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Biomedical subjects

A Pascual

Publications and source records attributed to A Pascual.

At least 91 records · Page 5Linked to original sources
PubMed1997

Comparison of the changes in facial profile after orthodontic treatment, with and without extractions.

A study was made of 31 patients with Angle Class II malocclusion. Fifteen patients did not undergo extraction of teeth (Group A), while 16 underwent extractions of four premolars (Group B). Data was obtained from the corresponding lateral radiographs of the head taken both before and after orthodontic treatment. The main aim of the study was to compare the response of the soft and hard tissues of the facial profile in Class II malocclusion treated with the extraction of four premolars and the response of borderline cases presenting with similar malocclusions, but not subjected to extraction. In this latter group reasonable doubt existed as to whether or not to remove teeth in order to solve the occlusal and aesthetic problems. It is concluded that significant hard tissue differences between the groups at the end of treatment were limited to a more retruded position of the incisors and a reduced overbite amongst those patients subjected to extraction. The main soft tissue differences between the groups at the end of treatment were a more retruded lower lip and a more pronounced lower labial sulcus in those patients subjected to extraction.

Adolescent↗
PubMed1997

Uptake and intracellular activity of trovafloxacin in human phagocytes and tissue-cultured epithelial cells.

The penetration of trovafloxacin into human polymorphonuclear leukocytes (PMNs), human peritoneal macrophages, and tissue-cultured epithelial cells (McCoy cells) was evaluated. The cellular concentration to extracellular concentration (C/E) ratios of trovafloxacin were greater than 9 for extracellular concentrations ranging from 0.5 to 25 micrograms/ml. The uptake of trovafloxacin by PMNs was rapid, reversible, nonsaturable, not energy dependent, and significantly increased at 4 degrees C. Ingestion of opsonized zymosan, but not opsonized Staphylococcus aureus, significantly increased the amount of PMN-associated trovafloxacin. This agent at concentrations of 0.5 and 1 microgram/ml induced a greater reduction in the survival of intracellular S. aureus in PMNs than ciprofloxacin and ofloxacin. It was concluded that trovafloxacin reaches concentrations within phagocytic and nonphagocytic cells several times higher than the extracellular ones, while it remains active in PMNs.

Anti-Infective Agents↗
PubMed1997

[Penetration of azithromycin into human neutrophils: effect of hydrogen peroxide production].

BACKGROUND: The aim of this study was to evaluate the uptake of azythromycin at therapeutic concentrations by human polymorphonuclear leukocytes (PMN), as well as the effect of environmental temperature, pH, and cell viability on this uptake. The effect of azythromycin and other macrolides on hydrogen peroxide production by PMN was also assessed. METHODS: Uptake of radiolabeled azythromycin by PMN was determined by a radiometric technique. Hydrogen peroxide production by PMN was measured by the phenol red method. RESULTS: The intracellular concentrations achieved by azythromycin in PMN were 20 to 60 fold the extracellular ones, even at extracellular concentration of 0.125 mg/l. The uptake was significantly affected by low temperature, acid pH, and cell viability. Hydrogen peroxide production was not affected by the macrolides studied. CONCLUSIONS: Azythromycin at therapeutical concentrations achieves high intracellular accumulation in human PMN. The effect of environmental temperature, pH and cell viability on uptake points out that a passive diffusion, with lysosome trapping, is the essential mechanism of azythromycin uptake by phagocytic cells. In spite of the high intracellular concentrations achieved by macrolides, hydrogen peroxide production by PMN is not affected by these compounds.

Anti-Bacterial Agents↗
PubMed1997

[Usefulness of the disk diffusion method for evaluating the sensitivity of Neisseria meningitidis to penicillin and cefotaxime].

