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Biomedical subjects

L Aguilar

Publications and source records attributed to L Aguilar.

At least 109 records · Page 6Linked to original sources

In vitro assessment of the effect of clavulanic acid at concentrations achieved in human serum on the bactericidal activity of amoxicillin at physiological concentrations against Staphylococcus aureus: implications for dosage regimens.

The effects on Staphylococcus aureus viability and beta-lactamase activity of concentrations that simulated those in human serum after a combined dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro pharmacodynamic model. Six hours of preexposure to concentrations of the amoxicillin-clavulanic acid combination that were higher than the amoxicillin-clavulanic acid MIC led to a reduction of the initial inoculum of >90% and to a significant decrease of beta-lactamase activity versus those of the control even from 6 h, when concentrations were subinhibitory. The postantibiotic effect and post-beta-lactamase inhibitor effect contributed to these results.

Amoxicillin↗

In vitro antibiotic sensitivity testing breakpoints and therapeutic activity in induced infections in animal models.

Antimicrobial susceptibility breakpoints are artificially designated to classify organisms as susceptible, intermediate or resistant but such values may differ according to the relative weight given to the microbiological, pharmacological and clinical information. Animal models of bacterial infections are considered necessary to establish tentative breakpoints before initiating clinical trials in humans. Studies in animals provide a preliminary indication of the most effective and least toxic concentration of the antibiotic and give a rational basis for the selection of dosages and schedules. Animal models of therapeutic efficacy have demonstrated the importance of the inoculum effect, showing that the minimum inhibitory concentration (MIC) determined with high inoculum (10(7)-10(8) CFU/ml) is, under some experimental conditions, a better predictor of therapeutic efficacy than the value obtained with standard (10(4)-10(5) CFU/Ml) inoculum. Studies in animals have demonstrated the failure of some fluoroquinolones in respiratory tract infections where Streptococcus pneumoniae was present or the efficacy of penicillins and third-generation cephalosporins for treating respiratory tract infections and meningitis by pneumococci with diminished susceptibility to such agents. Although most therapeutic models in animals should be carried out during preclinical studies, many are done during later phases of antibiotic development, as explicate models of what is seen in clinical practice.

Animals↗

Hairpin, dumbbell, and single-stranded phosphodiester oligonucleotides exhibit identical uptake in T lymphocyte cell lines.

The cellular binding, uptake, and intracellular distribution of structured double-stranded phosphodiester oligonucleotides (decoys) have been examined in T lymphocytes using fluorescein-labeled molecules. Intracellular localization of hairpin and dumbbell decoys was similar to that of single-stranded oligonucleotides. At short incubation times, oligonucleotides were localized only in cytoplasmic vesicles, whereas at longer times, they were also found in the nucleus. Cellular uptake was dependent on temperature, time, and extracellular concentration. Oligonucleotide efflux was similar for all types of molecules and was very rapid (t1/2 = 10-15 minutes). These results imply that phosphodiester double-stranded oligonucleotides can enter cellular compartments of interest for their potential biologic function and, thus, provide a potential tool to control gene transcription.

DNA, Single-Stranded↗

Ex vivo antibacterial properties of rufloxacin compared with those of norfloxacin in a study with healthy volunteers.

Twelve adult males participated in a randomized crossover phase I clinical trial comparing serum bactericidal titers (SBTs), urine bactericidal titers (UBTs), and urine killing rates (UKRs) against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, after the administration of single 400-mg doses of rufloxacin and norfloxacin at different times up to 72 h postdose. SBTs were significantly higher (P < 0.05) against E. coli from 8 to 48 h and against S. aureus from 4 to 24 h with rufloxacin. UBTs for E. coli were higher (P < 0.05) for norfloxacin at early sample times (0 to 8 h) but higher for rufloxacin (P < 0.05) at sample times from 16 h on for both E. coli and S. aureus. Similar UKRs were obtained for both quinolones for 0 to 2 h and 8 to 12 h, but the UKR was maintained for 72 h with rufloxacin. The high and sustained mean levels of rufloxacin in urine (> 35 micrograms/ml), median UBTs (> 32 for E. coli and 16 for S. aureus) and UKRs for E. coli suggest prolonged urine antibacterial activity (for at least 72 h) and its use as a single 400-mg dose in the treatment of uncomplicated cystitis.

Adult↗

Activities against Streptococcus pneumoniae of amoxicillin and cefotaxime at physiological concentrations: in vitro pharmacodynamic simulation.

