19 results on '"Zois Mellios"'
Search Results
2. Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data
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Eleni Gavriilaki, Emmanuel Nikolousis, Eudoxia-Evaggelia Koravou, Sotiria Dimou-Besikli, Charalampos Kartsios, Anna Papakonstantinou, Anastasia Mpanti, Charalampos Pontikoglou, Christina Kalpadaki, Aikaterini Bitsani, Ilianna Tassi, Tasoula Touloumenidou, Thomas Chatziconstantinou, Maria Papathanasiou, Antonia Syrigou, Eleutheria Ztriva, Georgia Kaiafa, Evdokia Mandala, Zois Mellios, Dimitrios Karakasis, Alexandra Kourakli, Argiris Symeonidis, Eleni Kapsali, Helen H. Papadaki, Chrysavgi Lalayanni, and Ioanna Sakellari
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caplacizumab ,thrombotic thrombocytopenic purpura ,plasma exchange ,ADAMTS13 ,multicenter real-world study ,Medicine (General) ,R5-920 - Abstract
Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1–43) from initial diagnosis for 32 (6–47) dosages. In the caplacizumab group, a median of 12 (8–23) patients required plasma exchange sessions versus 14 (6–32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6–320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p
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- 2023
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3. Convalescent plasma therapy in an immunocompromised patient with multiple COVID‐19 flares: a case report
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Frini Karaolidou, Natasa‐Eleni Loutsidi, Zois Mellios, Edison Jahaj, Konstantinos Eleftheriou, Maria Pagoni, Ioannis Mpaltadakis, Athanasios‐Meletios Dimopoulos, Ioannis Kalomenidis, and Apostolos G. Pappas
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B‐cell acute lymphocytic leukaemia ,convalescent plasma ,COVID‐19 ,immunosuppression ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Convalescent plasma (CP) transfusion has been utilized as a salvage therapy in immunocompromised patients with severe COVID‐19 pneumonia. We describe the case of a 45‐year‐old immunocompromised patient, who received CP, in order to control multiple COVID‐19 flares and prolonged SARS‐CoV‐2 viraemia lasting for 2 months after the initial diagnosis.
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- 2021
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4. Central Nervous System Relapse in Patients with Primary Mediastinal Large B-Cell Lymphoma: Incidence and Risk Factors in the Rituximab Era
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Theodoros P. Vassilakopoulos, Fotios Panitsas, Zois Mellios, John Apostolidis, Alexia Piperidou, Michalis D Michael, Ronit Gurion, Meltem Akay, Eleftheria Hatzimichael, Stamatis J. Karakatsanis, Maria Dimou, Christina Kalpadakis, Eirini Katodritou, Theoni Leonidopoulou, Ioannis Kotsianidis, Chara Giatra, Nikolaos Kanellias, Ayman Sayyed, Tamar Tadmor, Leylagul Kaynar, Miri Zektser, Argiris Symeonidis, SC Atalar, Evgenia Verrou, Odit Gutwein, Chezi Ganzel, Giorgos Karianakis, Jonathan Isenberg, Gabriela Gainaru, Theodora Triantafyllou, Efimia Vrakidou, Maria Palassopoulou, Mehmet Ozgur, Semra Paydas, Panagiotis Tsirigotis, Maria Tsirogianni, Tulin Tuglular, Chrysovalantou Chatzidimitriou, Maria Kotsopoulou, Evangelos Terpos, Panagiotis Zikos, Argyro Koumarianou, Christos Poziopoulos, Dimitrios Boutsis, Anat Gafter-Gvili, Themistoklis Karmiris, Maria K. Angelopoulou, Maria Bakiri Papaioannou, Gerassimos Pangalis, Panayiotis Panayiotidis, Burhan Ferhanoglu, Netanel A. Horowitz, and Sotirios Papageorgiou
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura: Real-World Multicenter Data on Re-Administration and Plasma Exchange Free Treatment
