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Biomedical subjects

L Breda

Publications and source records attributed to L Breda.

9 recordsLinked to original sources
PubMed2006

Relationship between damage accrual, disease flares and cumulative drug therapies in juvenile-onset systemic lupus erythematosus.

Our objective was to investigate the pattern of damage accumulation in patients with juvenile-onset systemic lupus erythematosus (JSLE) and the relationship between damage accrual, disease flares and cumulative drug therapies. All patients with SLE followed prospectively in three tertiary care centres were identified. Only patients who presented within 12 months of diagnosis and were followed for at least three years were included. Damage was measures based on chart review using the SLICC/ACR damage index (SDI), which was modified (M-SDI) by adding the item growth failure. Mild-moderate and severe disease flares were defined by the increase in SLEDAI-2K. The cumulative duration of drug therapies was calculated in each patient. Fifty-seven patients were included. The mean M-SDI score for the whole patient group increased over time, from 0.1 at one year to 0.8 at three years to 1.5 at five years. Ocular and renal damage and growth failure were observed most frequently. Compared to patients with stable damage, patients who accrued new damage had a significantly greater frequency of severe disease flare in the first three years of follow-up. No significant difference was observed in any cumulative drug therapy between patients who accrued damage and those who did not. Damage accrual was associated with severe disease flares, suggesting that judicious use of immunosuppressive agents to achieve prompt control of severe exacerbation of disease activity is important in minimizing damage in patients with JSLE.

Adolescent↗
PubMed2003

Modulation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) gene expression in isolated porcine hepatocytes perfused within a radial-flow bioreactor after low-temperature storing.

Due to the scarcity of available human livers, porcine hepatocytes are currently being evaluated as a xenogeneic cell source for extracorporeal bioartificial liver (BAL). Hypothermic storage of isolated porcine hepatocytes could support stocking of cell-loaded bioreactors for BAL use and may provide bioreactors ready to be used at the patient's bedside. For the development of this technology, it is of utmost importance to ensure cell viability and differentiated functions after low-temperature storage and following warm reperfusion. We compared cell viability, functional activity and apoptosis in isolated porcine hepatocytes which were perfused within a radial-flow bioreactor (RFB), stored at 4 degrees C and then reperfused at 37 degrees C. RFBs were loaded with 8 x 10(9), > or = 90% viable hepatocytes at 37 degrees C for 3 h. RFBs were then flushed with 4 degrees C University of Wisconsin solution (UW) and subsequently stored for 24 h or 48 h. RFBs were then reperfused for 8 h with recirculating medium plus serum at 37 degrees C . Cytochrome P450 (CYP) activity was studied before and after cold storage by means of monoethylglycinexylide (MEGX) detection in the effluent medium, after repeated lidocaine injections. After reperfusion experiments, hepatocytes were harvested for total RNA isolation. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used in order to amplify specific mRNAs for Bcl-2 and Bax genes, by using appropriate primers; beta-actin primers were used as control. Total RNA was extracted by northern blotting analysis and for Bcl-2, Bax and beta-actin RNA messenger detection, RT-PCR amplification was used. Freshly isolated hepatocytes perfused into the RFB showed a progressive increase of MEGX while a loss in Bax expression was paralleled by an increase in Bcl-2 expression, in comparison to starting hepatocytes. After 4 degrees C storage and warm reperfusion, MEGX production was preserved in 24 h- and 48 h-stored bioreactors as well as a sharp increase of Bcl-2 and a decrease of Bax mRNAs. Our study suggests that refrigeration of hepatocyte-bioreactors is a suitable strategy to maintain both viability and function of isolated hepatocytes, for up to 48 h a time-length that is compatible with long-distance delivery of ready-to-use bioreactors.

Animals↗
PubMed2001

Aromatic polyamidines inhibiting the Tat-induced HIV-1 transcription recognize structured TAR-RNA.

