Characterisation of native and decellularised porcine tendon under tension and compression: A closer look at glycosaminoglycan contribution to tendon mechanics.

Decellularised porcine superflexor tendon (pSFT) has been characterised as a suitable scaffold for anterior cruciate ligament replacement, with dimensions similar to hamstring tendon autograft. However, decellularisation of tissues may reduce or damage extracellular matrix components, leading to undesirable biomechanical changes at a whole tissue scale. Although the role of collagen in tendons is well established, the mechanical contribution of glycosaminoglycans (GAGs) is less evident and could be altered by the decellularisation process. In this study, the contribution of GAGs to the tensile and compressive mechanical properties of pSFT was determined and whether decellularisation affected these properties by reducing GAG content or functionality. PSFTs were either enzymatically treated using chondroitinase ABC to remove GAGs or decellularised using previously established methods. Native, GAG-depleted and decellularised pSFT groups were then subjected to quantitative assays and biomechanical characterisation. In tension, specimens underwent stress relaxation and strength testing. In compression, specimens underwent confined compression testing. The GAG-depleted group was found to have circa 86% reduction of GAG content compared to native and decellularised groups. There was no significant difference in GAG content between native (3.75 ± 0.58 µg/mg) and decellularised (3.40 ± 0.37 µg/mg) groups. Stress relaxation testing discovered the time-independent and time-dependent relaxation moduli of the decellularised group were reduced ≥50% compared to native and GAG-depleted groups. However, viscoelastic behaviour of native and GAG-depleted groups resulted similar. Strength testing discovered no differences between native and GAG-depleted group's properties, albeit a reduction ∼20% for decellularised specimens' linear modulus and tensile strength compared to native tissue. In compression testing, the aggregate modulus was found to be circa 74% lower in the GAG-depleted group than the native and decellularised groups, while the zero-strain permeability was significantly higher in the GAG-depleted group (0.86 ± 0.65 mm4/N) than the decellularised group (0.03 ± 0.04 mm4/N). The results indicate that GAGs may significantly contribute to the mechanical properties of pSFT in compression, but not in tension. Furthermore, the content and function of GAGs in pSFTs are unaffected by decellularisation and the mechanical properties of the tissue remain comparable to native tissue.

Prolactin Induces IL-2 Associated TRAIL Expression on Natural Killer Cells from Chronic Hepatitis C Patients In vivo and In vitro.

BACKGROUND: Natural killer cells (NKC) are a major component of the innate immune response to HCV, mediating their effects through TRAIL and IFN-γ. However, their function is diminished in chronic HCV patients (HCVp). Prolactin is an immunomodulatory hormone capable of activating NKC. OBJECTIVE: The study aims to explore if hyperprolactinemia can activate NKC in HCVp. METHODS: We treated twelve chronic HCVp (confidence level =95%, power =80%) for 15 days with Levosulpiride plus Cimetidine to induce mild hyperprolactinemia. Before and after treatment, we determined TRAIL and NKG2D expression on peripheral blood NKC, along with cytokine profiles, viral loads and liver function. We also evaluated in vitro effects of prolactin and/or IL-2 on NKC TRAIL or NKG2D expression and IFN-γ levels on cultured blood mononuclear cells from 8 HCVp and 7 healthy controls. RESULTS: The treatment induced mild hyperprolactinemia and increased TRAIL expression on NKC as well as the secretion of IL-1ra, IL-2, PDGF and IFN-γ. Viral loads decreased in six HCVp. IL-2 and TRAIL together explained the viral load decrease. In vitro, prolactin plus IL-2 synergized to increase TRAIL and NKG2D expression on NKC from HCVp but not in controls. CONCLUSION: Levosulpiride/Cimetidine treatment induced mild hyperprolactinaemia that was associated with NKC activation and Th1-type cytokine profile. Also, an increase in TRAIL and IL-2 was associated with viral load decrease. This treatment could potentially be used to reactivate NKC in HCVp.

Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics?

BACKGROUND: Assessment of the pathological characteristics of pancreatic neuroendocrine tumours is crucial for appropriate management. We compared preoperative pathological data with surgical specimens for accuracy. METHODS: Surgical patients with pancreatic neuroendocrine tumours who underwent preoperative endoscopic ultrasound-guided fine needle aspiration of the primary tumour or biopsy of liver metastasis were retrospectively included. Tumour differentiation and the Ki67 proliferation index on biopsies were compared with pancreatic specimens. RESULTS: Fifty-seven patients were included. A preoperative biopsy of the primary tumour or of a liver metastasis was obtained in 48 and 9 patients respectively. Tumour differentiation was high in 98%, and poor in 2% on biopsy and high in 100% of surgical specimens. Ki67 index values were 0 (0-19) and 2 (0-15) on biopsy and surgical specimens (p=0.01). Correlation between preoperative and surgical findings was stronger for liver (r=0.62, p=0.001) than for pancreas (r=0.23, p=0.11). Correlation for pancreas varied according to the tumour pattern: solid (r=0.24, p=0.16), mixed (r=0.91, p=0.0036) or cystic (r=0.04, p=0.89). Tumour grade was different between pancreatic biopsies and surgical specimens, for grade 1 (63% vs 37%) and grade 2 (28% vs 72%), p=0.0007. CONCLUSIONS: Tumour grade assessment is accurate in biopsies of liver metastases of pancreatic neuroendocrine tumours, while pancreatic fine-needle aspiration biopsies are less accurate.

Western and Asian features of multiple sclerosis in Mexican Mestizos.

OBJECTIVES: The objective of this study was to compare the clinical expression of MS in Mexican Mestizos with that of patients of European or Asian descent; as well as to compare the annual frequency of new cases with that observed in the previous decades. PATIENTS AND METHODS: All patients with diagnosis of definite MS seen at the National Institute of Neurology and Neurosurgery of Mexico from January 1993 to December 2003 were studied (n=312). Sociodemographic and clinical characteristics were compared with reports of patients from either Western or Asian origin; the long-term disability score was analyzed according to gender, age of onset of MS and the initial symptom. RESULTS: The clinical expression of MS in Mexican Mestizos shares some characteristics with both, Asian and Western forms of MS indicating that the genetic composition of Mexican Mestizos participates in the clinical expression of the disease. Also, at the prevalence date, the mean age of patients and the duration of the disease were lower in our patients than in MS patients from endemic countries suggesting a true increasing incidence in recent times, rather than only improved case ascertainment. CONCLUSIONS: Clinical expression of MS in Mexican Mestizos shows the coexistence of some features common in European and in Asian cases.