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  1. Article ; Online: Zafirlukast protects against hepatic ischemia-reperfusion injury in rats via modulating Bcl-2/Bax and NF-κB/SMAD-4 pathways.

    Mahmoud, Heba M / Elsayed Abouzed, Deiaa E / Abo-Youssef, Amira M / Hemeida, Ramadan A M

    International immunopharmacology

    2023  Volume 122, Page(s) 110498

    Abstract: Hepatic ischemia/reperfusion injury (IRI) is a clinical problem commonly during liver transplantation and other liver surgery. This study aimed to evaluate the protective effect of zafirlukast (ZFK) on IR-induced hepatic injury and investigate its ... ...

    Abstract Hepatic ischemia/reperfusion injury (IRI) is a clinical problem commonly during liver transplantation and other liver surgery. This study aimed to evaluate the protective effect of zafirlukast (ZFK) on IR-induced hepatic injury and investigate its relevant protective mechanism. Thirty-two male Wistar albino rats were randomly allocated to four groups: sham, IRI, ZFK, and ZFK + IR groups. ZFK was administered orally in a dose of 80 mg/kg/day for 10 consecutive days. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) levels, and gamma glutamyl transferase (GGT) activity were estimated. Liver tissues were used to assess oxidative stress biomarkers including malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx), and reduced glutathione (GSH) contents. Inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-33 (IL-33), in addition to apoptosis biomarkers, BCL2 associated X protein (Bax), B-cell lymphoma 2 (Bcl2) and galactine-9 (GAL9) proteins were also assessed. Western blot analysis was performed for vascular endothelial growth factor (VEGF) and fibrinogen expressions. Immunohistochemical analysis for hepatic nuclear factor-kappa B (NF-κB) and SMAD-4 was done in addition to histopathological examination. Our study revealed that ZFK pre-treatment resulted in liver function restoration and oxidative stress correction. Moreover, inflammatory cytokines were significantly reduced and a remarkable reduction of apoptosis, angiogenesis, and clotting formation has been indicated. Additionally, a significant reduction in SMAD-4 and NF-kB protein expressions was observed. These results were supported by hepatic architecture improvement. Our findings revealed that ZFK possesses a potential protective effect against liver IR possibly through its antioxidant, anti-inflammatory and anti-apoptotic properties.
    MeSH term(s) Rats ; Male ; Animals ; NF-kappa B/metabolism ; bcl-2-Associated X Protein/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Rats, Wistar ; Liver/pathology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Cytokines/metabolism ; Oxidative Stress ; Tumor Necrosis Factor-alpha/metabolism ; Reperfusion Injury/drug therapy ; Reperfusion Injury/prevention & control ; Reperfusion Injury/metabolism ; Biomarkers
    Chemical Substances NF-kappa B ; bcl-2-Associated X Protein ; zafirlukast (XZ629S5L50) ; Vascular Endothelial Growth Factor A ; Proto-Oncogene Proteins c-bcl-2 ; Cytokines ; Tumor Necrosis Factor-alpha ; Biomarkers
    Language English
    Publishing date 2023-07-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2023.110498
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    Zs.A 5408: Show issues Location:
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  2. Article ; Online: The enteroprotective effect of nifuroxazide against methotrexate-induced intestinal injury involves co-activation of PPAR-γ, SIRT1, Nrf2, and suppression of NF-κB and JAK1/STAT3 signals.

    Abd-Alhameed, Esraa K / Azouz, Amany A / Abo-Youssef, Amira M / Ali, Fares E M

    International immunopharmacology

    2023  Volume 127, Page(s) 111298

    Abstract: Methotrexate (MTX) has long manifested therapeutic efficacy in several neoplastic and autoimmune disorders. However, MTX-associated intestinal toxicity restricts the continuation of treatment. Nifuroxazide (NIF) is an oral antibiotic approved for ... ...