BACKGROUND: Routine susceptibility testing of Neisseria meningitidis to penicillin and other beta lactams is recommended after the isolation of N. meningitidis of moderately resistant to penicillin (MRP). We have evaluated the disk-diffusion method to determine susceptibility of N. meningitidis to penicillin (using disks of either penicillin or oxacillin) and to cefotaxime. METHODS: Fifty-four strains of N. meningitidis isolated from clinical samples were studied. MICs of penicillin and cefotaxime were determined by microdilution. Disks of 2 U of penicillin, 1 microgram of oxacillin and 30 micrograms of cefotaxime and two culture media, Mueller-Hinton agar (MHA) and MHA supplemented with 5% sheep blood (MHS) were used in the disk-diffusion assay. RESULTS: For disk of 2 U of penicillin assayed in MHA, 86.4% of the susceptible strains and 20% of MRP strains were considered susceptible when a breakpoint of 28 mm was considered. None of the MRP strains was considered susceptible when using MHS, but only 38.6% of susceptible strains appeared as such on this medium. When a 1 microgram oxacillin disk was used all MRP strains presented an inhibition zone < or = 10 mm on both MHA and MHS, but 54.4 and 4.5% of susceptible strains presented an inhibition zone > or = 11 mm on MHA and MHS, respectively. All strains were susceptible to cefotaxime, showing inhibition zones around a 30 micrograms disk on MHA and MHS of > or = 35 mm and > or = 25 mm, respectively. CONCLUSION: Disk diffusion with cefotaxime (30 micrograms) allows to determine susceptibility of N. meningitidis to this antimicrobial agent. Discs of penicillin (2 U) and oxacillin (1 microgram) are not useful for screening of MRP N. meningitidis.

Cefotaxime↗
PubMed1996

Cloning, purification and characterization of the protein subunit of ribonuclease P from the cyanobacterium Synechocystis sp. PCC 6803.

The rnpA gene from the cyanobacterium Synechocystis sp. PCC 6803, which codes for the protein subunit of ribonuclease P (RNase P), has been cloned by functional complementation of an Escherichia coli mutant. This protein had previously been characterized only in proteobacteria and gram-positive bacteria. rnpA and the closely linked rpmH gene, which code for the large subunit ribosomal protein L34, have been sequenced. The Synechocystis 6803 L34 protein is more similar to the homologous protein from some non-green chloroplasts than to the L34 protein from other bacteria. The protein subunit of RNase P from Synechocystis 6803 has been overexpressed in E. coli and purified to homogeneity. Antibodies raised against the Synechocystis 6803 RNase P protein did not recognize the homologous protein from E. coli (C5 protein). Similarly, antibodies raised against the E. coli C5 protein did not recognize significantly the Synechocystis 6803 protein. In spite of the lack of immunological cross-reactivity and the low level of sequence identity, the E. coli and Synechocystis 6803 proteins are functionally interchangeable. In enzymatic assays using either an E. coli precursor tRNA(Tyr) or a Synechocystis 6803 precursor tRNA(Gln) as substrates, we have detected RNase P activity with holoenzymes reconstituted with the RNA subunit from E. coli and the protein subunit from Synechocystis 6803 or with the RNA subunit from Synechocystis 6803 and the protein subunit from E. coli. The relative efficiency of cleavage of the different substrates is dependent on the origin of the protein subunit used to reconstitute the holoenzyme.

Amino Acid Sequence↗
PubMed1996

Nerve growth factor and ras regulate beta-amyloid precursor protein gene expression in PC12 cells.

The beta-amyloid protein, the major component of the vascular and plaque amyloid deposits that characterize Alzheimer's disease, derives from a larger beta-amyloid precursor protein (APP) that is expressed in both neural and nonneural cells. An increased expression of APP might actively contribute to the development of the pathology; however, the mechanisms involved in the regulation of APP gene expression are not yet well understood. In PC12 cells, a rat pheochromocytoma cell line, we have demonstrated that nerve growth factor (NGF) induces the APP gene expression and increases APP mRNA levels in the presence of 0.5 or 15% serum. Expression of activated ras in the PC12 cell subline UR61 also leads to a significant increase in content of APP transcripts, and a dominant negative mutant of ras blocks the NGF-induced response. Other ligands of tyrosine kinase receptors, such as fibroblast growth factor, which causes morphological differentiation, or epidermal growth factor, which induces cell growth, also increase APP mRNA levels in PC12 cells. These results suggest that ras mediates the induction of APP gene expression by NGF and other ligands of tyrosine kinase receptors.