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Eleni Gavriilaki, Evdoxia Koravou, Sotiria Dimou-Mpesikli, Emmanouil Nikolousis, Anastasia Banti, Charalampos Pontikoglou, Christina Kalpadakis, Aikaterini Bitsani, Iliana Tassi, Tasoula Touloumenidou, Thomas Chatzikonstantinou, Maria Papathanassiou, Antonia Syrigou, Eleutheria Ztriva, Georgia Kaiafa, Eudokia Mandala, Zois Mellios, Dimitrios Karakasis, Alexandra Kourakli, Argyris Symeonidis, Eleni Kapsali, Eleni Papadaki, Chrysavgi Lalayanni, and Ioanna Sakellari
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
6. Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies
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Themis Karmiris, Zois Mellios, Maria Kotsopoulou, Konstantinos Anargyrou, George Karianakis, Eleftheria Hatzimichael, Gerassimos A. Pangalis, Phivi Rondogianni, Evangelos Terpos, Stamatios Karakatsanis, Argyris Symeonidis, Theodoros P. Vassilakopoulos, Eirini Katodritou, Pavlina Konstantinidou, Catherine Mainta, Pantelis Tsirkinidis, Sotirios G. Papageorgiou, Theoni Leonidopoulou, Panagiotis Tsirigotis, Ioannis Kotsianidis, Christina Kalpadakis, Ioannis Datseris, Evridiki Michali, Marie-Christine Kyrtsonis, Anna Pigaditou, Maria K. Angelopoulou, Eleni Variamis, Maria Dimou, Helen A. Papadaki, Meletios-Athanassios Dimopoulos, Maria Arapaki, Effimia Vrakidou, Gabriella Gainaru, Paraskevi Roussou, Vassiliki Pappa, Vassilios Prassopoulos, Christos Poziopoulos, Marina P. Siakantaris, Theodora Assimakopoulou, S. Chatziioannou, Elissavet Vervessou, Dimitrios Boutsis, Kostas Konstantopoulos, Evdoxia Chatziharissi, Maria Papaioannou, Maria Palassopoulou, Chryssa Vadikolia, Maria Tsirogianni, Panayiotis Panayiotidis, and Sotirios Sachanas
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PET-CT ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Mediastinum ,Retrospective cohort study ,Hematology ,General Medicine ,CHOP ,medicine.disease ,Lymphoma ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Positron emission tomography ,030220 oncology & carcinogenesis ,medicine ,Rituximab ,Radiology ,business ,030215 immunology ,medicine.drug - Abstract
End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.
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- 2021
7. Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies
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Theodoros P, Vassilakopoulos, Sotirios G, Papageorgiou, Maria K, Angelopoulou, Sophia, Chatziioannou, Vassilios, Prassopoulos, Stamatios, Karakatsanis, Maria, Arapaki, Zois, Mellios, Sotirios, Sachanas, Christina, Kalpadakis, Eirini, Katodritou, Theoni, Leonidopoulou, Ioannis, Kotsianidis, Eleftheria, Hatzimichael, Maria, Kotsopoulou, Maria, Dimou, Eleni, Variamis, Dimitrios, Boutsis, Evangelos, Terpos, Evridiki, Michali, George, Karianakis, Pantelis, Tsirkinidis, Chryssa, Vadikolia, Christos, Poziopoulos, Anna, Pigaditou, Effimia, Vrakidou, Marina P, Siakantaris, Marie-Christine, Kyrtsonis, Argyris, Symeonidis, Konstantinos, Anargyrou, Maria, Papaioannou, Evdoxia, Chatziharissi, Elissavet, Vervessou, Maria, Tsirogianni, Maria, Palassopoulou, Gabriella, Gainaru, Catherine, Mainta, Panagiotis, Tsirigotis, Theodora, Assimakopoulou, Pavlina, Konstantinidou, Helen, Papadaki, Meletios-Athanassios, Dimopoulos, Vassiliki, Pappa, Themis, Karmiris, Paraskevi, Roussou, Ioannis, Datseris, Panayiotis, Panayiotidis, Kostas, Konstantopoulos, Gerassimos A, Pangalis, and Phivi, Rondogianni
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Adult ,Male ,Adolescent ,Middle Aged ,Mediastinal Neoplasms ,Young Adult ,Treatment Outcome ,Doxorubicin ,Vincristine ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Prednisone ,Female ,Lymphoma, Large B-Cell, Diffuse ,Rituximab ,Cyclophosphamide ,Aged ,Retrospective Studies - Abstract
End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.
