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Biomedical subjects

M L García

Publications and source records attributed to M L García.

At least 37 records · Page 2Linked to original sources

Ultrastructure of the myofibrillar component in cod (Gadus morhua L.) and hake (Merluccius merluccius L.) stored at -20 degrees C as a function of time.

Transmission electron microscopy and image analysis techniques were used to study the ultrastructure of the myofibrillar component in cod and hake muscle stored at -20 degrees C for varying periods of time. Cod muscle showed a deformation of the hexagonal array of thick filaments with the storage time, reflected in an increase in the eccentricity value, a parameter defined to measure changes in the ratio of maximum to minimum hexagon diameter, and an increase in the cross-linkings between the filaments. Degradation of cod thick filaments leading to detachment was also visible upon prolonged storage. In hake muscle significant changes were not found in the arrangement and morphology of thick filaments during frozen storage, suggesting a high incidence of intrafilament aggregation. The ultrastructural differences in the array of thick filaments between species were accompanied by a difference in the textural measurements.

Animals↗

Stability and in vitro drug release of flurbiprofen-loaded poly-epsilon-caprolactone nanospheres.

The effects of temperature and two different initial pH (2.67 and 7.00) on poly-epsilon-caprolactone (P epsilon CL) nanospheres loaded with flurbiprofen (FB) (aqueous suspensions) were studied to investigate their influence on the stability and physicochemical characteristics of these drug delivery systems. The drug release behavior was also studied. Release of the associated FB occurred very fast on high dilution in a buffered medium. The stability of the polymeric system depends on the temperature and the initial pH value; it is more degradable with the particles stored at 40 degrees C with an initial pH value of 2.67.

Administration, Topical↗

Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea.

A semi-nested, multiplex polymerase chain reaction (PCR) based on the amplification of the sequences of the 18S small subunit ribosomal RNA (ssrRNA) gene was tested in a field trial in Equatorial Guinea (a hyperendemic focus of malaria in west central Africa). The method uses a primary PCR amplification reaction with a universal reverse primer and two forward primers specific for the genus Plasmodium and to mammals (the mammalian-specific primer was included as a positive control to distinguish uninfected cases from inhibition of the PCR). The second amplification is carried out with the same Plasmodium genus-specific forward primer and four specific reverse primers for each human Plasmodium species. The PCR amplified products are differentiated by fragment size after electrophoresis on a 2% agarose gel. Four villages from three regions of the island of Bioko (Equatorial Guinea) and two suspected Plasmodium vivax-P. ovale infections from the hospital of Malabo were tested by microscopy and PCR. The PCR method showed greater sensitivity and specificity than microscopic examination and confirmed the existence of a focus of P. vivax infections in Equatorial Guinea suspected by microscopic examination. It also provided evidence of several mixed infections, mainly P. falciparum and P. malariae, the two predominant species causing malaria in Equatorial Guinea.

Animals↗

Analgesic, antiinflammatory, and antipyretic effects of S(+)-ketoprofen in vivo.

Many studies indicate that the S-enantiomers of arylpropionic (APA) nonsteroidal antiinflammatory drugs (NSAIDs) are the pharmacologically active enantiomers. S(+)-ketoprofen (dexketoprofen) stereoselectively inhibits cyclooxygenase (COX) in vitro but very little is known about the differential activity of ketoprofen enantiomers in vivo. We examined the analgesic, antiinflammatory, and antipyretic activities of S(+)-ketoprofen in rats and mice. First, we measured the antinociceptive action of S(+)-ketoprofen in abdominal pain models. After intravenous administration. 0.5 mg/kg S(+)-ketoprofen inhibited 92.1+/-2.2% of writhing in mice. Stereoselectivity in the activity was detected; intravenous administration of the R(-)-enantiomer resulted in no statistically significant activity in a dose range of 0.15-1 mg/kg. Similar results were obtained after oral administration in mice. In the rat, S(+)-ketoprofen was a more potent analgesic than diclofenac by both intravenous and oral administration. There was no significant difference between the analgesic effect of S(+)-ketoprofen treatment and the twofold dose of the racemic form in both the mouse and rat models. Second, we measured the antiinflammatory activity of S(+)-ketoprofen using a carrageenan-induced paw edema model in the rat. Intravenous administration of 5 mg/kg of S(+)-ketoprofen almost completely inhibited edema formation. After oral administration, S(+)-ketoprofen is both more potent and effective than diclofenac. Third, we measured antipyretic activity. S(+)-ketoprofen showed a marked antipyretic action (ED50 = 1.6 mg/kg) and was the most potent of the NSAIDs tested. S(+)-ketoprofen is a potent antiinflammatory, analgesic, and antipyretic agent in vivo, consistent with its potent anti-COX activity.

