Metabolism of ubiquinone in relation to vitamin a status in the rat

1. 1. Biosynthetic experiments in vitro with slices of livers from normal and vitamin A-deficient rats confirmed that synthesis of ubiquinone did not increase in vitamin A deficiency. 2. 2. During development of deficiency of vitamin A in the rat, there was a definite increase in the synthesis of ubiquinone at the 10-days stage but this reverted to low, initial level by 20 days and after. 3. 3. Vitamin A analogues, 3-dehydroretinal, 5,6-monoepoxyretinal and retinoic acid, which supported growth have restored ubiquinone concentration to the normal levels and relieved the lowering in its catabolism. The biologically inert 5,8-monoepoxyretinal was the least active of the analogues tested. 4. 4. The concentration and synthesis of ubiquinone in the liver decreased under conditions of hypervitaminosis A. 5. 5. The experimental evidence does not support the hypothesis of inverse relationship between vitamin A and ubiquinone synthesis.

Lipid composition of the silkworm Bombyx mori L

The constituents of silkworm fat were studied in detail. An unsaturated fat with a high concentration of phospholipid was generally observed. Its iodine value increased during metamorphosis. The free fatty acid concentration likewise increased from the spinning larvae to the moth stage. Analyses of silkworm organs revealed that the fat body had the most fat and the least free fatty acids, whereas haemolymph contained the least fat. Silk glands contained the maximum phospholipid percentage. Stearic acid predominated in those tissues that had a high percentage of phospholipid. Stearic acid was the predominant saturated fatty acid in both the phospholipids and lecithin, and it accounted for 35–50 per cent of the free fatty acids of all the tissues. Q10 was the ubiquinone present; also found were ubichromenol and tocopherol. Results show that silkworm sterol may be cholesterol. Intestines contained the maximum quantities of sterol, ubiquinone, ubichromenol, and tocopherol. The composition of silkworm phospholipids varies considerably from those of other insects, but lecithin is comparable in its composition with lecithins of other animals. The phospholipids had with them a highly complexed protein along with a polysaccharide. In experiments with snake venoms unsaturated fatty acids were found to be predominantly released from silkworm lecithin.

Sterol-binding proteins in late endosomes : Regulation of endosome motility and lipid metabolism

Despite its bad reputation in the mass media, cholesterol is an indispensable constituent of cellular membranes and vertebrate life. It is, however, also potentially lethal as it may accumulate in the arterial intima causing atherosclerosis or elsewhere in the body due to inherited conditions. Studying cholesterol in cells, and research on how the cell biology of cholesterol affects on system level is essential for a better understanding of the disease states associated with cholesterol and for the development of new therapies for these conditions. On its way to the cell, exogenous cholesterol traverses through endosomes, transport vesicles involved in internalizing material to cells, and needs to be transported out of this compartment. This endosomal pool of cholesterol is important for understanding both the common disorders of metabolism and the more rare hereditary disorders of cholesterol metabolism. The study of cholesterol in cells has been hampered by the lack of bright fluorescent sterol analogs that would resemble cholesterol enough to be used in cellular studies. In the first study of my thesis, we present a new sterol analog, Boron-Dipyrromethene (BODIPY)-cholesterol for visualizing sterols in living cells and organism. This fluorescent cholesterol derivative is shown to behave similarly to cholesterol both by atomic scale computer simulations and biochemical experiments. We characterize its localization inside different types of living cells and show that it can be used to study sterol trafficking in living organisms. Two sterol binding proteins associated with the endosomal membrane; the Niemann-Pick type C disease protein 1 (NPC1) and the Oxysterol Binding Protein Related Protein 1 (ORP1) are the subjects of the rest of this study. Sensing cholesterol on endosomes, transporting lipids away from this compartment and the effects these lipids play on cellular metabolism are considered. In the second study we characterize how the NPC1 protein affects lipid metabolism. We show that this cholesterol binding protein affects synthesis of triglycerides and that genetic polymorphisms or a genetic defect in the NPC1 gene affect triglyceride on the whole body level. These effects take place via regulation of carbon fluxes to different lipid classes in cells. In the third part we characterize the effects of another endosomal sterol binding protein, ORP1L on the function and motility of endosomes. Specifically we elucidate how a mutation in the ability of ORP1L to bind sterols affects its behavior in cells, and how a change in ORP1L levels in cells affects the localization, degradative capacity and motility of endosomes. In addition we show that ORP1L manipulations affect cholesterol balance also in macrophages, a cell type important for the development of atherosclerosis.

