTS: Compared with the normal population, the levels of expression of ADPN and NF-κB mRNA in the blood of patients with type 2 diabetes were significantly reduced (p < 0.05). The detection of ADPN gene protein expression in normal population and patients with type 2 diabetes by enzyme-linked immunosorbent assay showed that ADPN gene protein expression in type 2 diabetic patients (1.26 ± 0.73) µg/l was significantly lower (p < 0.05) than ADPN gene protein expression of the normal population (3.26 ± 1.25) µg/l. At the same time, the detection of the expression of NF-κB gene showed that the protein expression in type 2 diabetic patients (0.58 ± 0.15) µg/l was significantly lower (p < 0.05) than that in the normal population (1.67 ± 1.04) µg/l. The results of Western-blotting were consistent with the results of enzyme-linked immunosorbent assay. Immunohistochemical results also showed that the percentage of ADPN positive cells in patients with type 2 diabetes (25.47%) was significantly lower (p < 0.05) than that in the normal population (79.47%).

CONCLUSIONS: ADPN gene in the human body can be involved in the pathogenesis of T2DM through the NF-κB signaling pathway.

L'articolo The role of adiponectin gene mediated by NF-κB signaling pathway in the pathogenesis of type 2 diabetes sembra essere il primo su European Review.

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Impact of formulation on the iontophoretic delivery of the FOLFIRINOX regimen for the treatment of pancreatic cancer

Abstract

Purpose

Effective treatment of patients with locally advanced pancreatic cancer is a significant unmet clinical need. One major hurdle that exists is inadequate drug delivery due to the desmoplastic stroma and poor vascularization that is characteristic of pancreatic cancer. The local iontophoretic delivery of chemotherapies provides a novel way of improving treatment. With the growing practice of highly toxic combination therapies in the treatment of pancreatic cancer, the use of iontophoresis for local delivery can potentiate the anti-cancer effects of these therapies while sparing unwanted toxicity. The objective of this study was to investigate the impact of formulation on the electro-transport of the FOLFIRINOX regimen for the development of a new treatment for pancreatic cancer.

Methods

Three formulations of the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) were generated at a fixed pH of 6.0 and were referred to as formulation A (single drug solution with all four drugs combined), formulation B (two drug solutions with two drugs per solution), and formulation C (four individual drug solutions). Anodic iontophoresis of the three different formulations was evaluated in orthotopic patient-derived xenografts of pancreatic cancer.

Results

Iontophoretic transport of the FOLFIRINOX drugs was characterized according to organ exposure after a single device treatment in vivo. We report that the co-iontophoresis of two drug solutions, leucovorin + oxaliplatin and 5-fluorouracil + irinotecan, resulted in the highest levels of cytotoxic drugs in the tumor compared to drugs delivered individually or combined into one solution. There was no significant difference in plasma, pancreas, kidney, and liver exposure to the cytotoxic drugs delivered by the three different formulations. In addition, we found that reducing the duration of iontophoretic treatment from 10 to 5 min per solution resulted in a significant decrease in drug concentrations.

Conclusions

Underlying the difference in drug transport of the formulations was electrolyte concentrations, which includes both active and inactive components. Electrolyte concentrations can hinder or improve drug electro-transport. Overall, balancing electrolyte concentration is needed for optimal electro-transport.

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Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer

British Journal of Surgery, EarlyView.


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Construct and criterion validity testing of the Non‐Technical Skills for Surgeons (NOTSS) behaviour assessment tool using videos of simulated operations

British Journal of Surgery, EarlyView.


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