Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have determined the permeability properties of freshly isolated frog rod outer segments by observing their osmotic behavior in a simple continuous flow apparatus. Outer segments obtained by gently shaking a retina are sensitive but nonideal osmometers; a small restoring force prevents them from shrinking or swelling quite as much as expected for ideal behavior. We find that Na(+), Cl(-), No(3) (-), glycerol, acetate, and ammonium rapidly enter the outer segment, but K(+), SO(4) (=), and melezitose appear impermeable. The Na flux is rectified; for concentration gradients in the physiological range, 2 x 10(9) Na(+) ions/sec enter the outer segment, but we detect no efflux of Na(+), under our conditions, when the gradient is reversed. Illumination of the outer segment produces a specific increase in the resistance to Na(+) influx, but has no effect on the flux of other solutes. This light-dependent Na(+) resistance increases linearly with the number of rhodopsin molecules bleached. We find that excitation of a single rhodopsin molecule produces a transient ( approximately 1 sec) "photoresistance" which reduces the Na(+) influx by about 1%, thus preventing the entry of about 10(7) Na(+) ions. At considerably higher light levels, a stable afterimage resistance appears which reduces the Na influx by one-half when 10(6) rhodopsin molecules are bleached per rod. We have incorporated these findings into a model for the electrophysiological characteristics of the receptor.
 ...
PMID:Dark ionic flux and the effects of light in isolated rod outer segments. 453 79

Clifton, C. E. (Stanford University, Stanford, Calif.), and John Cherry. Influence of glutamic acid on the endogenous respiration of Bacillus subtilis. J. Bacteriol. 91:546-550. 1966.-Amino acids serve as the major initial endogenous substrate for Bacillus subtilis. The endogenous activity of freshly harvested washed cells is high and falls off rapidly with time of shaking at 30 C to lower but still significant levels. The rate of O(2) consumption after the addition of glutamic acid also decreases as the cells age, but more slowly than noted for endogenous respiration. When cells were fed glutamate as soon as possible after harvesting, an apparent stimulation of endogenous respiration was noted. However, endogenous activity was inhibited if the cell suspensions were shaken for at least 1 hr before addition of the glutamate. Similar results were obtained with glycerol or glucose as exogenous substrates. Variation in rates of respiration with age of the cells, inherent instability of B. subtilis, and possible utilization of substances initially excreted by the cells appear to account for the variations noted regarding the influence of an exogenous substrate on endogenous respiration.
 ...
PMID:Influence of glutamic acid on the endogenous respiration of Bacillus subtilis. 495 54

Adult male Porton albino rats received deltamethrin (0.5--40.0 mg/kg IP) or glycerol formal solvent IP. Their behaviour was observed during the subsequent 110 minutes and the incidence and latency of salivation, tremor and incoordination and spontaneous choreiform episodes were noted. Cyclic GMP levels in the cerebellum were determined by radioimmunoassay at various times after deltamethrin administration. The development of the motor syndrome was dose-dependent and followed a specific time course. The threshold dose for profuse salivation and tremor and incoordination was 2.5 mg/kg IP, and for spontaneous choreiform episodes, 5.0 mg/kg IP. The latency of tremor and incoordination decreased significantly as the deltamethrin dose was increased. The first significant increase in cyclic GMP levels in the cerebellum was at 70 minutes, which was 10 minutes after the mean latency of tremor and incoordination. The levels increased further at 100 minutes which was approximately 20 minutes after the mean latency of spontaneous choreiform episodes. Deltamethrin did not have a dose-dependent effect on cyclic GMP levels. The results suggest that deltamethrin changes cerebellar cyclic GMP levels indirectly.
 ...
PMID:Elevated cerebellar cyclic GMP levels during the deltamethrin-induced motor syndrome. 628 84

The optimal conditions for preparations of rifampicin-containing liposomes were determined with the methods of mechanical shaking, gas dispersion and and reversible phases. It was found that the percentage of rifampicin incorporation into liposomes depended on the molar ratio of the antibiotic to the lipid (the optimal ratio was 1 : 10), the size and structure of liposomes, the amount of cholesterol added and the lipid membrane charge. Incorporation of rifampicin amounted to 16.1 +/- 2.4, 39.2 +/- 3.2 and 60.5 +/- 2.9 per cent with respect to neutral lecithin multilamellar liposes, liposomes prepared with the gas dispersion method and liposomes prepared with the method of reversible phases, respectively. Cholesterol in a molar ratio to lecithin equal to 2 : 5 or higher and dicetyl phosphate imparting the negative charge to the membrane had an inhibitory effect on the drug uptake by liposomes, while stearyl amine having the positive charge had a stimulating effect. The effect of the cryoprotectors glucose, polyvinylpyrrolidone, poly-ethylene glycole-400 and glycerol on low-temperature preservation and storage of rifampicin-containing liposomes was studied. It was shown that 10--15 per cent solutions of sucrose and glucose had the highest cryoprotective effect, when the two-stage method of freezing was used. It provided almost 84 per cent preservation of liposomal rifampicin. Electron microscopy showed that after defrosting liposomes no significant changes in the size and structure of lipid membranes were observed.
 ...
PMID:[Isolation and low-temperature preservation of liposomes containing rifampicin]. 663 70