Amyloid beta-Protein Precursor↗
PubMed1996

Comparative in-vitro activity of sparfloxacin against genital pathogens.

The in-vitro activity of sparfloxacin against four pathogens commonly implicated in genital infections was compared with that of a number of other commonly administered antimicrobials. Sparfloxacin demonstrated excellent activity against Neisseria gonorrhoeae (MIC range of < or = 0.0002-5 mg/L for beta-lactamase producing strains, and < or = 0.0002-0.03 mg/L for non-beta-lactamase producing strains). This activity was similar to that of lomefloxacin and ciprofloxacin and was greater than that of ofloxacin. Sparfloxacin was more active against Ureaplasma urealyticum (MIC90 1 mg/L) than the other three quinolones (MIC90 4 mg/L). Sparfloxacin was much more active against Mycoplasma hominis (MIC90 0.06 mg/L) than the other quinolones (MIC90 1 mg/L). Sparfloxacin showed the most potent inhibitory and bactericidal activity of the quinolones against Chlamydia trachomatis with MIC and MBC of 0.06 mg/L (ofloxacin MIC and MBC 1 mg/L; ciprofloxacin and lomefloxacin MIC and MBC 2 mg/L). The results of this study and others performed by workers using different methods are consistently similar. Since sparfloxacin has broad activity against pathogens implicated in genital infections it may be a good therapeutic alternative for these syndromes.

Anti-Infective Agents↗
PubMed1996

Effect of paclitaxel alone or in combination on the intracellular penetration and activity of quinolones in human neutrophils.

We evaluated the effect of paclitaxel alone or in combination with cisplatin or doxorubicin, on the intracellular penetration and activity of ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin in human polymorphonuclear leukocytes (PMN). In general, paclitaxel either alone or in combination did not affect the intracellular concentrations of the quinolones evaluated (intracellular to extracellular concentration ratio (C/E > 4). However, at high concentrations (20 mg/L) paclitaxel decreased the penetration of ofloxacin and levofloxacin although the C/E ratios remained higher than 3. Paclitaxel alone or in combination affected neither the production of oxygen radicals by PMN nor the intracellular activity of the quinolones against Staphylococcus aureus.

Anti-Infective Agents↗
PubMed1996

Antimicrobial susceptibility pattern of Corynebacterium striatum.

The in vitro activities of 16 antimicrobial agents against 86 strains of Corynebacterium striatum were evaluated by microdilution using cation-adjusted Mueller-Hinton broth. MICs at which 90% of strains were inhibited were 0.06 microgram/ml for teicoplanin, 1 microgram/ml for vancomycin, 0.03 to 8 micrograms/ml for beta-lactams, 8 micrograms/ml for sparfloxacin, 16 micrograms/ml for ciprofloxacin, 16/304 micrograms/ml for co-trimoxazole (trimethoprim-sulfamethoxazole), 64 micrograms/ml for tetracycline, 128 micrograms/ml for gentamicin, and > 128 micrograms/ml for amikacin, erythromycin, and rifampin.

Anti-Bacterial Agents↗
PubMed1996

Comparison of broth microdilution and E-test for susceptibility testing of Neisseria meningitidis.