Administration, Oral↗

Bioavailability of S(+)-ketoprofen after oral administration of different mixtures of ketoprofen enantiomers to dogs.

Recent reports have disagreed on whether the bioavailability of S(+)-ketoprofen is affected by the presence of R(-)-ketoprofen. To examine this directly, we designed a randomized crossover study in beagle dogs. [14C]-S(+)-ketoprofen trometamol and R(-)-ketoprofen trometamol were administered in the following percentage ratios: A, 99:1; B, 95:5; C, 90:10; D, 70:30; E, 50:50. Treatments were administered as a single oral dose of 1 mg/kg tromnetamol salt. Each of eight dogs received all five combinations in random order with a 1-week wash-out period between doses. Blood samples were taken before drug administration and at regular intervals for 240 min after dosing. A progressive increase in the plasma concentration of [14C]-S(+)-ketoprofen was observed on going from treatment E (lowest dose of Senantiomer) to treatments containing the highest doses of [14C]-S(+)-ketoprofen. When the pharmacokinetic calculations were normalized to the dose of [14C]-S(+)-ketoprofen, we found no statistically significant differences among the normalized AUC and Cmax values of the five treatments. Therefore, S(+)-ketoprofen absorption was linear and was not influenced by the presence of R(-)-ketoprofen. Furthermore, there were no significant differences in tmax values among treatments, indicating that the rate of S(+)-ketoprofen absorption was also unaffected by the presence of R(-)-ketoprofen.

Administration, Oral↗

Intestinal ulcerogenic effect of S(+)-ketoprofen in the rat.

Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit prostaglandin synthesis in the gastrointestinal mucosa, which can lead not only to stomach ulcers but also ulcers in the small and large intestines. Ulcers of the small intestine are less common than those of the stomach, but intestinal lesions are more life threatening. Although the R(-)-enantiomers of the arylpropionic acid (APA) class of NSAIDs are assumed to lack the toxic effects of cyclooxygenase inhibition, they may contribute to the ulcerogenicity of racemates. We have examined the intestinal ulcerogenic effects of single oral doses of S(+)-ketoprofen compared with racemic ketoprofen in the small intestine and cecum of rats. The toxicity in the small intestine was measured as the weight ratio between portions of intestine showing lesions and the total weight of the tissue. Toxicity in the cecum was evaluated by measuring the size of the ulcers. S(+)-ketoprofen had no significant ulcerogenic effect at 10 or 20 mg/kg. However, racemic ketoprofen was clearly ulcerogenic in the small intestine and cecum at the 40 mg dose. R(-)-ketoprofen at 20 mg/kg does not show any effect in the cecum and only limited ulcerogenesis in the small intestine: The latter effect may be the result of racemic inversion. Therefore, the ulcerogenic action of racemic ketoprofen can be interpreted as a synergism between S(+)- and R(-)-ketoprofen. The mechanism of this synergism is not well understood but may be a general feature of APA NSAIDs.

Animals↗

Pharmacokinetics of dexketoprofen trometamol in healthy volunteers after single and repeated oral doses.

The pharmacokinetics of dexketoprofen trometamol were evaluated in two studies using healthy volunteers. In the first study, the relative bioavailability of a single oral capsule of dexketoprofen free acid 25 mg or dexketoprofen trometamol 25 mg (given as 37 mg of the trometamol salt) was compared to ketoprofen 50 mg in 18 healthy volunteers. In the second study, the pharmacokinetics and tolerability of oral dexketoprofen trometamol in tablet form were evaluated after either a single 25 mg dose (24 volunteers) or a repeated dose of 25 mg twice daily for 7 days (12 volunteers). The absorption of dexketoprofen from dexketoprofen trometamol capsules was bioequivalent to that of ketoprofen. On the other hand, the extent of absorption of dexketoprofen free acid was significantly lower than that for ketoprofen. Dexketoprofen trometamol showed the most rapid absorption rate, with highest Cmax and shortest t(max) values, whereas dexketoprofen free acid had the slowest absorption rate, and ketoprofen had an intermediate absorption rate. After repeated-dose administration of dexketoprofen trometamol, the pharmacokinetic parameters were similar to those obtained after single doses, indicating that no drug accumulation occurred. Dexketoprofen trometamol was well tolerated, with no clinically relevant adverse events reported.

Absorption↗

Stereoselective inhibition of rat brain cyclooxygenase by dexketoprofen.

