Giovanni Civati

Effect of familial hypertension on glomerular hemodynamics and tubulo-glomerular feedback after uninephrectomy☆

Familial hypertension, glomerular hemodynamic alterations, and dysregulation of tubulo-glomerular feedback (TGFB) have all been associated with the development of chronic renal failure. In the present study we evaluated renal and glomerular hemodynamics and TGFB responses in healthy kidney donors either with or without familial hypertension, before and after nephrectomy. Para-amino-hippurate plasma clearance (CPAH) and inulin plasma clearance (CInu) were measured in 15 kidney donors before and 1 year after nephrectomy. All subjects were normotensive and were kept in a sodium-replete state. Both clearances were measured after 40 min of constant infusion of PAH and Inu, as well as 20, 30, 50, and 60 min after the intravenous administration of acetazolamide (5 mg/kg). Glomerular hemodynamics were calculated by means of the Gomez formulae. Nephrectomy caused the expected decreases in CPAH and CInu and increase in the filtration fraction (all P < .0001). The decrease in renal resistances of the remaining kidney was greater at the afferent (-24%, P = .0075) than at the efferent arteriolar level (-17%, P < .0001). The TGFB activation was not altered by nephrectomy or by familial hypertension. Effective renal plasma flow (ERPF) decrease after TGFB activation appeared earlier than glomerular filtration rate (GFR) decrease before (P = .01), but not after, nephrectomy (P = .48). The presence of familial hypertension was associated with increased glomerular pressure (P = .0004). This study suggests that uninephrectomy in healthy human subjects causes a greater decrease in afferent arteriolar resistances, but that TGFB responses are not quantitatively altered. Familial hypertension is associated with a tendency toward higher glomerular pressures.

Autosomal dominant hypocalcemia caused by a novel mutation in the loop 2 region of the human calcium receptor extracellular domain.

We report a novel missense mutation N124K in the extracellular calcium receptor (CaR) identified in two related subjects with the phenotypic features of autosomal dominant hypocalcemia (ADH). Expression of the N124K mutant receptor created by site‐directed mutagenesis and transfected into HEK‐293 cells was comparable with that of the wild‐type (WT) receptor and two other mutant receptors N118K and L125P identified in subjects with ADH. Functional characterization by the extracellular Ca2+ ion ([Ca2+]0)‐stimulated phosphoinositide (PI) hydrolysis in transfected HEK‐293 cells showed that the N124K mutant receptor was left‐shifted in Ca2+ sensitivity. This biochemical gain‐of‐function is comparable with that seen in other missense mutations of the CaR identified in subjects with ADH. We tested a series of missense substitutions (R, Q, E, and G) in addition to K for N124 and found that only the N124K mutation and to a much lesser extent N124R caused a left shift in Ca2+ sensitivity. Thus, a specific substitution, not merely a mutation of the N124 residue, is required for receptor activation. The N124K mutation is one of eight naturally occurring mutations in subjects with ADH identified in a short segment A116‐C129 of the CaR extracellular domain (ECD). We present a hypothesis to explain receptor activation by mutations in this region based on the recently described three‐dimensional structure of the related metabotropic glutamate type 1 receptor (mGluR1).

Immune response to hepatitis B vaccine in staff and patients in renal dialysis units

Anti-HBs response was detected in 96 per cent of staff members in three haemodialysis units after three 20 microgram doses of hepatitis B vaccine and in 82 per cent of adult patients treated with three 40 microgram doses. The percentage of responders and levels of antibody remained unchanged at 12 months from the beginning of the trial. Three out of six children injected with three 20 microgram doses in a paediatric haemodialysis unit remained free from markers of HBV infection and had high levels of anti-HBs after the second dose of vaccine. The other three children who developed serological markers of HBV infection seroconverted to anti-HBc within six months from the first dose and, in one of them, antigenaemia at three and four months was detected.

Uremic inhibitors of erythropoiesis: A study during treatment with recombinant human erythropoietin

The effects of increasing amounts of uremic sera (US) on the growth of erythroid progenitor cells [burst-forming unit erythroid (BFU-E)] collected from peripheral blood of normal subjects were evaluated to assess the potential role of uremic inhibitors of erythropoiesis during a treatment with recombinant human erythropoietin (r-HuEpo). US were collected from 8 patients on regular dialysis with marked anemia (Hb 6 +/- 0.5 g%) before and after a treatment with high doses of r-HuEpo (from 300 to 525 U/kg/week). Standard cultures for BFU-E were performed in alpha-metylcellulose with fetal calf serum (FCS) and 4 U/ml of r-HuEpo (Cilag, Ortho). In successive cultures, US were added at increasing amounts to the standard culture in order to assess a possible inhibitory effect on BFU-E growth. Finally, in order to assess a possible lack of stimulatory factors, we partially substituted FCS with US. The addition of US collected either before or after therapy with r-HuEpo to the standard culture had no effect on the growth of BFU-E. Vice versa, the number of cultured BFU-E decreased when FCS was partially substituted with US collected before r-HuEpo. This effect was not evident when FCS was partially substituted with US collected after r-HuEpo. No significant differences were recorded in the tested sera collected before and after therapy considering erythropoietin levels and amino acid levels. We hypothesized that some other factors with erythropoietic stimulatory activity (burst-promoting activity?) may be deficient in uremic patients with marked anemia and can be induced during therapy with r-HuEpo.

Circulating burst-forming-unit erythroid and the responsiveness to recombinant human erythropoietin in patients on regular hemodialytic treatment

The dose of recombinant human erythropoietin (r-HuEpo) required to correct anemia of end-stage renal disease varies among patients. The possible factors that interfere with the responsiveness to r-HuEpo were not completely known. In 32 patients on regular hemodialytic treatment with marked anemia (Hb 5.6 +/- 0.7 g/dl), we evaluated circulating erythroid progenitor cells [burst-forming-unit erythroid (BFU-E)], erythropoietin, ferritin, folate and 1-84-parathormone levels before r-HuEpo therapy. In 12 patients, the aluminum levels after deferoxamine were also evaluated. The possible correlation between these factors and the response to r-HuEpo therapy was then evaluated. The number of circulating (c) BFU-E was highly variable (521 +/- 447 colonies/ml of blood; normal level 742 +/- 192) and does not correlate with erythropoietin, ferritin, folate, 1-84-parathormone or aluminum levels. A direct correlation between basal cBFU-E and the responsiveness to r-HuEpo therapy was recorded while no correlation was found with the other analyzed parameters. We hypothesized that low basal cBFU-E (interleukin-3 deficiency?) could reduce the response to r-HUEpo because of failure of this hematopoietic stem cell compartment to replenish the pool of more mature erythropoietic progenitor cells during the phase of accelerated maturation induced by r-HuEpo.

Neo Euclide: A Low-Cost System for Performance Animation and Puppetry

This paper presents a low-cost flexible Performance Animation system for gesture generation and mapping, easy to use and general purpose, focusing on the most ancient and classical idea of animation: Puppetry. A system designed for generic puppetry, and not for a special purpose that can be easily adapted to different scenarios and budgets. For this reason we chose consumer and mainstream technologies, common graphic libraries, PC graphic cards and cheap motion-capture equipment allowing the user to insert movies and sounds integrated with a three-dimensional scene.