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•New furoxan compounds lead to undetectable M. tuberculosis in a mouse model of infection.•High activity against MDR and XDR-TB.•Early-bactericidal effect.•No mutagenic results were ...detected by AMES.•No damages in histological tissues.
The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. Results: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 μM and 9.84 μM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 μM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 μM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. Conclusion: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.
Purpose
This study was performed to evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of patients affected by Budd-Chiari syndrome (BCS).
...Materials and methods
From January 1999 to December 2006, 15 patients (seven male and eight female subjects, age range 7–52 years) with BCS uncontrolled by medical therapy were treated with TIPS placement. In seven cases BCS was idiopathic, in four it was caused by myeloproliferative disorders and in four by other disorders. One patient also had portal vein thrombosis. In 5/15 cases TIPS was created through a transcaval approach. Eight patients (53.4%) received a bare stent, and seven (46.6%) received a stent graft. The follow-up lasted a median of 29.4 (range 3.2-68) months.
Results
Technical success was achieved in all patients without major complications. TIPS was very effective in decreasing the portosystemic pressure gradient from 26.2±5.8 to 10±6.2 mmHg. All patients but two were alive at the time of writing. Acute leukaemia was the cause of the single early death and was unrelated to the procedure. The patient with portal vein thrombosis underwent thrombolysis before TIPS, but the vein occluded again after 3 weeks, and the patient died 6 months later. The other patients showed significant improvements in liver function, ascites and symptoms related to portal hypertension. Primary patency was 53.3%, and primary assisted patency was 93.3%. No patient required or was scheduled for liver transplantation.
Conclusions
TIPS is an effective and safe treatment for BCS and may be considered a valuable alternative to traditional surgical portosystemic shunting or liver transplantation.
To explore a more direct method for evaluating tumor burden (TB) in Hodgkin's disease (HD) and to verify its prognostic importance.
The volume of TB at diagnosis was directly and retrospectively ...measured in 121 HD patients through images of the lesions recorded by computed tomographic (CT) scan of the thorax, abdomen, and pelvis for all deep sites of involvement and many superficial ones, and by ultrasonography (US) for the remaining superficial lesions.
The TB, which was obtained from the sum of the volumes of all the lesions measured on CT scans and US and normalized to body-surface area (relative TB rTB), showed a median value of 102.6 cm(3)/m(2) (range, 2.2 to 582.8). At multivariate analysis for prognostic value, rTB was the parameter that statistically correlated best with time to treatment failure (P = 2.2 x 10(-6)), followed by erythrocyte sedimentation rate (ESR) (P =.0003), and serum fibrinogen (P =.0112). The prognostic discrimination allowed by rTB alone proved to be clearly superior to that obtained with the score of the International Prognostic Factor Project. The rTB was found to be correlated with many clinical staging parameters (bulky disease, number of involved lymph node regions, serum lactate dehydrogenase, ESR, hemoglobin, Karnofsky index), but its predictability from these variables was low (R(2) =.668).
Relative TB is emerging as a strong prognostic factor in HD, more powerful than and largely independent of those hitherto known and used. Further studies are needed to confirm these results and exploit their clinical value, particularly the relationship among rTB, drug doses, and response.
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