An in vitro model simulating amoxicillin and cefotaxime concentrations in human serum (after standard doses) was used to explore the activities of these drugs over time against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae strains. An initial inoculum reduction percentage of > or = 90% was obtained with amoxicillin and maintained for 2 to 8 h, regardless of the strain tested. In contrast, experiments showed that cefotaxime had significantly (P < 0.001) less capability to reduce initial inocula of the penicillin-resistant pneumococci from 0.5 h on than amoxicillin, despite the same in vitro susceptibility to amoxicillin and cefotaxime in both strains.

Amoxicillin↗

Single-dose rufloxacin versus 3-day norfloxacin treatment of uncomplicated cystitis: clinical evaluation and pharmacodynamic considerations.

The efficacy and safety of rufloxacin (400 mg, single dose) were compared to those of norfloxacin (400 mg twice a day for 3 days) for the treatment of women with uncomplicated cystitis. In addition, urine levels, drug level/MIC ratio, and urine antibacterial activity 72 to 84 h after treatment initiation were determined in a subgroup of patients for pharmacodynamic assessment. A total of 203 women were included and treated in this open, randomized clinical trial; 100 patients received norfloxacin, whereas 103 received rufloxacin. Of these, 156 (74 and 82 patients in the norfloxacin and rufloxacin groups, respectively) were considered bacteriologically evaluable. At the first follow-up visits (3 to 12 days after starting the treatment), bacteriological cure rates were 99 and 94% for norfloxacin and rufloxacin, respectively. Seventy-nine percent (119 of 150) of bacteriologically cured patients attended a long-term follow-up visit (4 to 6 weeks after starting the treatment), where a relapse rate of 4% (2 of 54) and 5% (3 of 64) were found in the norfloxacin and rufloxacin groups, respectively. The pharmacodynamic evaluation performed in 35 patients showed similar median urine levels (approximately equal to 25 micrograms/ml) and urine antibacterial activity for both treatment groups against initial isolates, despite a higher norfloxacin level/MIC ratio due to the lower MIC of norfloxacin. Twenty-one patients (20%) in the rufloxacin group and 12 patients (12%) in the norfloxacin group reported 39 and 16 adverse events, respectively, almost all of them being mild and lasting < 24 h. Overall, gastrointestinal reactions were the most frequent adverse events reported. However, 12 patients treated with rufloxacin reported 15 central nervous system adverse events. This study shows that single doses of rufloxacin are as effective as a norfloxacin 3-day standard treatment in uncomplicated cystitis. The results obtained with rufloxacin are consistent with its pharmacodynamic properties.

Adult↗

[Immunogenicity and safety of a tetanus-diphtheria vaccine (adult type): clinical trial in adults].

BACKGROUND: The administration of tetanus-diphtheria vaccine (Td, "adult" type) as booster dose every ten years, instead of tetanus toxoid, is a usual practice in the U.S., and its is being envisaged by the Spanish health authorities. In the present trial, the immunogenic capacity and the safety profile of the administration of one dose of Td vaccine to healthy adults, previously immunized to tetanus and diphtheria, was evaluated. METHODS: Healthy adults, who received one i.m. (deltoid) dose of Td vaccine containing 1.5 Lf and 10 Lf of adsorbed diphtheria and tetanus toxoids, respectively, participated in the study. Just before vaccination (baseline), and 4 weeks later, tetanus and diphtheria antibodies titres were determined by Elisa. The cut-off of these tests is 0.1 IU/ml. In this study, antitoxin titres > or = 0.1 IU/ml were considered as protective. Titres < 0.1 IU/ml were arbitrarily given the value of 0.05 IU/ml. Participating subjects recorded during the 3 days post-vaccination any local and systemic adverse events. RESULTS: One hundred and thirty nine medical students and health care workers (age +/- SD: 26 +/- 6 years) participated in this trial. At baseline and 4 weeks, the seroprotective levels were 70% and 100% for tetanus, and 31% and 90% for diphtheria, respectively. The geometric mean titres for tetanus and diphtheria antibodies at baseline and 4 weeks were: 0.59 and 8.54 IU/ml and 0.09 and 1.63 IU/ml, respectively. 82% of the subjects recorded some kind of adverse events, most of them local and mild. 66% referred local pain 24 h after the administration of the vaccine. Only 12% reported any kind of systemic adverse event: malaise (5%) and headache (4%) were the most commonly reported. All the adverse events were transient and did not require any medical attention or therapy. CONCLUSIONS: The Td vaccine tested in this study, when administered as booster dose to previously immunized adults, is highly immunogenic and shows an acceptable safety profile.

