Heterotopic Implantation of Decellularized Pulmonary Artery Homografts In A Rodent Model: Technique Description and Preliminary Report

Purpose: Despite a substantial amount of literature on tissue-guided regeneration, decellularization process, repopulation time points and stem cell turnover, more in-depth study on the argument is required. Currently, there are plenty of reports involving large animals, as well as clinical studies facing cardiac repair with decellularized homografts, but no exhaustive rodent models are described. The purpose of this study was to develop such a model in rats; preliminary results are also herein reported. Material and Methods: Fresh or decellularized pulmonary homografts from wild type rats were implanted in the abdominal aorta of green fluorescent protein positive rats. Three experimental groups were build up: sham, fresh homograft recipients and decellularized homograft recipients. The homograft decellularization process was performed with three cycles of detergent-enzymatic treatment protocol. Surgical technique of pulmonary homograft implantation and postoperative ultrasonographic evaluation were also reported; gross, histology and immunohistochemistry analysis on unimplanted and postoperative homografts were also carried out. Results: The median total recipient operating time was 148 minutes, with a surgical success rate of 82%. The decellularization protocol resulted effective and showed a complete decellularization with intact extracellular matrix. At 15 days from surgery, the implanted decellularized pulmonary homografts exhibited cell repopulation in the outer media wall and partial endothelial lining in absence of rejection. Conclusions: Our technique is a feasible and reproducible model that can be fundamental for building a valid study for further exploitation on the field. Even in a short-term follow up, the decellularized pulmonary homografts showed autologous repopulation in absence of rejection.     

High-frequency vibration training increases muscle power in postmenopausal women

OBJECTIVE: To test whether training on a high-frequency (28Hz) vibrating platform improves muscle power and bone characteristics in postmenopausal women. DESIGN: Randomized controlled trial with 6-month follow-up. SETTING: Outpatient clinic in a general hospital in Italy. PARTICIPANTS: Twenty-nine postmenopausal women (intervention group, n=14; matched controls, n=15). INTERVENTION: Participants stood on a ground-based oscillating platform for three 2-minute sessions for a total of 6 minutes per training session, twice weekly for 6 months. The controls did not receive any training. Both groups were evaluated at baseline and after 6 months. MAIN OUTCOME MEASURES: Muscle power, calculated from ground reaction forces produced by landing after jumping as high as possible on a forceplate, cortical bone density, and biomarkers of bone turnover. RESULTS: Over 6 months, muscle power improved by about 5% in women who received the intervention, and it remained unchanged in controls (P=.004). Muscle force remained stable in both the intervention and control groups. No significant changes were observed in bone characteristics. CONCLUSION: Reflex muscular contractions induced by vibration training improve muscle power in postmenopausal women.     

Usefulness of six non-proprietary indirect markers of liver fibrosis in patients with chronic hepatitis C.

BACKGROUND: The aim of the study was to perform a comprehensive diagnostic evaluation of six popular, non-proprietary, indirect markers of liver fibrosis in a cohort of patients with chronic hepatitis C representing the full spectrum of disease severity. METHODS: A total of 167 consecutive, hepatitis C virus RNA positive, untreated patients with chronic hepatitis C were studied. Liver biopsy with histological evaluation and age/platelet index, aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, Bonacini's discriminant score, Forn's fibrosis index and FibroIndex were assessed in all patients. RESULTS: The area under the receiver operating characteristic curves of the six tests was always greater when performed to discriminate patients with METAVIR score F4 than when assessed to discriminate patients with METAVIR score > or =F2. At step-wise discriminant analysis the only indirect marker of fibrosis entered was FibroIndex, with the following correct classification of the patients: total=52.1, patients with scores F0-F1=62.2, patients with scores F2-F3=26.0 and patients with score F4=68.4. CONCLUSIONS: The ability to correctly classify patients using a panel of non-proprietary indirect markers of liver fibrosis is far from being ideal. Among them, FibroIndex appears to possess the best discriminating capacity. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.     

Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions.

