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1.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445055

RESUMO

BACKGROUND: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. METHODS: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. RESULTS: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. CONCLUSIONS: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients' survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.


Assuntos
COVID-19/terapia , Oxigênio/uso terapêutico , Probióticos/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Gasometria , Linhagem Celular , Feminino , Heparina , Humanos , Hipóxia , Itália , Pulmão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Front Med (Lausanne) ; 7: 389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733907

RESUMO

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.

3.
J Transl Med ; 17(1): 364, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706326

RESUMO

BACKGROUND: A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to counteract dysbiosis but the evidence in regard to their therapeutic use in the setting of difficult-to-treat cutaneous ulcers is still poor. AIM: CLINICAL REPORT: An 83-year-old woman suffering a critical limb ischemia and an infected difficult-to-treat ulcerated cutaneous lesion of the right leg, was complementary treated with local application of a mixture of probiotic bacteria. METHODS: Microbiological and metabolomic analysis were conducted on wound swabs obtained before and after bacteriotherapy. RESULTS: During the treatment course, a progressive healing of the lesion was observed with microbiological resolution of the polymicrobial infection of the wound. Metabolomic analysis showed a significant difference in the local concentration of propionate, 2-hydroxyisovalerate, 2-oxoisocaproate, 2,3-butanediol, putrescine, thymine, and trimethylamine before and after bacteriotherapy. CONCLUSION: The microbiological and metabolomic results seem to confirm the usefulness of complementary probiotic treatment in difficult-to-treat infected wounds. Further investigations are needed to confirm these preliminary findings.


Assuntos
Isquemia/terapia , Probióticos/uso terapêutico , Úlcera Cutânea/terapia , Infecção dos Ferimentos/terapia , Administração Tópica , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Isquemia/microbiologia , Isquemia/patologia , Perna (Membro) , Metaboloma , Probióticos/administração & dosagem , Pele/metabolismo , Pele/microbiologia , Pele/patologia , Úlcera Cutânea/microbiologia , Úlcera Cutânea/patologia , Pesquisa Médica Translacional , Cicatrização/fisiologia , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
4.
Front Immunol ; 8: 1474, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163538

RESUMO

Background: Variability in probiotics manufacturing may affect their properties, with potential implications for their efficacy and safety. This is of particular concern with probiotic products destined for use in patients with serious medical conditions, including human immunodeficiency virus (HIV) infection. The purpose of the study was to carry out a series of experiments comparing the properties of the US-made probiotic formulation originally commercialized under the brand name VSL#3®, with those of the Italian-made formulation now commercialized under the same name. The US-made formulation has previously shown beneficial effects at the intestinal and neurological levels in HIV-infected subjects as well as in patients with inflammatory bowel diseases and hepatic encephalopathy. Methods: Eleven subjects receiving combined antiretroviral therapy for HIV-1 were treated for 6 months with the US-made VSL#3 formulation. At baseline and 6 months, T-cells were analyzed for phenotype and activation markers, and fecal samples were analyzed for bifidobacteria, lactobacilli, and their metabolites. The fecal metabolome was assessed using 1H-NMR spectroscopy. Production of metabolites of interest by bacteria obtained from sachets of the two formulations was compared in vitro and their effects on a rat intestinal epithelial cell line (IEC-6) were assessed. Particular attention was paid to the metabolite 1,3-dihydroxyacetone (DHA). Results: At 6 months, fecal samples showed a significant increase in the specific bacterial genera contained in the probiotic supplement. Immune activation was reduced as shown by a significant reduction in the percentage of CD4+CD38+HLA-DR+ T-cells at 6 months. Fecal concentrations of DHA decreased significantly. In vitro, significant differences in the production and metabolism of DHA were found between bacteria from the US-made and Italian-made formulations: the US-made formulation was able to metabolize DHA whereas the bacteria in the Italian-made formulation were producing DHA. DHA reduced the viability of Streptococcus thermophilus, reduced IEC-6 cell viability in a dose-dependent manner, and also led to a lower rate of repair to scratched IEC-6 cell monolayer. Conclusion: Our data, in conjunction with previously published findings, confirm that the new Italian-made formulation of VSL#3® is different from the previous US-made VSL#3 and therefore its efficacy and safety in HIV-infected subjects is still unproven.

5.
Immun Inflamm Dis ; 5(3): 244-260, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28474815

RESUMO

INTRODUCTION: HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART-experienced HIV-1 patients was evaluated. METHODS: A sub-study of a longitudinal pilot study was performed in HIV-1 patients who received the probiotic supplement twice a day for 6 months (T6). T-cell activation and CD4+ and CD8+ T-cell subsets expressing IFNγ (Th1, Tc1) or IL-17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay. RESULTS: A reduction in the frequencies of CD4+ and CD8+ T-cell subsets, expressing CD38+ , HLA-DR+ , or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut-associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60. CONCLUSIONS: These findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART-treated HIV-1-positive patients.


