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PubMed1999

Adrenomedullin and membrane fluidity of erythrocytes in mild essential hypertension.

OBJECTIVE: Adrenomedullin is a newly discovered 52 amino acid peptide that has a potent vasodilating action. The present study was undertaken to investigate the role of adrenomedullin in the regulation of membrane fluidity of erythrocytes in patients with essential hypertension. METHODS AND RESULTS: We used an electron paramagnetic resonance and spin-labeling method. Adrenomedullin significantly decreased the order parameter for 5-nitroxide stearate and peak height ratio for 16-nitroxide stearate obtained from electron paramagnetic resonance spectra of erythrocyte membranes in normotensive volunteers (mean +/- SEM order parameter value: control, 0.718 +/- 0.003, n = 16; adrenomedullin at 10(-9) mol/l, 0.692 +/- 0.004, n = 16, P < 0.05; adrenomedullin at 10(-8) mol/l, 0.690 +/- 0.004, n = 16, P < 0.05; adrenomedullin at 10(-7) mol/l, 0.683 +/- 0.004, n = 16, P < 0.05). The findings showed that adrenomedullin increased the membrane fluidity of erythrocytes. In addition, the effect of adrenomedullin was significantly potentiated by prostaglandin E1 and dibutyryl cyclic AMP. In contrast, the calcium ionophore A23187 counteracted the actions of adrenomedullin. In patients with essential hypertension, who had higher order parameter values, the membrane fluidity of erythrocytes was significantly lower than in the normotensive control subjects (order parameter: 0.728 +/- 0.004 in hypertensives, n = 20; 0.692 +/- 0.002 in normotensives, n = 36, P < 0.01). The effect of adrenomedullin on membrane fluidity was more pronounced in the erythrocytes of essential hypertensive than in the erythrocytes of normotensive subjects (change in the order parameter with adrenomedullin at 10(-9) mol/l: -4.2 +/- 0.3% in hypertensives, n = 20; -1.8 +/- 0.2% in normotensives, n = 20, P < 0.05; adrenomedullin at 10(-8) mol/l: -4.5 +/- 0.3% in hypertensives, n = 20; -1.8 +/- 0.2% in normotensives, n = 36, P < 0.05). CONCLUSIONS: The results of the present study demonstrate that adrenomedullin significantly increased the membrane fluidity of erythrocytes. The mechanisms were partially mediated by a prostaglandin E1- and cyclic AMP-dependent pathway which might be linked to changes in intracellular calcium kinetics. The greater effect of adrenomedullin in patients with essential hypertension suggests that the peptide might actively participate in the regulation of membrane functions in hypertension.

Adrenomedullin↗
PubMed1995

Fatty Acid-Elongating Activity in Rapidly Expanding Leek Epidermis.

A microsomal fatty acid elongase activity measured in epidermis of rapidly expanding leek (Allium porrum L.) was 10-fold higher in specific activity than preparations from store-bought leek. These preparations elongated acyl chains effectively using endogenous or supplied primers. Elongation of C20:0 was specifically inhibited by 2 [mu]M cerulenin, and labeling experiments with [3H]cerulenin labeled two polypeptides (65 and 88 kD). ATP was required for maximal elongase activity in expanding leaves but was lost in nonexpanding tissues. Both [14C]stearoyl-coenzyme A (CoA) and [14C]stearate were maximally elongated in the presence of ATP. Addition of fully reduced CoA, however, inhibited [14C]stearate elongation, suggesting that stearoyl-CoA synthesis was not a prerequisite for elongation. Furthermore, microsomes preincubated with [14C]stearoyl-CoA plus ATP resulted in loss of radiolabel from the acyl-CoA pool without a corresponding loss in elongating activity. The lack of correlation between elongating activity and the label retained in the putative acyl-CoA substrate pool suggests that acyl-CoAs may not be the immediate precursors for elongation and that ATP plays a critical, yet undefined, role in the elongation process. We propose that an ATP-dependent elongating activity may generate the long-chain fatty acids required for wax biosynthesis.

Journal Article↗
PubMed1972

Fat Metabolism in Higher Plants: XLVII. The Effect of Nitrite and Other Anions on the Formation of Unsaturated Fatty Acids by Isolated Chloroplasts.