    Abstract Methotrexate (MTX) has long manifested therapeutic efficacy in several neoplastic and autoimmune disorders. However, MTX-associated intestinal toxicity restricts the continuation of treatment. Nifuroxazide (NIF) is an oral antibiotic approved for gastrointestinal infections as an effective antidiarrheal agent with a high safety profile. The current study was designed to explore the potential efficacy of NIF in alleviating intestinal toxicity associated with MTX chemotherapy with the elucidation of the proposed molecular mechanisms. Rats were administered NIF (50 mg/kg; p.o.) for ten days. On day five, a single i.p. injection of MTX (20 mg/kg) was given to induce intestinal intoxication. At the end of the experiment, duodenal tissue samples were isolated for biochemical, Western blotting, immunohistochemical (IHC), and histopathological analysis via H&E, PSA, and Alcian blue stains. NIF showed antioxidant enteroprotective effects against MTX intestinal intoxication through enhanced expression of the redox-sensitive signals of PPAR-γ, SIRT1, and Nrf2 estimated by IHC. Moreover, NIF down-regulated the pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), NF-κB protein expression, and the phosphorylation of JAK1/STAT3 proteins, leading to mitigation of intestinal inflammation. In accordance, the histological investigation revealed that NIF ameliorated the intestinal pathological changes, preserved the goblet cells, and reduced the inflammatory cells infiltration. Therefore, NIF could be a promising candidate for adjunctive therapy with MTX to mitigate the associated intestinal injury and increase its tolerability.
    MeSH term(s) Rats ; Animals ; NF-kappa B/metabolism ; Methotrexate/toxicity ; NF-E2-Related Factor 2/metabolism ; PPAR gamma/metabolism ; Sirtuin 1/metabolism ; Antioxidants/pharmacology ; Oxidative Stress ; Nitrofurans ; Hydroxybenzoates
    Chemical Substances NF-kappa B ; Methotrexate (YL5FZ2Y5U1) ; NF-E2-Related Factor 2 ; nifuroxazide (PM5LI0P38J) ; PPAR gamma ; Sirtuin 1 (EC 3.5.1.-) ; Antioxidants ; Nitrofurans ; Hydroxybenzoates
    Language English
    Publishing date 2023-12-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2023.111298
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  3. Article ; Online: Corrigendum to "Group Differences in Facial Emotion Expression in Autism: Evidence for the Utility of Machine Classification" [Behav. Therapy 50(4) (2019) 828-838].

    Capriola-Hall, Nicole N / Wieckowski, Andrea Trubanova / Swain, Deanna / Aly, Sherin / Youssef, Amira / Abbott, A Lynn / White, Susan W

    Behavior therapy

    2024  Volume 55, Issue 2, Page(s) 430

    Language English
    Publishing date 2024-01-30
    Publishing country England
    Document type Published Erratum
    ZDB-ID 211996-1
    ISSN 1878-1888 ; 0005-7894
    ISSN (online) 1878-1888
    ISSN 0005-7894
    DOI 10.1016/j.beth.2024.01.003
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  4. Article ; Online: Corrigendum to "Feasibility of Automated Training for Facial Emotion Expression and Recognition in Autism" [Behav. Therapy 49(6) (2018) 881-888].

    White, Susan W / Abbott, Lynn / Wieckowski, Andrea Trubanova / Capriola-Hall, Nicole N / Aly, Sherin / Youssef, Amira

    Behavior therapy

    2024  Volume 55, Issue 2, Page(s) 429

    Language English
    Publishing date 2024-01-30
    Publishing country England
    Document type Published Erratum
    ZDB-ID 211996-1
    ISSN 1878-1888 ; 0005-7894
    ISSN (online) 1878-1888
    ISSN 0005-7894
    DOI 10.1016/j.beth.2024.01.002
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  5. Article ; Online: Predicting COVID-19 outcomes with the Edmonton Obesity Staging System.

    Ali, Sajjad / Khan, Omar Sufyan / Youssef, Amira M / Saba, Iram / Alqahtani, Leena / Alduhaim, Renad Abdulaziz / Almesned, Renad

    Annals of Saudi medicine

    2024  Volume 44, Issue 2, Page(s) 116–125

    Abstract: Background: Multiple studies have demonstrated a correlation between a high body mass index and discriminatory COVID-19 outcomes. Studies appear to indicate that there is a correlation between obesity-related comorbidities and less favorable outcomes.!## ...