Dual-Drug Delivery System Based on In Situ Gel-Forming Nanosuspension of Forskolin to Enhance Antiglaucoma Efficacy

The present study was designed to improve the bioavailability of forskolin by the influence of precorneal residence time and dissolution characteristics. Nanosizing is an advanced approach to overcome the issue of poor aqueous solubility of active pharmaceutical ingredients. Forskolin nanocrystals have been successfully manufactured and stabilized by poloxamer 407. These nanocrystals have been characterized in terms of particle size by scanning electron microscopy and dynamic light scattering. By formulating Noveon AA-1 polycarbophil/poloxamer 407 platforms, at specific concentrations, it was possible to obtain a pH and thermoreversible gel with a pH(gel)/T-gel close to eye pH/temperature. The addition of forskolin nanocrystals did not alter the gelation properties of Noveon AA-1 polycarbophil/poloxamer 407 and nanocrystal properties of forskolin. The formulation was stable over a period of 6 months at room temperature. In vitro release experiments indicated that the optimized platform was able to prolong and control forskolin release for more than 5 h. The in vivo studies on dexamethasone-induced glaucomatous rabbits indicated that the intraocular pressure lowering efficacy for nanosuspension/hydrogel systems was 31% and lasted for 12 h, which is significantly better than the effect of traditional eye suspension (18%, 4-6 h). Hence, our investigations successfully prove that the pH and thermoreversible polymeric in situ gel-forming nanosuspension with ability of controlled drug release exhibits a greater potential for glaucoma therapy.

Thermal ignition studies on metallized fuel-oxidizer systems

The thermal ignition behaviour of various mixtures of organic fuels, magnesium and ammonium nitrate (AN) has been examined by differential thermal analysis technique. It has been observed that the thermal decomposition/ignition of organic fuel-AN mixtures is modified significantly in the presence of magnesium metal. The decomposition characteristics of the binary mixtures of AN with various metals indicate the specific action of magnesium and zinc in lowering the decomposition temperature. A possible explanation for the low temperature decomposition is given in terms of the solid state reaction causing the fusion of AN which further reacts with the metal resulting in a highly exothermic reaction.

New Solid State Forms of the Anti-HIV Drug Efavirenz. Conformational Flexibility and High Z ` Issues

Structural information on the solid forms of efavirenz, a non-nucleoside reverse transcriptase inhibitor, is limited, although various polymorphic forms of this drug have been patented. We report here structural studies of four new crystal forms a pure form, a cyclohexane solvate, and cocrystals with 1,4-cyclohexanedione and 4,4'-bipyridine. Temperature dependent single-crystal to single-crystal phase transitions are observed for the pure form and for the cyclohexane solvate with an increase in the number of symmetry independent molecules, Z', upon a lowering of temperature. Other issues related to these solid forms, such as thermal stability, conformational flexibility, and high Z' occurrences, are addressed by using a combined experimental and computational approach.

Generators contribution towards loads and line flows - A case study

n many parts of the world, the goal of electricity supply industries is always the introduction of competition and a lowering of the average consumer price. Because of this it has become much more important to be able to determine which generators are supplying a particular load, how much use each generator is making of a transmission line and what is generator's contribution to the system losses. In this paper a case study on generator contributions towards loads and transmission flows are illustrated with an equivalent 11-bus system, a part of Indian Southern Grid, based on the concepts of circuit flow directions, for normal and network contingency conditions.

Low temperature processing and chacterization of SrBi2Nb2O9 thin films grown by pulsed laser ablation

Ex-situ grown thin films of SrBi2Nb2O9 (SBN) were deposited on platinum substrates using laser ablation technique. A low substrate-temperature-processing route was chosen to avoid any diffusion of bismuth into the Pt electrode. It was observed that the as grown films showed an oriented growth along the 'c'-axis (with zero spontaneous polarization). The as grown films were subsequently annealed to enhance crystallization. Upon annealing, these films transformed into a polycrystalline structure, and exhibited excellent ferroelectric properties. The switching was made to be possible by lowering the thickness without losing the electrically insulating behavior of the films. The hysteresis results showed an excellent square-shaped loop with results (P-r = 4 muC/cm(2) E-c = 90 kV/cm) in good agreement with the earlier reports. The films also exhibited a dielectric constant of 190 and a dissipation factor of 0.02, which showed dispersion at low frequencies. The frequency dispersion was found to obey Jonscher's universal power law relation, and was attributed to the ionic charge hopping process according to earlier reports. The de transport studies indicated an ohmic behavior in the low voltage region, while higher voltages induced a bulk space charge and resulted in non-linear current-voltage dependence.