We have investigated the effects of aromatic polyamidines on HIV-1 transcription. We found a block to Tat-induced HIV-1 transcription assessed by inhibition of CAT activity in HL3T1 cells at a concentration lower than the IC50 value, suggesting that molecules with three (TAPB) and four (TAPP) benzamidine rings could be useful against HIV-1. In contrast, aromatic polyamidines with only two benzamidine rings (DAPP) did not block Tat-induced transcription. We reasoned that this effect could be due to binding of TAPB and TAPP to HIV-1 TAR RNA. By EMSA and filter binding assays, we studied possible interactions of aromatic polyamidines with HIV-1 TAR RNA. Wild-type TAR RNA or TAR RNA with mutations in the stem or bulge sequences, but retaining the stem-loop structure, was used to define the RNA-binding activities of these compounds. Our data suggest that aromatic polyamidines with two (DAPP) and four (TAPP) benzamidine rings, respectively, do not bind to TAR RNA or bind without sequence selectivity. Interestingly, an aromatic polyamidine with three benzamidine rings (TAPB) recognizes the wild-type TAR RNA in a specific manner. Furthermore, we found that introduction of one halogen atom into the benzamidine rings strongly increases the RNA-binding activity of these compounds.

Anti-HIV Agents↗
PubMed1998

Familial Mediterranean fever in two Italian brothers.

Familial Mediterranean fever (FMF) is an autosomal recessive disease of unknown etiology, characterized by recurrent self limited episodes of fever and polyserositis. Some patients develop generalized amyloidosis, which can be fatal. Colchicine therapy modifies the natural history of the disease by decreasing the attack frequency and preventing amyloid deposition. The disease is common among Sephardic Jews, Arabs, Armenians and has also been sporadically found in other ethnic groups of Mediterranean origin. We report two cases of FMF in brothers living in Abruzzo, Italy. They were born from consanguineous parents and complained typical symptoms since childhood. The boy suffered from one febrile attack every week; he presented three episodes of acute scrotum at age 8 and 9. The elder sister showed a spontaneous partial relief during adolescence. Juvenile rheumatoid arthritis was suspected and Aspirin was used for many years without any clinical improvement. Treatment with colchicine 1 mg/day was established at age 13 and 17 respectively, and a sudden reduction of frequency of attacks was obtained. A gingival biopsy did not show amyloid. The three elder brothers are, at present, in good health. Our experience point out the diagnostic difficulties of FMF especially in a country where the disease is uncommon.

Adolescent↗
PubMed1989

[Neonatal hyperthyroidism with early onset and protracted course].

Neonatal hyperthyroidism has often been described as a rare, transient disorder in which the mother has hyperthyroidism during her pregnancy. We have found 99 cases mentioned in recent literature, but not in all reports the clinical characteristics were described. This survey has shown that the prolonged clinical course, though less common than the transient one, is to be taken into account. A case of a female child who had signs of hyperthyroidism soon after the birth is presented. Now, at the age of 7.8 years, she continues to have hyperthyroidism with several problems in treatment.

Child↗
PubMed1989

[Methodologic approach to the therapeutic problem of infant and childhood obesity. Review of the literature and personal experience].

Notwithstanding the high prevalence and morbidity, current knowledge of obesity is rather rudimentary. Nevertheless recent findings have enabled us to surmount anachronistic nosographic generalizations whereby excess weight was attributed only to inappropriate and excessive food intake and the lack of physical exercise. Various studies indicate that there are complex interactions in determining weight excess: genetic, psychosocial, cultural but also biochemical factors are incriminated and it is now recognised that the aetiology of obesity is multifactorial and that, consequently, there are different types of obesity. However, in most studies concerning the therapeutic approach, it is noted that the same type of treatment is applied to groups of subjects that are probably highly heterogeneous for type of obesity. No easy or final solution to the problem is proposed as for the moment no ideal treatment exists. What is suggested is the need to attempt to identify possible factors linked to weight excess before commencing the therapeutic approach. For each single case, this could permit the use of the most appropriate treatment and make therapeutic results less frustrating.

Adolescent↗