Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.     

神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

In vivo and in vitro growth-inhibitory effect of bovine seminal ribonuclease on a system of rat thyroid epithelial transformed cells and tumors.

We investigated the antitumoral effect of bovine seminal RNase (BS-RNase) in vivo and in vitro on a model system of epithelial tumor- and metastasis-derived cells as well as on epithelial tumors derived from the same system. We found that while BS-RNase significantly inhibited the growth in vitro of the epithelial tumor-derived cells, its inhibitory effect was even more dramatic on the growth of metastasis-derived cells. BS-RNase exerted no appreciable growth inhibition on normal thyroid epithelial cells. When administered in vivo to rats bearing solid carcinomas, having the same thyroid origin, BS-RNase induced a drastic reduction in the tumor weight, with no detectable toxic effects on the treated animals. These data show, for the first time on a system of neoplastically transformed epithelial cells, that BS-RNase has a potent specific antitumoral activity.     

Blink reflex abnormalities in children with Tourette syndrome

Tourette syndrome (TS) is a common disorder which typically occurs during childhood or early adolescence. There is no definitive diagnostic test for TS. The objective of this study was to demonstrate whether neurophysiological abnormalities of the blink reflex can be observed in children with TS. We enrolled 15 children with TS, diagnosed according to DSM IV Diagnostic Criteria, and 15 controls. The blink reflex was elicited by stimulating the supraorbital nerve in order to measure the early response (R1), homolateral and contralateral R2 (late) responses, amplitude of R1 and duration of R2. The mean duration of R2 was significantly longer in TS patients than in the controls ( P  < 0.001, Student's t -test). An abnormal pattern of the blink reflex can be, even in childhood, an early neurophysiologic marker of TS, which is not related to the duration of TS or to the age of onset.     

Sodium removal and sodium concentration during peritoneal dialysis: effects of three methods of sodium measurement.

BACKGROUND: Sodium removal (NaR) may have a major impact on the survival of peritoneal dialysis patients. The dialysate/plasma sodium concentration ratio (D/P(Na)) is an indirect index of transcellular water transport by aquaporin channels, and thus of ultrafiltration. Sodium concentration can be assessed by means of flame photometry (F), and direct (D-ISE) or indirect ion-selective electrodes (I-ISE), but these methods have different properties. I-ISE is being used increasingly in clinical laboratories. The aim of this study was to evaluate NaR and D/P(Na) using the three different measurement methods. METHODS: We performed peritoneal equilibration tests (PETs) in 44 peritoneal dialysis patients and calculated the NaR. We also calculated D/P(Na) during the test; plasma and dialysate sodium concentrations were measured by F, D-ISE and I-ISE. RESULTS: NaR was lower (P<0.001) with D-ISE (69+/-29 mmol) than with F (81+/-29 mmol) or I-ISE (79+/-28 mmol). D/P(Na) was also lower at baseline (0.92+/-0.02 vs 0.95+/-0.02 and 0.95+/-0.02; P<0.001), after 60 min (0.87+/-0.03 vs 0.90+/-0.03 and 0.90+/-0.03; P<0.001) and at the end of PET (0.88+/-0.04 vs 0.92+/-0.04 and 0.92+/-0.04; P<0.001) when measured by D-ISE in comparison with F and I-ISE, respectively. CONCLUSIONS: NaR and D/P(Na) were lower when measured by the D-ISE method compared with the F and I-ISE methods. NaR and D/P(Na) were similar when measured by F or I-ISE. I-ISE can be used reliably in the evaluation of NaR and D/P(Na) in everyday clinical practice of peritoneal dialysis.     

Peritumoral lymphatic invasion in patients with node-negative mammary duct carcinoma.

Five hundred six consecutive cases of ductal infiltrating carcinoma of the breast (T1-T2,N0,M0) were evaluated to define the frequency of peritumoral lymphatic invasion (PLI) and verify its possible prognostic significance. Histologically, PLI was characterized by the presence of neoplastic emboli within vascular lumina lined by recognizable endothelial cells, adjacent to but outside the margins of the carcinoma. In routine histopathologic assessment the frequency of PLI was 68% whereas in a randomly selected group of 234 reviewed cases the frequency rose to 20%. Patients with routinely evaluated PLI had a worse prognosis than those without PLI with reference both to disease-free survival (P = 0.0001) and total survival rates (P = 0.0001). The difference for local recurrences was prognostically highly significant (P = 0.0001) and also significant for the development of metastases (P = 0.0576). In the reviewed material the difference in prognosis between PLI-positive and PLI-negative cases was not confirmed for total survival whereas the significance for the disease-free interval persisted. The assessment of PLI, carried out following strict histopathologic criteria, appears to select a group of node-negative breast cancer patients who have an increased risk of recurrences and might benefit from a treatment different from that reserved for node-negative and PLI-negative patients.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Electrical method for detection of endothelial cell shape change in real time: assessment of endothelial barrier function.

We have developed an electrical method to study endothelial cell shape changes in real time in order to examine the mechanisms of alterations in the endothelial barrier function. Endothelial shape changes were quantified by using a monolayer of endothelial cells grown on a small (10(-3) cm2) evaporated gold electrode and measuring the changes in electrical impedance. Bovine pulmonary microvessel endothelial cells and bovine pulmonary artery endothelial cells were used to study the effects of alpha-thrombin on cell-shape dynamics by the impedance measurement. alpha-Thrombin produced a dose-dependent decrease in impedance that occurred within 0.5 min in both cell types, indicative of retraction of endothelial cells and widening of interendothelial junctions because of "rounding up" of the cells. The alpha-thrombin-induced decrease in impedance persisted for approximately 2 hr, after which the value recovered to basal levels. Pretreatment of endothelial cells with the protein kinase C inhibitor, calphostin C, or with 8-bromoadenosine 3',5'-cyclic monophosphate prevented the decreased impedance, suggesting that the endothelial cell change is modulated by activation of second-messenger pathways. The alpha-thrombin-induced decrease in impedance was in agreement with the previously observed increases in transendothelial albumin permeability and evidence of formation of intercellular gaps after alpha-thrombin challenge. The impedance measurement may be a valuable in vitro method for the assessment of mechanisms of decreased endothelial barrier function occurring with inflammatory mediators. Since the rapidly occurring changes in endothelial cell shape in response to mediators such as thrombin are mediated activation of second-messenger pathways, the ability to monitor endothelial cell dynamics in real time may provide insights into the signal-transduction events mediating the increased endothelial permeability.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

Expression of actin isoforms and intermediate filament proteins in childhood orbital rhabdomyosarcomas

The diagnosis of orbital rhabdomyosarcoma (RMS) in childhood gives rise to several clinical and anatomo-pathological problems. Antibodies recognizing structural proteins and cytoskeletal components have been shown to increase the diagnostic accuracy of different neoplastic lesions. In this study we examined anatomo-clinically and, where possible, by means of immunohistochemistry and electron microscopy, a series of 14 cases of orbital RMS in childhood. In the 12 cases studied by immunohistochemistry, desmin was always present, although showing variable patterns, and alpha-sarcomeric actin was found in 10 cases. alpha-Smooth muscle actin was always absent. The other markers tested (myoglobin, polyclonal actin, vimentin and enolase) proved unreliable for several reasons. We conclude that antibodies against desmin and alpha-sarcomeric actin are useful for the diagnostic definition of RMS. In addition, immunohistochemical analysis supplies data regarding the degree of tumor differentiation and may be applied to monitor radio- and chemotherapy.