Intact spinach and barley chloroplast normally incorporate (14)C-acetate into palmitate and oleate as the major (14)C fatty acids. Addition of nitrite markedly altered the relative patterns of the products with the appearance of stearate, a drop in oleate, but no marked change in palmitate. Arsenite greatly increased appearance of palmitate with a concomitant decrease in the C(18) fatty acids. The effect of other anions was also examined. Spinach and barley plants grown under different nitrogen nutritional conditions also served as sources of chloroplasts, and their activities suggest a correlation between nitrite reductase activity and stearate accumulation.

Journal Article↗
PubMed1989

A comparison of the various routes of administration of erythromycin in cattle.

A comparison of i.v., i.m. and s.c. administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef-type calves of approximately 200 kg body weight. Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate. Absorption of erythromycin was very slow by both the i.m. and s.c. routes of administration with a Kab of 0.0135 min-1 and 0.0185 min-1 for i.m. and 0.0032 min-1 and 0.0074 min-1 for s.c. at 15 mg/kg and 30 mg/kg, respectively. The bioavailability (32-42%) and peak serum concentrations were much lower with s.c. than with i.m. (60-65%) administration. The disposition of erythromycin administered i.v. appeared to be representative of dose-dependent kinetics rather than dose-independent first-order kinetics inasmuch as the elimination half-time (t1/2B) increased from 174.5 +/- 13 min for the 15 mg/kg dosage to 239 +/- 10.8 min with 30 mg/kg dosage. An acute apparent cardiovascular effect accompanied i.v. administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg. Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.

Absorption↗
PubMed1988

Palmitate binding to serum albumin, measured by rate of dialysis.

Dialysis experiments were performed with an acetylcellulose membrane between two identical sample solutions; a trace amount of radiolabelled palmitate was added on one side and the rate of dialytic equilibration of the label was measured. By comparison with rates measured in standard experiments, using pure albumin solutions, we obtained the reserve albumin concentration for binding of palmitate, previously defined as the concentration of a pure standard albumin which binds the labelled ligand as tightly as it is bound in the sample. Two techniques were developed, one for 1-ml sample volumes, another for 25 microliter. Reserve albumin for binding of palmitate, measured in pure albumin solutions, decreased equally on addition of palmitate and stearate, slightly less with oleate and still less with linoleate, indicating that palmitate and stearate are bound competitively while interaction with binding of the unsaturated acids is less pronounced. Chloride ions compete with binding of palmitate. Reserve albumin concentration in serum samples from 33 male adults was 420 +/- 59 microM (mean +/- SD), and in 33 females, 351 +/- 50 microM. Umbilical cord sera from ten newborn infants averaged 172 +/- 56 microM. The reserve albumin concentrations in the sera of newborn infants are low compared with the normal albumin concentration, which is about 600 microM. This appears to indicate the presence of an albumin species with lower affinity for palmitate.

Adult↗
PubMed1977

Erythromycin jaundice: diagnosis by an in vitro challenge test.

A 53-year-old housewife who had developed severe cholestatic hepatitis following the administration of erythromycin estolate therapy two-and-a-half years previously, was studied by an in vitro "challenge" test in which peripheral venous lymphocytes were cultured in the presence of erythromycin estolate, erythromycin stearate and erythromycin base. Evidence of blastogenesis was observed in response to erythromycin estolate, but not to erythromycin stearate of erythromycin base. This test thus provided evidence that the patient was "sensitized" to erythromycin estolate without exposing her to the risk of in vivo challenge. Furthermore, in contrast to previous studies, the findings provide evidence that erythromycin estolate jaundice is mediated by immunological mechanisms.

Drug Hypersensitivity↗
PubMed1986

Asymmetry of diacylglycerol metabolism in rat cerebral hemispheres.

Diacylglycerols (DGs) were found to be asymmetrically distributed between the two cerebral hemispheres of rat brain. The left cerebral hemisphere (LCH) contained 100% more DG than the right cerebral hemisphere (RCH). The lateralization was enhanced in animals subjected to depolarization induced by a single electroconvulsive shock (ECS). During the acute phase of the convulsion, the DG pool increased in both hemispheres, with the LCH attaining a concentration 180% higher than the RCH. Stearate and arachidonate were the principal DG-acyl groups accumulated in the RCH, whereas in the LCH stearate and palmitate were mainly involved. After the last of a series of five shocks (one per day) the lateralization of the "DG response" was less accentuated during the acute phase of the ECS. Whereas DG release was drastically reduced in the LCH, in the RCH it was minimally affected. The DG sidedness after five shocks was nevertheless maintained at the level of arachidonate-containing DGs, which showed a higher accumulation in the LCH than in the RCH. The kinetics of DG removal showed a rapid phase during the first minute following a single or five ECSs. Total DG levels returned to basal values in the RCH, whereas in the LCH they remained slightly increased with respect to the initial levels 1 min after the convulsive episode. Minimal changes occurred in the subsequent 4 min. Chronic ECS altered the endogenous DG content and composition. Thus, 24 h after the last of four ECSs, total levels of DGs diminished by 40% in the RCH, whereas they remained unchanged in the LCH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Contact dermatitis from the old formula E45 cream.