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- 2020
8. Viral Reactivation after T Cell Replete Haploidentical Stem Cell Transplantation: Increased Incidence in Association with Immune Reconstitution
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Maria Bouzani, Zois Mellios, Maria Katsareli, Tatiana Tzenou, Dimitris Karakasis, Dimitra Oikonomopoulou, Chara Giatra, Ioannis Baltadakis, Dimitra Gardeli, Stavros Gigantes, Ioannis Tsonis, Themistoklis Karmiris, Maria-Eleni Karatza, and Eirini Grispou
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Transplantation ,medicine.medical_specialty ,Cellular immunity ,Myeloid ,Cyclophosphamide ,business.industry ,Hematology ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,BK virus ,Letermovir ,medicine.anatomical_structure ,Internal medicine ,medicine ,Rituximab ,business ,Hemorrhagic cystitis ,medicine.drug - Abstract
Feasibility of haploidentical stem cell transplantation (haploSCT) is enhanced by use of post-transplant cyclophosphamide (PTCY). Despite preservation of non-alloreactive T cells, delayed reconstitution of cellular immunity and viral reactivation may compromise the outcome of T cell replete haploSCT. The study included 47 patients, aged 19-70 (median, 53) years, who underwent haploSCT with PTCY for myeloid (n=35) or lymphoid (n=12) malignancies. Myeloablative conditioning was mainly utilized (n=36). Graft source was peripheral blood (n=29) or bone marrow (n=18). Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood in cases with hemorrhagic cystitis (HC). Preemptive therapy was the principal modality for CMV infection in all but 1 patient who received letermovir prophylaxis. Reconstitution of cellular immunity was assessed by flow cytometry. With a median follow-up of 30 months, cumulative incidences (CIN) of relapse and non-relapse mortality were 13.4% (95% CI, 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free and overall survival were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34/45 patients at risk. Recurrent CMV infection occurred in 17/34 with median 1.5 (range, 1-6) episodes per patient. Median duration of anti-CMV therapy was 27 (range, 14-199) days. CMV disease was documented in 2 patients. CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 1 year, and preemptive therapy with rituximab was required in 2 patients. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%). CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy was required in 5/13 and nephrostomy in 1/13 patients. Reconstitution of T cell immunity was considerably delayed, with median CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was associated with the recovery of CD4+ cells at 3 months (Figure, median CD4+ count of 191/uL versus 62/uL in patients with 1 or ³2 episodes of CMV reactivation, respectively; p=0.009). Haplo-SCT with PTCY is associated with substantial rates of viral reactivation resulting in the need for prolonged antiviral therapy and considerable morbidity as well. Strategies to prevent viral infection are strongly warranted. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution.
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- 2020
9. Increased Incidence of Viral Reactivation after T Cell Replete Haploidentical Stem Cell Transplantation in Association with Delayed Immune Reconstitution
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Tatiana Tzenou, Maria Bouzani, Ioannis Tsonis, Chara Giatra, Ioannis Baltadakis, Stavros Gigantes, Eirini Grispou, Maria Katsareli, Kimon Fountoulis, Dimitra Oikonomopoulou, Georgia Tounta, Themistoklis Karmiris, Maria-Eleni Karatza, Dimitrios Karakasis, and Zois Mellios
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Foscarnet ,Cellular immunity ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Immunosuppression ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Gastroenterology ,Transplantation ,Letermovir ,Internal medicine ,medicine ,business ,Viral load ,Hemorrhagic cystitis ,medicine.drug - Abstract
Introduction: The preferred method for haploidentical stem cell transplantation (haploSCT) is currently the use of post-transplantation cyclophosphamide (PTCY) since it obviates the need for depletion of T lymphocytes, which is associated with profound immunosuppression. Despite preservation of non-alloreactive donor T cells, reconstitution of pathogen-specific immunity may be delayed even after T cell replete haploSCT. The incidence and clinical sequelae of viral reactivation may thus compromise the outcomes of the procedure. Patients and Methods: The study included 47 patients, who underwent haploSCT with PTCY from 12/2013 until 05/2019 and achieved stable donor engraftment. Median age at transplant was 53 years (range, 19-70). The indications for transplant were acute myeloid (n=19) or lymphoblastic (n=10) leukemia, myelodysplastic syndrome (n=10), myelofibrosis (n=4), chronic myeloid (n=2) or lymphocytic (n=1) leukemia, and T-prolymphocytic leukemia (n=1). Myeloablative conditioning was mainly utilized (n=36), with the exception of certain patients who received reduced-intensity (n=10) or non-myeloablative (n=1) regimens. The graft source was peripheral blood in 29 and bone marrow in 18 cases. Tacrolimus in combination with mycophenolate mofetil was administered for prevention of graft-versus-host disease. Recipient/donor cytomegalovirus (CMV) serostatus was -/- (n=2), -/+ (n= 5), +/- (n=11), or +/+ (n=29). CMV, Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months post haploSCT. