103 research outputs found
The multifaceted role of serotonin in intestinal homeostasis
The monoamine serotonin, 5-hydroxytryptamine (5-HT), is a remarkable molecule with conserved production in prokaryotes and eukaryotes and a wide range of functions. In the gastrointestinal tract, enterochromaffin cells are the most important source for 5-HT production. Some intestinal bacterial species are also able to produce 5-HT. Besides its role as a neurotransmitter, 5-HT acts on immune cells to regulate their activation. Several lines of evidence indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. In this review, we discuss the current knowledge on the production, secretion, and signaling of 5-HT in the intestine. We present an inventory of intestinal immune and epithelial cells that respond to 5-HT and describe the effects of these signaling processes on intestinal homeostasis. Further, we detail the mechanisms by which 5-HT could affect inflammatory bowel disease course and describe the effects of interventions that target intestinal 5-HT signaling
Topotecan lacks third space sequestration
The objective of this study was to determine the influence of pleural and
ascitic fluid on the pharmacokinetics of the antitumor camptothecin
derivative topotecan. Four patients with histological proof of malignant
solid tumor received topotecan (0.45 or 1.5 mg/m2) p.o. on several
occasions in both the presence and absence of third space volumes. Serial
plasma and pleural or ascitic fluid samples were collected during each
dosing and analyzed by high-performance liquid chromatography for both the
intact lactone form of topotecan and its ring-opened carboxylate form. The
apparent topotecan clearance demonstrated substantial interpatient
variability but remained unchanged within the same patient in the presence
[110 +/- 55.6 liters/ h/m2 (mean +/- SD of eight courses)] or absence of
pleural and ascitic fluid [118 +/- 31.1 liters/h/m2 (mean +/- SD of seven
courses)]. Similarly, terminal half-lives and area under the
concentration-time curve ratios of lactone:total drug in plasma were
similar between courses within each patient. Topotecan penetration into
pleural and ascitic fluid demonstrated a mean lag time of 1.61 h (range,
1.37-1.86 h), and ratios with plasma concentration increased with time
after dosing in all patients. The mean ratio of third space topotecan
total drug area under the concentration-time curve to that in plasma was
0.55 (range, 0.26-0.87). These data indicate that topotecan can be safely
administered to patients with pleural effusions or ascites and that there
is substantial penetration of topotecan into these third spaces, which may
prove beneficial for local antitumor effects
Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130)
Inter- and intrapatient variability in oral topotecan pharmacokinetics: implications for body-surface area dosage regimens
Anticancer drugs still are dosed based on the body-surface area (BSA) of
the individual patient, although the BSA is not the main predictor of the
clearance for the majority of drugs. The relevance of BSA-based dosing has
not been evaluated for topotecan yet. A retrospective pharmacological
analysis was performed of kinetic data from four clinical Phase I studies
in which topotecan was administered p.o. as a single agent combined with
data from a combination study of topotecan and cisplatin. A strong
correlation (r = 0.91) was found between the area under the plasma
concentration time curve of the lactone and carboxylate forms of topotecan
by plotting 326 data sets obtained from 112 patients receiving oral
topotecan at dose levels ranging from 0.15-2.70 mg/m2. The intrapatient
variability, studied in 47 patients sampled for 3 or more days, for the
apparent lactone clearance, ranged from 7.4-69% (mean, 24 +/- 13%; median,
20%). The interpatient variabilities in the lactone clearance, calculated
with the data of all studied patients, expressed in liter/h/m2 and in
liter/h were 38% and 42%, respectively. In view of the relatively high
inter- and intrapatient variabilities in topotecan clearance, in contrast
to a variability of only 12% in the BSA of the studied patients, no
advantage of BSA-based dosing was found over fixed dose regimens
Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130)
Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice
Reproducibility of the Pleth Variability Index in premature infants
The aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm neonates in the first 48 h of life. On each occasion, pulse oximeter sensors were attached to two different limbs for 5 min. Reproducibility was assessed with the intra-class correlation coefficient (ICC) and Bland–Altman analysis. A total of 25 preterm neonates were included. Inter-limb comparison showed fair to moderate ICC’s with 95%-confidence intervals (95%-CI). Left hand–right hand ICC = 0.498, 95%-CI (0.119–0.753); right foot–right hand ICC = 0.314 (−0.088–0.644); right foot–left foot ICC = 0.315 (−0.089–0.628). Intra-limb comparison showed fair to moderate ICC for right foot–right foot ICC = 0.380 (−0.014–0.677); and good ICC for right hand–right hand ICC = 0.646 (0.194–0.852). Bland–Altman plots showed moderate reproducibility of measurements between different limbs and of the same limb in consecutive time periods, with large biases and wide limits of agreement. The findings from this study indicate that PVI measurement is poorly reproducible when measured on different limbs and on the same limb in stable and comfortable preterm neonates
- …