Although it has been assumed that the effects of nonsteroidal antiinflammatory drugs (NSAIDs) are mainly the result of their action on local synthesis of prostaglandins, there is growing evidence to suggest that they may also exert a central analgesic action. Some authors have suggested that inhibition of prostaglandin synthesis in the brain could contribute to the analgesic action. The effect of dexketoprofen trometamol (tromethamine salt of the enantiomer (+)-S-ketoprofen) on prostaglandin synthesis was investigated in rat brain fragments and in cyclooxygenase preparations from rat brain microsomes. Effects of the (-)-R-enantiomer and the racemic mixture were also evaluated. Significant levels of prostaglandin F2 alpha (PGF2 alpha) were synthesized in rat brain fragments after 10 min of incubation at 37 degrees C. Dexketoprofen was found to be a potent inhibitor of this PGF2 alpha production in rat brain (IC50 = 6.2 nM), and it completely suppressed PGF2 alpha production at 1 microM concentration. In addition, inhibition of PGF2 alpha synthesis by dexketoprofen was highly stereoselective since the enantiomer (-)-R-ketoprofen was significantly less potent (IC50 = 294 nM); with this enantiomer, even at high concentrations such as 1 microM, less than 60% inhibition was achieved. These results correlated with those obtained in the study of racemic ketoprofen and its enantiomers on cyclooxygenase activity of rat brain microsomes, where dexketoprofen also inhibited enzymatic activity stereoselectively. IC50 values obtained for dexketoprofen, (-)-R-ketoprofen, and rac-ketoprofen were 3.5 microM, 45.3 microM, and 5.8 microM, respectively. The above results could be related to the potent analgesic effect of dexketoprofen observed in vivo, which was also stereoselective. Taken together, these findings suggest that prostaglandin synthesis inhibition in rat brain by dexketoprofen could be associated, at least in part, with the analgesic effect of this NSAID.

Animals↗

Virulence factors-pathogenicity relationships for Aeromonas species from clinical and food isolates.

The presence of virulence factors in 96 Aeromonas strains isolated from food and clinical samples was studied. Neither cytotoxic activity and hydrophobicity, not the presence of pili or an extra surface layer made it possible to establish differences between food and clinical strains. Statistical studies showed that cytotoxin production was associated with a positive Voges-Proskauer reaction, inability to ferment arabinose and a positive lysine decarboxylation. Therefore, when comparing cytotoxic clinical and food strains with lysine decarboxylation phenotype, there was a significant difference (p < 0.05) between the two groups. The association of a cytotoxin production and lysine decarboxylation character should thus be considered as a possible virulence marker.

Aeromonas↗

Lactic acid bacteria: hydrophobicity and strength of attachment to meat surfaces.

The hydrophobicity and strength of attachment of several lactic acid bacteria with antimicrobial activity were studied. Hydrophobicity was determined by bacterial adherence to hydrocarbons (BATH; octane or xylene), adhesion to nitrocellulose filters (NCF), salt aggregation test (SAT) and adherence to phenyl-Sepharose beads (PSB). The relative hydrophobicity of lactic acid bacteria depended markedly on the method used. No correlation between either SAT or BATH (octane) and strength of attachment (Sr value) existed. However, a significant relationship between strength of attachment and BATH (xylene), NCF and PSB, respectively, was observed, showing the highest correlation coefficient (r = 0.778) for BATH (xylene).

Ammonium Sulfate↗

[Lafora and neuropathology].

This article wants to be a memory to the figure and neuro-pathologic work of D. Gonzalo Rodríguez-Lafora. The tediousness of its neurological work allows to divide it in its slopes neurophatologic, neurophysiologic, clinic and therapy. Also, it embraces other topics outside of the field of the neurology, centered fundamentally in the psychiatry. It is without a doubt the facet neuro-histopathologic the one that provides him bigger national and international prestige and it contributes to deepen in the histopathology of the senility, picking up in a definitive way in their work critical valuation of the discoveries histopathological in the senility (1952) their thought in this respect. Mention separated deserves its more important discovery: The inclusions amylaceous in cells ganglionars, in a certain type of epilepsy myoclonic that today takes its name. Other entities like the illness of Wernicke, the hemorrhages hipofisarias, the Parkinson (for scarce months he is not early to Levy in an important discovery), or the alterations of the malaria in the cerebral fabric plows object of their attention, of the work of Lafora highlights its anatomo-pathologics works next to figures as Kraepelin, Alzheimer, Vogt, Openheim or Brodmann. Professor Lafora's figure is known internationally as neuropathologist, recognizing its contribution, collection in the world literature, to the study of the myoclonic epilepsy: 'Lafora disease. A form of progressive myoclonus epilepsy.

