Do inositol supplements enhance phosphatidylinositol supply and thus support endoplasmic reticulum function?

AbstractThis review attempts to explain why consuming extramyoinositol (Ins), an essential component of membrane phospholipids, is often beneficial for patients with conditions characterised by insulin resistance, non-alcoholic fatty liver disease and endoplasmic reticulum (ER) stress. For decades we assumed that most human diets provide an adequate Ins supply, but newer evidence suggests that increasing Ins intake ameliorates several disorders, including polycystic ovary syndrome, gestational diabetes, metabolic syndrome, poor sperm development and retinopathy of prematurity. Proposed explanations often suggest functional enhancement of minor facets of Ins Biology such as insulin signalling through putative inositol-containing ‘mediators’, but offer no explanation for this selectivity. It is more likely that eating extra Ins corrects a deficiency of an abundant Ins-containing cell constituent, probably phosphatidylinositol (PtdIns). Much of a cell’s PtdIns is in ER membranes, and an increase in ER membrane synthesis, enhancing the ER’s functional capacity, is often an important part of cell responses to ER stress. This review: (a) reinterprets historical information on Ins deficiency as describing a set of events involving a failure of cells adequately to adapt to ER stress; (b) proposes that in the conditions that respond to dietary Ins there is an overstretching of Ins reserves that limits the stressed ER’s ability to make the ‘extra’ PtdIns needed for ER membrane expansion; and (c) suggests that eating Ins supplements increases the Ins supply to Ins-deficient and ER-stressed cells, allowing them to make more PtdIns and to expand the ER membrane system and sustain ER functions.</jats:p

High time resolution PFISR and optical observations of naturally enhanced ion acoustic lines

Observations of naturally enhanced ion acoustic lines (NEIALs) taken with the Poker Flat Incoherent Scatter Radar (PFISR) using a mode with very high time resolution are presented. The auroral event took place over Poker Flat, Alaska on 8 February 2007 at 09:35 UT (~22:00 MLT), and the radar data are complemented by common-volume high-resolution auroral imaging. The NEIALs occurred during only one of the standard 15-s integration periods. The raw data of this time show very intermittent NEIALs which occur only during a few very short time intervals (&amp;le;1 s) within the 15-s period. The time sampling of the raw data, ~19 ms on average, allows study of the time development of the NEIALs, though there are indications that even finer time resolution would be of interest. The analysis is based on the assumption that the NEIAL returns are the result of Bragg scattering from ion-acoustic waves that have been enhanced significantly above thermal levels. The spectra of the raw data indicate that although the up- and down-shifted shoulders can both become enhanced at the same time, (within 19 ms), they are most often enhanced individually. The overall power in the up-and down-shifted shoulders is approximately equal throughout the event, with the exception of one time, when very large up-shifted power was observed with no corresponding down-shifted power. This indicates that during the 480 μs pulse, the strongly enhanced ion-acoustic waves were only traveling downward and not upward. The exact time that the NEIALs occurred was when the radar beam was on the boundary of a fast-moving (~10 km/s), bright auroral structure, as seen in the high resolution auroral imaging of the magnetic zenith. When viewed with high time resolution, the occurrence of NEIALs is associated with rapid changes in auroral luminosity within the radar field of view due to fast-moving auroral fine structures

PFISR Nightside Observations of Naturally Enhanced Ion Acoustic Lines, and Their Relation to Boundary Auroral Features

We present results from a coordinated camera and radar study of the auroral ionosphere conducted during March of 2006 from Poker Flat, Alaska. The campaign was conducted to coincide with engineering tests of the first quarter installation of the Poker Flat Incoherent Scatter Radar (PFISR). On 31 March 2006, a moderately intense auroral arc, (~10 kR at 557.7 nm), was located in the local magnetic zenith at Poker Flat. During this event the radar observed 7 distinct periods of abnormally large backscattered power from the F-region. These were only observed in the field-aligned radar beam, and radar spectra from these seven times show naturally enhanced ion-acoustic lines (NEIALs), the first observed with PFISR. These times corresponded to (a) when the polar cap boundary of the auroral oval passed through the magnetic zenith, and (b) when small-scale filamentary dark structures were visible in the magnetic zenith. The presence of both (a) and (b) was necessary for their occurrence. Soft electron precipitation occurs near the magnetic zenith during these same times. The electron density in the vicinity where NEIALs have been observed by previous studies is roughly between 5 and 30×1010 m−3. Broad-band extremely low frequency (BBELF) wave activity is observed in situ by satellites and sounding rockets to occur with similar morphology, during active auroral conditions, associated with the poleward edge of the aurora and soft electron precipitation. The observations presented here suggest further investigation of the idea that NEIALs and BBELF wave activity are differently-observed aspects of the same wave phenomenon. If a connection between NEIALs and BBELF can be established with more data, this could provide a link between in situ measurements of downward current regions (DCRs) and dynamic aurora, and ground-based observations of dark auroral structures and NEIALs. Identification of in situ processes, namely wave activity, in ground-based signatures could have many implications. One specific example of interest is identifying and following the temporal and spatial evolution of regions of potential ion outflow over large spatial and temporal scales using ground-based optical observations

