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PubMedDate not supplied

Prediction of steady-state concentrations of valproic acid as determined from single plasma concentrations after the first dose.

A mathematical equation that predicts the maintenance dose needed to achieve a desired steady-state plasma concentration (Css) for first-order drugs from a single plasma concentration drawn after a single dose was tested for valproic acid. Six healthy volunteers received a single oral 500-mg dose of valproic acid and plasma concentrations were determined at 0, 1, 2, 4, 6, 8, 10, 24, and 32 hours. Each subject then received 750 mg of valproic acid daily in three divided doses for four days and a Css was determined. The equation was rearranged to predict the Css of valproic acid from plasma concentrations drawn at 1, 2, 4, 6, 8, and 10 hours after the single dose of valproic acid, using individually determined and mean terminal rate constant (k) values. The predicted Css were then compared with the actual Css. There was no difference in the predicted and actual Css using plasma concentrations collected at 6, 8, or 10 hours regardless of the derivation of the k values. The four-hour concentration predicted a lower Css if the mean (rather than the individual) k values were used. The one- and two-hour concentrations were not accurate predictors. While a 6-, 8-, or 10-hour plasma concentration would be adequate for predicting the Css, the 10-hour concentration had the least difference between the predicted and actual values. The time and cost of titrating valproic acid to a desired Css may be decreased by using this mathematical equation to predict the necessary maintenance dose.

Adult↗

PubMed1998

Follicular fluid immunoreactive-inhibin concentrations in relation to follicular diameter and estradiol-17 beta, progesterone and testosterone concentrations in individual ovarian follicles in buffalo, Bubalus bubalis.

The objective of this study was to measure the concentrations of immunoreactive inhibin (ir-inhibin) in follicular fluid from individual ovarian follicles and relate them to follicular diameter and follicular fluid concentrations of estradiol-17 beta, progesterone and testosterone in buffalo. Follicular size was measured with an ultrasound machine and follicles were categorized as small (4 to 5 mm diam.), medium (6 to 9 mm diam.) and large (10 mm and above in diam.). Ir-inhibin concentrations varied markedly between and within follicles of same size category. Follicular fluid ir-inhibin concentrations (microgram/ml) were positively related to follicular diameter (R = 0.32, n = 262, P < 0.001) and were significantly higher (P < 0.05) in large (8.32 +/- 0.56) in comparison to medium (7.02 +/- 0.31) follicles which, in turn had inhibin concentrations significantly higher (P < 0.001) than those in small follicles (5.13 +/- 0.48). Ir-inhibin and estradiol-17 beta concentrations were positively related in medium (R = 0.38, n = 128, P < 0.001) and large (R = 0.64, n = 35, P < 0.001) but not in small follicles. There was a negative relationship between ir-inhibin and progesterone concentrations in large follicles (R = 0.46, n = 33, P < 0.01), with no relationship between the two hormones in small and medium follicles. Ir-inhibin was positively related to molar ratios of estradiol-17 beta to progesterone in medium (R = 0.30, n = 124, P < 0.01) and large (R = 0.49, n = 24, P < 0.01) but not in small follicles. There was no relationship between ir-inhibin and testosterone concentrations in follicles of all size categories. The results of the present study suggest that follicular inhibin production is related to follicular size as well as intrafollicular estradiol-17 beta and progesterone concentrations.

Animals↗

PubMed1976

Abomasal displacement in cattle: influence of concentrates in the ration on fatty acid concentrations in ruminal, abomasal, and duodenal contents.

The primary causative factor in abomasal displacement appears to be atony or hypotony of the abomasum. Seemingly, high-concentrate feeding inhibits abomasal motility by increasing the amount of fatty acids which enter the abomasum. In the present study, cows with ruminal, abomasal, and duodenal fistulas were fed a hay ad libitum ration or a hay and concentration ration and were compared. It was shown that a considerable increase in ruminal volatile free fatty acid (VFFA) concentrations was not followed by a subsequent increase in abomasal VFFA concentrations. Differences in abomasal VFFA levels between the 2 rations could not be found. There was a slight, but insignificant, increase in duodenal VFFA concentrations after cows were fed the hay ration. One cow given the hay and concentrate diet had a small, but significant, increase in duodenal VFFA concentrations during the first 2 hours after feeding. The VFFA concentrations in duodenal fluid were too low to support the hypothesis that changes in duodenal VFFA concentrations could be responsible for abomasal hypotony.