Adult↗

A double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of mupirocin calcium ointment for eliminating nasal carriage of Staphylococcus aureus among hospital personnel.

Sixty-eight health care workers were enrolled in a double-blind clinical trial and randomized to receive either mupirocin calcium ointment or placebo, intranasally bid for 5 days. Nasal cultures were taken immediately before starting treatment, 1 and 2 during treatment, at the end of treatment, 3 days later, weekly for 1-5 weeks and then monthly for 2-6 months after treatment. Mupirocin eliminated nasal carriage with Staphylococcus aureus in 58% of subjects within two days and 86.7% subjects by the end of therapy compared to 9.4% subjects at the end of treatment with placebo (P < 0.001). Post-treatment colonization rates of 43%, 56% and 67% were attained after 1 month, 2-4 and 6 months treatment with mupirocin respectively and recolonisation with the same strain of S. aureus that had been isolated before treatment was noted in 32%, 40% and 48%. No resistance to mupirocin developed and the drug was well tolerated. Mupirocin is safe and effective in suppressing nasal carriage of S. aureus.

Administration, Intranasal↗

Comparison of rufloxacin and norfloxacin effects on faecal flora.

The suppression of faecal Escherichia coli by quinolones was studied in a randomized cross-over phase I trial with single oral doses of 400 mg rufloxacin or norfloxacin. Both drugs caused > 70% decontamination in a similar number of subjects in the 72 h post-dose period (83% vs 100% respectively), but suppression of E. coli at 168 h was significantly (P < 0.05) higher after rufloxacin (83.3 vs 40%).

Adult↗

[Evaluation of immunogenicity and safety in healthy adults of an inactivated anti-hepatitis A vaccine].

BACKGROUND: The evaluation of the safety and immunogenicity of an inactivated vaccine against the hepatitis A virus (HAV) in healthy adults was performed. METHODS: A descriptive clinical trial was carried out including a population of 100 healthy subjects of ages from 19 to 25-years. The subjects were intramuscularly injected (deltoid muscle) with an inactivated vaccine against hepatitis A (720 units ELISA) following a schedule of 0.1 months and a booster dose at 6 months. The titers of anti HAV antibodies were determined by the ELISA method prior to vaccination and following the administration of each doses. The safety of the vaccine was also parallelly evaluated after each doses from both a local and systemic point of view. RESULTS: With respect to safety, local signs and symptoms were presented in 34.6% of the subjects while systemic signs and symptoms were observed in 6.8% following administration of the 3 doses. At one month of the first doses 95.8% of the subjects had seroconverted (> or = 20 mUI/ml) with this rising to 100% at one month of receiving the second and third doses. The geometric mean of the antibody titer one month after having received each of the three doses was 158 mUI/ml, 832 mUI/ml and 4,135 mUI/ml, respectively. CONCLUSIONS: The vaccine was well tolerated and demonstrated great safety with a 100% rate of seroconversion following the primary cycle with two doses. The administration of the reminder doses at 6 months increased the antibody titer five fold after the primary cycle.

Adult↗

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↗

Randomised controlled trial of efficacy of albendazole in intra-abdominal hydatid disease.

The efficacy of albendazole in hydatid disease is still unclear, because there has been no study that assessed the status of the parasite after treatment. The significance of albendazole-induced echographic changes in the cyst therefore cannot be judged. We did a prospective, controlled, randomised, open study of albendazole in patients with liver hydatid disease, and assessed parasite viability after treatment. 18 patients received no albendazole treatment (controls), 18 received albendazole (10 mg/kg daily) for 1 month (group A), and 19 received the drug for about 3 months (group B). Echography was done before and during treatment; all patients underwent surgery on completion. Parasite (protoscolex viability and development of cysts in mice) and ultrastructure studies were done for all cysts removed. 8 (50%) of cysts in the control group, 13 (72%) in group A, and 16 (94%) in group B were non-viable (p = 0.015). Protoscolex and cyst viability were significantly (p = 0.039 and p = 0.018, respectively) lower in treated patients than in controls. Treatment was also significantly associated with total cyst membrane disintegration. 68% of cysts treated for 3 months showed echographic changes, and only 1 of 20 cysts showing echographic changes during treatment was judged viable. The efficacy of albendazole at a dose of 10 mg/kg daily for 3 months suggests that it is a suitable alternative to surgery in uncomplicated hydatid liver disease, as initial treatment.

Adult↗

Distribution of three retinal proteins in developing octopus photoreceptors.

