Infusion of autologous bone marrow mononuclear cells through hepatic artery results in a short-term improvement of liver function in patients with chronic liver disease: a pilot randomized controlled study.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-11-27T19:22:21Z No. of bitstreams: 1 Lyra AC Infusion of....pdf: 209231 bytes, checksum: e2e73897c822b277bd8642ef46389981 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-11-27T19:22:30Z (GMT) No. of bitstreams: 1 Lyra AC Infusion of....pdf: 209231 bytes, checksum: e2e73897c822b277bd8642ef46389981 (MD5)Made available in DSpace on 2014-11-27T19:40:51Z (GMT). No. of bitstreams: 1 Lyra AC Infusion of....pdf: 209231 bytes, checksum: e2e73897c822b277bd8642ef46389981 (MD5) Previous issue date: 2010Hospital Sao Rafael. Salvador, BA, Brasil / Hospital Universitário Professor Edgard Santos. Federal Univeristy of Bahia. Medicine-Gastro-Hepatology Service. Salvador, BA, BrasilHospital São Rafael. Regenerative Medicine. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital Sao Rafael. Medicine. Hematology. Salvador, BA, BrasilHospital Sao Rafael. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Radiology. Salvador, BA, BrasilHospital São Rafael. Regenerative Medicine. Salvador, BA, BrasilBGStats Consulting. Graz, AustriaHospital São Rafael. Regenerative Medicine. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital Sao Rafael. Salvador, BA, BrasilAIM: This randomized controlled study evaluated the effect of autologous infusion of bone marrow cells (BMC) in patients with hepatic cirrhosis. METHODS: Thirty patients on the liver transplant waiting list were randomly assigned to receive BMC therapy or no treatment. They were followed up for 1 year. The study was nonblinded. Autologous mononuclear-enriched BMC were infused into the hepatic artery; liver function scores/tests were chosen as endpoints to assess efficacy. Statistical analysis calculated mean relative changes (RC) from baseline and fitted a random-effects model. RESULTS: Mean age, baseline model for end-stage liver disease, and Child-Pugh score were similar in both groups. Child-Pugh score improved in the first 90 days in the cell therapy group compared with controls (P = 0.017, BMC group RC = -8%, controls RC = +5%). The model for end-stage liver disease score remained stable in the treated patients (RC -2 to +6%), whereas it increased during follow-up in the control group (RC +6 to +18%). Albumin levels improved in the treatment arm, whereas they remained stable among controls in the first 90 days (P = 0.034; BMC group RC = +16%, control group RC = +2%). Bilirubin levels increased among controls, whereas they decreased in the therapy arm during the first 60 days; INR RC differences between groups reached up to 10%. The changes observed did not persist beyond 90 days. CONCLUSION: Transplantation of autologous BMC into the hepatic artery improved liver function in patients with advanced cirrhosis in the first 90 days. However, larger studies are necessary to define the role of BMC therapy in cirrhotic patients. Repeated autologous BMC infusions or combination therapy with granulocyte-colony-stimulating factor might improve or sustain the treatment response

Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-17T17:28:02Z No. of bitstreams: 1 Lyra A C Feasibility and safety....pdf: 721437 bytes, checksum: 75ac96704d2533501891f5209c8b6837 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-17T17:50:23Z (GMT) No. of bitstreams: 1 Lyra A C Feasibility and safety....pdf: 721437 bytes, checksum: 75ac96704d2533501891f5209c8b6837 (MD5)Made available in DSpace on 2015-04-17T17:50:23Z (GMT). No. of bitstreams: 1 Lyra A C Feasibility and safety....pdf: 721437 bytes, checksum: 75ac96704d2533501891f5209c8b6837 (MD5) Previous issue date: 2007Hospital São Rafael. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhaes. Recife, PE, BrasilHospital São Rafael. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilBGStats Consulting. Graz, AustriaHospital São Rafael. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilAIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 +/- 0.9) and 4 mo (2.10 +/- 1.0) after cell transplantation that baseline levels (2.78 +/- 1.2). Albumin levels 4 mo after BMC infusion (3.73 +/- 0.5) were higher than baseline levels (3.47 +/- 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease

Evaluation of antioxidant, toxicological and anxiolytic-like effect of ethanolic extracts of Ziziphus cotinifolia Reissek in adult zebrafish (Danio rerio)

Background: The GABAergic and serotoninergic neurotransmission pathways are involved in the control of anxiety and ensure emotional balance. Some plant species have substances with anxiolytic activity, a therapeutic effect associated with the presence of phenolic compounds. Methods: Before assessing the existence of anxiolytic activity, ethanolic extracts from leaves, branches and roots of Ziziphus cotinifolia Reissek were evaluated regarding biological activity and absence of toxicity. Later the influences of the samples on locomotor and anxiolytic activity, anxiolytic pathways and probable mechanisms of neurotransmission were evaluated. Results: The EEtFJ extract (0.5 mg/mL) did not have its anxiolytic activity reversed by the GABAergic receptor antagonist (Fmz + EEtFJ = EEjFJ; p<0.05). The twig extracts and flumazenil only partially reduced the time spent in the light zone (Fmz + EEtGJ < + EEtGJ; p<0.05), the root extract was not reversed by flumazenil (Fmz + EEtFRJ = EEtFRJ). Conclusion: The initial analysis data reveal the presence of phenolic compounds that explain the biological activities found and, as they act on different targets of neurotransmission systems involved in the control of anxiety disorders, they have potential for the production of herbal medicines with synergistic action

Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-27T16:55:57Z No. of bitstreams: 1 Mendonça MVP Safety....pdf: 1520611 bytes, checksum: c73d72436dfa4e3a49b2829957c29b40 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-27T17:27:22Z (GMT) No. of bitstreams: 1 Mendonça MVP Safety....pdf: 1520611 bytes, checksum: c73d72436dfa4e3a49b2829957c29b40 (MD5)Made available in DSpace on 2015-05-27T17:27:22Z (GMT). No. of bitstreams: 1 Mendonça MVP Safety....pdf: 1520611 bytes, checksum: c73d72436dfa4e3a49b2829957c29b40 (MD5) Previous issue date: 2014Hospital Espanhol. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia, Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilCentro Universitário Estácio da Bahia. FIB. Salvador, BA, BrasilHospital Espanhol. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilINTRODUCTION: The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Mesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for autologous transplantation and have been previously shown to induce regeneration of the spinal cord in experimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation of mesenchymal stem cells in subjects with chronic complete SCI. METHOD: We conducted a phase I, non-controlled study in 14 subjects of both genders aging between 18 to 65 years, with chronic traumatic SCI (>6 months), at thoracic or lumbar levels, classified as American Spinal Injury Association (ASIA) A - complete injury. Baseline somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Pain rating was performed using the McGill Pain Questionnaire and a visual analogue score scale. Bone marrow-derived mesenchymal stem cells were cultured and characterized by flow cytometry, cell differentiation assays and G-band karyotyping. Mesenchymal stem cells were injected directly into the lesion following laminectomy and durotomy. RESULTS: Cell transplantation was an overall safe and well-tolerated procedure. All subjects displayed variable improvements in tactile sensitivity and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven subjects presented sacral sparing and improved American Spinal Injury Association impairment scale (AIS) grades to B or C - incomplete injury. Nine subjects had improvements in urologic function. One subject presented changes in SSEP 3 and 6 months after mesenchymal stem cells transplantation. Statistically significant correlations between the improvements in neurological function and both injury size and level were found. CONCLUSION: Intralesional transplantation of autologous mesenchymal stem cells in subjects with chronic, complete spinal cord injury is safe, feasible, and may promote neurological improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325103 - Registered 28 March 2011

Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology

Abstract: Background: The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. Objectives: We aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19. Methods: We performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection. Results: We found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage. Conclusion: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy

Sensitivity of South American tropical forests to an extreme climate anomaly

NERC Knowledge Exchange Fellowship (NE/V018760/1) to E.N.H.C.The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha−1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected.Publisher PDFPeer reviewe