Abomasum↗

PubMed2000

Plasma insulin concentration is more tightly linked to plasma leptin concentration than is the body mass index.

This study tested the hypothesis that the integrated plasma insulin response to oral glucose is a more sensitive predictor of the fasting plasma leptin concentration than the body mass index (BMI) or waist to hip ratio (WHR). For this purpose, we determined the fasting plasma leptin concentration and plasma insulin response to a 75-g oral glucose challenge in 76 healthy female subjects, with a BMI of 19.1 to 36.6 kg/m2 and a WHR of 0.57 to 1.1. The results demonstrated that fasting plasma leptin concentrations were significantly correlated with both the BMI (r = .64, P < .001) and the plasma insulin response to glucose (r = .61, P < .001), but not with the WHR (r = .27). Since the BMI and the insulin response were also significantly related (r = .34, P = .003), multivariate analysis was performed to determine if the BMI and insulin response were independent determinants of the fasting leptin concentration. This analysis indicated that both the BMI and insulin response were significantly related to plasma leptin (P < .001). To pursue this issue further, the population was divided into tertiles on the basis of the (1) plasma leptin concentration, (2) BMI, and (3) integrated insulin response. The two variables that were most closely linked to each other were the leptin concentration and insulin response. In contrast, the BMI was relatively easily disassociated from the other two variables. These results indicate that while both the plasma insulin response to glucose and the BMI are significantly associated with the fasting plasma leptin concentration, the plasma insulin response appears more closely associated with the plasma leptin concentration.

Administration, Oral↗

PubMedDate not supplied

Saliva concentrations of disopyramide cannot substitute the drug's plasma concentrations.

For many drugs the salivary concentration corresponds to the free plasma drug concentration, which may be more closely related to drug activity or toxicity than the total plasma drug concentration. In this study a preliminary investigation was undertaken to determine the feasibility of monitoring saliva levels of disopyramide, an antiarrhythmic drug, for clinical and toxicological purposes. Single oral doses of this compound were administered to healthy volunteers. Stimulated mixed saliva and plasma levels were measured by the EMIT technique. The concentrations of disopyramide in the stimulated mixed saliva tended to be lower than those found in the corresponding plasma sample (fp 0.3-0.5), and the saliva-to-plasma concentration ratio increased with a decreasing salivary pH (pH 6.89, S/P = 0.25; pH 8.15, S/P = 0.08). The correlation between the saliva and the total plasma concentrations was significant but relatively poor, however. Consequently, mixed salivary disopyramide concentrations are a poor indicator of plasma concentrations, even if correction is made for pH change.

Disopyramide↗

PubMed1989

Serum phosphate concentration. Effect on serum ionized calcium concentration in vitro.

We examined the effects of variations of serum phosphate levels on serum ionized calcium concentrations in vitro. A single donor serum sample was divided into 25 aliquots stored in tubes sealed with carbon dioxide and divided into 5 subsets of tubes. The pH was altered in 4 of the 5 subsets by adding various concentrations of hydrochloric acid or sodium hydroxide. The pH levels studied ranged from 7.09 to 7.63. The phosphate concentration was altered in each subset by adding various concentrations of a phosphate buffer. The phosphate concentrations studied ranged between 0.81 and 3.58 mmol/L. There was an inverse relationship between ionized calcium and phosphate at all pH levels studied. The ionized calcium concentration correlated inversely with pH. We suggest that in addition to factors well known to influence serum ionized calcium concentration (such as protein, bicarbonate, and pH values), serum phosphate concentration also plays an important role.

Calcium↗

PubMed1989

Relationship between concentration and anticonvulsant effect of phenytoin against electroshock-induced seizures in rats: comparison of sampling sites for concentration determinations.