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood specimens in cases with symptoms suggestive of hemorrhagic cystitis (HC). Prophylaxis with letermovir was available in 1 patient only, and preemptive antiviral therapy was the principal modality for the management of CMV infection. Cellular immunity reconstitution was assessed by flow cytometry at 3, 6, and 12 months after transplant. Results: With a median follow-up time of 30 months (range, 2-64), the cumulative incidences (CIN) of relapse and non-relapse mortality (NRM) were 13.4% (95% confidence interval [CI], 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free (DFS) and overall survival (OS) were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. The CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34 out of 45 patients who were at risk, whereas recurrent CMV reactivation was observed in 17 patients with a median number of 1.5 episodes (range, 1-6) per patient. The median total duration of antiviral therapy for CMV infection was 27 days (range, 14-199). CMV disease (pneumonia) was documented in 2 patients. The CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 12 months. No case of EBV-related post-transplant lymphoproliferative disorder was observed, however preemptive therapy with rituximab was required in 2 patients with rapidly increasing EBV viral load. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%), but only one required therapy with foscarnet due to high viral load (>10,000 copies/ml). The CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy for bladder hemostasis was required in 5/13 and nephrostomy in 1/11 patients with HC. Reconstitution of helper T cell immunity was considerably delayed, with median absolute CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was significantly associated with the recovery of CD4+ cells at 3 months (Figure; median CD4+ count of 191/uL versus 62/uL in patients with 1 and 2 or more episodes of CMV reactivation, respectively; p=0.009). Conclusions: HaploSCT with PTCY is associated with substantial rates of viral reactivation (especially CMV and BKV) resulting in the need for prolonged antiviral therapy and considerable morbidity. Strategies to prevent viral infection are strongly warranted in haploidentical stem cell transplantation. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution following haploSCT. Figure Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Gilead: Other: Travel Grant; Aenorasis: Other: Travel Grant; Takeda: Other: Travel Grant; Pfizer: Other: Travel Grant; Innovis: Other: Travel Grant.
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- 2019
10. Short-Term Exposure to Nickel Alters the Adult Rat Brain Antioxidant Status and the Activities of Crucial Membrane-Bound Enzymes: Neuroprotection by L-Cysteine
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Konstantinos Voumvourakis, Stylianos Tsakiris, Stamatios Theocharis, Zois Mellios, Nikolina Skandali, Elena Gkrouzman, Charis Liapi, Apostolos Zarros, Hussam Al-Humadi, and Foteini Anifantaki
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Male ,Antioxidant ,Aché ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmacology ,Biochemistry ,Neuroprotection ,Antioxidants ,Inorganic Chemistry ,chemistry.chemical_compound ,Nickel ,In vivo ,medicine ,Animals ,Cysteine ,Rats, Wistar ,Na+/K+-ATPase ,Ca(2+) Mg(2+)-ATPase ,Chemistry ,Biochemistry (medical) ,Brain ,General Medicine ,Acetylcholinesterase ,language.human_language ,Rats ,Neuroprotective Agents ,language ,Sodium-Potassium-Exchanging ATPase - Abstract
Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation) and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of short-term Ni-administration (as NiCl(2), 13 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase, and Mg(2+)-ATPase; in addition, the potential effect of the co-administration of the antioxidant L-cysteine (Cys, 7 mg/kg) on the above parameters was studied. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Ni), C (Cys), and D (Ni and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above-mentioned parameters were measured spectrophotometrically. Rats treated with Ni exhibited a significant reduction in brain TAS (-47%, p 0.001, BvsA) that was efficiently limited by the co-administration of Cys (-4%, p 0.05, DvsA; +83%, p 0.001, DvsB), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Ni (+30%, p 0.001, BvsA) and Cys (+62%, p 0.001, CvsA), while it tended to adjust to control levels by the co-administration of Ni and Cys (+13%, p 0.001, DvsA; -13%, p 0.001, DvsB). The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by Ni-administration (-49%, p 0.001, BvsA), while Cys supplementation could not reverse this decrease (-44%, p 0.001, DvsA). The activity of Mg(2+)-ATPase was not affected by Ni-administration (-3%, p 0.05, BvsA), but was significantly reduced when combined with Cys administration (-17%, p 0.001, DvsA). The above findings suggest that Ni short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed to control levels by Cys co-administration; Cys could thus be considered (for future applications) as a potential neuroprotective agent against chronic exposure to Ni. The activity of Na(+),K(+)-ATPase that was inhibited by Ni, could not be reversed by Cys co-administration. The matter requires further investigation in order to fully elucidate the spectrum of the neurotoxic effects of Ni.
