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BMJ Neurology Open 2021[This corrects the article DOI: 10.1136/bmjno-2020-000096.].
[This corrects the article DOI: 10.1136/bmjno-2020-000096.].
PubMed: 34396130
DOI: 10.1136/bmjno-2020-000096corr1 -
Scientific Reports Sep 2019Emergence of new molecules acting directly on the hepatitic C virus (HCV) has improved treatment outcomes. However, there is a risk of selecting viral escape mutants, so... (Comparative Study)
Comparative Study
Addition of Epigallocatechin Gallate 400 mg to Sofosbuvir 400 mg + Daclatisvir 60 mg With or Without Ribavirin in Treatment of Patients with Chronic Hepatitis C Improves the Safety Profile: A Pilot Study.
Emergence of new molecules acting directly on the hepatitic C virus (HCV) has improved treatment outcomes. However, there is a risk of selecting viral escape mutants, so a new combination is needed using different inhibitors that target different steps of the HCV infectious cycle. Novel single tablet formulations were developed: Dactavira, composed of sofosbuvir (SOF) 400 mg/daclatisvir (DCV) 60 mg/epigallocatechin gallate (EGCG) 400 mg without ribavirin (RBV); and Dactavira plus, which includes RBV 800 mg. A randomized, open-label study was carried out on treatment-naïve non-cirrhotic (Group A, n = 50) and treatment-naïve cirrhotic (Group B, n = 22) patients with genotype 4 HCV infection. Group A was randomly assigned to receive a single daily fixed-dose (Dactavira, n = 25) or the standard of care [SOF 400 mg/DCV 60 mg] (n = 25) daily for 12 weeks. Group B was randomly assigned to receive a single daily fixed-dose (Dactavira plus, n = 11) or the standard of care + RBV 800 mg (n = 11) daily for 12 weeks. Patients receiving Dactavira or Dactavira plus had a significantly more rapid rate of viral load decline as compared to patients receiving the standard of care therapy. Sustained virological response for 12 weeks for Dactavira or Dactavira plus showed no statistically significant difference when compared to the standard of care. Also, they did not affect normal hemoglobin levels (p < 0.001) versus the standard of care. The incorporated EGCG interferes with the viral entry mechanisms, as reported by several investigators, and in turn enhances efficacy and prevents relapse as compared to the standard of care. Also, its antihemeolytic and antifibrotic activities may improve the safety and tolerability of the therapy.
Topics: Adult; Catechin; Daclizumab; Drug Administration Schedule; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Male; Middle Aged; Pilot Projects; Random Allocation; Ribavirin; Sofosbuvir; Standard of Care; Sustained Virologic Response; Tablets; Treatment Outcome; Viral Load
PubMed: 31537880
DOI: 10.1038/s41598-019-49973-6 -
Fluids and Barriers of the CNS Feb 2020The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this...
BACKGROUND
The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood-brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP).
OBJECTIVE
Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4 T-cell subsets across the BBB versus the BCSFB.
METHODS
Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4 T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro.
RESULTS
While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration.
CONCLUSIONS
Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.
Topics: Biological Transport; Blood-Brain Barrier; CD4-Positive T-Lymphocytes; Cell Movement; Central Nervous System; Choroid Plexus; Endothelial Cells; Epithelial Cells; Humans; T-Lymphocyte Subsets
PubMed: 32008573
DOI: 10.1186/s12987-019-0165-2