The purpose of this investigation was to determine the optimum sampling site for phenytoin concentration measurements in the context of pharmacodynamic studies of the anticonvulsant effect of phenytoin. Determination of drug concentrations in the serum, serum water, brain, and cerebrospinal fluid (CSF) of rats as a function of time after iv injection of a 6-mg/kg dose revealed a significant disequilibrium between brain and serum water for 15 min and between CSF and serum water for 5 min after injection. The concentrations of phenytoin in serum water 1 min after injection of 3 mg/kg (0.371 +/- 0.054 microgram/mL) and 45 min after injection of 8 mg/kg (0.399 +/- 0.049 microgram/mL) were not significantly different, but drug concentrations in the CSF and brain were appreciably higher after the latter dose. There was no protection against electroshock-induced seizures 1 min after the 3-mg/kg dose, but there was complete protection 45 min after the 8-mg/kg dose. At 15 min after drug injection, phenytoin concentrations in CSF and serum water were essentially identical over a wide concentration range. Fifty female Lewis rats weighing approximately 225 g, that consistently exhibited maximal electroshock-induced seizures in three preliminary trials on separate days, received 1, 2, 4, 6, or 8 mg/kg of phenytoin by iv injection. Electroshock was applied 15 min later, the percentage of animals protected from seizure by each dose was determined, and drug concentrations in serum, serum water, brain, and CSF were measured by gas chromatography. The relationship between anticonvulsant activity and drug concentration could be described by a Hill-type equation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2006

The effect of dietary taurine supplementation on plasma and liver lipid concentrations and free amino acid concentrations in rats fed a high-cholesterol diet.

The purpose of this study was to investigate the effect of dietary taurine supplementation on plasma and liver lipid concentrations, and free amino acid concentrations in rats fed a high-cholesterol diet. Twenty male rats (body weight 151 +/- 1.9 g) were randomly divided into two groups. The rats in the control group were fed on 1.5% cholesterol diet (control) and those in the experimental group were fed with 1.5% cholesterol and 1.5% taurine diet (TSD). All rats were fed with the experimental diets and deionized water ad libitum for 5 weeks. The plasma glucose and lipid concentrations were measured using commercial kits with enzymatic methods and liver lipid concentrations with the Folch method. The concentrations of free amino acids in plasma were determined with an automated amino acid analyzer based on ion-exchange chromatography. There were no significant differences in the body weight gain, food intake and food efficiency ratio between the control and experimental groups. The rats fed TSD had significantly lower liver weight and liver weight/body weight ratio than those fed control diet. The plasma concentrations of total cholesterol, glucose and LDL-cholesterol were significantly reduced in the rats fed TSD compared to those fed control diet. The rats fed TSD showed significantly decreased liver levels of cholesterol and triglyceride. The HDL-cholesterol level was higher in the rats fed TSD than those fed control diet. The plasma taurine concentrations were not significantly different between two groups. They exhibited significant negative correlation with the plasma total cholesterol and liver triglyceride concentrations. These results suggest the possible role of taurine as a hypocholesterolemic agent in the rats fed a high cholesterol diet. Taurine supplementation did not cause any characteristic changes in the plasma aminogram pattern, body weight gain, and food intake.

Amino Acids↗

PubMed1999

Unbound plasma concentrations may predict neuroprotective brain concentrations: a brain microdialysis and pharmacokinetic study of enadoline in rats.

A rat brain microdialysis study of enadoline (CI-977), a k-opioid agonist, was conducted in nonanesthetized healthy rats to determine brain extracellular fluid (ECF) concentrations of CI-977 associated with neuroprotective subcutaneous (s.c.) doses. Three groups of 3 to 4 nonanesthetized yet restrained Sprague-Dawley rats with jugular cannulas and implanted brain (striatum) microdialysis probes received single s.c. doses of 0.3, 1.0, or 3.0 mg/kg CI-977. Blood and microdialysate samples were collected over a 12-hour period. Extent of rat plasma protein binding was 77.5%. Unbound plasma concentrations associated with neuroprotection were 10-50 ng eq/mL. At each dose, brain ECF concentration-time profiles (corrected for probe recovery) were nearly coincident with enadoline plasma unbound concentration-time profiles. Consequently, at each dose the ratio of AUCecf/AUCffplasma, (AUC = Area Under the concentration-time Curve; ffplasma = free fraction in plasma = unbound plasma) which represents the distribution of drug between plasma and brain, was determined to be unity within experimental error. These results suggest that unbound plasma concentrations may predict brain ECF concentrations of CI-977. Further, our findings allow us to postulate enadoline unbound brain ECF concentrations necessary for neuroprotection.

Animals↗

PubMed2006

Fresh frozen plasma and platelet concentrates may increase plasma anti-diphtheria toxin IgG concentrations: Implications for diphtheria fusion protein therapy.

