Adiponectin in children on peritoneal dialysis: relationship to insulin resistance and nutritional status.

AIM: To study whether adiponectin and resistin serum concentrations in children on peritoneal dialysis (PD) were related to insulin resistance (IR) and anthropometric parameters of nutritional status, 11 PD patients, 9 chronic kidney disease (CKD) patients and 10 healthy children were studied. METHODS: Glucose and insulin were measured during the oral glucose tolerance test. Levels of adiponectin and resistin were evaluated by ELISA, insulin by RIA. RESULTS: In CKD patients, higher homeostasis model assessment-insulin resistance (HOMA-IR), fasting and 2-hour serum insulin levels were shown compared to control and to PD patients. Body mass index (BMI) and body fat content were severely decreased while serum adiponectin levels were significantly higher in PD patients relative to controls. No differences among groups were shown in resistin levels. On regression modeling, inverse independent associations were observed between adiponectin with percentile BMI, weight and height z-score, and with body fat content. In contrast, no relationship was found between adiponectin and IR parameters. In multiple regression analysis, adiponectin was negatively correlated with BMI. A negative association of adiponectin and resistin with glomerular filtration rate was also shown. CONCLUSION: A role for adiponectin in terms of its association with clinical wasting parameters in PD pediatric patients might be suggested.

Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity.

The development of refractory disease is often associated with the overexpression of multidrug resistance (MDR) proteins, especially in several hematological malignancies, such as acute myeloid leukemias (AML), multiple myeloma (MM) and non-Hodgkin's lymphomas (NHL). Since the recognition of these proteins, several attempts have been made to modulate their expression and activity (protein kinase C inhibitors, anti-MDR-1 oligonucleotides, pharmacological competitors and transcriptional inhibitors). Six new compounds (MM 36, CTS 4, CTS 9, CTS 12, CTS 27 and CTS 41), derived from verapamil (VRP), were designed and synthesized to improve their MDR-reverting activity and reduce cardiovascular effects. Cytotoxicity (WST-1 methods) and functional (calcein-acetoxymethyl (Calcein-AM)) assays were performed on a resistant cell line K-562/doxR and on the mononuclear cells (MNCs) of patients with AML. Furthermore, the six molecules were tested for their vasodilator, inotropic and chronotropic activity on guinea pig aortic strip and isolated atrium preparations, respectively. Comparison between survival plots and relative ID50, obtained from the K-562/doxR cells treated with Idarubicin (IDA), in the presence or absence of inhibitors, showed that these compounds function well. All the resistance modifying agents potentiated IDA activity inducing a significant reduction (P<0.01) in ID(50) values in comparison to VRP at each of the concentrations tested, but MM 36, CTS 27 and CTS 41 demonstrated the strongest activity. Results obtained from the MNCs were superimposible to K-562/doxR. Further studies on pump functional analysis confirmed the cytotoxic test results: MM 36, CTS 27 and CTS 41 showed a striking inhibition of P-glycoprotein (Pgp) efflux in K-562/doxR and MNCs. Cardiovascular activity of MM 36, CTS 27 and CTS 41, that are the most interesting compounds as MDR inhibitors, followed this course: MM 36>CTS 27>CTS 41, the last one presenting no cardiovascular activity. Chemosensivity to IDA in K-562/doxR cells and AML blasts could be enhanced in vitro by the adjuvant use of the six new VRP analogues. Compared to VRP, all the new compounds presented good MDR-reverting- and reduced cardiovascular activities along with no vasorelaxant effects. The particularly favourable results in some cases (MM 36, CTS 27 and CTS 41) suggests that anti-MDR activity should be further evaluated in clinical trials in patients with myeloid malignancies.

PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia.

Females with the monoclonal type of essential thrombocythaemia (ET), based on the X-chromosome inactivation pattern (XCIP), have previously been shown to present a higher incidence of thrombosis than polyclonal ones. We aimed to assess correlations between XCIP, thrombosis, and three epigenetic markers of ET, namely PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P = 0.009). The frequency of abnormalities of PRV-1, EEC, or Mpl was similar in monoclonal and polyclonal subjects (respectively, 28%, 48%, 75%, and 37%, 27%, 63%), and none of them correlated with thrombosis. We conclude that the exploited epigenetic markers constitute independent phenotypic variations and are not clustered according to monoclonality of myelopoiesis in ET; none of them could serve as a surrogate marker of thrombotic risk in male subjects with ET.

In vitro antileukemic effect of a new anthracycline analogue, MEN 11079.

The biological activity of MEN 11079, a new daunorubucin analogue with a fluorine atom in C(8) of ring A, was investigated in the human leukemic cell lines K-562 and in mononuclear cells (MNCs) of 40 patients with acute myeloid leukemia (AML) and the activity compared to two well-characterized anthracyclines, idarubicin (IDA) and doxorubicin (DOXO). IDA and MEN 11079 were more active than DOXO in cytotoxicity tests (WST-1 assay). IDA and MEN 11079 ID(50) values were also significantly different from each other (K-562: P=0.038; MNCs: P=0.003). Moreover, the range was 0.002-4.300 microM for IDA and 0.002-0.670 microM for MEN 11079, in the MNCs. Therefore, the latter appeared to assure a smaller variability of response in the AML cells. Apoptosis assays (performed using Annexin-V assay and propidium iodide) and cell cycle studies demonstrated that the MEN 11079 effective concentration was 10-fold lower than the DOXO and IDA ones. MDR (Pgp and MRP1 proteins), as measured by semiquantitative RT-PCR, cytofluorimetric and functional analysis of proteins, was similarly elicited by IDA and MEN 11079. In conclusion, the response of the cells to the new anthracycline indicates that there is greater cytotoxic activity of this molecule than IDA and DOXO. Its narrower ID(50) range may allow for a more predictable response in the clinical setting.

Guanasa y metabolitos en pancreatitis isquemica experimental / Guanase and metabolites in experimental ischemic pancreatitis

El dano provocado por la pancreatitis experimental en perros, determina un aumento significativo de la actividad de la Guanasa. Este aumento se produce a las 2 hs de la isquemia en tejidos y a las 24 hs en suero. Asi mismo se determina que la actividad es similar en cabeza y cola y está ausentela actividad en el cuerpo del páncreas. Finalmente se observa que mientras las oxipurinas séricas, aumentan en forma similar a la Guanasa sérica, la Guanina sé-rica, disminuye significativamente recién a las 24 hs. Estos resultados indicanque la actividad de guanasa es un excelente "marcador" del dano pancreático en perros

Enzimas y metabolitos purínicos durante el embarazo / Purine metablic enzymes during of pregnancy

Se estudia el metabolismo purínico en 64 mujeres, 48 embarazadas y 16 no embarazadas. Los resultados se confrontaron estadísticamente y se concluye que: no se observa actividad de guanasa, a diferencia del suero, en saliva de mujeres embarazadas o no embarazadas. Las oxipurinas, xantina + hipoxantina, salivales, aumentan progresivamente durante el embarazo, siendo los valores más significativos en el 3er. trimestre. El ácido úrico sérico y salival, y la xantina oxidasa salival, disminuyen progresivamente durante la gestación, observando los valores más significativos en el 3er. trimestre. Se establecen los valores normales de xantina oxidasa, oxipurinas y ácido úrico en la saliva de las mujeres estudiadas.