Assuntos
Antirretrovirais/administração & dosagem , Soropositividade para HIV , HIV-1/imunologia , Mucosa Intestinal/imunologia , Ativação Linfocitária/efeitos dos fármacos , Mitocôndrias/imunologia , Probióticos/administração & dosagem , Células Th17/imunologia , Adulto , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/imunologia , Soropositividade para HIV/patologia , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/patologia , Células Th1/imunologia , Células Th1/patologia , Células Th17/patologia
6.
New Microbiol ; 35(4): 495-501, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23109019

RESUMO

Lactococcus garvieae is a human opportunistic pathogen with low virulence, but it is a well-known pathogen in aquaculture. A total of 21 human infections have been reported in the literature, mostly endocarditis. Automated methods can wrongly identify this microorganism as Enterococcus spp with a non-standard phenotype, leading to an underestimation of the incidence of this infection. The route of infection could be the ingestion of raw fish, grilled fish or fresh dairy products. We describe the first case of L. garvieae mitral valve endocarditis in Italy, in a patient with mitral valve repair with autologous pericardium, mechanic prosthetic aortic valve and colonic diverticulosis.


Assuntos
Endocardite Bacteriana/microbiologia , Lactococcus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diverticulose Cólica , Endocardite Bacteriana/diagnóstico , Feminino , Humanos , Itália , Lactococcus/fisiologia , Masculino , Pessoa de Meia-Idade
7.
Cardiovasc Hematol Agents Med Chem ; 10(4): 362-75, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22721442

RESUMO

BACKGROUND: The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patient's quality of life. OBJECTIVES: To review currently available measures and investigational agents to prevent OM in hematological patients. METHODS: we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. RESULTS/CONCLUSIONS: Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.


Assuntos
Fator 7 de Crescimento de Fibroblastos/uso terapêutico , Neoplasias Hematológicas/complicações , Mucosa Bucal/efeitos dos fármacos , Estomatite/complicações , Estomatite/prevenção & controle , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estomatite/tratamento farmacológico , Condicionamento Pré-Transplante/efeitos adversos
8.
Int J Infect Dis ; 14(6): e533-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19758832
9.
J Clin Gastroenterol ; 42 Suppl 3 Pt 1: S133-5, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18806705

RESUMO

Transporter proteins of the solute carriers (SLCs) family play a role in epithelial permeability and barrier function in the intestine, and polymorphisms in SLC genes are associated with inflammatory bowel disease. Many SLCs also mediate the bioavailability of pharmaceutical compounds, and the modulation of such transport systems to increase drug efficacy is, therefore, of great interest. We have undertaken a large-scale project to evaluate whether bacteria can modulate the expression of SLCs in the intestine. Here we report the effect of VSL[sharp]3 (a high-potency probiotic preparation) on the expression of 3 large solute carrier families, SLC4, SLC21, and SLC22, which are involved in the transport of bicarbonates, organic anions and cations, and affect the bioavailability of several pharmaceutical compounds. Two groups of animals (VSL[sharp]3 and phosphate-buffered saline controls) were studied for SLC expression in the intestine by Real-Time PCR at the beginning (day 1) and at the end (day 20) of the treatment, and 7 days after the interruption of the treatment. An effect of VSL[sharp]3 administration was detected on the expression of 10% of the studied genes. This reached statistical significance (P=0.01) for the poorly characterized sodium-borate cotransporter SLC4A11, which showed a 5-times lower expression in VSL[sharp]3 than in control mice on day 1 of probiotic treatment. VSL[sharp]3-driven changes in the expression levels of SLC transporters might contribute to its reported effects on intestinal permeability. The elucidation of SLC4A11 function in the intestine will be the key to fully evaluate the relevance of specific findings.


Assuntos
Doenças Inflamatórias Intestinais/terapia , Bombas de Íon/metabolismo , Probióticos/uso terapêutico , Animais , Bifidobacterium/classificação , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Bombas de Íon/classificação , Bombas de Íon/genética , Lactobacillus/classificação , Camundongos , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Projetos Piloto , Reação em Cadeia da Polimerase , Probióticos/administração & dosagem , Simportadores de Sódio-Bicarbonato/genética , Simportadores de Sódio-Bicarbonato/metabolismo , Streptococcus thermophilus , Resultado do Tratamento
10.
Ann N Y Acad Sci ; 1033: 132-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15591010

