8 research outputs found
Long-term effect of latanoprost/timolol fixed combination in patients with glaucoma or ocular hypertension: A prospective, observational, noninterventional study
Background: Prospective, observational studies that enroll large numbers of patients with few exclusion criteria may better reflect actual ongoing clinical experience than randomized clinical trials. Our purpose was to obtain efficacy and safety information from a cohort of subjects exposed to latanoprost/timolol fixed combination (FC) for [greater than or equal to]18 months using a prospective, observational design. Methods: In all, 577 office-based ophthalmologists in Germany switched 2339 patients with glaucoma or ocular hypertension to latanoprost/timolol FC for medical reasons. Follow-up visits were scheduled for every 6 months over 24 months; physicians followed usual care routines. Intraocular pressure (IOP), visual field status, optic nerve head findings, and adverse events were recorded. Efficacy parameters were evaluated for the per protocol (PP) population; the safety population included subjects receiving [greater than or equal to]1 drop of FC. Physicians rated efficacy, tolerability, and subject compliance at month 24. Results: Of the 2339 subjects switched to latanoprost/timolol FC (safety population), the primary reasons for switching were inadequate IOP reduction (78.2%) and desire to simplify treatment with once-daily dosing (29.4%; multiple reasons possible). In all, 1317 (56.3%) subjects completed the study, and 1028 (44.0%) were included in the PP population. Most discontinuations were due to loss to follow-up. Change in mean IOP from baseline to month 6 was -4.0 +/- 4.31 mmHg, a reduction that was maintained throughout (P<0.05 for change at all time points). By investigator assessments, optic disc parameters and visual field were stable over 24 months, and there was no relationship between IOP reduction over 24 months and development of a visual field defect. More than 90% of physicians rated latanoprost/timolol FC as "very good" or "good" for efficacy (PP population), tolerability, and compliance. The FC was safe and well tolerated. No change in iris color was reported by most subjects (83.1%) at month 24. Conclusions: Over 24 months, latanoprost/timolol FC effectively lowers IOP levels and is well tolerated in patients with glaucoma or ocular hypertension who change from their previous ocular hypotensive therapy for medical reasons. Investigator assessments found optic disc parameters and visual field to be stable throughout 24 months of follow-up
Modulation of the intestinal barrier - signaling pathways and mechanisms of Escherichia coli Nissle 1917 and enteral nutrition
Einleitung: Bei chronisch entzĂĽndlichen Darmerkrankungen kommt es zu einer
Störung der intestinalen Barrierefunktion. Ihre Rekonstitution ist essentiell
zur Wiederherstellung der mukosalen und peripheren Immunhomöostase. Das Ziel
der vorliegenden Arbeit war es, die Modulation der intestinalen Barriere durch
das Probiotikum E. coli Nissle 1917 und enterale Ernährung zu
charakterisieren. Methode: Im experimentellen DSS-Kolitis Modell der Maus
wurden Wildtyp sowie TLR-2-/- und TLR-4-/- Mäuse mit E. coli Nissle 1917
rektal oder oral behandelt. Die makroskopische Krankheitsaktivität, die
Schädigung der Mukosa und die Zytokinsekretion der Mäuse wurden analysiert. Um
den Einfluss des Probiotikums auf humane T-Zellsubklassen zu untersuchen,
wurden isolierte αβ und γδ T-Zellen stimuliert und mit E. coli Nissle 1917
konditioniertem Medium kultiviert. Die Aktivität, Zellzyklusprogression,
Apoptose, Nekrose und Zytokinsekretion der Zellen wurde durchflusszytometrisch
analysiert. Der Einfluss von enteraler und parenteraler Ernährung auf die
Integrität intestinaler Epithelzellen wurde anhand des transepithelialen
Widerstands und eines etablierten Wundheilungsmodells bestimmt.