Comparative assessment of efficacy of lignocaine (1.5 mg/kg), esmolol (300 µg/kg), and dexmedetomidine (0.5 µg/kg) in minimizing the pressor response to laryngoscopy and intubation

Background: The objectives of the present study were to compare the effect of lignocaine (1.5 mg/kg IV given 3 mins before laryngoscopy and intubation), esmolol (300 µg/kg as a bolus 2 mins before intubation), and dexmedetomidine (0.5 µg/kg IV over 10 mins) on the pressor response in non-hypertensive American Society of Anesthesiologists (ASA) Grade I and II patients posted for elective surgery and the pharmacoeconomic and pharmacoepidemiological inferences drawn on comparison of these drugs.Methods: After approval by the Institutional Ethics Committee, 90 consenting adult patients aged 18-65 years of age of either sex of non-hypertensive ASA Grade I or II undergoing elective surgery under general anesthesia with endotracheal intubation were included in this randomized, prospective study protocol. (1) Group L: Patients were given IV lignocaine 1.5 mg/kg. (2) Group E: Patients were given IV esmolol 300 µg/kg. (3) Group D: Patients were given IV dexmedetomidine 0.5 μg/kg. Adequate monitoring, oxygenation, and hydration were established on the entry in the operating room (OR). All hemodynamic data were measured on arrival in OR, before induction, before intubation, and at 1, 3, 5 mins after intubation by an independent observer. Anesthesia was induced with thiopental sodium and fentanyl 2 μg/kg; intubation was performed with cuffed oral endotracheal tube of appropriate size for airway management. Surgery was allowed to start only after 5 mins of intubation.Results: Esmolol effectively blunted the blood pressure response to intubation, but incompletely attenuated the increase in heart rate (HR). Dexmedetomidine was more effective than lignocaine in minimizing the increase in HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) subsequent to endotracheal intubation.Conclusion: Dexmedetomidine 0.5 µg/kg has manifested to maintain hemodynamic stability associated with intubation and hence may prove beneficial for cardiac patients where the stress response to laryngoscopy and intubation is highly undesirable

Calcium ion-dependent diacylglycerol accumulation in erythrocytes is associated with microvesiculation but not with efflux of potassium ions

Erythrocytes from several different species were exposed to Ca2+ and the bivalent-cation ionophore A23187. The lipid composition, morphology and K+ permeability of the treated cells were investigated. Erythrocytes from human, rat, guinea pig and rabbit (a) showed an increased concentration of 1,2-diacyl-sn-glycerol and enhanced labelling of phosphatidate with 32P, (b) underwent echinocytosis and outward vesiculation, and (c) rapidly released much of their intracellular K+. Pig cells showed only the K+ loss, and ox and sheep (high-K+) cells showed none of these Ca2+-evoked effects. All of the cells underwent stomatocytosis and inward vesiculation when treated externally with Clostridium perfringens phospholipase C. These results support the idea that there is a correlation between the asymmetric insertion of diacylglycerol (or ceramide) into the membrane and the shape-changes leading to microvesiculation, but they indicate that Ca2+-triggered K+ efflux and diacylglycerol production are unrelated events. Erythrocytes of chicken and turkey showed no Ca2+-stimulated K+ efflux. They showed slight ionophore A23187-stimulated vesiculation, but this appeared to be associated with the appearance in the membrane of ceramide rather than of diacylglycerol. Phospholipase C treatment caused very similar changes in morphology and phosphatidate labelling to those seen in mammalian erythrocytes