Brain↗

Stereoselective inhibition of inducible cyclooxygenase by chiral nonsteroidal antiinflammatory drugs.

The stereoselective inhibition of inducible cyclooxygenase (COX-2) by chiral nonsteroidal antiinflammatory drugs (NSAIDs)--ketoprofen, flurbiprofen, and ketorolac--has been investigated. The activity and inhibition of COX-2 was assessed in three different in vitro systems: guinea pig whole blood, lipopolysaccharide (LPS)-stimulated human monocytes, and purified preparations of COX-2 from sheep placenta. The results were compared with the inhibition of constitutive cyclooxygenase (COX-1) in three parallel in vitro models: clotting guinea pig blood, human polymorphonuclear leukocytes, and purified COX-1 from ram seminal vesicles. In the whole blood model, both isoenzymes were inhibited by S-enantiomers with equal potency but S-ketoprofen was the most active on COX-2 (IC50 = 0.024 mumol/L). In contrast, both isoenzymes were inhibited less than 40% by all three R-enantiomers at high concentration (> 1 mumol/L). The inhibition of COX by the R-enantiomers may be attributed to contamination with the S-enantiomers (approximately 0.5%). A significant degree of enantioselectivity in COX-2 inhibition was also observed in intact cells. The S-enantiomers inhibited COX-2 from monocytes with IC50 values in the range of 2 to 25 nmol/L, being 100 to 500-fold more potent than the corresponding R-enantiomers. Finally, S-ketoprofen inhibited COX-2 from sheep placenta (IC50 = 5.3 mumol/L) with slightly less potency than S-ketorolac (IC50 = 0.9 mumol/L) and S-flurbiprofen (IC50 = 0.48 mumol/L), whereas the R-enantiomers were found to be essentially inactive (IC50 > or = 80 mumol/L). It is concluded that the chiral NSAIDs studied here inhibit with comparable stereoselectivity both COX-2 and COX-1 isoenzymes, and that the inhibition of COX-2 previously observed for racemic NSAIDs should be attributed almost exclusively to their S-enantiomers.

Animals↗

Attachment of lactic acid bacteria to beef-muscle surfaces.

The effect of immersion time and cell concentration in the attachment of several lactic acid bacteria with antibacterial activity to beef-muscle surface was studied. The number of firmly attached bacteria increased with immersion time in the case of Pediococcus acidilacti, Lactobacillus sake, Lactococcus cremoris (two strains) and Pediococcus acidilacti. Pediococcus pentosaceus, Lactococcus lactis and Lactobacillus curvatus reached maximum adhesion after 15-30 min. The highest strength of attachment (Sr values) were observed after 15-30 min of contact time except for P. pentosaceus. For all strains, the number of bacteria adhering to meat increased with increasing cell concentration in the adhesion medium. The highest strength of attachment was observed at a cell concentration of 10(5)/mL mainly for L. sake, L. lactis and L. cremoris. Due to their attachment characteristics, L. sake, L. lactis and L. cremoris are proposed as potential biocontrol agents because they could grow on meat surface and limit the potential attachment of pathogenic microorganisms.

Animals↗

Preclinical and clinical development of dexketoprofen.