Durchflusszytometrisch wurde zudem die Modulation der Apoptose,
Zellaktivierung, Zellzyklusprogression und Zytokinsekretion isolierter und
stimulierter peripherer mononukleärer Blutzellen (PBMC) und Lamina propria
mononukleärer Zellen (LPMC) untersucht. Ergebnisse: TLR-4-/- Mäuse
entwickelten eine signifikant schwächere Entzündung. In Wildtyp Mäusen
milderte E. coli Nissle die Entzündung und erhöhte die Sekretion
antiinflammatorischer Zytokine. In γδ T-Zellen, aber nicht in αβ T-Zellen,
erhöhte E. coli konditioniertes Medium die Aktivität und Zellzykluspogression
und induzierte die Apoptose via TLR-2 über Caspase und FasL abhängige
Signalwege. Durch die Inkubation mit enteraler und parenteraler Ernährung
wurde die Integrität und Migration intestinaler Epithelzellen gefördert. Bei
den Epithelzellen wurde die Apoptose durch parenterale Ernährung, bei den LPMC
und PBMC durch enterale Ernährung induziert. Die Zytokinsekretion wurde bei
den untersuchten Zellen sehr distinkt moduliert. Diskussion: E. coli Nissle
1917 mildert die DSS-Kolitis über TLR-2 und TLR-4 abhängige Signalwege. In
vitro induziert das Probiotikum die Apoptose von γδ T-Zellen, die eine
wichtige Rolle in der bakteriellen Antigenerkennung und Perturbation
inflammatorischer Prozesse spielen. Enterale und parenterale Ernährung fördert
die Integrität intestinaler Epithelzellen und moduliert distinkt das periphere
und intestinale Immunsystem.Introduction: Inflammatory bowel disease is characterized by a disrupted
intestinal barrier function. Its reconstitution is essential to maintain
mucosal and peripheral immune homeostasis. The aim of this study was to
investigate the effect of probiotic E. coli Nissle 1917 and enteral nutrition
on the intestinal barrier function. Methods: Dextran sodium sulfate
(DSS)-induced experimental colitis was treated with E. coli Nissle 1917 orally
and rectally in wild-typ and TLR-2-/- and TLR-4-/- mice. Disease activity,
mucosal damage and cytokine secretion were analysed. To determine the
influence of E. coli Nissle 1917 on T cell subsets we cultured isolated and
stimulated αβ and γδ T cells with E. coli conditioned media. Activation
status, cell cycle progression, apoptosis and necrosis and cytokine secretion
was determined by flow cytometric analysis. Furthermore we investigated the
effect of enteral and parenteral nutrition on epithelial cell integrity by the
measurement of the transepithelial resistence (TER) and an established wound
healing assay. Flow cytometric analysis was used to determine the influence of
enteral and parenteral nutrition on apoptosis, activation status, cell cycle
progression and cytokine secretion of isolated and stimulated peripheral blood
mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC). Results:
TLR-4-/- mice developed significantly less inflammation. In wild-typ mice E.
coli Nissle ameliorated colitis and increased anti-inflammatory cytokine
response. E. coli Nissle conditioned media increased the activation status and
cell cycle progression of γδ T cells but not of αβ T cells. Apoptosis of γδ T
cells was induced via TLR-2 by caspase and FasL dependent pathways. Culturing
epithelial cells with enteral and parenteral nutrition promoted monolayer
integrity and migration. Apoptosis of epithelial cells was induced by
parenteral nutrition in PBMC and by enteral nutrition in LPMC. Modulation of
cytokine secretion was distinct in different cell types. Conclusion: E.c oli
Nissle 1917 ameliorates DSS induced colitis in mice via TLR-2 and TLR-4
dependent pathways. Apoptosis of γδ T cells, which play an important role in
the recognition of bacterial antigens and perturbation of inflammatory
processes, is induced by E. coli Nissle 1917 in-vitro. Parenteral and enteral
nutrition promotes the integrity of epithelial cells and distinctivly
modulates peripheral and intestinal immunity