Electronic structure of high-Tc Ba0.6K0.4BiO3 by x-ray photoelectron spectroscopy

We have investigated the electronic structure of Ba1-xKxBiO3 (0

Experimental approach for studying structural changes in axonal membrane upon nerve excitation

The Hodgkin and Huxley (HH) model of action potential has become a central paradigm of neuroscience. Despite its ability to predict action potentials with remarkable accuracy, it fails to explain several biophysical findings related to the initiation and propagation of the nerve impulse. The isentropic heat release and optical phenomena demonstrated by various experiments suggest that action potential is accompanied by a transient phase change in the axonal membrane. In this study a method was developed for preparing a giant axon from the crayfish abdominal cord for studying the molecular mechanisms of action potential simultaneously by electrophysiological and optical methods. Also an alternative setup using a single-cell culture of an Aplysia sensory neuron is presented. In addition to the description of the method, the preliminary results on the effect of phloretin, a dipole potential lowering compound, on the excitability of a crayfish giant axon are presented.

Solid-state chemistry of high-temperature oxide superconductors:The experimental situation

High-temperature superconductivity in oxides of the type(La, Ln)2?xBax(Sr)xCuO4, Y(Ln)Ba2Cu3O7??, La3?xBa3+xCu6O14, and related systems is discussed with emphasis on aspects related to experimental solid-state chemistry. All of these oxides possess perovskite-related structures. Oxygen-excess and La-deficient La2CuO4 also exhibit superconductivity in the 20�40 K just as La2?xBax(Srx)CuO4; these oxides are orthorhombic in the superconductivity phase. The crucial role of oxygen stoichiometry in the superconductivity ofYBa2Cu3O7?? (Tc = 95 ± 5K) is examined; this oxide remains orthorhombic up to ? ? 0.6 and becomes tetragonal and nonsuperconducting beyond this value of ?. Oxygen stoichiometry in this and related oxides has to be understood in terms of structure and disorder. The structure of La3?xBa3+xCu6O14 is related to that of YBa2Cu3O7, the orthorhombic structure manifesting itself when the population of O1 oxygens (along the Cusingle bondOsingle bondCu chains) is preponderant compared to that of O5 oxygens (along thea-axis); nearly equal populations of O1 and O5 sites give rise to the tetragonal structure. A transition from a high-Tc (95 K) superconductivity regime to a low-Tc (not, vert, similar60 K) regime occurs in YBa2Cu3O7?? accompanying a change in ?. There is no evidence for Cu3+ in these nominally mixed valent copper oxides. Instead, holes are present on oxygens giving rise to O? or O2?2 species, the concentration of these species increasing with the lowering of temperature. Certain interesting aspects of the superconducting oxides such as domain or twin boundaries, Raman spectra, microwave absorption, and anomalous high-temperature resistivity drops are presented along with the important material parameters. Preparative aspects of the superconducting oxides are briefly discussed. Phase transitions seem to occur atTc as well as at not, vert, similar240 K in YBa2Cu3O7.

Studies on LDPE-cyanoethylated lignocellulosics blends using epoxy functionalized LDPE as compatibilizer

Rubberwood flour and cellulose have been plasticized by cyanoethylation and then blended with low-density polyethylene (LDPE). A small quantity of epoxy functionalized polyethylene i.e., polyethylene-co-glycidyl methacrylate (PEGMA) has been added to further enhance the mechanical properties. The mechanical properties were measured according to the standard ASTM methods. SEM analysis was performed for both fractured and unfractured blend specimens. The mechanical properties were improved by the addition of PEGMA compatibilizer. LDPE blends with cyanoethylated wood flour (CYWF) showed higher tensile strength and modulus than cyanoethylated cellulose CYC-LDPE blends. However CYC-LDPE blends exhibited higher relative elongation at break values as compared with the former. The TGA analysis showed lowering of thermal stability as the filler content is increased and degradation temperature of LDPE is shifted slightly to lower temperature. DSC analysis showed loss of crystallinity for the LDPE phase as the filler content is increased for both types of blends. Dielectric properties of the blends were similar to LDPE, but were lowered on adding PEGMA. (c) 2006 Wiley Periodicals, Inc.