    Abstract Background: Multiple studies have demonstrated a correlation between a high body mass index and discriminatory COVID-19 outcomes. Studies appear to indicate that there is a correlation between obesity-related comorbidities and less favorable outcomes.
    Objectives: The primary aim of the current investigation is to conduct a thorough assessment of the correlation between BMI and comorbidities associated with obesity, and their potential impact on the severity and consequences of COVID-19 infection among patients receiving care in a tertiary healthcare setting.
    Design: Retrospective cohort.
    Settings: Tertiary rehabilitation center, Riyadh, Saudi Arabia.
    Patients and methods: The study included all individuals who received medical treatment and tested positive for COVID-19 by means of RT-PCR during the period from March to September 2020. COVID-19 patients were classified using Edmonton Obesity Staging System (EOSS).
    Main outcome measures: COVID-19-related complications, including pneumonia and cytokine release syndrome, as well as the time length to COVID-19 negativization.
    Sample size: 315 patients.
    Results: The median (25th-75th percentiles) age of the patients was 38 (31.5-49) years old. Males outnumbered females, and 66% of patients were non-Saudis. Forty-eight patients (15.2%) had obesity class I, whereas 13 patients (4.1%) had class II. Thirty-two patients (10.2%) were classified as EOSS stage 1, 105 patients (33.3%) were classified as EOSS stage 2, and 25 patients (7.9%) were assigned to EOSS stage 3. Males predominated in EOSS stages 1 and 2, whereas females predominated in stage 3. In EOSS stage 3, 52% of cases had moderate severity and 48% had severe illness.
    Conclusions: EOSS distinguishes the COVID-19 risks of poor outcomes beyond BMI. Patients who were overweight or obese but remained in the stage 1 of the EOSS had a lower risk of a poor COVID-19 outome than normal-weight patients. The health status of obese patients is a more precise indicator of the progression of COVID-19 during hospitalization than BMI alone.
    Limitations: Given the limited capacity of urgent care facilities to conduct a comprehensive evaluation of comorbidities and other relevant outcomes in all patients, it is plausible that certain patients may have been erroneously classified with an EOSS stage 2 diagnosis, when in fact they ought to have been assigned a stage 3 diagnosis.
    MeSH term(s) Female ; Male ; Humans ; Adult ; Middle Aged ; COVID-19/diagnosis ; COVID-19/epidemiology ; Retrospective Studies ; Obesity/complications ; Obesity/epidemiology ; Overweight ; Body Mass Index
    Language English
    Publishing date 2024-04-04
    Publishing country Saudi Arabia
    Document type Journal Article
    ZDB-ID 639014-6
    ISSN 0975-4466 ; 0256-4947
    ISSN (online) 0975-4466
    ISSN 0256-4947
    DOI 10.5144/0256-4947.2024.116
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  6. Article ; Online: Protective effects of rivaroxaban against cisplatin-induced testicular damage in rats: Impact on oxidative stress, coagulation, and p–NF–κB/VCAM-1 signaling

    Shafiey, Sara I. / Abo-Saif, Ali A. / Abo-Youssef, Amira M. / Mohamed, Wafaa R.

    Food and Chemical Toxicology. 2022 Nov., v. 169 p.113419-

    2022  

    Abstract: Coagulation is a main pathway in various diseases pathogenesis including testicular damage. This study evaluated rivaroxaban (RVX) protective effects in testicular impairment by cisplatin (CP). Rats were randomly allocated into five groups: Control, RVX ( ...