The expression of proteins unique to plasma membrane domains of developing photoreceptors is used as a marker for retinal differentiation in vertebrates. Invertebrate photoreceptors are also compartmentalized, but little information is available on the development of these compartments or the expression of retinal proteins specific to these cellular regions. Using routine electron microscopy techniques, we have made observations on the formation of photoreceptor organelles, including myeloid bodies and rhabdomeres, in embryonic octopus eyes from an early stage in development through hatching. Immunocytochemical experiments on the embryos demonstrate a timed expression of three retinal proteins during development, and the early separation of the octopus photoreceptor plasma membrane into distinct domains. Using polyclonal antibodies for opsin, retinochrome and retinal binding protein we have shown that opsin appears first and is confined to the distal end of the photoreceptor that will eventually differentiate into rhabdomeres. This membrane domain is separated from the proximal/inner segment plasma membrane by a septate junction. Retinochrome is expressed later when the myeloid bodies appear in the inner segments, and retinal binding protein is apparently not synthesized until sometime after hatching. These results suggest that, in the cephalopod retina, protein components of the retinoid cycling apparatus appear in a specific developmental sequence during the differentiation of this tissue.

Animals↗

Plants used in Guatemala for the treatment of gastrointestinal disorders. 3. Confirmation of activity against enterobacteria of 16 plants.

Ethnobotanical surveys and literature review identified 408 plants used in Guatemala for the treatment of gastrointestinal disorders. The screening of 84 showed that 34 inhibit one or more enterobacteria; 16 of these were selected for further investigation. Extracts were obtained with three solvents of different polarity (n-hexane, acetone and alcohol) and the in vitro activity was demonstrated against enteropathogenic Escherichia coli, Salmonella enteritidis and Shigella flexneri. The activity of nine ethanolic extracts against enterobacteria, particularly Acalypha guatemalensis, Diphysa robinioides, Lippia dulcis, Psidium guajava and Spondias purpurea was confirmed. The plants with antibacterial activity are discussed.

Diarrhea↗

[Seroprotection against hepatitis A, measles, rubella, and parotiditis in an urban school population].

BACKGROUND: To find out the presence of hepatitis A antibodies (anti-HA) in an urban population of Madrid, age ranging from 6 to 18 years. At the same time, the immunity level is evaluated with respect to measles, rubella and mumps in a sub-group aged between 6 and 13 years old. METHODS: The study was carried out in two schools population of the north area of Madrid. RESULTS: Anti-HA prevalence in the whole population under study (707 subjects) was of 6%; a direct correlation was observed between prevalence and age. With respect to the seroprotection study against measles, rubella and mumps, 81% out of the 385 vaccinated subjects is protected against the three viruses. Seroprotection rate is of 79% if this is evaluated with respect to the total 6-13 age group under study (458 subjects). CONCLUSIONS: The results of anti-HA prevalence obtained in the eldest groups reveal that a high percentage of the study population aged 17 (92%) and 18 (84%), is anti-HA negative, which means that they might be susceptible to the infection when reaching the adult age. 21% of the school age group studied with respect to measles, rubella and mumps is seronegative to some of the three viruses. Considering the above results, it appears that it could be interesting to evaluate whether the administration of a booster dose to children in school age would enable to reduce the number of unprotected subjects in the referred ages.

Adolescent↗

Plants used in Guatemala for the treatment of gastrointestinal disorders. 1. Screening of 84 plants against enterobacteria.

Gastrointestinal disorders are important causes of morbidity in developing countries. Natural healing is the traditional way of treating these diseases in Guatemala. Ethnobotanical surveys and literature reviews showed that 385 plants from 95 families are used in Guatemala for the treatment of gastrointestinal disorders. The activity of 84 of the most commonly used plants was screened in vitro against five enterobacteria pathogenic to man (enteropathogenic Escherichia coli, Salmonella enteritidis, Salmonella typhi, Shigella dysenteriae and Shigella flexneri). Results indicate that 34 (40.48%) plants inhibit one or more of the enterobacteria tested. The most commonly inhibited bacterium was S. typhi (33.73%) and the most resistant was E. coli (7.35%). The plants of American origin which exhibited the best antibacterial activity were: Byrsonima crassifolia, Diphysa robinioides, Gnaphalium stramineum, Guazuma ulmifolia, Psidium guajava, Sambucus mexicana, Simarouba glauca, Smilax lundelii, Spondias purpurea and Tagetes lucida. These results indicate a scientific basis for use of these medicinal plants for attacking enterobacterial infections in man.

Anti-Bacterial Agents↗