We are developing two fusion proteins consisting of a diphtheria toxin (DT) linked to either granulocyte macrophage colony stimulating factor (DT388-GMCSF) or interleukin-3 (DT388-IL3). In trials, patients with anti-DT IgG concentrations >2.5 microg/ml had significantly lower concentrations of either fusion protein. DT389-IL2 is currently FDA approved for the treatment of cutaneous T-cell lymphomas. We noted increased concentrations of anti-DT IgG after administration of platelet concentrates (PC). Because many of these patients require transfusions, we measured the anti-DT IgG content of FFP and PC. We assayed 14 bags of FFP and 12 bags of single-donor PCs for anti-DT IgG by an enzymoimmunoassay against DT389-IL2, DT388-IL3, DT388-GMCSF. The median (percent of samples positive) of anti-DT IgG concentrations in PC against DT388-GMCSF, DT388-IL3, DT389-IL2 was 0.8 microg/ml (83%), 0.7 microg/ml (83%), and 0.3 microg/ml (58%), respectively. The median (percent of samples positive) anti-DT IgG concentration in FFP against DT388-GMCSF, DT388-IL3, and DT389-IL2 was 2.1 microg/ml (86%), 1.9 microg/ml (93%), and 1.4 microg/ml (86%), respectively. There was a strong association between anti-DT389IL2 IgG, anti-DT388IL3 IgG, and anti-DT388GMCSF IgG concentrations in both the FFP (95.6%) and PC (76.3%). Assuming a plasma volume of 3 l in a 70 kg patient, a single FFP unit would increase the plasma anti-DT389IL2 IgG, anti-DT388IL3 IgG, and anti-DT388GMCSF IgG by 0.13 microg/ml, 0.17 microg/ml, and 0.19 microg/ml, respectively. For PC, a single unit would increase plasma anti-DT389-IL2 IgG, anti-DT388-IL3 IgG, and anti-DT388-GMCSF IgG by 0.03 microg/ml, 0.06 microg/ml, and 0.07 microg/ml, respectively. In conclusion, a single FFP or PC appears to minimally increase anti-DT IgG concentrations, but multiple units may significantly do such.

Blood Platelets↗

PubMed1984

Relations between fatty acid synthesis, pyruvate concentration and cell concentration of suspensions of isolated rat hepatocytes.

The cell concentration of suspensions of isolated rat hepatocytes affects both the rate of pyruvate accumulation in the incubation medium and the rate of fatty acid synthesis. At low cell concentrations pyruvate accumulation is directly related to the cell concentration but levels off at higher concentrations even when maximum pyruvate concentrations in the medium are not yet reached. The rate of fatty acid synthesis in the 30-60-min incubation interval is proportional to the cell concentration. In contrast, the rate of fatty acid synthesis during the 0-30-min incubation period decreases with increasing cell concentrations and subsequently becomes independent of the cell concentration.

Animals↗

PubMed1990

Associations of lecithin: cholesterol acyltransferase (LCAT) mass concentrations with exercise, weight loss, and plasma lipoprotein subfraction concentrations in men.

The relationships between plasma lecithin:cholesterol acyltransferase (LCAT) mass concentrations and lipids, apolipoprotein, and lipoprotein subfraction concentrations were studied in men assigned at random to a one-year exercise program (n = 48) and to a sedentary control condition (n = 31). Exercise training did not significantly affect mean concentrations of LCAT-mass. Moreover changes in LCAT within the exercise group were unrelated to distance run and weight loss. The baseline data and the one-year change data showed consistent positive correlations between LCAT concentrations and total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, and apolipoprotein B concentrations, and consistently weak correlations between LCAT concentrations and high density lipoprotein (HDL)-cholesterol, HDL2, and apolipoprotein A-I concentrations. The strong correlation between LCAT and total cholesterol may account for LCAT's relationships with lipoprotein subfractions, apolipoprotein B and other lipoprotein cholesterol concentrations.

Adult↗

PubMed2005

Chloride concentration affects Kv channel voltage-gating kinetics: Importance of experimental anion concentrations.

