PubMed Health⌕ Search

Biomedical subjects

L Biancone

Publications and source records attributed to L Biancone.

97 records · Page 6Linked to original sources
PubMedDate not supplied

Current treatment modalities in active Crohn's disease.

The aetiology of Crohn's disease is unknown and, therefore, no curative treatments are currently available. Crohn's disease treatment requires knowledge of several variables affecting patient's responsiveness including: characteristics of the disease and of the host, as well as the specific purposes of treatment and the characteristics of the effective drugs. Currently available drugs for active Crohn's disease include: a) old drugs (oral/topical salicylates, conventional steroids); b) old drugs with a new face (immunosuppressives, antibacterial drugs); c) new drugs (budesonide, anti-cytokines/cytokines, probiotics). Among the old drugs, corticosteroids (1 mg/kg) are the most effective, with a 65-85% induction of remission, when compared to high dose sulphasalazine (3-5 g/day) (12%) and 5-aminosalicylic acid (4 g/day) (25%). The following drugs represent current treatment modalities in steroid/refractory active Crohn's disease. Immunosuppressives, including azathioprine (2-2.5 mg/kg) and 6-mercaptopurine (1-1.5 mg/kg) are less effective than steroids (30-40% vs 65-85%), but in chronic active Crohn's disease they show a 76% "steroid-sparing" effect and 63% fistula closure. The reported efficacy of methotrexate (25 mg/kg) and cyclosporine A in fistulous Crohn's disease needs to be confirmed. Antibiotics, such as metronidazole and ciprofloxacin (1 g/day) are effective in perianal or colonic active Crohn's disease. Budesonide, a steroid with low systemic absorption, shows an efficacy comparable to prednisone in active small bowel Crohn's disease. Bowel rest and enteral feeding are effective in active Crohn's disease. To summarize, conventional steroids still represent the most effective drugs in active Crohn's disease. However, refractory disease, steroid-dependence, drug-side effects and/or complications may require two main alternative management strategies: a) surgical resection in localized or primary Crohn's disease; b) alternative drugs in extensive or recurrent Crohn's disease.

Crohn Disease↗
PubMedDate not supplied

Henoch-Schönlein purpura after 20 years of renal replacement therapy.

While the clinical impact of the impaired immune response, commonly described in chronic dialysis patients, is still a matter of discussion, it is usually considered that immunological diseases tend to become progressively less active after the start of regular renal replacement therapy (RRT). We reported a case of Henoch-Schonlein Purpura in a 51-year-old male, on RRT for 20 years, 8 on dialysis and 12 with renal graft, because of ESRD of unknown origin (chronic glomerulonephritis?). The acute onset of the syndrome, presenting purpuric rash, abdominal discomfort and asymmetric joint pain with edema and local signs of acute inflammation, was followed by several relapses over a 2 years period. This biopsy proven diagnosis offered an explanation for his chronic renal failure; furthermore, we conclude that, possibly because of the usually good correction of uremic immunodepression by efficient dialysis (this patient's Kt/V ranged from 1.1 to 1.3 according to Lowrie's formula), the possibility of immune diseases should be carefully considered even in long long-term RRT patients.

Humans↗
PubMedDate not supplied

The expression of CD154 by Kaposi's sarcoma cells mediates the anti-apoptotic and migratory effects of HIV-1-TAT protein.