- Published
- 2011
11. Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase: modulation by L-cysteine
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Apostolos Zarros, Stylianos Tsakiris, Hussam Al-Humadi, Elena Gkrouzman, Zois Mellios, Kyriakoula Marinou, Foteini Anifantaki, Charis Liapi, Panagiota Galanopoulou, and Nikolina Skandali
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Male ,medicine.medical_specialty ,Antioxidant ,Aché ,ATPase ,medicine.medical_treatment ,Biochemistry ,Antioxidants ,Statistics, Nonparametric ,Diabetes Mellitus, Experimental ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,In vivo ,Internal medicine ,medicine ,Animals ,Cysteine ,Rats, Wistar ,Na+/K+-ATPase ,Adenosine Triphosphatases ,Ca(2+) Mg(2+)-ATPase ,Analysis of Variance ,biology ,Brain Diseases, Metabolic ,Age Factors ,Brain ,Streptozotocin ,Acetylcholinesterase ,language.human_language ,Rats ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,biology.protein ,language ,Neurology (clinical) ,Sodium-Potassium-Exchanging ATPase ,medicine.drug - Abstract
Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L: -cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase. Thirty-eight male Wistar rats were divided into six groups: C(A) (8-week-control), C(B) (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), D(A) (8-week-diabetic), D(B) (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated). All diabetic rats were once treated with an intraperitoneal (i.p.) STZ injection (50 mg/kg body weight) at the beginning of the experiment, while all Cys-treated groups received i.p. injections of Cys 7 mg/kg body weight (daily, for 1-week, during the 9th-week). Whole rat brain parameters were measured spectrophotometrically. In vitro incubation with 0.83 mM of Cys or 10 mM of STZ for 3 h was performed on brain homogenate samples from groups C(B) and D(B), in order to study the enzymes' activities. Diabetic rats exhibited a statistically significant reduction in brain TAS (-28%, D(A) vs C(A);-30%, D(B) vs C(B)) that was reversed after 1-week-Cys-administration into basal levels. Diabetes caused a significant increase in AChE activity (+27%, D(A) vs C(A); +15%, D(B) vs C(B)), that was further enhanced by Cys-administration (+57%, D + Cys vs C(B)). The C + Cys group exhibited no significant difference compared to the C(B) group in TAS (+2%), but showed a significantly increased AChE activity (+66%, C + Cys vs C(B)). Diabetic rats exhibited a significant reduction in the activity of Na(+),K(+)-ATPase (-36%, D(A) vs C(A);-48%, D(B) vs C(B)) that was not reversed after 1-week Cys administration. However, in vitro incubation with Cys partially reversed the diabetes-induced Na(+),K(+)-ATPase inhibition. Mg(2+)-ATPase activity was not affected by STZ-induced diabetes, while Cys caused a significant inhibition of the enzyme, both in vivo (-14%, C + Cys vs C(B);-17%, D + Cys vs C(B)) and in vitro (-16%, D(B) + in vitro Cys vs C(B)). In vitro incubation with STZ had no effect on the studied enzymes. The present data revealed a protective role for Cys towards the oxidative effect of diabetes on the adult rat brain. Moreover, an increase in whole brain AChE activity due to diabetes was recorded (not repeatedly established in the literature, since contradictory findings exist), that was further increased by Cys. The inhibition of Na(+),K(+)-ATPase reflects a possible mechanism through which untreated diabetes could affect neuronal excitability, metabolic energy production and certain systems of neurotransmission. As concerns the use of Cys as a neuroprotective agent against diabetes, our in vitro findings could be indicative of a possible protective role of Cys under different in vivo experimental conditions.