Chloride concentration has been shown to have a dramatic impact on protein folding and subsequent tertiary conformation [K.D. Collins, Ions from the Hofmeister series and osmolytes: effects on proteins in solution and in the crystallization process, Methods 34 (2004) 300-311; I. Jelesarov, E. Durr, R.M. Thomas, H.R. Bosshard, Salt effects on hydrophobic interaction and charge screening in the folding of a negatively charged peptide to a coiled coil (leucine zipper), Biochemistry 37 (1998) 7539-7550]. As it is known that Kv channel gating is linked to the stability of the cytoplasmic T1 multimerization domain conformation [D.L. Minor, Y.F. Lin, B.C. Mobley, A. Avelar, Y.N. Jan, L.Y. Jan, J.M. Berger, The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel, Cell 102 (2000) 657-670; B.A. Yi, D.L. Minor Jr., Y.F. Lin, Y.N. Jan, L.Y. Jan, Controlling potassium channel activities: interplay between the membrane and intracellular factors, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 11016-11023] and that intracellular chloride concentration has been linked to Kv channel kinetics [L.K. Bekar, W. Walz, Intracellular chloride modulates A-type potassium currents in astrocytes, Glia 39 (2002) 207-216; W.B. Thoreson, S.L. Stella, Anion modulation of calcium current voltage dependence and amplitude in salamander rods, Biochim. Biophys. Acta 1464 (2000) 142-150], the objective of the present study was to address how chloride concentration changes affect Kv channel kinetics more closely in an isolated expression system. Initially, no significant chloride concentration-dependent effects on channel steady-state gating kinetics were observed. Only after disruption of the cytoskeleton with cytochalasin-D did we see significant chloride concentration-dependent shifts in gating kinetics. This suggests that the shift in gating kinetics is mediated through effects of intracellular chloride concentration on cytoplasmic domain tertiary conformation as cytoskeletal interaction appears to mask the effect. Furthermore, as cytoskeletal disruption only impacts channel gating kinetics at low physiological intracellular chloride concentrations, these studies highlight the importance of paying close attention to anion concentrations used under experimental conditions.

Cell Line↗

PubMed2006

Nonsupplemented children of Latino immigrants have low vitamin E intakes and plasma concentrations and normal vitamin C, selenium, and carotenoid intakes and plasma concentrations.

OBJECTIVE: This study sought to determine and evaluate the intakes and plasma concentrations of vitamin E (alpha-tocopherol), gamma-tocopherol, vitamin C, selenium, and carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene) of nonsupplemented boys and girls, 4 to 8 years old, of Latino immigrants living in rural Nebraska. DESIGN: Dietary intakes of the Latino children were estimated. Their plasma samples (fasting) were analyzed for vitamin E, vitamin C, selenium, and carotenoid concentrations. Data were evaluated by sex. SUBJECTS: The subjects were a convenience sample of 4- to 8-year-old (n=29), apparently healthy, nonsupplemented children of Latino immigrants living in rural Nebraska. STATISTICAL ANALYSIS: Sex differences in parameter values were determined using general linear models; Pearson r was used for determining correlations. RESULTS: No significant differences in parameter values were observed by sex, with the exception of plasma lutein/zeaxanthin concentration. The majority (69%) had plasma vitamin E (alpha-tocopherol) concentrations<0.516 mg/dL (12 micromol/L), which is indicative of vitamin E inadequacy, and over half (59%) reported consuming less than the Estimated Average Requirement for vitamin E. All subjects had plasma vitamin C and selenium concentrations indicative of adequacy (>0.41 mg/dL or >23 micromol/L, and >6.32 microg/dL or >0.8 micromol/L, respectively), and consumed at least the Recommended Dietary Allowances for these nutrients. The plasma carotenoid concentrations of the children may be useful as norms. CONCLUSIONS: These children of Latino immigrants who did not take supplements had low plasma vitamin E (alpha-tocopherol) concentrations but normal plasma vitamin C and selenium concentrations. IMPLICATIONS: Dietetics professionals and others involved in health care need to work with Latino immigrant parents so that their children consume adequate amounts of vitamin E.

Ascorbic Acid↗

PubMed2004

Increased (E)-4-hydroxy-2-nonenal and asymmetric dimethylarginine concentrations and decreased nitric oxide concentrations in the plasma of patients with major depression.