Kaposi's sarcoma (KS) is a malignancy associated to conditions of immune system impairment such as HIV-1 infection and post-transplantation therapy. Here we report that HIV-1-Tat protein, at concentrations well below those detected in AIDS patients, up-regulates the expression of both CD40 and CD154 on KS cells. This occurred also in the presence of vincristine, that at doses shown to induce apoptosis decreased the expression of both CD40 and CD154 on KS cells. The treatment with a soluble CD40-muIg fusion protein (CD40 fp) that prevents the binding of CD154 with cell surface CD40, as well as the transfection with a vector for soluble CD40 (KS sCD40), decreased the anti-apoptotic effect of Tat. Moreover, Tat-induced motility of KS cells was inhibited by soluble CD40 fp. Tat also enhanced the expression of intracellular proteins known to transduce signals triggered by CD40 engagement, in particular TRAF-3. Tat as well as soluble CD154 (sCD154) prevented vincristine-induced reduction of TRAF-3 in KS cells transfected with a vector for neomycin resistance (KS psv-neo), but not in KS sCD40. Immunoprecipitation studies showed that Tat induced CD40 / TRAF-3 association and that this binding was abrogated upon the incubation with the soluble CD40 fp. These data suggest that Tat activates the CD40-CD154 pathway by enhancing the membrane expression of CD40 and in particular of CD154, and by activating the TRAF-3-dependent signaling pathway of CD40. These findings indicate that the CD40-CD154 pathway mediates the anti-apoptotic and migratory effects of HIV-1- Tat, suggesting the potential therapeutic benefits of blocking CD40 activation in HIV-1-associated KS.

Apoptosis↗
PubMedDate not supplied

Evidence against colonic mucosa colonisation by Helicobacter pylori. Lack of a specific antibody response in homogenates of rectal endoscopic biopsies.

Aim of this study is to provide indirect evidence that human colonic mucosa harbour Helicobacter pylori. The antibody response of IgG and IgA class against Helicobacter pylori was examined in autologous homogenate of gastric and rectal endoscopic biopsies from 26 patients and in rectal samples of a further 36. All had a documented (histology and/or serology) Helicobacter pylori status. Helicobacter pylori specific IgG and IgA were measured by an in-house ELISA. In Helicobacter pylori positive patients having both gastric and rectal homogenate, mean level of Helicobacter pylori IgG and IgA was higher in gastric than in rectal samples (0.810 +/- 0.668 optical density vs 0.329 +/- 0.509 optical density for IgG, p = 0.007 and 0.660 +/- 0.477 vs 0.116 +/- 0.229 for IgA, p < 0.001, respectively). In each patient, level of the two isotypes was clearly higher in gastric than in autologous rectal sample. In the overall study population, mean level of Helicobacter pylori IgG in rectal homogenate was not significantly (p = 0.16) different between Helicobacter pylori positive (48/62, 77%, 0.243 +/- 0.388 optical density) and negative (14/62, 23%; 0.095 +/- 0.088) patients. In same material, levels of Helicobacter pylori IgA were very low and undetectable either in Helicobacter pylori positive or negative patients. Although Helicobacter pylori IgG are detectable in rectal homogenates of Helicobacter pylori positive patients, present data suggest that these antibodies may not be local in origin but rather reflect circulating response. These observations do not support the view that large bowel mucosa is colonised by Helicobacter pylori.

Adult↗
PubMedDate not supplied

Escherichia coli porin induces proinflammatory alterations in renal tubular cells.

BACKGROUND/AIMS: Several bacterial components may contribute to the development of renal injury during Gram-negative sepsis. In the present study, we evaluated the proinflammatory effect on cultured human proximal tubular epithelial cells (PTEC) of a 36-kD porin purified from escherichia coli METHODS: PTEC were stimulated with E. coli porin to evaluate 45Ca2+ influx, cytoskeleton changes, generation of reactive oxygen species (ROS) as detected by chemiluminescence and cytochrome c reduction. Production of TNF-alpha, IL-6 and IL-8 was evaluated at the mRNA and protein levels. RESULTS: Stimulation of PTEC with porin was followed by a rapid and sustained 45Ca2+ influx and by an altered distribution of actin fibers and of vinculin streaks. Porin was able to induce generation of ROS and production of proinflammatory cytokines from PTEC. TNF-alpha production peaked at 6 h after exposure to porin and preceded that of IL-6 and IL-8. CONCLUSIONS: E. coli porin - at doses attainable in vivo - appears to stimulate PTEC to produce ROS and cytokines. Porin-induced PTEC activation may contribute to renal injury in the course of Gram-negative infection.

Actins↗