ABSTRACT
We report the 8-year follow-up of 34 patients aged >/= 69 years old with NHL included in a phase IIb open-label randomized parallel groups study to evaluate the effectiveness of amifostine in preventing the toxicity of cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP regime]. Patients were randomized to receive classical CHOP [cyclophosphamide 750 mg/ m[2], doxorubicin 50 mg/m[2], vincristine 1.4 mg/m[2] [maximum 2 mg] on day 1 and prednisone 100 mg/day for 5 days] or CHOP plus amifostine [6 cycles of amifostine 910 mg/m[2] on day 1]. Efficacy [time to progression, TTP; disease-free survival, DFS; overall survival, OS] and toxicity endpoints were evaluated. Thirty-four patients were randomized to A-CHOP [n=18] or CHOP [n=16]. Patients with A-CHOP vs CHOP had significantly lower toxicity; neutropenia grade 4 ocurred in 13/92 [13%] vs 23/85 [27%, P=0.007] cycles, febrile neutropenia in 3/92 A-CHOP [3%] vs 8/85 [10%, P=.056] CHOP cycles, hospitalization for toxicity in 4/92 [4%] A-CHOP vs 11/85 [13%, P=.05] CHOP cycles. Median hospitalization stay for toxicity was 5 days with A-CHOP vs 8 days with CHOP [P=.05]. There were no significant differences at 8 years in TTP [A-CHOP, 48.9% vs CHOP, 36.3%; P=.65], DFS [A-CHOP, 72.9% vs CHOP 55.6%; P=.50] and OS [A-CHOP, 44.3% vs CHOP, 54.4%]. There was no long-term toxicity of clinical interest. The only prognostic factor identified to 8 years was the International Prognostic Index [IPI low/low intermediate risk vs high intermediate/high risk; HR=2.98; CI 95%:1.01-8.77; P=.048]. These results show that amifostine can be added to the standard CHOP treatment schedule with less acute toxicity and without influencing the outcome
ABSTRACT
En el presente trabajo se estudiaron 74 bacterias lácticas para determinar su capacidad de inhibir el desarrollo de Listeria monocytogenes ATCC 7644 o L. innocua ATCC 33090. Dentro de las 7 que exhibieron actividad, 2 se seleccionaron para estudios complementarios y se identificaron por métodos fenotípicos y genotípicos como Enterococcus mundtii Tw 56 y Lactococcus lactis subsp. lactis Tw 34. Después de la neutralización con NaOH y tratamiento térmico (100 ºC y 121 ºC durante 5 min) la actividad antagonista del sobrenadante libre de células se mantuvo activa. El tratamiento con lisozima, lipasa y catalasa no afectó la actividad antimicrobiana. Sin embargo, la actividad enzimática de la tripsina suprimió la acción inhibitoria del sobrenadante, confirmando la naturaleza proteica del compuesto activo. En ambos casos, el título de la actividad antilisteria no se vio afectado luego de la inducción mediada por nisina o galactosa. La combinación de los sobrenadantes libres de células no exhibió antagonismo o sinergia. Las características bioquímicas y fisicoquímicas de los agentes antilisteria producidos por las cepas seleccionadas sugieren que pueden ser clasificadas como bacteriocinas tipo I o II. Se deben realizar estudios complementarios para determinar el uso potencial de las cepas seleccionadas como cultivos bioprotectores en el control de la seguridad alimentaria.
In the present work, 74 strains of lactic bacteria isolated from the marine environment were studied in order to determinate their ability to inhibit the growth of Listeria monocytogenes ATCC 7644 or L. innocua ATCC 33090. Among the 7 strains that exhibited some activity, 2 were selected for further studies and identified by phenotypic and genotypic methods as Enterococcus mundtii Tw 56 y Lactococcus lactis subsp. lactis Tw 34. After neutralization with NaOH and heat treatment (100 ºC and 121 ºC for 5 min) the antagonistic activity of cell-free supernatants of the two strains studied remained active. Treatment with lysozime, lipase and catalase did not affect the antimicrobial activity; however enzymatic activity of trypsin abolished the inhibitory action of the supernatant, confirming the proteinacious nature of the active compound. In both cases, the titre of antilisterial activity was not affected after nisin or galactose-mediated induction. The combination of cell-free supernatants of both strains did not display antagonism or synergy. The biochemical and physicochemical characteristics of antilisterial agents produced by the selected strains suggest that they can be classified as type I or II bacteriocins. Further studies will be adressed to determine the potential use of the selected strains as bioprotective cultures in food safety control.
No presente trabalho foram estudadas 74 bactérias lácticas para determinar sua capacidade de inibir o desenvolvimento de Listeria monocytogenes ATCC 7644 ou L. innocua ATCC 33090. Dentro das 7 que exibiram atividade, 2 foram selecionadas para estudos complementares e se identificaram por métodos fenotípicos e genotípicos como Enterococcus mundtii Tw 56 e Lactococcus lactis subsp. lactis Tw 34. Depois da neutralização com NaOH e tratamento térmico (100 ºC e 121 ºC durante 5 min) a atividade antagonista do sobrenadante livre de células se manteve ativa. O tratamento com lisozima, lipase e catalase não afetou a atividade antimicrobiana. Entretanto, a atividade enzimática da tripsina suprimiu a ação inibidora do sobrenadante, confirmando a natureza proteica do composto ativo. Em ambos os casos, o título da atividade antilisteria não se viu afetado depois da indução mediada por nisina ou galactose. A combinação dos sobrenadantes livres de células não exibiu antagonismo ou sinergia. As características bioquímicas e fisioquimicas dos agentes antilisteria produzidos pelas cepas selecionadas sugerem que podem ser classificadas como bacteriocinas tipo I ou II. Devem ser realizados estudos complementares para determinar o uso potencial das cepas selecionadas como culturas bioprotetoras no controle da segurança alimentar.