Preterm birth and risk factors for chronic disease : Helsinki Study of Very Low Birth Weight Adults

Background: The improved prognosis of early preterm birth has created a generation of surviving very low birth weight (< 1500 g, VLBW) infants whose health risks in adulthood are poorly known. Of every 1000 live-born infants in Finland, about 8 are born at VLBW. Variation in birth weight, even within the normal range, relates to considerable variation in the risk for several common adult disorders, including cardiovascular disease and osteoporosis. Small preterm infants frequently exhibit severe postnatal or prenatal growth retardation, or both. Much reason for concern thus exists, regarding adverse health effects in surviving small preterm infants later lives. We studied young adults, aiming at exploring whether VLBW birth and postnatal events after such a birth are associated with higher levels of risk factors for cardiovascular disease or osteoporosis. Subjects and Methods: A follow-up study for VLBW infants began in 1978; by the end of 1985, 335 VLBW survivors at Helsinki University Central Hospital participated in the follow-up. Their gestational ages ranged from 24 to 35 weeks, mean 29.2 and standard deviation 2.2 weeks. In 2004, we invited for a clinic visit 255 subjects, aged 18 to 27, who still lived in the greater Helsinki area. From the same birth hospitals, we also invited 314 term-born controls of similar age and sex. These two study groups underwent measurements of body size and composition, function of brachial arterial endothelium (flow-mediated dilatation, FMD) and carotid artery intima-media thickness (cIMT) by ultrasound. In addition, we measured plasma lipid concentrations, ambulatory blood pressure, fasting insulin, glucose tolerance and, by dual-energy x-ray densitometry, bone-mineral density. Results: 172 control and 166 VLBW participants underwent lipid measurements and a glucose tolerance test. VLBW adults fasting insulin (adjusted for body mass index) was 12.6% (95% confidence interval, 0.8 to 25.8) higher than that of the controls. The glucose and insulin concentrations 120 minutes after 75 g glucose ingestion showed similar differences (N=332) (I). VLBW adults had 3.9 mmHg (1.3 to 6.4) higher office systolic blood pressure, 3.5 mmHg (1.7 to 5.2) higher office diastolic blood pressure (I), and, when adjusted for body mass index and height, 3.1 mmHg (0.5 to 5.5) higher 24-hour mean systolic blood pressure (N=238) (II). VLBW birth was associated neither with HDL- or total cholesterol nor triglyceride concentrations (N=332) (I), nor was it associated with a low FMD or a high cIMT (N=160) (III). VLBW adults had 0.51-unit (0.28 to 0.75) lower lumbar spine Z scores and 0.56-unit (0.34 to 0.78) lower femoral neck Z scores (N=283). Adjustments for size attenuated the differences, but only partially (IV). Conclusions: These results imply that those born at VLBW, although mostly healthy as young adults, already bear several risk factors for chronic adult disease. The significantly higher fasting insulin level in adults with VLBW suggests increased insulin resistance. The higher blood pressure in young adults born at VLBW may indicate they later are at risk for hypertension, although their unaffected endothelial function may be evidence for some form of protection from cardiovascular disease. Lower bone mineral density around the age of peak bone mass may suggest increased risk for later osteoporotic fractures. Because cardiovascular disease and osteoporosis are frequent, and their prevention is relatively cheap and safe, one should focus on prevention now. When initiated early, preventive measures are likely to have sufficient time to be effective in preventing or postponing the onset of chronic disease.

