Posttransplant proteinuria associated with everolimus.

Anti-mTOR may induce proteinuria when utilized after renal transplantation. Little is known about the pathogenesis and composition of proteinuria. To clarify this unresolved aspect, we analyzed urinary protein composition utilizing an integrated proteomics approach, including quantitative assays, 2-dimensional electrophoresis, MALDI-TOF, and Western blots among 48 renal transplant recipients treated with everolimus (EVL; n = 31) or enteric-coated mycophenolic acid (EC-MPA; n = 17). High (>3 g/d) or intermediate levels of proteinuria (1-3 g) developed in 12 EVL patients (39%) compared with 4 subjects (23%) in the EC-MPA group. Proteinuria, which started during the first 2 days after EVL, tended to reduce during the follow-up. Quantitative proteomics showed an increase in low molecular proteins beta2 microglobulin (P < .001) and alpha1 microglobulin (P < .025). Qualitative proteomics showed a marked increase among all urinary components in EVL and EC-MPA patients. Major changes involved typical components of glomerular damage: albumin, Zn-alpha1 glycoprotein, alpha2HS glycoprotein, and leucine-rich alpha2 glycoprotein. In addition, we observed specific biomarkers for EVL: clusters of alpha1-antitrypsin fragments and monoclonal lambda chains. In conclusion, EVL induced proteinuria of a mixed glomerular and tubular origin that correlated with the start of treatment and reached nephrotic ranges in few cases. The specific urinary markers may reflect renal alterations related to the transplant or specific alterations associated with the drug.

Effects of triamcinolone acetonide on adult human lung fibroblasts: decrease in proliferation, surface molecule expression and mediator release.

BACKGROUND: Lung fibroblasts may have a pivotal role in airway inflammation as they are involved in continuous cycles of mediator secretion, proliferation, activation and cross-talk with recruited inflammatory cells. The role of fibroblasts as intermediate participants in the inflammatory network suggests that they could represent an important target for drugs commonly used in asthma; thus, we investigated the effects of triamcinolone acetonide (TAA) on primary human lung fibroblasts. METHODS: The in vitro activity of increasing concentrations (10(-9) to 10(-7) M) of TAA in fibroblast cultures was evaluated as regards the following parameters: proliferation, extracellular matrix (ECM) release, cytokine/chemokine secretion and surface antigen expression. RESULTS: All concentrations of TAA decreased fetal calf serum (FCS)-induced fibroblast proliferation, whereas in the presence of FCS plus basic fibroblast growth factor TAA was only effective at 10(-8) and 10(-7) M. TAA failed to decrease ECM, whereas at 10(-8) and 10(-7) M it decreased IL-6 and IL-8 secretion to different extents. In the presence of IFN-gamma the drug was able to reduce VCAM-1 expression at all of the tested concentrations; on the other hand, in TGF-beta 1-driven cultures a decrease in CD54 expression was detected with TAA at 10(-8) and 10(-7) M. CONCLUSIONS: TAA acts on some functional properties of human lung fibroblasts that make these cells active participants in the inflammatory network. The ability of TAA to inhibit lung fibroblast proliferation may prevent or even reverse some of the histological changes that characterize airway remodeling in chronic inflammatory diseases; moreover, IL-6, IL-8 and surface molecule decreases by TAA may suggest a direct anti-inflammatory effect of the drug by suppression of resident lung cell function.

Quantitative and qualitative evaluation of blood salvaged after extracorporeal circulation (ECC) in paediatric heart surgery. Study of biochemical, morphological and structural variations of RBC after ECC and after salvaging of ECC circuit priming blood.

The salvaging of ECC circuit priming blood is essential for reducing the morbidity related to homologous blood transfusions and the importance of this technique is inversely proportionate to the age and weight of the child. In infants, the washing and centrifugation of blood not only drastically reduce the risk of contracting blood-transmitted diseases and cut management costs, but are also of considerable hemodynamic importance, producing a rapid normalization of the patient's hematocrit and hemoglobin and balancing the O2 consumption/demand ratio. The marketing of miniaturized salvagin devices with 55 ml bowls by Dideco has made possible the recovery of small quantities of blood, so as to normalise the hematic crisis and permit the application of total hemodilution in low-weight patients. The salvaged blood shows an average hematocrit of 52.7+/-9.7% (max 68.1%) and an average hemoglobin of 17.6 +/- 2.9 g/dl (max 20.7 g/dl), and maintains its structural components, osmotic resistance, concentration of intraerythrocytic hemoglobin and mean corpuscular hemoglobin all intact. Washing with isoosmotic and isoionic hydroelectrolytic solutions normalizes the ionic situation in the post-operative period and activated blood salvaging after Extracorporeal Circulation. The use of solutions without nutritional substances results however in a considerable fall in the number of enzymes in the intraerythrocytic metabolic glucide chain (G6PDH: -40.7 +/- 14.3% p<0.001), (PK: -23.8 +/- 20.5% p<0.03). This drop may be responsible for erythrocytic morphological alterations (echinocytic change) and probably for the release of hemoglobin from the red blood cells. Washing with isoionic, isoosmotic solutions containing G5% and adenine could, at least in theory, improve the quality of the salvaged blood, by normalizing the morphology and the volume of the RBC and by increasing the hematocrit.