Elevated plasma homocysteine (Hcy) concentrations are associated with Alzheimer's disease and vascular dementia. Several recent reports have indicated that L-dopa treatment is an acquired cause of hyperhomo-cysteinemia. Despite the fact that a large proportion of Parkinson's disease (PD) patients develop cognitive dysfunctions or dementia, particularly in the late stages of the illness and after long-term L-dopa treatment, the relationship between Hcy and dementia in PD has not been fully investigated. The aim of this study was to evaluate plasma Hcy levels in a group of L-dopa-treated PD patients with cognitive impairment and to elucidate a possible role of Hcy in the development of cognitive dysfunctions in PD. We compared Hcy, vitamin B12 and folate levels in 35 parkinsonian patients treated with L-dopa (14 with cognitive dysfunctions, 21 without cognitive impairment). Analysis of the data revealed that mean Hcy levels were significantly higher in the group with cognitive dysfunctions (21.2+/-7.4 vs. 15.8+/-4.4 micromol/L; p=0.0001), while there was no difference in age, sex, B12 and folate levels. In addition, logistic regression analysis showed that the risk of cognitive dysfunction progressively increased according to Hcy levels after correction for age, sex and B-vitamin status (odds ratio, 19.1; 95% CI, 1.5-241.4; p=0.02). Our results raise the possibility of a relationship between Hcy levels and cognitive dysfunctions in this group of L-dopa-treated PD patients. However, prospective studies on large cohorts of patients should be performed to clarify such an association.     

Solitary metachronous metastasis of the sternum from pancreatic adenocarcinoma

Sternal metastases from adenocarcinoma of the pancreas are extremely rare, and even more so when solitary. Two years earlier, the patient reported on here, a 67-year-old man with a solitary osteolytic lesion of the sternal manubrium, had undergone a duodeno-cephalopancreatectomy for adenocarcinoma of the pancreas (G2, pY3, pN1) followed by adjuvant radio-chemotherapy. PET/CT scans, in response to the onset of burning pain in the sternal region, revealed a hypermetabolic area only at the level of the manubrium, while MRI showed a bulging manubrium due to the presence of extensive solid pathological tissue towards the right articulations of the ribs. Abnormal tumour markers were: CEA = 12, n.v. 0-4; Ca 15-3 = 512, n.v. 0-51, Ca 19-9 = 8777, n.v. 0-18. A partial sternectomy was performed with en-bloc resection of the hemiclavicles and the anterior tract of the 1st and 2nd ribs bilaterally with a mediastinic lymphadenectomy and repair with a sandwich prosthesis of prolene mesh and methacrylate, protecting the supra-aortic trunks and the anonymous vein with a polytetrafluoroethylene patch. The histological examination revealed secondary adenocarcinoma with 3 mediastinal metastatic lymph nodes. In view of the severe prognosis, a resection with palliative intent was also performed, which, when carried out in specialised centres, presents no contraindications in terms of cost-benefits.     

Negative BOLD effect on somato-motor inhibitory processing: An fMRI study

Inhibiting inappropriate behavior and thoughts in the current context is an essential ability for humans, but the neural mechanisms for response inhibitory processing are a matter of continuous debate. The aim of this event-related functional magnetic resonance imaging (fMRI) study was to evaluate the negative blood oxygen level dependent (BOLD) effect on inhibitory processing during go/no-go paradigms. Fifteen subjects performed two different types of somatosensory go/no-go paradigm: (1) button press and (2) count. Go and no-go stimuli were presented with an even probability. We observed a common negative activation during Movement No-go and Count No-go trials in the right SFG, corresponding to BA 8. These findings suggest that the right SFG region was responsible for the negative BOLD effect on inhibitory processing, which was independent of the required response mode. We hypothesized several possible explanations for the deactivation of the SFG during no-go trials.     

Heart to heart with trastuzumab: a review on cardiac toxicity

Trastuzumab is regarded as the foundation of care for HER2-positive breast cancer as it has revolutionized the treatment of this disease across all settings. Although generally well tolerated, patients may develop symptomatic or asymptomatic cardiotoxicity, forcing a discontinuation of treatment, therefore preventing patients from benefiting from maximal disease control. Evolving research supports that trastuzumab-induced cardiotoxicity may be prevented or at least minimized by a number of prophylactic measures, such as identification of patients at risk and close monitoring. Optimized chemotherapy regimens, scheduling and formulations also contribute to minimizing cardiac adverse events. Equally important, if cardiotoxicity develops, medical interventions are now available that facilitate the reintroduction of trastuzumab once normal cardiac function has been restored. Awareness of this still-evolving information may lead to optimal use of trastuzumab, especially in combination regimens, maximizing antitumor benefit, while minimizing risk.