    Abstract Coagulation is a main pathway in various diseases pathogenesis including testicular damage. This study evaluated rivaroxaban (RVX) protective effects in testicular impairment by cisplatin (CP). Rats were randomly allocated into five groups: Control, RVX (7 mg/kg/day), CP (10 mg/kg), RVX 5 mg + CP and RVX 7 mg + CP. Serum testosterone and testicular ALT, AST, and ALP were assessed. Testicular oxidative stress and antioxidant parameters and inflammatory indicators including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were assessed. qRT-PCR was used to determine mRNA expression of 3β-hydroxysteroid dehydrogenase (3β–HSD), 17β-hydroxysteroid dehydrogenase (17β–HSD), and steroidogenic acute regulatory protein (stAR). Protein expressions of p-Nuclear factor kappa B (p- NF-κB) and vascular cell adhesion protein-1 (VCAM-1) were analyzed by Western blot analysis. Tissue factor (TF) expression was immunohistochemically analyzed. Results revealed that RVX significantly increased serum testosterone and sperm count while significantly reduced IL-1β and TNF-α. It significantly decreased tissue MDA and NO contents while increased SOD and GPx. In addition, RVX attenuated CP-induced histopathological aberrations and normalized TF. It also decreased the VCAM-1 and p–NF–κB expression and showed strong expression of 3β-HSD, 17β-HSD, and stAR, indicating improvement of steroidogenesis. In conclusion, RVX counteracted testicular damage by CP via suppressing oxidative stress, inflammation, and coagulation and downregulating p–NF–κB/VCAM-1 signaling.
    Keywords 17-beta-hydroxysteroid dehydrogenase ; Western blotting ; antioxidants ; blood serum ; cell adhesion ; cisplatin ; coagulation ; gene expression ; histopathology ; immunohistochemistry ; inflammation ; necrosis ; neoplasms ; oxidative stress ; pathogenesis ; spermatozoa ; steroidogenesis ; steroidogenic acute regulatory protein ; testes ; testosterone ; toxicology ; vascular cell adhesion molecules ; Rivaroxaban ; Testicular damage
    Language English
    Dates of publication 2022-11
    Publishing place Elsevier Ltd
    Document type Article ; Online
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2022.113419
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  7. Article ; Online: Protective effect of rosiglitazone, quercetin, and their combination on fructose-induced metabolic syndrome in rats.

    Abo-Youssef, Amira M

    Indian journal of pharmacology

    2015  Volume 47, Issue 6, Page(s) 620–626

    Abstract: Objectives: Quercetin exhibits a wide range of biological functions. The present study aimed to investigate the possible beneficial effects of rosiglitazone, quercetin as well as their combination on metabolic and biochemical changes associated with the ...

    Abstract Objectives: Quercetin exhibits a wide range of biological functions. The present study aimed to investigate the possible beneficial effects of rosiglitazone, quercetin as well as their combination on metabolic and biochemical changes associated with the fructose-induced metabolic syndrome (MS).
    Materials and methods: Four groups of rats were fed on fructose-enriched diet for 14 weeks. One group served as fructose-enriched diet control, while the remaining groups were treated with rosiglitazone (4 mg/kg/day), quercetin (50 mg/kg/day), and their combination during the last 4 weeks. A fifth group was fed on normal laboratory diet. At the end of the experiment, blood samples were withdrawn for the estimation of markers of MS.
    Results: Rosiglitazone or quercetin attenuated the biochemical and metabolic changes associated with MS. The combination of rosiglitazone and quercetin nearly normalized these changes.
    Conclusion: Quercetin, as well as its combination with rosiglitazone, showed beneficial protective effects against metabolic and biochemical changes associated with MS.
    MeSH term(s) Animals ; Antioxidants/therapeutic use ; Body Weight/drug effects ; Dietary Carbohydrates/adverse effects ; Drug Therapy, Combination ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Fructose/adverse effects ; Hypoglycemic Agents/therapeutic use ; Insulin Resistance ; Liver/blood supply ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Male ; Metabolic Syndrome/drug therapy ; Metabolic Syndrome/etiology ; Metabolic Syndrome/metabolism ; Metabolic Syndrome/pathology ; Nitric Oxide Synthase Type II/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Oxidative Stress/drug effects ; Quercetin/therapeutic use ; Random Allocation ; Rats, Wistar ; Thiazolidinediones/therapeutic use ; Tumor Necrosis Factor-alpha/blood
    Chemical Substances Antioxidants ; Dietary Carbohydrates ; Hypoglycemic Agents ; Thiazolidinediones ; Tumor Necrosis Factor-alpha ; rosiglitazone (05V02F2KDG) ; Fructose (30237-26-4) ; Quercetin (9IKM0I5T1E) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Nos2 protein, rat (EC 1.14.13.39) ; Nos3 protein, rat (EC 1.14.13.39)
    Language English
    Publishing date 2015-11
    Publishing country India
    Document type Comparative Study ; Journal Article
    ZDB-ID 605829-2
    ISSN 1998-3751 ; 0253-7613
    ISSN (online) 1998-3751
    ISSN 0253-7613
    DOI 10.4103/0253-7613.169577
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    Zs.MO 311: Show issues

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  8. Article ; Online: lncRNA GAS5 and RUNX1 Genes in Children With Primary Immune Thrombocytopenia.