BACKGROUND: (E)-4-Hydroxy-2-nonenal (HNE) is a highly electrophilic end-product of lipid peroxidation. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (NOS). ADMA is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). DDAH contains a nucleophilic cysteine residue in its active site. There is an increase in lipid peroxidation in major depression. Major depression is associated with the development of coronary heart disease (CHD) and greatly increases morbidity and mortality. There is an increase in circulating ADMA in CHD and vascular risk factors. OBJECTIVES: To determine plasma HNE, ADME and nitric oxide (NO) concentrations in patients with major depression compared to normal volunteers and to examine the effect of HNE on ADMA formation and DDAH activity in cultured endothelial cells. METHODS: The study was conducted in 25 patients with major depression (DSM-IV criteria) and 25 healthy control subjects. Plasma concentrations of HNE were determined as the O-pentafluorylbenzyl oxime using capillary column GC-MS and deuterated HNE as the internal standard; ADME by LC-MS-MS using 13C6-L-arginine as the internal standard; and NO by GC-MS following reduction to nitrate and nitrite and derivatisation to the pentafluorobenzyl derivative using [15N]nitrate and [15N]nitrite as the internal standards. Human umbilical vein endothelial cells were incubated in serum-free medium in the presence of HNE. The concentration of ADMA in the medium was determined by LC-MS-MS. DDAH activity was determined by measuring L-citrulline in endothelial cell lysates using LC-MS. RESULTS: There was a significant increase in the plasma concentration of HNE (P<0.0001) and ADMA (P<0.0002) in patients with major depression. There was a significant decrease in the plasma concentration of NO (P<0.0001). A significant positive correlation was found between the plasma concentrations of HNE and ADMA (r=0.63, P<0.0001). A significant negative correlation was detected between the plasma concentrations of ADMA and NO (r=-0.595, P<0.0001). HNE significantly increased ADMA formation (P<0.0001) and significantly decreased DDAH activity (P<0.0001) in cultured endothelial cells. The effects of HNE on DDAH activity were significantly attenuated by the addition of glutathione (P<0.0001). LIMITATIONS: No allowance was made for the phase of the menstrual cycle which could influence plasma nitric oxide concentrations. CONCLUSIONS: There is an increase in circulating HNE in major depression. HNE inactivates the cysteine residue in the active site of endothelial DDAH leading to the accumulation of ADMA in the circulation. The ADMA then decreases the production of eNOS. This could reduce the amount of NO diffusing from cerebral blood vessels to nearby neurons and influence the release of neurotransmitters. ADMA also constricts cerebral blood vessels and may contribute to the decreased regional perfusion in major depression. The accumulation of ADMA could explain the increased risk of CHD in major depression. The preservation of DDAH activity and the reduction of ADMA accumulation may represent a novel therapeutic approach to the treatment of major depression.

Aldehydes↗

PubMed2003

Despite the general correlation of the serotonin transporter gene regulatory region polymorphism (5-HTTLPR) and platelet serotonin concentration, lower platelet serotonin concentration in migraine patients is independent of the 5-HTTLPR variants.

Platelet serotonin (5-HT) concentrations in a headache-free period during the mid-follicular phase and the serotonin transporter gene regulatory region polymorphism (5-HTTLPR) were measured in female migraine patients without aura (n = 64) and healthy controls (n = 42). High-pressure liquid chromatography (HPLC) was used to determine the platelet 5-HT concentration and genetic polymorphism was determined by polymerase chain reaction. Significantly lower platelet 5-HT concentrations were found in migraine patients compared to controls. Concerning the 5-HTTLPR polymorphism, the S/S genotype was associated with a significantly higher platelet 5-HT concentration (P = 0.027) in the whole study population. This association between the 5-HTTLPR genotypes and platelet 5-HT concentrations was independent of the diagnosis. In addition, the platelet 5-HT concentration was lower in migraineurs in all genotypes (S/S, S/L, L/L). In conclusion, 5-HTTLPR variants may have an effect on the platelet 5-HT concentrations, but the lower 5-HT concentrations in migraine patients seem to be determined by other factors.

Adult↗

PubMed2003

Concentrations of low and high molecular weight thiols in wheat dough as affected by different concentrations of ascorbic acid.

