Primary hydatidosis of the peripheral muscles: treatment with albendazole.
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Administration, Oral↗
Biomedical subjects
R Montero
Publications and source records attributed to R Montero.
[Anesthesia in lung transplantation].
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Anesthesia, General↗
Genotoxicity studies on ebrotidine.
Five genotoxicity studies on ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio] ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542), including at least four of the battery of tests recommended by toxicological regulatory guidelines for new drugs, were conducted. These tests were the Ames test for determination of bacterial gene mutations, sex-linked recessive lethal mutation test in Drosophila for gene mutations in eukaryotic systems, in vitro chromosome aberration test and micronucleus test for evaluation of structural and numerical aberrations, and sister chromatid exchange frequency test for assessment of non-specific damage to chromatin. Negative and positive controls were used in all the experiments. The effects were investigated in the absence or presence of metabolic activation by S-9 microsomal fraction from rat liver homogenate. A dose range toxicity study was also performed to determine the dosage levels or concentrations to be tested for the assessment of genotoxic effects. None of the tests showed a significant increase in the genotoxic parameters, both in vitro and in vivo in somatic or germ cells. It is, therefore, concluded that ebrotidine has not caused mutagenic or clastogenic effects in any of the experimental systems tested.
Animals↗
Genotoxic effects of Karwinskia humboldtiana toxin T-514 in peripheral blood lymphocytes.
Toxicity by Karwinskia humboldtiana, a Rhamnaceae plant, has been assessed in a number of studies. Four dimmeric anthracenones, named T-496, T-514, T-516 and T-544 for their molecular weight, have been isolated from this plant. T-514, in particular, has been shown to be toxic to liver and lung as well as to tumoral cell lines, preferentially to those from liver tumors. For this reason it has been suggested that the toxin could be used as an antineoplastic agent. The present study was performed to characterize the biological activity of T-514 as a potential cytostatic and genotoxic agent. Peripheral blood lymphocytes in culture were used as a test system, where chromosomal aberrations and sister chromatid exchanges were scored in order to evaluate genotoxicity, and mitotic index and cell proliferation kinetics were used as parameters for cytostatic and cytotoxic ability. Genotoxicity to lymphocytes was negative. However, proliferation was affected by the toxin, demonstrating a cytostatic activity independent of genotoxic damage.
Adult↗
[Anesthetic complications in sequential bipulmonary transplantation in patients with cystic fibrosis. Apropos of 6 cases].
Cystic fibrosis (CF) is a disease characterized mainly by altered exocrine gland function that eventually produces irreversible dysfunction of the pancreas and lungs. The respiratory insufficiency that develops in CF patients in the advanced stages of disease can only be corrected at this time by lung or heart-lung transplantation. We describe our experience with 6 terminal phase CF patients who underwent sequential double lung transplantation (SDLT). Anesthesia was intravenous, with exhaustive hemodynamic and respiratory monitoring. During surgery the most frequently encountered hemodynamic complications were low minute volume, arterial hypotension and irregular heart rate. The main respiratory complications were hypoxemia, hypercapnia and pulmonary edema of the implanted lung, which developed in all cases to varying degrees related to the organ's state of preservation and duration of ischemia. Other complications were the need for extracorporeal circulation in 1 case, oliguria and blood loss requiring multiple transfusions. The most critical moments were at the time of clamping the pulmonary artery, the period after revascularization of the donated lung, and at the start of patient ventilation through the first implanted lung so that the second could be implanted. Although our series is small, it is of interest given the limited Spanish experience with lung transplantation in CF patients, and the good early results obtained, which are similar to those reported for other diseases.
Adolescent↗
Genotoxic monitoring of workers at a hazardous waste disposal site in Mexico.
Chromosomal aberration and sister chromatid exchange (SCE) frequencies were determined in lymphocytes cultured from 12 high-risk individuals working at a landfill for hazardous waste disposal. Cell proliferation kinetics (CPK) was also determined. Compared with 7 control individuals, no effects were observed with respect to SCE nor on CPK. However, the workers exhibited significantly higher frequencies of chromatid and chromosomal deletions, the magnitude of which was related with exposure time. This study suggests that when high-risk exposure is suspected, determining biomarkers of genotoxic damage (e.g., chromosomal aberrations), is useful for risk assessments.
Cell Division↗
[Selection and maintenance of lung donors].
Lung transplantation is a relatively modern procedure that can afford improvement in quality of life to certain terminal patients with irreversible respiratory failure. Selection of the donor and the recipient must be both strict and flexible, as we apply criteria that are constantly being revised and extended. The care afforded the donor must include certain elements: exhaustive monitorization that serves to guide the intravenous replacement of fluids and maintenance of hemodynamic stability; assisted ventilation with PEEP, FiO2 under 0.4 and adequate flow volumes; prevention and treatment of neurogenic pulmonary edema; and prevention of infections through careful airways management involving appropriate antibiotic prophylaxis. The same protocol must be maintained while the organ is being extracted and the organ itself must be properly preserved until implanted. The anesthesiologist is fully involved in optimum management of the lung donor. We consider that such care is essential for achieving more and better quality lung donations.
Female↗
Metronidazole hprt mutation induction in sheep and the relationship with its elimination rate.
Gene mutations at the hprt locus were determined in peripheral blood lymphocytes from nine sheep treated with metronidazole (MZ) at therapeutic doses for amebiasis. Pharmacokinetic studies were also carried out, including the calculation of the apparent first-order elimination rate constant (K10) and the steady state concentration of MZ in plasma. Three sheep showed an increase of variant frequencies (Vf) at the hprt locus. A proportional relationship was found between the highest Vf and the highest steady state in plasma, and an inverse relationship between Vf and K10. The finding that the animals with the lowest elimination rates of MZ had increased gene mutations indicates that differences in pharmacokinetics constitute one potential mechanism of genotoxic susceptibility.