Preterm birth and risk factors for chronic disease : Helsinki Study of Very Low Birth Weight Adults

Background: The improved prognosis of early preterm birth has created a generation of surviving very low birth weight (PIENEMPI KUIN 1500 g, VLBW) infants whose health risks in adulthood are poorly known. Of every 1000 live-born infants in Finland, about 8 are born at VLBW. Variation in birth weight, even within the normal range, relates to considerable variation in the risk for several common adult disorders, including cardiovascular disease and osteoporosis. Small preterm infants frequently exhibit severe postnatal or prenatal growth retardation, or both. Much reason for concern thus exists, regarding adverse health effects in surviving small preterm infants later lives. We studied young adults, aiming at exploring whether VLBW birth and postnatal events after such a birth are associated with higher levels of risk factors for cardiovascular disease or osteoporosis. Subjects and Methods: A follow-up study for VLBW infants began in 1978; by the end of 1985, 335 VLBW survivors at Helsinki University Central Hospital participated in the follow-up. Their gestational ages ranged from 24 to 35 weeks, mean 29.2 and standard deviation 2.2 weeks. In 2004, we invited for a clinic visit 255 subjects, aged 18 to 27, who still lived in the greater Helsinki area. From the same birth hospitals, we also invited 314 term-born controls of similar age and sex. These two study groups underwent measurements of body size and composition, function of brachial arterial endothelium (flow-mediated dilatation, FMD) and carotid artery intima-media thickness (cIMT) by ultrasound. In addition, we measured plasma lipid concentrations, ambulatory blood pressure, fasting insulin, glucose tolerance and, by dual-energy x-ray densitometry, bone-mineral density. Results: 172 control and 166 VLBW participants underwent lipid measurements and a glucose tolerance test. VLBW adults fasting insulin (adjusted for body mass index) was 12.6% (95% confidence interval, 0.8 to 25.8) higher than that of the controls. The glucose and insulin concentrations 120 minutes after 75 g glucose ingestion showed similar differences (N=332) (I). VLBW adults had 3.9 mmHg (1.3 to 6.4) higher office systolic blood pressure, 3.5 mmHg (1.7 to 5.2) higher office diastolic blood pressure (I), and, when adjusted for body mass index and height, 3.1 mmHg (0.5 to 5.5) higher 24-hour mean systolic blood pressure (N=238) (II). VLBW birth was associated neither with HDL- or total cholesterol nor triglyceride concentrations (N=332) (I), nor was it associated with a low FMD or a high cIMT (N=160) (III). VLBW adults had 0.51-unit (0.28 to 0.75) lower lumbar spine Z scores and 0.56-unit (0.34 to 0.78) lower femoral neck Z scores (N=283). Adjustments for size attenuated the differences, but only partially (IV). Conclusions: These results imply that those born at VLBW, although mostly healthy as young adults, already bear several risk factors for chronic adult disease. The significantly higher fasting insulin level in adults with VLBW suggests increased insulin resistance. The higher blood pressure in young adults born at VLBW may indicate they later are at risk for hypertension, although their unaffected endothelial function may be evidence for some form of protection from cardiovascular disease. Lower bone mineral density around the age of peak bone mass may suggest increased risk for later osteoporotic fractures. Because cardiovascular disease and osteoporosis are frequent, and their prevention is relatively cheap and safe, one should focus on prevention now. When initiated early, preventive measures are likely to have sufficient time to be effective in preventing or postponing the onset of chronic disease.

Effect of Neutralization of Endogenous Follicle Stimulating Hormone (FSH) or Luteinizing Hormone (LH) on Ovarian Lipids in the Hamster: A Histochemical and Biochemical Evaluation

The effect of neutralizing FSH or LH on ovarian lipids in the cycling hamster was studied. In the normal cycling hamster on the day of proestrus, histochemical examination revealed the presence of sudanophilic lipids in the granulosa cells of the follicles and in the interstitium. A clear reduction in the intensity of lipid staining was observed on proestrus in the ovary of hamsters treated with FSH antiserum on the previous proestrus. Similar treatment with antiserum to LH, on the other hand, caused an accumulation of lipids in these structures. Estimation of the free and esterified fractions of cholesterol and triglycerides in the nonluteal tissue of the ovary of hamsters on proestrus following treatment with FSH antiserum on the previous proestrus revealed a significant reduction in all 3 lipid components. Even a short term deprivation of FSH caused a similar reduction in these lipids in the ovary. In contrast, treatment with LH antiserum either on the previous proestrus or on the previous day (diestrus-2) resulted in an enhancement in esterified cholesterol and triglycerides, while it caused a reduction in the free cholesterol fraction of the ovary on proestrus.It is suggested that though treatment with antisera to either FSH or LH causes a disruption in follicular maturation, their effect on lipid metabolism is different. A positive role for FSH and LH in maintaining normal sterol and triglyceride levels in the nonluteal ovarian tissue of cycling hamster is indicated.