    Hodeib, Hossam / El Amrousy, Doaa / Elaskary, Eman / Hablas, Nahed / Youssef, Amira / Abdelhai, Dina

    Journal of pediatric hematology/oncology

    2022  Volume 45, Issue 3, Page(s) e395–e400

    Abstract: We aimed to evaluate the expression levels and the prognostic value of growth arrest specific 5 (GAS5) and runt-related transcription factor 1 (RUNX1) genes in children with ITP. This prospective cohort study included 100 patients with newly diagnosed ... ...

    Abstract We aimed to evaluate the expression levels and the prognostic value of growth arrest specific 5 (GAS5) and runt-related transcription factor 1 (RUNX1) genes in children with ITP. This prospective cohort study included 100 patients with newly diagnosed ITP (patient group) and 100 healthy children of matched age and sex (control group). We evaluated the expression levels of both GAS5 and RUNX1 genes at the time of diagnosis before the introduction of treatment. GAS5 was under-expressed, while RUNX1 was over-expressed among the newly diagnosed ITP children compared with the control group. Patients with GAS5 levels >0.50 had a significantly faster recovery compared with patients with levels≤0.50 while patients with levels of RUNX1≤2.6 had a significantly faster recovery compared with patients with levels >2.6. The best cut-off values of GAS5 and RUNX1 to predict complete recovery of ITP were ˃0.40 and ˂3.18, respectively, yielding a sensitivity of 76.47% and 79.41%, respectively. The best cut-off values of GAS5 and RUNX1 expression that predict chronic ITP were ˂0.17 and ˃4.1, respectively, yielding sensitivity of 88.89% and 77.78%, respectively. GAS5 and RUNX1 could be useful markers in children with primary ITP to predict disease course.
    MeSH term(s) Humans ; Child ; Purpura, Thrombocytopenic, Idiopathic/genetics ; Purpura, Thrombocytopenic, Idiopathic/diagnosis ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Core Binding Factor Alpha 2 Subunit/genetics ; Prospective Studies ; Prognosis
    Chemical Substances RNA, Long Noncoding ; Core Binding Factor Alpha 2 Subunit ; RUNX1 protein, human
    Language English
    Publishing date 2022-10-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1231152-2
    ISSN 1536-3678 ; 1077-4114 ; 0192-8562
    ISSN (online) 1536-3678
    ISSN 1077-4114 ; 0192-8562
    DOI 10.1097/MPH.0000000000002580
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    Zs.A 1537: Show issues Location:
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  9. Article ; Online: Protective effects of rivaroxaban against cisplatin-induced testicular damage in rats: Impact on oxidative stress, coagulation, and p-NF-κB/VCAM-1 signaling.

    Shafiey, Sara I / Abo-Saif, Ali A / Abo-Youssef, Amira M / Mohamed, Wafaa R

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

    2022  Volume 169, Page(s) 113419

    Abstract: Coagulation is a main pathway in various diseases pathogenesis including testicular damage. This study evaluated rivaroxaban (RVX) protective effects in testicular impairment by cisplatin (CP). Rats were randomly allocated into five groups: Control, RVX ( ...