Chickens inoculated with inactivated-virus Newcastle disease vaccines containing different emulsion adjuvants were challenge exposed with viscerotropic velogenic Newcastle disease virus. Adjuvant activity was evident in all of 9 vaccines containing mineral oil emulsion (OE), but was not evident in 2 vaccines which contained a metabolizable lipid emulsion (LE) adjuvant consisting of peanut oil, glycerol, and lecithin. Serologic responses of chickens inoculated with OE vaccines were 10- to 100-fold higher than those of chickens inoculated with LE vaccines. One of 106 chickens given OE vaccine, 12 of 24 given LE vaccine, and all of 24 nonvaccinated control chickens were clinically affected or died after challenge exposure. Five OE vaccines emulsified only by brief vigorous shaking had adjuvant activity similar to 4 OE vaccines emulsified by conventional homogenization.
 ...
PMID:Comparison of inactivated Newcastle disease viral vaccines containing different emulsion adjuvants. 682 28

A series of ara-CDP-rac-1-O-alkyl-2-O-acylglycerols (9a-f), analogues of highly active ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (1) and Cytoros2 (2), was prepared, and solubility, lipophilicity, and structure-activity relationships of these conjugates were investigated. Conjugates 9a-f containing sn-1 alkyl (< C16) and sn-2 fatty acyl (< C14) and sn-1 alkyl (< C14) and sn-2 fatty acyl (< C16) substituents of the glycerol were water-soluble by shaking, while those with the sn-1 alkyl (> C16) and the sn-2 fatty acyl (> C16) such as conjugate 1 were sparingly soluble. Conjugates 9a-c,e were almost completely solubilized in water by shaking. However, a large portion of conjugates 9d and 9f in water by shaking exist in micelles with mean diameters ranging 7.0-55.2 nm. The partition coefficients (1-octanol/PBS) of the water-soluble conjugates were about 9-18 times greater than that of ara-C. A single dose (300 mg/kg) of conjugates 9d and 9f produced a significant increase in life span (ILS 206 to > 543%) with 17-67% long-term survivors (> 45 days) in mice bearing ip-implanted L1210 lymphoid leukemia. These results were comparable to those of the previous conjugate 1 and Cytoros (2). In contrast, conjugates 9a-c,e at single doses were less effective (ILS 69-178% with no long-term survivors). However, two (qd, 1, 7) or three (qd 1, 5, 9) divided doses of these conjugates were found to be as effective as a single dose of the previous conjugates. The three divided doses (150 mg/kg per day) of conjugates 9d, 9e, and 9f produced a remarkable antitumor activity in L1210 leukemic mice (ILS > 350% with > 50% long-term survivors). Because of the convenient formulation and the significant antitumor activities, the water-soluble conjugates 9d, 9e, and 9f warrant further investigation.
 ...
PMID:Nucleoside conjugates. 14. Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugates of ether lipids with improved water solubility. 775 87

Cis-bis-neodecanoato-trans-R,R-1,2 diaminocyclohexane platinum(II) (NDDP) is a lipophilic cisplatin derivative that has been formulated entrapped in multilamellar liposomes composed of dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG). A phase I clinical study with liposome-entrapped NDDP (L-NDDP) administered i.v. every 4 weeks has been recently completed. L-NDDP was synthesized, manufactured, and reconstituted for clinical use in our laboratories. L-NDDP was prepared as a lyophilized powder containing the NDDP and the phospholipids (NDDP-lipid weight ratio 1:15; DMPC-DMPG molar ratio 7:3). The liposome suspension was obtained on the day of use just before administration to the patients by adding normal saline (final concentration 1 mg NDDP/ml) and shaking in a water-bath shaker at room temperature according to an established protocol. A total of 54 batches of lyophilized L-NDDP were prepared. Physical appearance, phospholipid content and integrity, and elemental platinum content were determined in all batches and found to be reproducible. All batches contained < 0.24 ng/ml endotoxin. The amount of residual organic solvents was < 0.05 per cent. In all reconstituted doses, drug entrapment was > 90 per cent, and the proportion of liposomes measuring > 5 microns was < 20 per cent. Our results show that reproducible batches of liposomal preparations of new compounds can be prepared in the laboratory facilities of academic institutions, thus allowing for early clinical trials with novel therapeutic agents.
 ...
PMID:Preparation and characterization of liposomes containing a lipophilic cisplatin derivative for clinical use. 813 74

