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Biomedical subjects

J Frias

Publications and source records attributed to J Frias.

At least 37 records · Page 2Linked to original sources

Evaluation of sex differences in the pharmacokinetics of ranitidine in humans.

A bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half-life of ranitidine was 7% shorter and the oral apparent clearance 10.5% higher in women (1.44 L/h/kg) than in men (1.29 L/h/kg), although this difference did not reach statistical significance. No differences were observed in maximum concentration (Cmax) or the time of its occurrence (tmax). Sex, age, and weight did not correlate significantly with oral clearance. These results suggest that there are no sex differences in the pharmacokinetics of ranitidine, or that any differences would not be of clinical relevance. It also should be emphasized that bioequivalence trials also can be used to study other pharmacokinetic or pharmacodynamic characteristics of drugs without damaging the main endpoint of the study.

Adult↗

Evolution and kinetics of monosaccharides, disaccharides and alpha-galactosides during germination of lentils.

The effect of light and seed rinsing during the germination of lentil seeds (Lens culinaris var. vulgaris, cultivar Magda-20) on the level of monosaccharides, disaccharides and alpha-galactosides (raffinose, ciceritol and stachyose) was investigated. The total soluble sugar content corresponded to about 9% of the mature seed weight, about 65% of which was alpha-galactosides. Germination brought about a large decrease in alpha-galactosides: 18% to 40% losses after 3 days and 100% after 6 days. However, glucose, which was not detected in ungerminated seeds, as well as fructose and sucrose gradually increased during germination. The content of alpha-galactosides decreased more rapidly when germinating seeds were given 6 h light per day, but under these conditions there was also a major reduction in the levels of fructose, glucose and sucrose. Seeds rinsed daily showed a greater reduction of alpha-galactosides and an increase in the levels of fructose, glucose and sucrose. When seeds were germinated for 10 days in the dark with daily rinsing, the content of alpha-galactosides decreased gradually during the first 4 days and they were not detected after 6 days. Under these conditions, fructose, glucose and sucrose, which represented about 3% of the mature seed weight, started increasing after day 2 and represented more than 13% of the germinated seed dry weight after 10 days.

Disaccharides↗

Evolution of soluble carbohydrates during the development of pea, faba bean and lupin seeds.

Seeds of pea (Pisum sativum L. cv. Ergo), faba bean (Vicia faba ssp. minor Harz., cv. Tibo) and yellow pea lupin (Lupinus luteus L. cv. Juno) were sampled at different days after flowering (DAF) and their content of soluble carbohydrates was determined. Analysis of samples showed that myo-inositol, fructose, glucose, galactose and sucrose were found in high abundance early in development and their content decreased gradually during maturation. alpha-Galactosides, which includes the content of raffinose, stachyose and verbascose, started to appear later in seed development, at 37 DAF in peas, 40 DAF in faba beans and 45 DAF in lupins. Their accumulation increased considerably during seed growth, and the maximum content was obtained in mature seeds; 3.8% in peas, 4.5% in faba beans and 10.4% in lupins. Results obtained for these sugars during seed development were fitted to modelling curves in order to predict sugar content at different development stages.

Carbohydrates↗

Effect of CRF injected into the median eminence on GH secretion in female rats under different steroid status.

To evaluate whether the median eminence (ME) is a site of action of CRF (corticotropin releasing factor) on GH secretion and to determine the possible role of estradiol and progesterone in modifying theses secretion, we injected CRF (0.25, 0.75, 1, and 1.5 nmol of peptide dissolved in 1 microliter of water) directly into the ME in three experimental groups of rats: Long-term ovariectomized (OVX); OVX primed by estradiol (OVX +/- E) and OVX primed by estradiol plus progesterone (OVX +/- EP). Blood was collected to determine GH (30, 60, 90, and 120 min postinjection). Serum T3, T4, and glucose levels were measured in OVX +/- E rats 30 min postinjection. CRF at all doses studied significantly decreased serum GH levels in the three experimental groups. Serum T3, T4, and glucose levels were unchanged after CRF administration. The results suggest that: CRF inhibits "per se" GH secretion, at least in part, by a central action in the ME. The inhibitory effect of CRF on GH is independent of the estrogen/progesterone status of the animal. CRF at ME levels may participate in a variety of stress-related responses, including growth inhibition, through GH suppression.

Animals↗

A Bacteroides thetaiotaomicron outer membrane protein that is essential for utilization of maltooligosaccharides and starch.

Previous studies suggested that the first step in utilization of starch by Bacteroides thetaiotaomicron was binding of the polysaccharide to the cell surface, followed by translocation of the polysaccharide across the outer membrane into the periplasm. In this study, we report the molecular characterization of a gene that encodes an outer membrane protein that is essential for utilization of both maltooligosaccharides and starch. The gene, susC, encoded a protein of 115.3 kDa. Antibodies were raised against SusC, and the outer membrane location of SusC could be confirmed by Western blot (immunoblot) analysis. SusC had a possible signal sequence of between 20 and 39 amino acids, depending on which N-terminal methionine initiates the start of the protein. It also had some features typical of well-characterized outer membrane proteins from members of the family Enterobacteriaceae, such as a terminal phenylalanine residue and a region in the amino portion of the protein thought to be involved in stabilizing the protein in the outer membrane. The amino acid sequence, together with results of gene disruption experiments, suggested that SusC was not an amylolytic enzyme. Transcriptional fusion experiments, using beta-glucuronidase as a reporter group, showed that expression of susC was maltose regulated at the transcriptional level. This is the first molecular characterization of a B. thetaiotaomicron outer membrane protein involved in maltooligosaccharide and starch utilization.