The susceptibilities of 54 clinical isolates of Neisseria meningitidis to penicillin, cefotaxime, ceftriaxone, cefepime, imipenem, ciprofloxacin, chloramphenicol, and rifampin were determined by the microdilution method in both cation-adjusted Mueller-Hinton broth (CAMHB) and Haemophilus test medium (HTM). Poor growth was observed in 16.6 and 9% of the strains in CAMHB and HTM, respectively. As a result, the growth of the 54 N. meningitidis strains was evaluated in three other commercially available batches of CAMHB and in one in-house batch of HTM. Poor growth was observed for 9.3 to 16.6% of the strains in all four batches. More important, three of the CAMHB batches failed to support growth for 3.7 to 33.3% of the strains; 3.7% of the strains did not grow in the in-house-prepared HTM. Ten (18.7%) strains were relatively resistant to penicillin (RRP; MIC, > 0.125 mu g/ml) in CAMHB and 13 (24%) strains were RRP in HTM. The percentages of agreement obtained by using CAMHB as the reference ranged from 78% for cefepime to 100% for ceftriaxone. Seven minor errors were observed for penicillin; five of them were for strains susceptible to penicillin in CAMHB and RRP in HTM. All strains were susceptible to the other antimicrobial agents evaluated. The growth of N. meningitidis was also evaluated in four batches of Mueller-Hinton agar (MHA). In two of them, 3.7 and 44.4% of the strains did not grow, and considering all four batches, 5.5 to 11.1% grew poorly. All strains grew adequately in MHA supplemented with blood (MHA-b). The activities of penicillin and cefotaxime were also evaluated by the E-test in MHA and MHA-b. The proportion of RRP strains were 24% in MHA and 59% in MHA-b. For penicillin, the percentages of agreement of the E-test with the microdilution method in CAMHB (reference) were 64.8 and 70.3% in MHA and MHA-b, respectively. For cefotaxime, the agreement was 98.1%. Minor errors for the penicillin MIC were detected for 38% of the strains tested. Further studies are needed to define adequate culture media for reference methods to evaluate the susceptibility of N. meningitidis to antimicrobial agents.

Humans↗
PubMed1996

Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated.

PURPOSE: To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS: From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS: Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION: The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.

Adult↗
PubMed1996

[Intracellular penetration of 5 quinolones into non-phagocytic cells].

BACKGROUND: The intracellular penetration and activity of antimicrobial agents can be an important factor in the treatment of infections caused by intracellular pathogens. The new quinolones are able to penetrate into phagocytes, but only a few studies have evaluated other types of cells. The purpose of this study is to evaluate the intracellular penetration of ofloxacin, levofloxacin, lomefloxacin, sparfloxacin and BAY Y 3118 into human polymorphonuclear leukocytes and tissue cultured epithelial cells. METHODS: Intracellular penetration was evaluated by a fluorometric assay for all the quinolones evaluated except for sparfloxacin, which was evaluated by a radiometric assay. RESULTS: All the quinolones evaluated reached intracellular concentrations higher than extracellular ones. The penetration of sparfloxacin and BAY Y 3118 into the epithelial cells was similar to those observed for PMNs (cellular to extracellular concentration ratio; C/E > or = 4). The C/E values of ofloxacin, levofloxacin and lomefloxacin for epithelial cells were lower than those observed in PMN, but still yielding C/E values > or = 2.

Cells, Cultured↗
PubMed1996

[Uptake of 5 fluoroquinolones into human polymorphonuclear cells].

BACKGROUND: A comparative evaluation of the intracellular penetration of norfloxacin, ofloxacin, levofloxacin, fleroxacin and lomefloxacin was carried out in human polymorphonuclear leucocytes (PMNs). METHODS: The fluorometric method was used based on the natural fluorescence of some fluoroquinolones. RESULTS: All the fluoroquinolones accumulated within the human polymorphonuclear leucocytes achieving a quotient of between 4 to 6 in intracellular and extracellular concentration (I/C) with no significant differences being observed between the two. Penetration was rapid and was not saturable within the intervals of extracellular concentrations tested. The intracellular penetration of these fluoroquinolones was dependent on temperature and cell viability was altered in only levofloxacin and norfloxacin. The I/E values obtained significantly decreased when the cells were incubated at 4 degrees C. These values showed an important increase to pH 5 and decreased to pH 9, with this pH being statistically significant only in ofloxacin. CONCLUSIONS: All the fluoroquinolones evaluated penetrated rapidly into the phagocytic cells achieving intracellular concentrations which were several fold higher than the extracellular concentrations, with no notable differences being observed being the two, thus providing an additional advantage for their use in infections produced by microorganisms capable of surviving intracellularly.

Anti-Infective Agents↗