Microtubules Regulate Local Ca2+ Spiking in Secretory Epithelial Cells

The role of the cytoskeleton in regulating Ca2+ release has been explored in epithelial cells. Trains of local Ca2+ spikes were elicited in pancreatic acinar cells by infusion of inositol trisphosphate through a whole cell patch pipette, and the Ca2+-dependent Cl- current spikes were recorded. The spikes were only transiently inhibited by cytochalasin B, an agent that acts on microfilaments. In contrast, nocodazole (5-100 µM), an agent that disrupts the microtubular network, dose-dependently reduced spike frequency and decreased spike amplitude leading to total blockade of the response. Consistent with an effect of microtubular disruption, colchicine also inhibited spiking but neither Me2SO nor beta -lumicolchicine, an inactive analogue of colchicine, had any effect. The microtubule-stabilizing agent, taxol, also inhibited spiking. The nocodazole effects were not due to complete loss of function of the Ca2+ signaling apparatus, because supramaximal carbachol concentrations were still able to mobilize a Ca2+ response. Finally, as visualized by 2-photon excitation microscopy of ER-Tracker, nocodazole promoted a loss of the endoplasmic reticulum in the secretory pole region. We conclude that microtubules specifically maintain localized Ca2+ spikes at least in part because of the local positioning of the endoplasmic reticulum

Microscopic structure of the polymer-induced liquid precursor for calcium carbonate

Many biomineral crystals form complex non-equilibrium shapes, often via transient amorphous precursors. Also in vitro crystals can be grown with non-equilibrium morphologies, such as thin films or nanorods. In many cases this involves charged polymeric additives that form a polymer-induced liquid precursor (PILP). Here, we investigate the CaCO3 based PILP process with a variety of techniques including cryoTEM and NMR. The initial products are 30–50 nm amorphous calcium carbonate (ACC) nanoparticles with ~2 nm nanoparticulate texture. We show the polymers strongly interact with ACC in the early stages, and become excluded during crystallization, with no liquid–liquid phase separation detected during the process. Our results suggest that “PILP” is actually a polymer-driven assembly of ACC clusters, and that its liquid-like behavior at the macroscopic level is due to the small size and surface properties of the assemblies. We propose that a similar biopolymer-stabilized nanogranular phase may be active in biomineralization

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

APPLICATION OF MODIFIED NEI VFQ-25 AFTER RETINAL DETACHMENT TO VISION-RELATED QUALITY OF LIFE

We examined the postoperative visual recovery and quality of life after retinal detachment (RD) surgery. In addition to a baseline clinical examination, patients filled out the National Eye Institute Visual Functioning Questionnaire at three time points: preoperatively and 1 and 3 months postoperatively (M1 and M3, respectively). We analyzed the composite score and short-form scores (socioemotional scale [SFSES] and visual functioning scale [SFVFS]). One hundred ninety-four patients were enrolled in this study; 47 (26 macula-ON RD and 21 macula-OFF RD) returned all three questionnaires. The best corrected visual acuity was Snellen equivalent 20/25, 20/25, and 20/20 at the preoperative, M1, and M3 assessment, respectively. At M3, we found a positive correlation between SFSES and best corrected visual acuity measures among macula-OFF patients (P < 0.001, R2 = 0.58). A significant correlation with the best corrected visual acuity among macula-ON patients was observed only at M3 with the SFVFS score (P < 0.001, R2 = 0.41). The quality of life differs between ON and OFF RD in regard to the composite score and especially SFSES and SFVFS. We found a transient decrease in the quality of life at M1 for macula-ON patients, whereas the quality of life improved throughout follow-up among macula-OFF patients. These data may help improve the management of patients' expectations after RD surgery