Acute rejection of non-functional allograft in kidney transplant recipients with hepatitis C treated with peginterferon alpha-2a: Reply

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Specific issues concerning the management of patients on the waiting list and after liver transplantation

The present document is a second contribution collecting the recommendations of an expert panel of transplant hepatologists appointed by the Italian Association for the Study of the Liver (AISF) concerning the management of certain aspects of liver transplantation, including: the issue of prompt referral; the management of difficult candidates; malnutrition; living related liver transplants; hepatocellular carcinoma; and the role of direct acting antiviral agents before and after transplantation. The statements on each topic were approved by participants at the AISF Transplant Hepatology Expert Meeting organized by the Permanent Liver Transplant Commission in Mondello on 12-13 May 2017. They are graded according to the GRADE grading system

Muscle sympathetic nerve activity in patients with acromegaly

Muscle sympathetic nerve activity was measured in nine acromegalic patients (age, 35 +/- 4 yr; body mass index, 28 +/- 2 kg/m2) and eight healthy subjects (age, 32 +/- 3 yr; body mass index, 25 +/- 2 kg/m2) by combining the forearm arterial-venous difference technique with the tracer method [infusion of tritiated norepinephrine (NE)]. Muscle NE release was quantified both at rest and during physiological hyperinsulinemia while maintaining euglycemia (approximately 90 mg/dL) by means of the euglycemic clamp. Arterial plasma NE was similar in the two groups at rest (197 +/- 28 and 200 +/- 27 pg/mL (-1) and slightly increased during insulin infusion. Forearm NE release was 2.33 +/- 0.55 ng x liter(-1) x min(-1) in healthy subjects and 2.67 +/- 0.61 ng x liter(-1) x min(-1) in acromegalic subjects in the basal state and increased to a similar extent during insulin infusion in both groups (3.13 +/- 0.71 and 3.32 +/- 0.75 ng x L(-1) x min(-1), P < 0.05 vs. basal), indicating a normal stimulatory effect of insulin on muscle sympathetic activity. In contrast, insulin-stimulated forearm glucose uptake was markedly lower in acromegalic patients (2.3 +/- 0.4 mg x L(-1) x min(-1)) than in control subjects (7.9 +/- 1.3 mg x L(-1) x min(-1), P < 0.001), indicating the presence of severe insulin resistance involving glucose metabolism. Our data demonstrate that patients with long-term acromegaly have normal sympathetic activity in the skeletal muscle in the basal, postabsorptive state and normal increments in NE spillover in response to the sympatho-excitatory effect of insulin. Thus, the presence of severe insulin resistance in acromegaly is not accounted for by adrenergic mechanisms

The expression of B23 and EGR1 proteins is functionally linked in tumor cells under stress conditions

PCR analysis of ChIP samples. Analysis on agarose gel of PCR amplification products of B23 promoter immunoprecipitated with antibody to EGR1 from extracts of transfected HeLa cells at 0.2 % FBS transfected with full length EGR1. (PSD 10140 kb

The ligand-receptor interactions based on silicon technology

We explored the use of porous silicon (pSi) technology for the construction of a biotechnological device, in which the ligand-receptor interactions are revealed by means of laser optical measurements. Here we report the settling of chemical procedures for the functionalization of the silicon wafers and for the subsequent anchoring of biological molecules such as a purified murine monoclonal antibody (UN1 mAb), an antibody anti-P8 protein of M13 phage and an antibody anti-A20 murine lymphoma cell line. The optical analysis of the interaction on the biochips between the bound biomolecules and their corresponding ligands indicated that the pSi is suitable for thi

silicon based technology for ligand receptor molecular identification

One of the most important goals in the fields of biology and medicine is the possibility to dispose of efficient tools for the characterization of the extraordinary complexity of ligand-receptor interactions. To approach this theme, we explored the use of crystalline silicon (cSi) technology for the realization of a biotechnological device in which the ligand-receptor interactions are revealed by means of optical measurements. Here, we describe a chemical procedure for the functionalization of microwell etched on silicon wafers, and the subsequent anchoring of biological molecules like an antibody anti-A20 murine lymphoma cell line. The optical analysis of the interaction on the biochips between the bound biomolecule and their corresponding ligand indicated that the functionalized cSi is suitable for this application