    Abstract Coagulation is a main pathway in various diseases pathogenesis including testicular damage. This study evaluated rivaroxaban (RVX) protective effects in testicular impairment by cisplatin (CP). Rats were randomly allocated into five groups: Control, RVX (7 mg/kg/day), CP (10 mg/kg), RVX 5 mg + CP and RVX 7 mg + CP. Serum testosterone and testicular ALT, AST, and ALP were assessed. Testicular oxidative stress and antioxidant parameters and inflammatory indicators including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were assessed. qRT-PCR was used to determine mRNA expression of 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and steroidogenic acute regulatory protein (stAR). Protein expressions of p-Nuclear factor kappa B (p- NF-κB) and vascular cell adhesion protein-1 (VCAM-1) were analyzed by Western blot analysis. Tissue factor (TF) expression was immunohistochemically analyzed. Results revealed that RVX significantly increased serum testosterone and sperm count while significantly reduced IL-1β and TNF-α. It significantly decreased tissue MDA and NO contents while increased SOD and GPx. In addition, RVX attenuated CP-induced histopathological aberrations and normalized TF. It also decreased the VCAM-1 and p-NF-κB expression and showed strong expression of 3β-HSD, 17β-HSD, and stAR, indicating improvement of steroidogenesis. In conclusion, RVX counteracted testicular damage by CP via suppressing oxidative stress, inflammation, and coagulation and downregulating p-NF-κB/VCAM-1 signaling.
    MeSH term(s) Animals ; Male ; Rats ; Cisplatin/toxicity ; Interleukin-1beta/metabolism ; NF-kappa B/metabolism ; Oxidative Stress/drug effects ; Rivaroxaban/pharmacology ; Rivaroxaban/therapeutic use ; RNA, Messenger/metabolism ; Semen/metabolism ; Superoxide Dismutase/metabolism ; Testis/drug effects ; Testosterone/metabolism ; Thromboplastin/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Cell Adhesion Molecule-1/metabolism ; Testicular Diseases/chemically induced ; Testicular Diseases/prevention & control ; Antineoplastic Agents/toxicity ; Blood Coagulation/drug effects
    Chemical Substances Cisplatin (Q20Q21Q62J) ; Interleukin-1beta ; NF-kappa B ; Rivaroxaban (9NDF7JZ4M3) ; RNA, Messenger ; Superoxide Dismutase (EC 1.15.1.1) ; Testosterone (3XMK78S47O) ; Thromboplastin (9035-58-9) ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1 ; Antineoplastic Agents
    Language English
    Publishing date 2022-09-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2022.113419
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  10. Article ; Online: BAFF rs9514828 gene polymorphism and the risk of the development of inhibitors in children with severe haemophilia A.

    Hodeib, Hossam / El Amrousy, Doaa / Youssef, Amira / Elaskary, Eman / Fouda, Mohamed H

    Haemophilia : the official journal of the World Federation of Hemophilia

    2022  Volume 28, Issue 3, Page(s) 472–479

    Abstract: Introduction: Haemophilia A (HA) is an x-linked recessive disease due to deficiency of coagulation factor VIII (FVIII). The development of neutralizing antibodies (inhibitors) against infused FVIII is a major concern. B cell activating factor (BAFF) has ...

    Abstract Introduction: Haemophilia A (HA) is an x-linked recessive disease due to deficiency of coagulation factor VIII (FVIII). The development of neutralizing antibodies (inhibitors) against infused FVIII is a major concern. B cell activating factor (BAFF) has been implicated in several autoimmune diseases.
    Aim: We aimed to evaluate the possible association of BAFF rs9514828 gene polymorphism and the risk of the development of FVIII inhibitor in children with severe HA.
    Methods: This cohort study was carried out on 100 newly diagnosed boys with severe HA who were never treated before with FVIII concentrate. Assessment of serum levels of BAFF and BAFF rs9514828 genotyping at first diagnosis was performed and the patients were followed up for the completion of a total of 50 exposure days or the development of inhibitors whichever occurred first. The patients were divided as positive or negative according to the presence or absence of inhibitors.
    Results: The risk allele for BAFF rs9514828 (T) was significantly more frequent in the inhibitor positive patients than the inhibitor negative patients (P = .003). In addition, CT+TT genotypes were associated with increased risk of FVIII inhibitor development. Receiver operating characteristics (ROC) analysis showed that BAFF levels could predict the development of FVIII inhibitors at a cut-off value of ≥ .92 with a sensitivity of 85.9% and a specificity of 80.2%.
    Conclusion: BAFF rs9514828 gene polymorphism could be independent risk factor and elevated BAFF levels might be useful prognostic marker for the development of FVIII inhibitor in newly diagnosed children with severe HA.
    MeSH term(s) Alleles ; B-Cell Activating Factor/genetics ; Child ; Cohort Studies ; Factor VIII/antagonists & inhibitors ; Factor VIII/genetics ; Hemophilia A/drug therapy ; Hemophilia A/genetics ; Hemostatics ; Humans ; Male ; Polymorphism, Single Nucleotide
    Chemical Substances B-Cell Activating Factor ; Hemostatics ; TNFSF13B protein, human ; Factor VIII (9001-27-8)
    Language English
    Publishing date 2022-03-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 1229713-6
    ISSN 1365-2516 ; 1351-8216 ; 1355-0691
    ISSN (online) 1365-2516
    ISSN 1351-8216 ; 1355-0691
    DOI 10.1111/hae.14555
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