Amino Acid Sequence↗

Nimodipine transfer into human breast milk and cerebrospinal fluid.

OBJECTIVE: To report nimodipine concentrations in breast milk and cerebrospinal fluid (CSF) of a lactating woman who was given the drug to prevent a vascular spasm secondary to angiographic examination. METHODS: A 36-year-old woman received a total dose of nimodipine 46 mg iv over 24 hours. She extracted milk when she noted mammary tightness, and blood samples were taken simultaneously by venipuncture in the arm contralateral to that of the nimodipine infusion. A CSF sample also was taken in a diagnostic lumbar puncture. RESULTS: Nimodipine concentration in milk was much lower than that in serum, with a milk/serum ratio of 0.06-0.15. The CSF/serum ratio was 0.01. We estimate that the infant would have received between 0.008% and 0.092% of the weight-adjusted dose that was administered to the mother if the baby had been nursed. CONCLUSIONS: Nimodipine is transferred to human milk in a lower proportion than are other calcium-channel blockers. These results suggest that treating the mother with nimodipine would entail no risk to the nursing infant.

Adult↗

Activated charcoal increases digoxin elimination in patients.

Digoxin continues to be an important cause of drug toxicity. On the basis of a healthy volunteer study, activated charcoal has been proposed as a treatment for digoxin chronic intoxication. In order to evaluate the effect of activated charcoal on digoxin elimination in intoxicated patients during routine practice, we reviewed all Serum Digoxin Level Requests for adult in-patients from 1991 to 1993, with digoxin levels > 2.5 ng/ml. Of a total of 39 cases, 23 had been treated with activated charcoal while 16 had not. Digoxin elimination half-life during activated charcoal therapy was 36 h (S.D. 14 h; 95% C.I. 30-42 h) while in the non-treated group it was 68 h (S.D. 19 h, 95% C.I. 57-78). Calculated total body clearance of digoxin was 55 ml/min (S.D. 17 ml/min; 95% C.I. 45-64 ml/min) for the non-treated group versus 98 ml/min (S.D. 34 ml/min; 95% C.I. 83-113 ml/min) for the group receiving charcoal, representing an 78% increase in digoxin elimination.

Aged↗

Natural fermentation of lentils. Influence of time, concentration and temperature on protein content, trypsin inhibitor activity and phenolic compound content.

Lentil (Lens culinaris var. vulgaris) flour was naturally fermented for 4 days at different temperatures (28 degrees C, 35 degrees C and 42 degrees C) and concentrations (79 milligrams, 150 milligrams and 221 milligrams). Samples were analysed to establish the changes of total protein content and in vitro protein digestibility, trypsin inhibitor activity (TIA) and phenolic compound content during natural fermentation of lentils. The preparation of lentil flour suspensions to be fermented caused a slight increase in total protein and in vitro protein digestibility content, a decrease of TIA and a sharp decrease the tannin/catechin ratio. During the whole fermentation procedure, the minimum initial lentil concentration and temperature used (79 milligrams, 28 degrees C) achieved the maximum protein content and the lowest tannin/catechin ratio. The TIA was more affected by temperature than by concentration, and a 62.5% reduction was observed at 42 degrees C and 79 milligrams.

Catechin↗

Thallium poisoning presenting with abdominal colic, paresthesia, and irritability.

A case of acute thallium poisoning presenting with sudden abdominal pain, paraesthesiae and irritability is described. The peripheral nervous system was later affected along with loss of hair and the development of streaks (Mee's lines) on the nails of the hands and feet. The diagnosis was established by thallium assays of blood and urine. Thallium was undetectable in the blood by day 70. The manifestations cleared in six months with symptomatic treatment only. We review the characteristics and differential diagnosis of thallium poisoning and stress the importance of a high index of clinical suspicion.

Adult↗

Comparative bioavailability of a dispersible formulation of diclofenac and finding of double plasma peaks.