- Published
- 2009
12. The neuroprotective role of l-cysteine towards the effects of short-term exposure to lanthanum on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase
- Author
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Stamatios Theocharis, Elena Gkrouzman, Zois Mellios, Apostolos Zarros, Stylianos Tsakiris, Hussam Al-Humadi, Nikolina Skandali, Charis Liapi, and Foteini Anifantaki
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Antioxidant ,Aché ,medicine.medical_treatment ,chemistry.chemical_element ,Neuroprotection ,Antioxidants ,General Biochemistry, Genetics and Molecular Biology ,Biomaterials ,chemistry.chemical_compound ,Lanthanum ,In vivo ,Internal medicine ,medicine ,Animals ,Cysteine ,Rats, Wistar ,chemistry.chemical_classification ,Metals and Alloys ,Brain ,Acetylcholinesterase ,language.human_language ,Rats ,Endocrinology ,Enzyme ,chemistry ,Biochemistry ,Spectrophotometry ,language ,Ca(2+) Mg(2+)-ATPase ,Sodium-Potassium-Exchanging ATPase ,General Agricultural and Biological Sciences ,Injections, Intraperitoneal - Abstract
Lanthanum (La) is a rare earth element that is widely used for industrial, medical and agricultural purposes. Its neurotoxic effects are linked to its physical and chemical properties and its interaction with certain trace elements and membrane-bound enzymes. The aim of this study was to investigate the effects of short-term La-administration (as LaCl(3), 53 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase, as well as the potential effect of the co-administration of the antioxidant L: -cysteine (Cys, 7 mg/kg) on the above parameters. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (La), C (Cys),and D (La and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above mentioned parameters were measured spectrophotometrically. Rats treated with La exhibited a significant reduction in brain TAS (-36%, P < 0.001, BvsA), that was partially limited by the co-administration of Cys (-13%, P < 0.01, DvsA), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both La (+23%, P < 0.001, BvsA) and Cys (+59%, P < 0.001, CvsA), while it was adjusted to control levels by the co-administration of La and Cys. The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by La-administration (-28%, P < 0.001, BvsA), while Cys supplementation could not reverse this decrease. The activity of Mg(2+)-ATPase exhibited a slight but statistically significant reduction due to La (-8%, P < 0.01, BvsA), that was further reduced by Cys co-administration (-25%, P < 0.001, DvsA). The above findings suggest that La short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed into control levels by Cys co-administration, which could thus be considered for future applications as a neuroprotective agent against chronic exposure to La. The activities of Na(+),K(+)- and Mg(2+)-ATPase that were inhibited by La, could not be reversed by Cys co-administration. A role for the already reported concentration-dependent interaction of La with Ca-binding sites (such as Ca(2+)-ATPase) might be considered for certain of the above phenomena.
- Published
- 2008
13. Effects of Short-Term Exposure to Manganese on the Adult Rat Brain Antioxidant Status and the Activities of Acetylcholinesterase, (Na+,K+)-ATPase and Mg2+-ATPase: Modulation by l-Cysteine
- Author
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Stylianos Tsakiris, Hussam Al-Humadi, Charis Liapi, Apostolos Zarros, Zois Mellios, Panagiota Galanopoulou, Nikolina Skandali, Foteini Anifantaki, Stamatios Theocharis, and Elena Gkrouzman
- Subjects
Pharmacology ,Ca(2+) Mg(2+)-ATPase ,medicine.medical_specialty ,Antioxidant ,biology ,Aché ,medicine.medical_treatment ,ATPase ,Biological activity ,General Medicine ,Toxicology ,medicine.disease ,Acetylcholinesterase ,language.human_language ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Biochemistry ,Internal medicine ,medicine ,language ,Manganism ,biology.protein ,Na+/K+-ATPase - Abstract
Manganese (Mn) is an essential metalloenzyme component that in high doses can exert serious oxidative and neurotoxic effects. The aim of this study was to investigate the potential effect of the antioxidant L-cysteine (Cys, 7 mg/kg) on the adult rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase induced by short-term Mn administration (as Mn chloride, 50 mg/kg). Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Mn), C (Cys) and D (Mn and Cys). All rats were treated once daily, for 1 week with intraperitoneal injections of the tested compounds. Rats were killed by decapitation and mentioned parameters were measured spectrophotometrically. Rats treated with Mn exhibited a significant reduction in brain TAS (-39%, P < 0.001, B versus A) that was partially reversed by Cys co-administration (-13%, P < 0.01, D versus A), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Mn (+21%, P < 0.001, B versus A) and Cys (+61%, P < 0.001, C versus A), while it was adjusted into the control levels by the co-administration of Mn and Cys. The activity of rat brain Na+,K+-ATPase was not affected by Mn administration, while Mg2+-ATPase exhibited a slight but statistically significant reduction in its activity (-9%, P < 0.01, B versus A) due to Mn, which was further reduced by Cys co-administration. The above findings suggest that short-term Mn in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed into the control levels by Cys co-administration (which could thus be considered for future applications as a neuroprotective agent against chronic exposure to Mn and the treatment of manganism). The activity of Na+,K+-ATPase is not affected by Mn, while Mg2+-ATPase activity is slightly (but significantly) inhibited by Mn, possibly due to Mg replacement.