In the past 4 years, a high incidence (118/362) of positive patch test reactions to E45 cream were noted in 2 patch testing clinics. 18/54 of those patch tested to all the ingredients demonstrated allergies to ingredients. The most frequent was triethanolamine; lanolin allergy occurring in only 1 patient. The remaining reactions may be explained as irritant reactions resulting from triethanolamine stearate (TES) formation within the cream. The irritancy of triethanolamine stearate was demonstrated in patients and controls. Conductivity studies showed that TES arises from the combination of the ingredients triethanolamine and stearic acid. The formulation of E45 cream was being changed at the time of writing, with the removal of triethanolamine from the product.

Chemistry, Pharmaceutical↗
PubMed1979

The release of a model low-dose drug (riboflavine) from hard gelatin capsule formulations.

The in vitro release of a model low dose drug, riboflavine, from hard gelatin capsules, formulated with a range of diluents, in the absence and presence of magnesium stearate (0.5, 1.0 and 2.0% w/w), has been assessed by a dissolution technique. Comparison of the values of the time for 50% of the drug content of the capsule to appear in solution T50, by analysis of variance, indicated that the type of diluent significantly influenced the drug release. Irrespective of the magnesium stearate content, the diluents could be ranked in the following order of effectiveness: Primojel greater than sodium bicarbonate greater than Avicel congruent to Dri-flo starch congruent to lactose greater than Emcompress congruent to kaolin greater than starch. Correction of the T50 values for possible adsorption of riboflavine onto the water insoluble diluents, using experimentally determined adsorption isotherms, altered the relative order of effectiveness of the diluents to Primojel greater than sodium bicarbonate greater than kaolin congruent to lactose greater than Avicel congruent to Dri-flo starch greater than Emcompress greater than starch. Comparison of the urinary excretion of riboflavine, after administration of capsule formulations containing lactose, Emcompress or kaolin as the diluent, to volunteers, suggests that the dissolution results not corrected for adsorption provide a better indication of the in vivo performance of the formulations.

Capsules↗
PubMed1988

Variations in the friction coefficients of tablet lubricants and relationship to their physicochemical properties.

A previously described modified annular shear cell (MASC) has been used to measure the friction coefficients of some powdered tablet lubricants on a steel surface. Commonly used lubricants, as well as others belonging to the stearate group, differed in their friction coefficients at equivalent sample sizes and in the degree of their ability to reduce friction with increasing amounts when evaluated by the apparatus. In all comparisons, magnesium stearate had the lowest friction coefficient. Divalent salts of stearic acid appeared to be better than the other lubricants tested, and among themselves differed only in the extent of their ability to decrease friction. The lubricants also differed in their physical and chemical properties. On evaluation by stepwise regression analysis, such physical properties as projected surface area of lubricant particles, Martin's diameter and bulk density accounted for most of the variation in friction coefficients of the lubricants rather than moisture content or melting point. It could therefore be suggested that particle size and/or surface area parameters be incorporated in product specifications to ensure reproducible functionality.

Chemical Phenomena↗
PubMed1992

Compatibility study between acetylcysteine and some commonly used tablet excipients.

Differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), HPLC and TLC were used to investigate the interactions between the mucolytic drug acetylcysteine and a number of commonly used tablet and capsule excipients. Acetylcysteine was found to be compatible with microcrystalline cellulose (Avicel PH 101), sodium carboxymethylcellulose, amorphous silicon dioxide (Aerosil), PVP, cross-linked PVP (Polyplasdone XL), corn starch, saccharose and magnesium stearate. Acetylcysteine thermal stability (onset degradation temperature) was decreased in mixtures with corn starch, magnesium stearate, saccharose and lactose. Interactions of acetylcysteine with lactose, PEG 4000 and 6000, glycine, adipic acid and saccharin sodium were found using DSC and studied in detail with FT-IR, HPLC and TLC. The results suggest that acetylcysteine in mixtures with PEG 4000, glycine or saccharin sodium is degraded during storage at conditions of high temperature and humidity.