We carried out a comparative study of the bioavailability of a typical, enteric-coated diclofenac with regard to a new dispersible formulation whose faster dissolution results in an earlier onset of its analgesic effect. This randomized, crossover study was conducted in 12 healthy male volunteers, who received in fasting 100 mg of enteric-coated diclofenac (Dolotrén, FAES) and 100 mg of dispersible diclofenac (Dolotrén Dispersable, FAES), with one-week interval between both. Blood samples were taken at pre-established times during the 24 hours after dosing, and plasma concentrations of diclofenac were determined by HPLC. Possible adverse experiences were monitored with a check-list, and blood and urinalysis were performed for safety assessment. The dispersible formulation showed a relative extent of bioavailability between 78% and 99% (90% CI) for the AUC0-infinity, being the 90% CI for the Cmax 63%-129%. The time to Cmax (Tmax) was significantly shorter with the dispersible than with the enteric-coated formulation (95% CI for the difference = 1.5-4.25 hours) as the T0(lag) or time to measurable plasma concentrations (1.9-4.2 hours, 95% CI). A relevant feature in the study was the finding of a second peak at 2-2.5 hours post-dosing in 7 out of 11 profiles of subjects receiving the dispersible formulation. Both formulations were well tolerated in clinical and laboratory terms. In conclusion, the new dispersible formulation of diclofenac allows absorption to begin more rapidly and plasma peak is reached earlier, a fact that may be relevant to the analgesic treatment of acute pain.

Absorption↗

Retroperitoneal haematoma in a patient treated with acenocoumarol, phenytoin and paroxetine.

Coumarin anticoagulants must be strictly monitored because of their narrow therapeutic index and their potential interactions with other drugs. The high probability of interactions can be explained by two pharmacokinetic properties of coumarins: high binding to plasma albumin (99%), being displaced by other drugs with greater affinity to this protein, and metabolism by liver microsomal enzymes (cytochrome P450), which can be induced or inhibited by other compounds (Shinn & Shrewsbury 1985). A case is reported of a clinically relevant drug interaction of phenytoin and acenocoumarol, possibly potentiated by concomitant treatment with paroxetine, leading to a retroperitoneal haematoma.

Acenocoumarol↗

Effect of corticotropin releasing factor (CRF) in the median eminence on gonadotropins in ovariectomized rats with or without steroid priming: dose-response study.

We determined the dose-response relationship and examined the time related effect of CRF (corticotropin releasing factor) injected directly into the median eminence (ME) on LH and FSH secretion in conscious female rats of different steroid status. Doses of 0.25, 0.75, 1, and 1.5 nM CRF dissolved in 1 microliter of water were injected into the ME in 5 experimental groups of rats: Short-term (2 days) ovariectomized (sOVX); long-term (3-4 weeks) ovariectomized (lOVX); lOVX primed by estradiol benzoate (EB) 4 h before the experiment (lOVX+E); lOVX primed by EB 36 h before the experiment (lOVXE) and lOVX primed by EB 72 h and progesterone 6 h before experiment (lOVXP). Blood was collected at 30, 60, 90, and 120 min postinjection to determine LH and FSH by RIA. CRF at the doses of 0.75, 1, and 1.5 nM significantly decreased serum LH levels in all groups. The dose of 0.25 nM CRF was ineffective. The highest dose (1.5 nM) of CRF had no effect on serum FSH levels. The results suggest that CRF inhibits LH secretion, at least in part, by a central action of GnRH release in the ME, and that this effect is independent of the estrogen/progesterone status of the animal.

Animals↗

Cefminox: correlation between in-vitro susceptibility and pharmacokinetics and serum bactericidal activity in healthy volunteers.

Plasma concentration of cefminox and serum bactericidal activity against four ATCC strains (Escherichia coli 25992, Klebsiella pneumoniae 13833, Serratia marcescens 8100 and Bacteroides fragilis 25285), were determined over a 24 h period after administration of cefminox 1 and 2 g to six healthy volunteers in a randomized, cross-over, single blind study. The increase observed in the area under the bactericidal curve (AUBC) with the 2 g dose was at least 3.5 times that seen with the 1 g dose for all four test strains and was larger than predicted by the corresponding increase (1.84 times) in the area under the serum concentration versus time curve (AUC); a correlation (r = 0.88, P = 0.0001) between the cefminox concentration and the serum bactericidal titres was, however, observed with all four strains tested. The MBC6h showed a better association with the serum bactericidal titre (P < 0.01) than did the MIC or MBC.

Adult↗

Effect of natural fermentation on carbohydrates, riboflavin and trypsin inhibitor activity of lentils.

Lentils were subjected to natural fermentation for 4 days at 30 degrees C. The pH value fell to 3.8 during the process. alpha-Galactosides and sucrose were not detected in fermented lentils but a significant increase in the fructose content was observed. In fermented lentils the neutral detergent fibre, cellulose and hemicellulose contents decreased and the lignin content increased. After fermentation the riboflavin content was higher and the trypsin inhibitor activity decreased.

Carbohydrates↗

Comparison of different media for the identification and quantification of Aeromonas spp. in water.

In order to assess the suitability of the Starch glutamate ampicillin penicillin-10C agar for the isolation of Aeromonas spp. from waters it was necessary to compare the properties of this medium with those of three others, Starch ampicillin agar, Ampicillin dextrin agar and m-Aeromonas medium, and to monitor different kinds of waters. A selection of forty eight samples were taken from moderately polluted river water, highly polluted river water, polluted sea water (littoral) and treatment & distribution water and monitored using these media. The results were similar with Ampicillin dextrin agar, m-Aeromonas medium and Starch glutamate ampicillin penicillin-10C, but the simplicity of composition and use and its selectivity recommends the last medium as the most adequate for the isolation of Aeromonas spp.

Aeromonas↗