- Published
- 2008
14. Effects of short-term exposure to manganese on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na,K)-ATPase and Mg-ATPase: modulation by L-cysteine
- Author
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Charis, Liapi, Apostolos, Zarros, Panagiota, Galanopoulou, Stamatios, Theocharis, Nikolina, Skandali, Hussam, Al-Humadi, Foteini, Anifantaki, Elena, Gkrouzman, Zois, Mellios, and Stylianos, Tsakiris
- Subjects
Male ,Time Factors ,Manganese Poisoning ,Brain ,Antioxidants ,Rats ,Chlorides ,Manganese Compounds ,Acetylcholinesterase ,Animals ,Ca(2+) Mg(2+)-ATPase ,Cysteine ,Rats, Wistar ,Sodium-Potassium-Exchanging ATPase - Abstract
Manganese (Mn) is an essential metalloenzyme component that in high doses can exert serious oxidative and neurotoxic effects. The aim of this study was to investigate the potential effect of the antioxidant L-cysteine (Cys, 7 mg/kg) on the adult rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase induced by short-term Mn administration (as Mn chloride, 50 mg/kg). Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Mn), C (Cys) and D (Mn and Cys). All rats were treated once daily, for 1 week with intraperitoneal injections of the tested compounds. Rats were killed by decapitation and mentioned parameters were measured spectrophotometrically. Rats treated with Mn exhibited a significant reduction in brain TAS (-39%, P0.001, B versus A) that was partially reversed by Cys co-administration (-13%, P0.01, D versus A), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Mn (+21%, P0.001, B versus A) and Cys (+61%, P0.001, C versus A), while it was adjusted into the control levels by the co-administration of Mn and Cys. The activity of rat brain Na+,K+-ATPase was not affected by Mn administration, while Mg2+-ATPase exhibited a slight but statistically significant reduction in its activity (-9%, P0.01, B versus A) due to Mn, which was further reduced by Cys co-administration. The above findings suggest that short-term Mn in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed into the control levels by Cys co-administration (which could thus be considered for future applications as a neuroprotective agent against chronic exposure to Mn and the treatment of manganism). The activity of Na+,K+-ATPase is not affected by Mn, while Mg2+-ATPase activity is slightly (but significantly) inhibited by Mn, possibly due to Mg replacement.
- Published
- 2008
15. Changes in the adult rat brain activities of Na+,K+-ATPase and Mg2+-ATPase due to 30-day dietary choline-deprivation and/or thioacetamide administration
- Author
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Charis Liapi, Vasileios Stolakis, Stylianos Tsakiris, Apostolos Zarros, Hussam Al-Humadi, Elena Gkrouzman, Nikolina Skandali, Zois Mellios, Foteini Anifantaki, and Panagiota Galanopoulou
- Subjects
chemistry.chemical_compound ,medicine.medical_specialty ,Endocrinology ,chemistry ,Mg2+-ATPase ,Internal medicine ,medicine ,Choline ,General Medicine ,Na+/K+-ATPase ,Thioacetamide ,Toxicology ,Rat brain - Published
- 2008
16. Effects of nickel on the adult rat brain antioxidant status and the activity of acetylcholinesterase: l-Cysteine as a modulator
- Author
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Nikolina Skandali, Charis Liapi, Stylianos Tsakiris, Hussam Al-Humadi, Apostolos Zarros, Stamatios Theocharis, Zois Mellios, Elena Gkrouzman, Foteini Anifantaki, and Panagiota Galanopoulou
- Subjects
chemistry.chemical_compound ,Nickel ,Antioxidant ,chemistry ,Biochemistry ,medicine.medical_treatment ,medicine ,chemistry.chemical_element ,General Medicine ,Toxicology ,Rat brain ,Acetylcholinesterase ,Cysteine - Published
- 2008
17. Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats.