Different amounts of ascorbic acid (AA) were added to flour, and the concentrations of low and high molecular weight thiols in the dough were determined. For the determination of the low molecular weight thiols, glutathione, cysteine, and the corresponding disulfides, an isotope dilution assay with a (14)C-labeled internal standard was used. For the determination of the high molecular weight thiols, a method was developed that involved derivatization of dough with Ellman's reagent, removal of excess reagent by dialysis, micro-Osborne fractionation, release of the label by reduction, and determination of reduced Ellman's reagent by reversed-phase high-performance liquid chromatography. Mixing of flour without AA led to a decrease of the glutathione and an increase of the cysteine concentration. Addition of AA reduced the concentration of both thiols to a minimum when 125 mg of AA/kg of flour was applied. Furthermore, the concentrations of high molecular weight thiols in the glutenins of flours from different wheat cultivars were determined. The values ranged from 5.6 to 8.2 micromol/kg of protein and showed a correlation between flour quality and SH concentration. On addition of AA and mixing of a dough, the concentrations of the protein thiols in the glutenins isolated from the dough increased to a maximum when 100 mg of AA/kg of flour was added. Higher concentrations of AA led to a decrease of the SH concentration. The last results are not in accordance with previously published data or with current hypotheses about the mechanism of the AA improver action.

Ascorbic Acid↗

PubMed2003

The minimally effective concentration of adrenaline in a low-concentration thoracic epidural analgesic infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomized, double-blind, dose-finding study.

BACKGROUND: We have documented that adrenaline 2.0 micro g.ml- 1 markedly improves relief of dynamic pain when added to a thoracic epidural analgesic infusion of bupivacaine 1 mg.ml- 1 and fentanyl 2 micro g.ml- 1. Concern about possible adverse effects on spinal cord blood flow, expressed by others, prompted us to find the lowest concentration of adrenaline needed to produce effective and reliable pain relief after major surgery. METHODS: A prospective, randomized, double-blind, parallel group study was carried out in 36 patients after major thoracic or upper abdominal surgery. Patients with only mild pain when coughing during titrated thoracic epidural infusion of approximately 9 ml per hour of bupivacaine 1 mg.ml- 1, fentanyl 2 micro g.ml- 1, and adrenaline 2.0 micro g.ml- 1 were included. The study was conducted as a dose-finding study comparing three different adrenaline concentrations in the epidural mixture (0.5, 1.0, and 1.5 micro g.ml- 1) with each other and with adrenaline 2.0 micro g.ml- 1 in our standard epidural mixture. On the 1st postoperative day, the patients were randomly allocated into three equal groups of 12 patients each, and given a double-blind epidural infusion at the same rate, but with different adrenaline concentrations (0.5, 1.0, or 1.5 micro g.ml- 1). The effects were observed for 4 h or until pain when coughing became unacceptable in spite of rescue analgesia. Rescue analgesia consisted of up to two patient-controlled epidural bolus injections per hour (4 ml) and subsequent i.v. morphine, if necessary. All patients received rectal paracetamol 1 g, every 6th hour. Main outcome measures were pain intensity at rest and when coughing, evaluated by a visual analogue scale and an overall quality of pain relief score. The extent of sensory blockade was evaluated by determining dermatomal hypaesthesia to cold. RESULTS: Pain intensity when coughing increased (P < 0.001) and the number of hypaesthetic dermatomal segments decreased (P < 0.002) when the concentration of adrenaline was reduced below 1.5 micro g.ml- 1 in the triple epidural mixture. This change started within two hours after reducing the concentration of adrenaline below 1.5 micro g.ml- 1. The differences in pain intensities at rest were less pronounced. After 4 h with adrenaline 0.5 or 1.0 micro g.ml- 1 pain intensity when coughing was unacceptable in spite of rescue analgesia. After restarting the standard epidural mixture with adrenaline 2.0 micro g.ml- 1, pain intensity was again reduced to mild pain when coughing and the sensory blockade was restored. Occurrence of pruritus increased with a decreasing adrenaline concentration. CONCLUSIONS: Adrenaline in a dose-related manner improves the pain-relieving effect and sensory blockade and decreases the occurrence of pruritus of a low-concentration thoracic epidural analgesic infusion of bupivacaine 1 mg. ml- 1 and fentanyl 2 micro g.ml- 1 after major thoracic or upper abdominal surgery. The minimally effective concentration of adrenaline, when added to bupivacaine 1 mg.ml- 1 and fentanyl 2 micro g.ml- 1, to maintain relief of dynamic pain is approximately 1.5 micro g.ml- 1. The data clearly document that dynamic, cough-provoked pain is a more sensitive outcome measure for postoperative pain relief than pain at rest.

Adrenergic beta-Agonists↗