Bioengineered Surfaces for Real-Time Label-Free Detection of Cancer Cells

Biosensing technology is an advancing field that benefits from the properties of biological processes combined to functional materials. Recently, biosensors have emerged as essential tools in biomedical applications, offering advantages over conventional clinical techniques for diagnosis and therapy. Optical biosensors provide fast, selective, direct, and cost-effective analyses allowing label-free and real-time tests. They have also shown exceptional potential for integration in lab-on-a-chip (LOC) devices. The major challenge in the biosensor field is to achieve a fully operative LOC platform that can be used in any place at any time. The choice of an appropriate strategy to immobilize the biological element on the sensor surface becomes the key factor to obtain an applicable analytical tool. In this chapter, after a brief description of the main biofunctionalization procedures on silicon devices, two silicon-based chips that present an (i) IgG antibody or (ii) an Id-peptide as molecular probe, directed against the B-cell receptor of lymphoma cancer cells, will be presented. From a comparison in detecting cells, the Id-peptide device was able to detect lymphoma cells also at low cell concentrations (8.5 × 10−3 cells/μm2) and in the presence of a large amount of non-specific cells. This recognition strategy could represent a proof-of-concept for an innovative tool for the targeting of patient-specific neoplastic B cells during the minimal residual disease; in addition, it represents an encouraging starting point for the construction of a lab-on-a-chip system for the specific recognition of neoplastic cells in biological fluids enabling the follow-up of the changes of cancer cells number in patients, highly demanded for therapy monitoring applications

Do more with less? Lobectomy vs. segmentectomy for patients with congenital pulmonary malformations

Background: Congenital Pulmonary Malformations (CPMs) are rare benign lesions potentially causing infective complications and/or malignant transformation, requiring surgery even when asymptomatic. CPMs are rare in adulthood but potentially detected at any age. There is not a consensus on the correct extent of resection in both adults and paediatrics. This retrospective multicentric study aims to identify the appropriate surgical resection to prevent the recurrence of the related respiratory symptoms. Methods: Between 2010 and 2020, a total of 96 patients (adults and pediatrics) underwent surgery for CPMs in 4 centers. A 2:1 propensity score matching (considering sex and lesion side) was performed, identifying 2 groups: 50 patients underwent lobectomy (group A) and 25 sub-lobar resections (group B). Clinical and histopathological characteristics, early and late complications, and symptom recurrence were retrospectively analyzed and compared between the two groups by univariate and multivariate analysis. Results: Patients who underwent lobectomy had a statistically significant lower rate of recurrence (4% vs. 24% of group B, p = 0.014) and a lower rate of intraoperative complications (p = 0.014). Logistic regression identified sub-lobar resection (p = 0.040), intra- and post-operative complications (p = 0.105 and 0.022),and associated developed neoplasm (p = 0.062) as possible risk factors for symptom recurrence after surgery. Conclusions: Pulmonary lobectomy seems to be the most effective surgical treatment for CPMs, guaranteeing the stable remission of symptoms and a lower rate of intra- and postoperative complications. To our knowledge, this is one of the largest studies comparing lobectomy and sub-lobar resections in patients affected by CPMs, considering the low incidence worldwide

Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension

INTRODUCTION: The use of low-dose dobutamine to maintain hemodynamic stability in pulmonary hypertension may have a detrimental effect on gas exchange. The aim of this study was to investigate whether inhaled nitric oxide (INO), dobutamine and a combination of the two have beneficial effects in patients with end-stage airway lung disease and pulmonary hypertension. METHOD: Hemodynamic evaluation was assessed 10 min after the administration of each drug and of their combination, in 28 candidates for lung transplantation. RESULTS: Administration of INO caused a reduction in mean pulmonary arterial pressure (MPAP), an increase in PaO(2) with a significant reduction in venous admixture effect (Q(s)/Q(t)).Dobutamine administration caused an increase in cardiac index and MPAP, with a decrease in PaO(2) as a result of a higher Q(s)/Q(t). Administration of a combination of the two drugs caused an increase in the cardiac index without MPAP modification and an increase in PaO(2) and Q(s)/Q(t). CONCLUSION: Dobutamine and INO have complementary effects on pulmonary circulation. Their association may be beneficial in the treatment of patients with mild to moderate pulmonary hypertension

Remote adipose tissue-derived stromal cells of patients with lung adenocarcinoma generate a similar malignant microenvironment of the lung stromal counterpart

Cancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumors may alter distant niches of stromal cells is still unclear, especially at early stages. In this short report, we attempt to better understand the biology of this cross-talk. In our “autologous stromal experimental setting,” we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases such as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC for up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similar to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analyzed by arrays, a small pool of 5 upregulated molecules including IL1-β, IL-3, MCP-1, TNF-α, and EGF, was commonly shared by both malignant-like autologous A- and L-MSC derived microenvironments vs those benign. The bioinformatics analysis revealed that these proteins were strictly and functionally interconnected to lung fibrosis and proinflammation and that miR-126, 101, 486, and let-7-g were their main targets. Accordingly, we found that in lung cancer tissues and blood samples from the same set of patients here employed, miR-126 and miR-486 displayed the highest expression levels in tissue and blood, respectively. When the miR-126-3p was silenced in A549 treated with AMSC-derived conditioned media from patients with lung adenocarcinoma, cell proliferation decreased compared to control media