Swine experimental model to evaluate stem cells implant post myocardial infarction by perfusion gated-SPET

Autologous bone marrow stromal cells (BMSC) implant after swine experimental myocardial infarct (MI) was investigated by serial technetium-99m ((99m)Tc)-tetrofosmin gated single photon emission tomography (G-SPET) and compared with immuno-histochemical findings. The aim was to evaluate if intramyocardial BMSC implant produces any prolonged effect in the left ventricle (LV) perfusion and function. Eleven pigs underwent left anterior descending artery (LAD) ligature; in seven of them BMSC were injected in the border zone of the MI, while in the remaining four saline solution was injected at the same site. After LAD ligature G-SPET scans at 48h and at 5 and 10 weeks (w) after the implant were performed. Uptake defect size and LV function analysis were performed comparing 48h to 5w and 10w studies. Statistical evaluation was performed with Friedman test and unpaired Wilcoxon test. The comparison between a progressive reduction of Perfusion Image Score was observed from 48h to 5w and to 10w in the treated group (Friedman test: χ2= 13.56; P=0.01). No variation was observed in the control group (Friedman test: χ2=3; P= 0.223). Comparison of the absolute variation (Δ) between treated and control group resulted significant (Wilcoxon test W=10; P=0.007). Similar positive results were also observed for the relative extension of the uptake defect, wall motion and LVEF analysis. Histological data of our swine model demonstrated that autologous BMSC implanted in the damaged myocardium area had survived and differentiated into cells with typical features of myocardiocytes. Gated SPET is a reliable tool to evaluate prolonged positive effects of autologous BMSC implant in swine experimental MI model. In conclusion, autologous BMSC implanted can improve perfusion, induce cell regeneration, reduce wall motion abnormalities and prevent severe LV dysfunction in swines.     

ELECTRON MICROSCOPIC STUDIES OF EXPERIMENTAL NEPHRITIS WITH FERRITIN-CONJUGATED ANTIBODY : THE BASEMENT MEMBRANES AND CISTERNAE OF VISCERAL EITHELIAL CELLS IN NEPHRITIC RAT GLOMERULI

Ferritin-conjugated antibody has been used to identify by electron microscopy the sites at which nephrotoxic globulins localize in rat kidney during acute experimental glomerulonephritis. Antibody was concentrated in the glomerular basement membrane and in basement membrane-like material contained in distended cisternae of the endoplasmic reticulum. These data confirm and amplify, at the ultrastructural level, the results of studies obtained with the fluorescent antibody technique, and are consistent with the hypothesis that the cisternae and capillary basement membrane possess common proteins.     

Tomographic imaging of the spleen: the role of morphological and metabolic features in differentiating benign from malignant diseases

To evaluate the tomographic features in differentiating benign from malignant splenic diseases, 54 patients with a cytohistological examination and a contrast-enhanced multidetector computed tomography (ce-MDCT) and/or positron emission tomography/computed tomography (PET/CT) were retrospectively selected. Significant associations were observed between ce-MDCT Pattern 3 (focal hyperdense lesion) and Pattern 4 (infarcts/cysts) as well as PET/CT Pattern 3 (focal photopenia/diffuse uptake相似文献   

Ketoprofen controlled release from composite microcapsules for cell encapsulation: effect on post-transplant acute inflammation.

Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic islets is a promising approach for the final solution of Type 1 diabetes. Unfortunately, evidence of long-term encapsulated islet graft survival and functional competence lies behind expectancy. Failure was often ascribed to the lack of biocompatibility generating inflammatory response, or limited immunobarrier competence or hypoxia or finally, low beta-cell replication. In order to prevent severe inflammation at early stages after implantation, composite microcapsules were designed. Biodegradable microspheres containing ketoprofen were enveloped into the well established alginate/poly-L-ornithine/alginate capsules. Polyester microspheres were prepared, by solvent evaporation, and characterized for encapsulation efficiency, particle size and in vitro release. Biocompatibility and efficacy to prevent the inflammatory response were studied in vivo. Good encapsulation efficiency and the desired particle size were achieved. In vitro release studies evidenced a high burst effect probably due to a plasticizing effect of both water and ketoprofen. The composite systems showed good biocompatibility and capacity to completely avoid the inflammatory response and the pericapsular cell overgrowth. In conclusion, the inflammatory response in the immediate post-transplant period can be circumvented using multicompartment microcapsules releasing non-steroidal anti inflammatory drugs.     

Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells

The majority of thyroid carcinomas maintain the expression of the cell growth suppressor p27, an inhibitor of cyclin-dependent kinase-2 (Cdk2). However, we find that 80% of p27-expressing tumors show an uncommon cytoplasmic localization of p27 protein, associated with high Cdk2 activity. To reproduce such a situation, a mutant p27 devoid of its COOH-terminal nuclear-localization signal was generated (p27-NLS). p27-NLS accumulates in the cytoplasm and fails to induce growth arrest in 2 different cell lines, indicating that cytoplasm-residing p27 is inactive as a growth inhibitor, presumably because it does not interact with nuclear Cdk2. Overexpression of cyclin D3 may account in part for p27 cytoplasmic localization. In thyroid tumors and cell lines, cyclin D3 expression was associated with cytoplasmic localization of p27. Moreover, expression of cyclin D3 in thyroid carcinoma cells induced cytoplasmic retention of cotransfected p27 and rescued p27-imposed growth arrest. Endogenous p27 also localized prevalently to the cytoplasm in normal thyrocytes engineered to stably overexpress cyclin D3 (PC-D3 cells). In these cells, cyclin D3 induced the formation of cytoplasmic p27-cyclin D3-Cdk complexes, which titrated p27 away from intranuclear complexes that contain cyclins A-E and Cdk2. Our results demonstrate a novel mechanism that may contribute to overcoming the p27 inhibitory threshold in transformed thyroid cells.     

Upstream Effect for Atrial Fibrillation: Still a Dilemma?

Atrial fibrillation is the most common arrhythmia in clinical practice. Ion channel blocking agents are often characterized by limited long-term efficacy and several side effects. In addition, ablative invasive procedures are neither easily accessible nor always efficacious. The "upstream therapy," which includes angiotensin-converting enzyme inhibitors, aldosterone receptor antagonists, statins, glucocorticoids, and ω-3 poly-unsaturated fatty acids, targets arrhythmia substrate, influencing atrial structural and electrical remodeling that play an essential role in atrial fibrillation induction and maintenance. The mechanisms involved and the most important clinical evidence regarding the upstream therapy influence on atrial fibrillation are presented in this review. Some open questions are also proposed.     

Jaundice and the sepsis syndrome: a neglected link

The relationship between the sepsis syndrome and the development of jaundice is intriguing, with jaundice having been described as the presenting sign of septicaemia in very few cases. We describe a patient who developed a deep jaundice with conjugated hyperbilirubinaemia caused by Staphylococcus aureus during the early course of septicaemia, when no other sign of the sepsis syndrome could be recognised. It is generally accepted that a mild jaundice may complicate the course of the sepsis syndrome, but it is most unusual to observe such a protracted phase of jaundice before the emergence of other specific clinical signs and laboratory abnormalities. Clinicians should be aware of this presentation of the sepsis syndrome in order to avoid a potentially harmful delay in diagnosis and treatment.