97 research outputs found
Cerebrospinal fluid sodium rhythms
Background: Cerebrospinal fluid (CSF) sodium levels have been reported to rise during episodic migraine. Since
migraine frequently starts in early morning or late afternoon, we hypothesized that natural sodium chronobiology
may predispose susceptible persons when extracellular CSF sodium increases. Since no mammalian brain sodium
rhythms are known, we designed a study of healthy humans to test if cation rhythms exist in CSF.
Methods: Lumbar CSF was collected every ten minutes at 0.1 mL/min for 24 h from six healthy participants. CSF
sodium and potassium concentrations were measured by ion chromatography, total protein by fluorescent
spectrometry, and osmolarity by freezing point depression. We analyzed cation and protein distributions over the
24 h period and spectral and permutation tests to identify significant rhythms. We applied the False Discovery Rate
method to adjust significance levels for multiple tests and Spearman correlations to compare sodium fluctuations
with potassium, protein, and osmolarity.
Results: The distribution of sodium varied much more than potassium, and there were statistically significant
rhythms at 12 and 1.65 h periods. Curve fitting to the average time course of the mean sodium of all six subjects
revealed the lowest sodium levels at 03.20 h and highest at 08.00 h, a second nadir at 09.50 h and a second peak
at 18.10 h. Sodium levels were not correlated with potassium or protein concentration, or with osmolarity.
Conclusion: These CSF rhythms are the first reports of sodium chronobiology in the human nervous system. The
results are consistent with our hypothesis that rising levels of extracellular sodium may contribute to the timing of
migraine onset. The physiological importance of sodium in the nervous system suggests that these rhythms may
have additional repercussions on ultradian functions
Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions
Efflux Protein Expression in Human Stem Cell-Derived Retinal Pigment Epithelial Cells
Retinal pigment epithelial (RPE) cells in the back of the eye nourish photoreceptor cells and form a selective barrier that influences drug transport from the blood to the photoreceptor cells. At the molecular level, ATP-dependent efflux transporters have a major role in drug delivery in human RPE. In this study, we assessed the relative expression of several ATP-dependent efflux transporter genes (MRP1, -2, -3, -4, -5, -6, p-gp, and BCRP), the protein expression and localization of MRP1, MRP4, and MRP5, and the functionality of MRP1 efflux pumps at different maturation stages of undifferentiated human embryonic stem cells (hESC) and RPE derived from the hESC (hESC-RPE). Our findings revealed that the gene expression of ATP-dependent efflux transporters MRP1, -3, -4, -5, and p-gp fluctuated during hESC-RPE maturation from undifferentiated hESC to fusiform, epithelioid, and finally to cobblestone hESC-RPE. Epithelioid hESC-RPE had the highest expression of MRP1, -3, -4, and P-gp, whereas the most mature cobblestone hESC-RPE had the highest expression of MRP5 and MRP6. These findings indicate that a similar efflux protein profile is shared between hESC-RPE and the human RPE cell line, ARPE-19, and suggest that hESC-RPE cells are suitable in vitro RPE models for drug transport studies. Embryonic stem cell model might provide a novel tool to study retinal cell differentiation, mechanisms of RPE -derived diseases, drug testing and targeted drug therapy
Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model
Simulating Intravitreal Injections in Anatomically Accurate Models for Rabbit, Monkey, and Human Eyes
Ion transporters in brain endothelial cells that contribute to formation of brain interstitial fluid
Enhanced renal prostaglandin production in the dog. The effect of sodium arachidonate in nonfiltering kidney.
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