Acetylcysteine↗
PubMed1995

Tableting characteristics of micro-aggregated egg albumin particles containing paracetamol.

The tableting characteristics of micro-aggregated egg albumin particles containing paracetamol were evaluated and compared with non-micro-encapsulated paracetamol and coagulated egg albumin particles. Mean yield pressure values of micro-aggregated egg albumin particles containing paracetamol and coagulated egg albumin particles were 30.5 and 49.3 MPa, respectively, which were lower than the mean yield pressure obtained for paracetamol (97.5 MPa). Paracetamol tablets obtained with micro-aggregated egg albumin particles did not show the capping characteristic of conventional paracetamol tablets. Crushing strength of paracetamol tablets obtained with egg micro-aggegated particles was similar to that obtained using paracetamol granulated with povidone and gelatin as binders at 3 and 6% (w/w) concentrations. Drug release from the paracetamol tablets depends on the choice of excipients. Crospovidone showed good protective characteristics for the tableting of micro-aggregated particles. Crushing strength of paracetamol tablets formed from egg albumin-coated particles could be increased using crospovidone or microcrystalline cellulose as fillers and was decreased by the use of magnesium stearate. Nevertheless, magnesium stearate was useful to decrease the ejection force.

Acetaminophen↗
PubMed1968

Osmotic stability of blood platelets.

1. Hypotonic solutions added to human platelet-containing plasma cause a transient decrease of absorbancy of light at 610 mmu which is followed by a gradual increase of absorbancy.2. When platelets are stored for 7 hr at 4 degrees C the absorbancy changes with variations of osmolarity and their aggregation with adenosine diphosphate (ADP) remain the same. However, the reversal of absorbancy declines during storage of platelet-containing plasma.3. Platelets are not aggregated by stearate. Platelets appear to be only slightly affected by stearate concentration higher than 0.8 mM, but oleate has no effect.4. Hypertonic solutions of NaCl and urea cause increase in absorbancy of platelet-containing human plasma. Hypertonic sucrose solutions produce no more change than isotonic solutions. Hypertonic NaCl produces permanent increases in absorbancy. In human platelet-containing plasma the increased absorbancy caused by hypertonic urea is transient and declines.5. The osmotic platelet changes occur in isolated platelets as well as in platelet-containing plasma.6. The absorbancy of frozen and thawed platelet-containing plasma is not significantly altered by hypotonic solutions but the absorbancy changes caused by hypertonic solutions are similar to that of unfrozen plasma.7. The immediate absorbancy changes caused by hypo- and by hypertonic solutions are the same at 5 degrees C and 30 degrees C and are therefore probably of a physical nature. The reversal of absorbancy and aggregation of platelets by added adenosine diphosphate have Q(10) > 1 and are therefore probably of a chemical-enzymic nature.8. Divalent cations and contact activation are not required for the osmotic platelet changes and 10(-3)M-Cu(2+) and Zn(2+) do not interfere. Inhibitors of oxidative phosphorylation, electron transfer, sodium, potassium activated adenosine triphosphatases and adenosine triphosphate do not inhibit reversal of absorbancy of platelets exposed to hypotonic solutions. Cyanide, 5 x 10(-3)M, fluoride, 1.23 x 10(-2)M, iodoacetamide, 10(-2)M, are moderately effective inhibitors. At hydrogen ion concentrations above pH 8, complete inhibition occurs.9. N-ethyl-maleimide, 10(-3)M, and mercloran inhibit completely reversal of absorbancy, indicating the necessity for sulphydryl compounds.10. Intact platelets are essential for the reversal of absorbancy after hypotonic swelling. Osmotic changes by hypotonic solutions are independent of ADP aggregation of platelets.

Adenine Nucleotides↗
PubMed1982

Isoelectric points and surface hydrophobicity of Gram-positive cocci as determined by cross-partition and hydrophobic affinity partition in aqueous two-phase systems.