RESUMO

Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide spectrum of disorders characterized by unregulated or impaired immune responses ranging from sepsis syndrome to systemic sclerosis, infection with human immunodeficiency virus, and chronic fatigue syndrome. Furthermore, experimental studies have consistently reported that the deranged immune responses and the less efficient inflammation towards infectious organisms associated with aging may be enhanced or modulated by treatment with carnitines. There is also evidence that carnitine deprivation could adversely affect the course of the sepsis syndrome, at least in experimental models, and preliminary studies suggest that carnitine deficiency is ultimately implicated in the pathophysiology of endotoxin-mediated multiple organ failure. Several data indicate that carnitine deficiency is a contributing factor to the progression of infection with human immunodeficiency virus, and carnitine therapy in those patients could counteract the unregulated process of lymphocyte apoptosis and improve CD4 counts. Some case reports have suggested the use of carnitine for the treatment of the severe lactic acidosis that complicates in some patients the use of reverse transcriptase inhibitors.


Assuntos
Carnitina/metabolismo , Imunidade nas Mucosas/fisiologia , Inflamação/metabolismo , Animais , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Humanos , Imunidade nas Mucosas/imunologia , Inflamação/imunologia , Ratos , Síndrome de Resposta Inflamatória Sistêmica/metabolismo
11.
Curr Pharm Des ; 9(24): 1973-80, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12871183

RESUMO

Inflammatory bowel disease, such as ulcerative colitis and Crohn's disease, results from an interaction between susceptibility genes, the host's bacterial environment, gut barrier defects, and immunological factors. New management approaches have been evolved from advances in our understanding of the pathobiology of this common gut disorder In particular, the therapeutic manipulation of the bacterial microenvironment in the gut seems to offer an innovative tool for the treatment of those patients. Since the gut is a highly sensitizing organ that contributes to the systemic immune response, potent treatments need to be developed to reduce gut inflammation in this disorder. Recent studies have demonstrated that probiotic lactobacilli, and also immunostimulatory DNA sequences from those same bacteria have an important anti-inflammatory potential in this context. Future research should better define among patients with inflammatory bowel disease the various clinical phenotypes with the greatest potential of response to probiotic treatment. Identification of the genes leading to the disease and a rather better understanding of the underlying immunoregulatory abnormalities will be crucial steps to define the different profiles of interaction between endogenous digestive bacterial flora and the immune system in each individual patient. Such advances will probably lead to targeting of effective treatments, including bacteriotherapy with probiotic lactobacilli, to subsets of patients with inflammatory bowel disease.


Assuntos
Colite Ulcerativa/terapia , Doença de Crohn/terapia , Lactobacillus/imunologia , Probióticos/uso terapêutico , Animais , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Modelos Animais de Doenças , Humanos , Inflamação/imunologia , Inflamação/terapia , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Intestinos/patologia
13.
Antioxid Redox Signal ; 4(3): 391-403, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12215207

RESUMO

Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV-1) infection. It appears reasonable that antiretroviral therapies may not achieve a full control of the infection in the absence of an impact on apoptosis. We assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to receive either zidovudine (AZT), and didanosine (DDI) or the same regimen plus L-carnitine, a known antiapoptotic drug, for 7 months. Immunologic and virologic parameters were measured at baseline and after 15, 60, 120, and 210 days of treatment. We assessed on each time point the following: (a) the frequency of peripheral blood apoptotic CD4 and CD8 lymphocytes, CD4 and CD8 cells with disrupted mitochondrial membrane potential, and CD4 and CD8 cells undergoing oxidant stress; (b) the expression of the molecular markers of apoptosis Fas and caspase-1; and (c) the expression of p35/cdk-5 regulatory subunit that is involved in regulating cell survival and apoptosis. Absolute CD4 and CD8 counts and plasma viremia were also measured. Apoptotic CD4 and CD8 cells, lymphocytes with disrupted mitochondrial membrane potential, and lymphocytes undergoing oxidant stress were greatly reduced in subjects treated with AZT and DDI plus L-carnitine compared with those who did not receive L-carnitine. Fas and caspase-1 were down-expressed and p35 over-expressed in lymphocytes from patients of the L-carnitine group. No difference was found in CD4 and CD8 counts and viremia between the groups. No toxicity of L-carnitine was recognized. The addition of L-carnitine is safe and allows apoptosis and oxidant stress to be greatly reduced in lymphocytes from subjects treated with AZT and DDI.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Apoptose/fisiologia , Carnitina/uso terapêutico , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Estresse Oxidativo , Linfócitos T/metabolismo , Zidovudina/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Carnitina/administração & dosagem , Carnitina/efeitos adversos , Quimioterapia Combinada , Citometria de Fluxo , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , HIV-1/imunologia , HIV-1/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Potenciais da Membrana/fisiologia , Mitocôndrias/metabolismo , Oxidantes/metabolismo , Fenótipo , Inibidores da Transcriptase Reversa/uso terapêutico , Superóxidos/metabolismo , Receptor fas/metabolismo
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