Unsteady effects during resistance tests on a ship model in a towing tank

It is known that there are oscillations in the wave resistance during the constantvelocity phase of a towing-tank resistance test on a ship model. In this work, the unsteady thin-ship resistance theory has been applied to this case. The results have been compared with experiment data obtained using a towing carriage the velocity history of which can be programmed. It is demonstrated here that generally excellent correlation exists between the theory and the experiments. In particular, one can predict the influence of Froude number, rate of acceleration, and type of smoothing of the acceleration on the characteristics of the oscillations. These characteristics include the amplitude, rate of decay, frequency, and phasing of the oscillations in the curve of wave resistance versus time

The relationship of calcium to receptor-controlled stimulation of phosphatidylinositol turnover. Effects of acetylcholine, adrenaline, calcium ions, cinchocaine and a bivalent cation ionophore on rat parotid-gland fragments

The possibility that Ca2+ ions are involved in the control of the increased phosphatidylinositol turnover which is provoked by alpha-adrenergic or muscarinic cholinergic stimulation of rat parotid-gland fragments has been investigated. Both types of stimulation provoked phosphatidylinositol breakdown, which was detected either chemically or radiochemically, and provoked a compensatory synthesis of the lipid, detected as an increased rate of incorporation of 32Pi into phosphatidylinositol. Acetylcholine had little effect on the incorporation of labelled glycerol, whereas adrenaline stimulated it significantly, but to a much lower extent than 32P incorporation: this suggests that the response to acetylcholine was entirely accounted for by renewal of the phosphorylinositol head-group of the lipid, but that some synthesis de novo was involved in the response to adrenaline. The responses to both types of stimulation, whether measured as phosphatidylinositol breakdown or as phosphatidylinositol labelling, occurred equally well in incubation media containing 2.5 mm-Ca2+ or 0.2 mm-EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid]. Incubation with a bivalent cation ionophore (A23187) led to a small and more variable increase in phosphatidylinositol labelling with 32Pi, which occurred whether or not Ca2+ was available in the extracellular medium: this was not accompanied by significant phosphatidylinositol breakdown. Cinchocaine, a local anaesthetic, produced parallel increases in the incorporation of Pi and glycerol into phosphatidylinositol. This is compatible with its known ability to inhibit phosphatidate phosphohydrolase (EC 3.1.3.4) and increase phosphatidylinositol synthesis de novo in other cells. These results indicate that the phosphatidylinositol turnover evoked by alpha-adrenergic or muscarinic cholinergic stimuli in rat parotid gland probably does not depend on an influx of Ca2+ into the cells in response to stimulation. This is in marked contrast with the K+ efflux from this tissue, which is controlled by the same receptors, but is strictly dependent on the presence of extracellular Ca2+. The Ca2+-independence of stimulated phosphatidylinositol metabolism may mean that it is controlled through a mode of receptor function different from that which controls other cell responses. Alternatively, it can be interpreted as indicating that stimulated phosphatidylinositol breakdown is intimately involved in the mechanisms of action of alpha-adrenergic and muscarinic cholinergic receptor systems

Muscarinic cholinergic stimulation of phosphatidylinositol turnover in the longitudinal smooth muscle of guinea-pig ileum

1. The metabolism of phosphatidylinositol and phosphatidate was investigated in fragments of longitudinal smooth muscle from guinea-pig ileum incubated with cholinergic and anticholinergic drugs. 2. Incorporation of Pi into these lipids was enhanced by acetylcholine and carbamoylcholine. 3. The receptor responsible for triggering this response was of the muscarinic type, since (a) the response was also produced by the muscarinic agonists acetyl-beta-methylcholine, carbamoyl-beta-methylcholine and pilocarpine, and (b) the response was prevented by atropine and prophylbenzilylcholine mustard, but not by tubocurarine. 4. Increased phosphatidylinositol labellin was clearly observed within 5 min in tissue treated with a high concentration of carbamoylcholine. 5. Halfmaximal stimulation of phosphatidylinositol labelling occurred at approx. 10 muM-muM-carbamoylcholine. 6. Incubation of muscle fragments with carbamoylcholine provoked a decrease in phosphatidylinositol concentration, as would be expected if phosphatidyl-inositol breakdown is the reaction controlled by agonists. 7. This information all appears consistent with the proposal that phosphatidylinositol breakdown may be a reaction intrinsic to the mechanisms of muscarinic cholinergic receptor systems