Dexketoprofen trometamol is a water-soluble salt of the dextrorotatory enantiomer of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen. Racemic ketoprofen is used as an analgesic and an anti-inflammatory agent, and is one of the most potent in vitro inhibitors of prostaglandin synthesis. This effect is due to the S(+)-enantiomer (dexketoprofen), while the R(-)-enantiomer is devoid of such activity. The pharmacokinetic profile of ketoprofen and its enantiomers was assessed in several animals species and in human volunteers. In humans, the relative bioavailability of oral dexketoprofen trometamol (12.5 and 25 mg, respectively) is similar to that of oral racemic ketoprofen (25 and 50 mg, respectively), as measured in all cases by the area under the concentration-time curve values for S(+)-ketoprofen. Dexketoprofen trometamol, given as a tablet, is rapidly absorbed, with a time to maximum plasma concentration (tmax) of between 0.25 and 0.75 hours, whereas the tmax for the S-enantiomer after the racemic drug, administered as tablets or capsules prepared with the free acid, is between 0.5 and 3 hours. Peak plasma concentrations of 1.4 and 3.1 mg/L are reached after administration of dexketoprofen trometamol 12.5 and 25 mg, respectively. From 70 to 80% of the administered dose is recovered in the urine during the first 12 hours, mainly as the acyl-glucuronoconjugated parent drug. No R(-)-ketoprofen is found in the urine after administration of dexketoprofen [S(+)-ketoprofen], confirming the absence of bioinversion of the S(+)-enantiomer in humans. in animal studies, the anti-inflammatory potency of dexketoprofen was always equivalent to that demonstrated by twice the dose of ketoprofen. Similarly, animal studies showed a high analgesic potency for dexketoprofen trometamol. The R(-)-enantiomer demonstrated a much lower potency, its analgesic action being apparent only in conditions where the metabolic bioinversion to the S(+)-enantiomer was significant. The gastric ulcerogenic effect of dexketoprofen at various oral doses (1.5 to 6 mg/kg) in the rat do not differ from those of the corresponding double doses (3 to 12 mg/kg) of racemic ketoprofen. Repeated (5-day) oral administration of dexketoprofen as the trometamol salt causes less gastric ulceration than was observed after the acid form of both dexketoprofen and the racemate. In addition, single dose dexketoprofen as the free acid at 10 to 20 mg/kg does not show a significant intestinal ulcerogenic effect in rats, while racemic ketoprofen 20 or 40 mg/kg is clearly ulcerogenic to the small intestine. The analgesic efficacy of oral dexketoprofen trometamol 10 to 20 mg is superior to that of placebo and similar to that of ibuprofen 400 mg in patients with moderate to serve pain after third molar extraction. The time to onset of pain relief appeared to be shorter in patients treated with dexketoprofen trometamol than in those treated with ibuprofen 400 mg. Dexketoprofen trometamol was well tolerated, with a reported incidence of adverse events similar to that of placebo.

Analgesia↗

Numerical taxonomy of an 'atypical' population of gram-positive cocci isolated from freshly dressed lamb carcasses.

One hundred Gram-positive, catalase-positive strains were isolated from freshly dressed lamb carcasses. They were randomly selected from a non-selective medium and tested for 75 characters. Only nine cultures could be identified by conventional methods. A numerical taxonomic study was conducted on the whole population and 25 reference strains. At the 80% similarity level (Ssm), ten clusters were formed. Five of them were entirely composed of reference strains. Phena V and VIII contained seven isolates and two reference strains of Micrococcus. Phena VI (six unidentified isolates), VII (nine staphylococci) and IX (69 unidentified isolates) were more related to M. kristinae than to the remaining reference strains. Properties with possible implications in meat spoilage were: strong lipolytic activity (76%), anaerobic growth (85%), tolerance to 15% (w/v) NaCl (95%) and ability to grow at 15 degrees C (95%) and 4 degrees C (26%).

Animals↗

Differences in production of several extracellular virulence factors in clinical and food Aeromonas spp. strains.

Production of several extracellular virulence factors (lipase, protease and haemolysin) was compared in 15 Aeromonas spp. isolated from faeces of patients with Aeromonas-associated gastroenteritis and 81 strains isolated from food. Strains from food did not show differences in production of these factors when compared with strains isolated from faeces. However, if strains were considered in relation to autoagglutination (AA) character, the AA+ differed from AA- strains in lipase and protease production. Supernatant fluids of AA+ food and human strains showed 2.5-fold more protease production than that observed in AA- strains. These two characteristics of certain Aeromonas strains could be related with the more virulent capacity.

Aeromonas↗

Coating of liposomes with transferrin: physicochemical study of the transferrin-lipid system.

Transferrin was incorporated into the external surface of liposomes that were previously derivatized with ceramides. This new hydrophobic derivative of transferrin was incubated with liposomes at different protein-to-lipid ratios. The surface activity of both native and derivatized transferrin was determined with monomolecular layers as a membrane model. The maximal interaction was found with dipalmitoylphosphatidylcholine in all the experiences.

1,2-Dipalmitoylphosphatidylcholine↗

Virulence factors in clinical and food isolates of Aeromonas species.

Virulence factors were compared in 15 Aeromonas spp. isolated from faeces of patients with Aeromonas-associated gastroenteritis and in 81 strains isolated from food. Strains from food did not show differences in the distribution of virulence factors when compared with strains isolated from faeces. However, 88.8% of Aeromonas strains isolated from food were capable of producing possible virulence factors. Characterization of 28 autoagglutinating (AA+) Aeromonas spp. indicated that the human strains differed from the food strains in hemagglutinating and hemolytic capacities. These results suggest that autoagglutination associated with hemagglutinating and hemolytic capacities in food strains may be a helpful indicator of potential pathogenicity.

Acriflavine↗