ABSTRACT
Although early aggressive and prolonged treatment with specific antibiotics can extend survival in patients with cystic fibrosis (CF) colonized by opportunistic Pseudomonas aeruginosa (PA), antibiotics fail to eradicate the infecting multidrug-resistant (MDR) PA strains in CF. Century-long research has suggested treating patients with bacteriophages (phages, prokaryotic viruses) naturally hosted by bacteria. Although the only phage types used in therapy, lytic phages, lyse PA aggregated in biofilm matrix by depolymerase degrading enzymes, how they can effectively, safely, and persistently do so in patients with CF is unclear. Even though advanced techniques for formulating phage cocktails, training phages and collecting phage libraries have improved efficacy in vitro, whether personalized or ready-to-use therapeutic approaches or phages and antibiotics combined are effective and safe in vivo, and can reduce PA biofilms, remains debatable. Hence, to advance clinical research on phage therapy in clinical trials, also involving mucoid and non-mucoid multidrug-resistant PA in CF, and overcome problems in Western international regulations, we need reliable and repeatable information from experiments in vitro and in vivo on phage characterization, cocktail selection, personalized approaches, and phages combined with antibiotics. These findings, challenges, and promises prompted us to undertake this argumentative review to seek up-to-date information from papers describing lytic phage activity tested in vitro on PA laboratory strains, and PA strains from chronic infections including CF. We also reviewed in vivo studies on phage activity on pulmonary and non-pulmonary animal host models infected by laboratory or CF PA strains. Our argumentative review provides essential information showing that future phage clinical research in CF should use well-characterized and selected phages isolated against CF PA, tested in vitro under dynamic conditions in cocktails or combined with antibiotics, and in vivo on non-pulmonary and pulmonary host models infected with mucoid and non-mucoid CF MDR PA. Our findings should encourage pharmaceutical industries to conduct clinical trials in vitro and in vivo testing patented genomic engineered phages from phage libraries combined with antibiotics to treat or even prevent multidrug-resistant PA in CF, thus helping international regulatory agencies to plan future clinical research on phage therapy in CF.
ABSTRACT
Objective To study the therapeutic effect of anti-LPS antibody and different antibiotic in treatment and prevention of sepsis a common complication of serious burns.Methods Twenty-nine patients were divied into anti-LPS+antibiotic treatment group and antibiotic treatment group.Plasma endotoxin,serum TNF,IL-6 and IL-8 were detected at different time phase after burn.Results The results showed that the antibodies to LPS could decrease the level of LPS,IL-6,IL-8 and TNF obviously,but some antibiotic couldn't decrease the level of LPS,IL-6,IL-8 and TNF obviously in blood.Impenem was a weak endotoxin inducer and ceftazidime and ciprofloxacin were stronger endotoxin inducers.Conclusion The appropriate selection of antibiotics and anti-LPS antibody has a considerable influence on treating sepsis and its complications after serious burns.
ABSTRACT
FUNDAMENTOS: Na hanseníase dimorfa é comum a ocorrência de reações tipo 1 antes, durante ou depois da poliquimioterapia (PQT). Trabalhos recentes sugerem que a reação tipo 1 seria um desequilíbrio imunológico entre citocinas pró-inflamatórias e antiinflamatórias. OBJETIVOS: Compreender melhor a fisiopatologia das reações tipo 1. MÉTODOS: Estudaram-se biópsias cutâneas de 10 indivíduos com hanseníase dimorfa-tuberculóide reacional não tratada (DTR) e 10 dimorfos em reação reversa após o início da PQT (DRR), comparando-se os parâmetros morfológicos e imunológicos por meio de colorações HE e Faraco-Fite, e técnicas imuno-histoquímicas (CD4, CD8, CD20, CD79a, CD57, iNOS, IL-10, LAM e BCG). RESULTADOS: Houve, nos DRR, mais macrófagos multivacuolados, maior marcação nos macrófagos para a enzima óxido nítrico sintase induzível (iNOS) e menos linfócitos T CD8+ (p<0,05). Afora a presença de bacilos típicos nos DTR e sua ausência nos DRR, não houve diferenças na baciloscopia ou na marcação para antígenos micobacterianos (LAM e BCG) entre os grupos. O número de células IL-10+ foi similar nos dois grupos, porém houve correlação negativa entre essa citocina e a proporção CD4/CD8 apenas nos pacientes DRR (p<0,05). Houve tendência à redução do infiltrado específico e ao maior número de células NK nos DRR. CONCLUSÃO: Na presença de muitos bacilos viáveis em um paciente sem imunidade celular plena, haveria tendência à piora imunológica (downgrading). A PQT, ao reduzir a carga bacilar, melhoraria a imunidade celular (upgrading), com posterior desvio da imunidade adquirida para a inespecífica (resposta Th3), evoluindo para a cura.
BACKGROUND: Type 1 reactions are common in borderline leprosy, and can occur before, during or after multidrugtherapy (MDT). Recent papers suggest that these reactions could be a result of an imbalance between proinflammatory and anti-inflammatory citokines. OBJECTIVE: To understand better the physiopathology of type 1 reactions. METHODS: We studied skin biopsies from 10 non-treated patients with reactional borderline tuberculoid leprosy (BTR) and 10 from borderline leprosy with reversal reactions after the beginning of MDT (BRR), to compare morphological and immunological parameters by routine staining (H-E and Faraco-Fite) and immunohistochemical technics (CD4, CD8, CD20, CD79a, CD57, iNOS, IL-10, LAM and BCG). RESULTS: We found, in BRR group, stronger staining for iNOS into macrofages, fewer CD8+ T cells and more multivacuolated macrofages than BTR group (p<0,05). Despite the presence of viable bacilli in BTR and its absence in BRR, there weren't differences in baciloscopy and staining for mycobacterial antigens (LAM and BCG) between the groups. The number of IL-10+ cells was similar in both groups, but there was a negative correlation between this cytokine and the CD4:CD8 ratio only in BRR group (p<0,05). It was seen a tendency for a decreased specific infiltrate and increased number of NK cells in BRR group. CONCLUSIONS: The presence of many viable bacilli in a patient with partial cellular immunity could worse the immunological status (downgrading). Once started MDT, the reduction bacilli charge would improve cellular immunity (upgrading), with latter shift to innate immunity (Th3 response), evolving to cure.