Treatment with bindarit, an inhibitor of MCP-1 synthesis, protects mice against trinitrobenzene sulfonic acid-induced colitis.

OBJECTIVE: Chemokines play a fundamental role in trafficking and activation of leukocytes in colonic inflammation. We investigated the ability of bindarit, an inhibitor of monocyte chemoattractant protein-1 (MCP-1/CCL2) synthesis, to inhibit chemokine production by human intestinal epithelial cells (HT-29) and its effect in trinitro-benzene sulfonic acid (TNBS)-induced colitis in mice. MATERIALS AND METHODS: HT-29 cells were incubated with bindarit in the presence of TNF-alpha/IFN-gamma and 24 h later supernatants were collected for MCP-1, IL-8 and RANTES measurement. A 1 mg enema of TNBS was given to BALB/c mice, and bindarit (100 mg/kg) was orally administered twice daily starting from two days before colitis induction. Weight loss, histology, and MCP-1 level and myeloperoxidase (MPO) activity in colon extracts were assessed. RESULTS: In HT-29 cells, bindarit concentration-dependently and selectively inhibited MCP-1 secretion (as well as mRNA expression) primed by TNF-alpha/IFN-gamma. Moreover treatment with bindarit reduced clinical and histopathological severity of TNBS-induced colitis. These effects were associated with significant inhibition of MCP-1 and MPO in colon extracts. CONCLUSIONS: Bindarit exhibits a potent bioactivity in reducing leukocyte infiltration, down-regulating MCP-1 synthesis, and preventing the development of severe colitis in a mice model of TNBS-induced colitis. These observations suggest a potential use of MCP-1 synthesis blockers in intestinal inflammation in humans.

[Usefulness of directional power Doppler sonography in the ultrasound-guided percutaneous native kidney biopsy]. / Utilita' dell'Eco Power Doppler direzionale nella biopsia transcutanea su rene nativo.

BACKGROUND: The study was aimed to analyze the pattern of bleeding throughout the kidney tissue after renal biopsy and evaluate its relationship with the onset of renal biopsy side effects by using directional power-Doppler sonography. PATIENTS: Eighty-five consecutive subjects with clinical evidence of renal disease underwent to percutaneous renal biopsy using directional power Doppler sonography. In each patient, the pattern of kidney hemorrhage immediately after the renal biopsy was evaluated. RESULTS: Fifty-seven patients, representing 67% of all biopsies performed, evidenced renal bleeding lasting 5.3+/-5.7 min; fifty-five patients, representing 65% of all biopsies, developed a post biopsy hematoma (x = 2.9+/-2.0 cm); 36% of patients developed a perirenal hematoma (x = 1.8+/-2.1 cm). A subcapsular hematoma was experienced by 45% of patients (x = 2.7+/-1.1 cm); 16% of these patients had a combined perirenal-subcapsular hematoma; 5% of hematomas were larger than 5 cm. Hematoma dimensions were related to the length of bleeding (r = 0.6331; p < 0.0001). Hemoglobin and hematocrit levels significantly reduced from 12.7+/-2.3 g/dL to 11.7+/-2.3 g/dL (-7%, p < 0.0001) and 37.6+/-6.5% to 35.4+/-6.5% (-6%, p < 0.0001) respectively, and such variations were related to the hematoma size (Delta Hb: r = -0.5171; p < 0.0001; Delta Htc: r = -0.3465; p < 0.0001). CONCLUSIONS: This study demonstrates that directional power Doppler sonography allows medical personnel to clearly evidence all renal biopsy-related side effects and identify, through the evaluation of renal bleeding immediately after the kidney biopsy, those patients who will develop renal hematomas.

Short-term effects of low protein-normal sodium diet on renal function in chronic renal failure.

To investigate the short-term renal effects of protein restriction and unchanged salt intake in chronic renal failure (CRF), patients with moderate CRF (creatinine clearance 41 +/- 5 ml/min) and healthy controls (CON) ate a normal protein diet (NPD) for four weeks, and thereafter a low protein diet (LPD, 0.4 g/kg body wt/day) for three weeks. The two diets were isocaloric and with a salt intake of 10 to 13 g/day. No differences in body weight, serum proteins and plasma sodium were recorded throughout the study. During LPD, inulin and PAH clearances in CON demonstrated a progressive 25% decline of basal GFR and RPF; on the contrary, in CRF, basal renal function did not change in presence of a significant reduction of proteinuria. In CON patients after protein restriction, fractional free-water generation (CH2O/CIn) and fractional urinary excretion of sodium (FENa) measured under maximal water diuresis increased progressively, both being doubled at the end of LPD, while in CRF, CH2O/CIn did not change and FENa values remained unmodified and much higher (above 4%) than in CON after both diets. The renal response to an acute oral protein load (OPL) and i.v. low-doses of dopamine (D) was measured at the end of each period; in the two groups, GFR and RPF significantly increased following OPL + D after both diets. In CRF, however, the vasodilatory response was blunted overall being reduced after both LPD and NPD, and, unlike CON, it did not increase after LPD.(ABSTRACT TRUNCATED AT 250 WORDS)