- Author
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Charis Liapi, Hussam Al-Humadi, Panagiota Galanopoulou, Elena Gkrouzman, Zois Mellios, Nikolina Skandali, Foteini Anifantaki, and Stylianos Tsakiris
- Subjects
ACETAMIDE ,SERUM ,BRAIN ,ENZYME kinetics ,CHOLINE ,NERVOUS system ,ACETYLCHOLINESTERASE ,HEPATOTOXICOLOGY - Abstract
Abstract  Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na,K+ATPase and Mg2+ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD䰀). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (â11% vs Control, pâpâpâpâ,K+ATPase activity (% vs Control, pâ2+ATPase. Exposure to TAA had no significant effect on Na,K+ATPase, but inhibited Mg2+ATPase (â20% vs Control, pâ,K+ATPase activity (â41% vs Control, pâ2+ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na,K+ATPase, but caused a dramatic decrease in its activity (â41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na,K+ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission). [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
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18. Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase: modulation by <span style="font-variant:small-caps">L</span>-cysteine
- Author
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Charis Liapi, Panagiota Galanopoulou, Kyriakoula Marinou, Zois Mellios, Nikolina Skandali, Hussam Al-Humadi, Foteini Anifantaki, Elena Gkrouzman, and Stylianos Tsakiris
- Subjects
STREPTOZOTOCIN ,DIABETES ,ANTIOXIDANTS ,NERVOUS system - Abstract
Abstract Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L-cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg2+-ATPase. Thirty-eight male Wistar rats were divided into six groups: CA (8-week-control), CB (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), DA (8-week-diabetic), DB (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated). All diabetic rats were once treated with an intraperitoneal (i.p.) STZ injection (50 mg/kg body weight) at the beginning of the experiment, while all Cys-treated groups received i.p. injections of Cys 7 mg/kg body weight (daily, for 1-week, during the 9th-week). Whole rat brain parameters were measured spectrophotometrically. In vitro incubation with 0.83 mM of Cys or 10 mM of STZ for 3 h was performed on brain homogenate samples from groups CB and DB, in order to study the enzymes’ activities. Diabetic rats exhibited a statistically significant reduction in brain TAS (−28%, DA vs CA;−30%, DB vs CB) that was reversed after 1-week-Cys-administration into basal levels. Diabetes caused a significant increase in AChE activity (+27%, DA vs CA; +15%, DB vs CB), that was further enhanced by Cys-administration (+57%, D + Cys vs CB). The C + Cys group exhibited no significant difference compared to the CB group in TAS (+2%), but showed a significantly increased AChE activity (+66%, C + Cys vs CB). Diabetic rats exhibited a significant reduction in the activity of Na+,K+-ATPase (−36%, DA vs CA;−48%, DB vs CB) that was not reversed after 1-week Cys administration. However, in vitro incubation with Cys partially reversed the diabetes-induced Na+,K+-ATPase inhibition. Mg2+-ATPase activity was not affected by STZ-induced diabetes, while Cys caused a significant inhibition of the enzyme, both in vivo (−14%, C + Cys vs CB;−17%, D + Cys vs CB) and in vitro (−16%, DB + in vitro Cys vs CB). In vitro incubation with STZ had no effect on the studied enzymes. The present data revealed a protective role for Cys towards the oxidative effect of diabetes on the adult rat brain. Moreover, an increase in whole brain AChE activity due to diabetes was recorded (not repeatedly established in the literature, since contradictory findings exist), that was further increased by Cys. The inhibition of Na+,K+-ATPase reflects a possible mechanism through which untreated diabetes could affect neuronal excitability, metabolic energy production and certain systems of neurotransmission. As concerns the use of Cys as a neuroprotective agent against diabetes, our in vitro findings could be indicative of a possible protective role of Cys under different in vivo experimental conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2009
19. Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats
- Author
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Elena Gkrouzman, Stylianos Tsakiris, Apostolos Zarros, Foteini Anifantaki, Hussam Al-Humadi, Charis Liapi, Vasileios Stolakis, Nikolina Skandali, Zois Mellios, and Panagiota Galanopoulou
- Subjects
Male ,medicine.medical_specialty ,Antioxidant ,Aché ,medicine.medical_treatment ,Thioacetamide ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Internal medicine ,medicine ,Choline ,Animals ,Na+/K+-ATPase ,Rats, Wistar ,Ca(2+) Mg(2+)-ATPase ,Brain Chemistry ,Body Weight ,Brain ,Acetylcholinesterase ,language.human_language ,Choline Deficiency ,Rats ,Oxidative Stress ,Endocrinology ,chemistry ,language ,Carcinogens ,Neurology (clinical) ,Sodium-Potassium-Exchanging ATPase ,Oxidative stress - Abstract
Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (-11% vs Control, p < 0.01) and CD+TAA administration (-19% vs Control, p < 0.001), but was not significantly altered due to TAA administration. The rat brain AChE activity was found significantly increased by TAA administration (+11% vs Control, p < 0.01), as well as by CD+TAA administration (+14% vs Control, p < 0.01). However, AChE was not found to be significantly altered by the 30-day dietary CD. On the other hand, CD caused a significant increase in brain Na(+),K(+)-ATPase activity (+16% vs Control, p < 0.05) and had no significant effect on Mg(2+)-ATPase. Exposure to TAA had no significant effect on Na(+),K(+)-ATPase, but inhibited Mg(2+)-ATPase (-20% vs Control, p < 0.05). When administered to CD rats, TAA caused a significant decrease in Na(+),K(+)-ATPase activity (-41% vs Control, p < 0.001), but Mg(2+)-ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na(+),K(+)-ATPase, but caused a dramatic decrease in its activity (-41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na(+),K(+)-ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission).
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