Retinol (vitamin A) and retinal-binding protein serum levels in children with cancer at onset.

The aim of the study was to evaluate vitamin A (Vit A) plasma levels in children with newly diagnosed neoplasia (NDN) admitted to the Department of Hematology-Oncology of G. Gaslini Institute. Vit A levels, retinol-binding protein (RBP), and nutritional status were evaluated in 54 children with NDN (22 solid tumors other than neuroblastoma, 16 neuroblastomas, 9 lymphomas, 7 acute lymphoblastic leukemia). Biochemical test results were also compared with those of 47 healthy controls (HC) comparable for sex and age. In children with NDN, mean Vit A plasma level results were 350 micrograms/L (95% CI 288-412); in HC they were 517 micrograms/L (95% CI 471-563), P < 0.001. Mean RBP value results were 3.2 mg/dL (95% CI 2.6-3.9) in NDN and 4.9 mg/dL in HC (95% CI 4.5-5.3), P < 0.001. Fifteen (28%) out of 54 children with NDN were classified as well-nourished, 27/54 (50%) were considered at risk of malnutrition, and 12 (22%) were malnourished. Children with NDN presented reduced Vit A and RBP mean values compared with those of HC. Further studies are needed to better evaluate Vit A metabolism in children with cancer at onset.

Early efficacy of liposomal amphotericin B in the treatment of visceral leishmaniasis.

The rapidity and efficacy of a short course of liposomal amphotericin B was evaluated in 29 children affected by visceral leishmaniasis (Leishmania infantum). Their overall health status was assessed using the prognostic inflammatory and nutritional index (PINI), and their haematological status by the reticulocyte count and haemoglobin blood levels. All these quantities were measured on day 0, and 3 and 10 d after starting therapy. A significant decrease of inflammatory signs, associated with an improved reticulocyte count, was recorded after 3 d of therapy. A significant increase of haemoglobin levels was also observed 10 d after the start of treatment. The early reduction of inflammatory signs and the improvement of bone marrow function in most patients confirmed the validity of amphotericin B therapy. The PINI score is helpful in assessing the severity of visceral leishmaniasis and the follow-up of its treatment.

Quantitative determination of fibronectin (FN): evaluation of immunoturbidimetric and rate nephelometric techniques for FN assay in the different biologic materials.

Aim of this study is to determine fibronectin concentration in the different biological materials to study its changes in the anatomic districts where the cell interactions in which FN participates do occur. The traditional immunoturbidimetric method and the nephelometric method are compared. An alternative method using a support for the collection of very small samples is proposed and the results obtained are discussed. This approach with solid phase immunonephelometry can be used both in amounts of biological fluids too small for traditional methods and in concentrations < 4.5 mg/dL. It is hoped that less complex techniques will be studied, allowing routine tests that can be performed by all laboratories. Unfortunately, at present this method is still investigated, however, it would be useful to adopt it in case of difficult sample collection.

Macroamylasemia: a possible cause of unexplained hyperamylasemia in rheumatoid arthritis.

Macroamylasemia is a benign acquired condition, characterized by a serum amylase unusually large in molecular size that has been found to occur in apparently healthy humans as well as in a variety of diseases including liver disease, diabetes, cancer malabsorption and autoimmune disorders. Most commonly macroamylasemia results from the formation of immune complexes between amylase and immunoglobulins. We describe the first case of an association between macroamylasemia/hyperamylasemia and rheumatoid arthritis characterized by the absence of immunoglobulins, as amylase binding globulins, within the macroamylase complex. Failure to identify macroamylase as the cause of unexplained but benign hyperamylasemia correctly, can lead to costly studies (e.g. ultrasonography, computerized tomography) to rule out pancreatic disease, and could induce prescription of unnecessary elemental diets and replacement therapies, as reported in our patient.

[Urine culture and analysis of data using a computer]. / L'urinocoltura, analisi dei dati mediante computer.

A computerized investigation of microbiological data concerning 7042 culture exams of urines has been carried out. Interesting data from the epidemiological point of view came out: positivity percentages in relation to the different months of the year, strains frequency, incidence of the urinary pathology in relation to sexes. It is also interesting the analysis of positivity percentages in relation to the derivation of samples, since it is clear a significant negativity of non-hospital samples. The use of computerized analysis of data in the microbiological laboratory is discussed and is a well considered the need to use computer not only to identify microorganisms and to determine the sensibility of antibiotics, but also for data management especially from the epidemiological point of view. Therefore the use of computer as file is desired in order to obtain by the statistic analysis, evidence of epidemiological character, plannings, work plans finalized to a more efficient answer to the growing need of culture exams.