We investigated whether the putative beta 3-adrenoceptors mediated metabolic responses to isoprenaline. Seven normal volunteers received infusions of isoprenaline, a (beta 1, beta 2 and beta 3-agonist), at 0.5-3.0 micrograms/min. They were pretreated with either placebo, 25 mg atenolol (a selective beta 1 antagonist), or 5, 20 and 80 mg nadolol (which blocks beta 1 and beta 2 but not beta 3-adrenoceptors). Isoprenaline markedly (30.6%) increased basal metabolic rate (BMR): this increase was significantly reduced by 25 mg atenolol but not by 5 mg nadolol. Significant beta 2-blockade (from tremor data) occurred with 5 mg nadolol but not with 25 mg atenolol. This suggests that beta 1 but not beta 2-adrenoceptors are involved in the mediating thermogenic effects of isoprenaline. However, the rise in BMR was not totally blocked even by 80 mg nadolol (9.5%), which produced complete beta 1/beta 2 blockade, as evidenced by the elimination of the chronotropic effect of isoprenaline. This implies that the thermogenic response has a non-beta 1/beta 2-mediated component. There were also significant increases in plasma free fatty acids, glycerol, glucose, insulin and lactate, but these were completely abolished by beta 1/beta 2 blockade. Overall, isoprenaline produced an increase in BMR which is only partly due to stimulation of beta 1-adrenoceptors, and which is not associated with beta 1/beta 2-mediated effects on carbohydrate and fat metabolism. This suggests the possibility of thermogenic beta 3-adrenoceptors in man, although their location and role remain unknown.
 ...
PMID:Do beta 3-adrenoceptors mediate metabolic responses to isoprenaline. 825 74

We report a method of preparing a submicron and stable liposome formulation of the non-cross-resistant anthracycline annamycin. The lipids were dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG) at a 7:3 molar ratio and the optimal lipid:drug ratio was 50:1 (w/w). The selected formulation was a preliposome lyophilized powder that contained the phospholipids, annamycin, and Tween 20. The liposome suspension was obtained on the day of use by adding normal saline at 37 degrees C (1 ml/mg annamycin) and hand shaking for 1 min. The presence of Tween 20 was essential in shortening the reconstitution step (from > 2 h to 1 min), avoiding the early formation of free drug crystals, and reducing the median particle size by tenfold (from 1.5 microm to 0.15 microm) without destroying the liposome vesicles. At room temperature, the preliposome powder was chemically stable for > 3 months, and the liposome suspension was chemically and physically stable for > 24 h. The in vitro cytotoxicity of the formulation was equivalent to that of the same lipid composition prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the size of liposome suspensions obtained from lyophilized preliposome powders. The formulation described is being used for ongoing clinical trials with liposomal annamycin.
 ...
PMID:Lyophilized preliposomal formulation of the non-cross-resistant anthracycline annamycin: effect of surfactant on liposome formation, stability and size. 899 6

Ashbya gossypii can grow on triacyglycerol as carbon source. A degradation rate of 0.05 g x g-1 mycelial dry mass x h-1 was detected for soybean oil. Although this rate was within the sensitivity range of lipase assays no activity was detectable. On the other hand, extracellular lipase activity could be visualized by clearance halos round the growing mycelium when trioleoylglycerol was emulsified as the sole carbon source in agar plates. Variation of the culture conditions revealed that reduced shaking speed and decreased fat content in the medium led to detectable amounts of lipase in the supernatant of flask cultures. A maximal activity of 800 U x l-1 was obtained after 32 h of cultivation in flasks containing 1% yeast extract and incubated at 60 rpm. Because of its pI of 9.0, the enzyme could be purified in a single step by preparative isoelectric focusing. It appeared as a homogeneous protein in analytical isoelectric focusing and SDS/PAGE (M 35,000). The lipase was inactivated within minutes in stirred gas/water, trioleoylglycerol/water or oleic acid/water mixtures. These effects suggested an interface inactivation. This idea was supported by a stability modulation observed with the surfactant Pluronic F-68. Inactivation by oleic acid led to an aggregation of the lipase shown by gel filtration. Growth experiments performed under lipase-stabilizing conditions revealed a negative influence of glucose, glycerol or oleic acid on detectable lipase activity, probably due to a regulation of lipase formation. Inactivation and regulation thus explained the lack of detectable lipase activity in cultures of A. gossypii growing on triacylglycerol.
 ...
PMID:Regulation and properties of a fungal lipase showing interfacial inactivation by gas bubbles, or droplets of lipid or fatty acid. 906 67


<< Previous 1 2 3 4 5 6 7 8 Next >>