Thirty-nine streptococcal strains belonging to groups A, C, and G and 12 staphylococcal strains were investigated with respect to surface charge and hydrophobicity. Isoelectric points of the bacteria were determined by cross-partition experiments in dextran-polyethylene glycol two-phase systems containing charged polymers. The results obtained indicate that group A, C, and G streptococci have isoelectric points of pH 3.75 +/- 0.15 standard deviation. Staphylococci show an isoelectric point of around pH 2 and thereby differ markedly from the streptococci. Pretreatment of bacteria with human serum resulted in a significant change in the isoelectric points of streptococci. In a second series of experiments, an aqueous dextran-polyethylene glycol two-phase system containing polyethylene glycol palmitate or stearate was used to study the hydrophobic surface properties of the bacterial cells. The partition of the staphylococci was not influenced by the addition of up to 1% (wt/wt) polyethylene glycol palmitate or stearate, whereas the streptococci showed a large variation in affinity for polyethylene glycol-bound hydrophobic groups. The bacterial strains included in the study were also tested for uptake of human serum proteins. A positive correlation was found between the hydrophobic affinity of group A streptococci and the density of receptors for aggregated beta-2-microglobulin.

Blood↗
PubMed1983

Erythromycin estolate and jaundice.

Using prescription-event monitoring to determine whether erythromycin estolate was a more frequent cause of jaundice than erythromycin stearate or tetracycline 12 208 patients, for whom 5343 doctors had prescribed one of the three drugs, were identified by the Prescription Pricing Authority. Of the questionnaires sent to general practitioners about the possible occurrence of jaundice, 76% were returned. There were 16 reports of jaundice, of which four were attributable to gall stones, three to cancer, six to viral hepatitis, and only three were possibly related to an antibiotic. All three patients, in whom the antibiotic was a possible cause, had been treated with erythromycin stearate. No case was attributable to the estolate which had previously been suspected of being a more frequent cause of jaundice. Although the incidence is unknown, it is very unlikely to be more than one in 100.

Adolescent↗
PubMed1969

X-ray diffraction studies of the composition of gallstones from English and Australian patients.

The crystalline composition of two collections of gallstones from patients in England and Australia have been determined by the x-ray powder diffraction technique. Twelve substances have been identified including a form of cholesterol which hitherto has not been reported. The weighted percentage composition averaged over each collection shows that cholesterol is the major constituent of the Australian stones and cholesterol and cholesterol monohydrate the major constituents of the English calculi. The cholesterol is possibly a decomposition product of the monohydrate. The calcium carbonates-calcite, aragonite, and vaterite-constitute most of the remainder of the calculi. Although their percentage composition is much smaller than that of the cholesterols, they are nevertheless present in a high proportion of stones. Small traces of apatite, whitlockite, sodium chloride, calcium stearate and palmitic acid (or other long-chain compounds having closely related spacings) have been found. Small spheroids scattered throughout some stones appear to be mainly calcium stearate, although the total quantity available is too small and too impure for a definite identification.

Apatites↗
PubMed1983

Chronic alcoholic skeletal muscle myopathy: a clinical, histological and biochemical assessment of muscle lipid.

Muscle biopsy samples were analysed from five control subjects, four patients with mild to moderate fibre atrophy and four patients with severe atrophy. Patchy increase in lipid was noted with oil red O staining but there was no consistent association of lipid with selective fibre types. Ultrastructural studies demonstrated lipid droplets both subjacent to the sarcolemma and between fibrils. Quantitative analysis showed that the increased lipid was solely due to excess triglyceride. GLC analysis of free and esterified acids was performed. The profiles were essentially similar for the phospholipid and free fatty acid fractions. The triglyceride fraction showed a decrease of myristate, stearate and linoleate with an increase in oleate and arachidate in the alcoholic tissue compared with control. The cholesteryl ester fraction showed an increase in palmitate with a decrease in stearate and oleate in the alcoholic muscle. The accumulation of lipid correlated with mean daily alcohol consumption but not with degree of atrophy suggesting that the two processes probably had different pathogenic mechanisms.

Adult↗
PubMed1981

Fluorimetric and microbiological assays of erythromycin concentrations in plasma and vaginal washings.

Using a microbiological and a fluorimetric assay to determine penetration of erythromycin into vaginal fluids, concentrations were measured in plasma from nine men one hour after a single oral dose of erythromycin stearate 2 g and in vaginal washings and plasma samples taken simultaneously from 11 women two hours after the last dose of a 10-day course of erythromycin stearate (250 mg four times daily). Both assay methods gave accurate and reproducible results in plasma but only the fluorimetric method was capable of measuring concentrations of erythromycin in vaginal washings. The latter method had many advantages in estimating drug concentrations in body fluids such as vaginal washings and the results from it may provide an index of tissue penetration and of patient compliance in adhering to drug regimens.

Adolescent↗