Animals↗
Lymphocyte proliferation kinetics and sister-chromatid exchanges in individuals treated with metronidazole.
Metronidazole, an effective agent for the treatment of protozoan infections, is frequently used in developing countries. However, the employment of this drug has been questioned in view of its mutagenicity in bacteria and carcinogenicity in mice. A genotoxic study was carried out in which cellular proliferation kinetics and the frequency of sister-chromatid exchanges were determined in human peripheral blood lymphocytes from 12 individuals treated with therapeutic doses of metronidazole. No effect was observed on mitotic index with the treatment, although a significant increase was found in three individuals after treatment. No increase of sister-chromatid exchanges was detected. The rate of lymphocyte proliferation kinetics showed an increase after the metronidazole treatment in all patients, indicating a possible immunostimulatory action.
Adult↗
Evaluation of the carcinogenic and genotoxic potential of praziquantel in the Syrian hamster embryo cell transformation assay.
Praziquantel, a drug used for the treatment of neurocysticercosis, was tested for its ability to induce morphological transformation of Syrian hamster embryo fibroblasts. Results indicate that praziquantel transforms these cells without affecting their viability. Further experiments were carried out to investigate its possible mechanism of action in the same cell system. Micronucleus formation was observed in cultures treated with concentrations which induced morphological transformation, about 40% of these micronuclei were positive to a kinetochore antibody. No induction of DNA repair synthesis was observed even at cytotoxic concentrations. These results suggest that praziquantel has an aneugenic effect which could be responsible for its ability to transform morphologically these cells. Risk-benefit analysis should be carried out whenever this drug is utilized.
Animals↗
Mutation at the HPRT locus in patients with neurocysticercosis treated with praziquantel.
Praziquantel (PZQ) is the drug of choice in the treatment of neurocysticercosis (NC), a parasitic disease caused by Taenia solium larvae. Variant frequencies at the hprt locus were analyzed in a group of NC patients before and after treatment with PZQ as well as in two control groups: healthy donors and non-parasitic neurological patients. Data show that PZQ does not induce hprt mutations, but that cysticerci by themselves or together with palliative treatment administered to NC patients could induce mutations in some patients.
Adolescent↗
Altered urinary porphyrin excretion in a human population chronically exposed to arsenic in Mexico.
1. A detailed study of the urinary excretion pattern of porphyrins in humans chronically exposed to As via drinking water was performed using high performance liquid chromatography (HPLC) 2. Thirty-six individuals (15 men and 21 women) were selected from a town which had 0.400 mg L-1 of As in drinking water. The control group consisted of thirty-one individuals (13 men and 18 women) whose As concentration in drinking water was 0.020 mg L-1. 3. The major abnormalities in the urinary porphyrin excretion pattern observed in arsenic-exposed individuals were: (a) significant reductions in coproporphyrin III excretion resulting in decreases in the COPRO III/COPRO I ratio, and (b) significant increases in uroporphyrin excretion. Both alterations were responsible for the decrease in the COPRO/URO ratio. 4. No porphyrinogenic response was found in individuals with urinary As concentrations below 1,000 micrograms of As g-1 of creatinine. However, as arsenic concentrations exceeded this value, the excretion of porphyrins (except coproporphyrin III) increased proportionally. 5. The prevalence of clinical signs of arsenicism showed a direct relationship to both As concentration in urine and time-weighted exposure to As. A direct relationship between time-weighted exposure and alterations in urinary porphyrin excretion ratios was also observed. 6. The alterations found are compatible with a lower uroporphyrinogen decarboxylase activity in arsenic-exposed individuals. However, the similarities in the urinary porphyrin excretion pattern between As-exposed individuals and Dubin-Johnson syndrome patients suggest that impairments in the excretion of coproporphyrin isomers may also contribute to the pattern observed.
Adult↗
Mitotic index and cell proliferation kinetics for identification of antineoplastic activity.
The mitotic index (MI) and cell proliferation kinetics (CPK) of human blood lymphocyte cultures were determined to evaluate the effects of six antineoplastic drugs with well known cytostatic activity: cisplatin, melphalan, bleomycin, methotrexate, 5-fluorouracil and 6-mercaptopurine. All six drugs showed a clear effect on the inhibition of MI. The first three drugs interact directly with DNA showing a dose-related retardation of CPK. Methotrexate, 5-fluorouracil and 6-mercaptopurine, which act on ribonucleotide biosynthesis, showed no significant effects on CPK. The results suggest that CPK and MI measurements are useful for the prescreening of drugs with potential cytostatic activity.
Adult↗
The HPRT short-term assay in monitoring individuals exposed to genotoxic agents.
This paper reviews several monitoring studies where the short-term HPRT assay has been applied. The original method uses autoradiography to detect 3H-thymidine incorporation in variant cells that have undergone DNA synthesis; the bromodeoxyuridine modification employs this thymidine analog and fluorescence plus Giemsa staining. The studies discussed here were accomplished with either of these methods. methods. Exposures analyzed include radiation and chemotherapy as medical treatments and accidental exposures to radiation; these studies have been useful in the validation of the assay because radiation and anticancer drugs are well-known mutagens. Other potential mutagens such as environmental arsenic and a parasitic infection and praziquantel, used for its treatment, have also been monitored for hprt locus mutation. An overview of the results obtained with different agents and routes of exposure is presented here as well as some methodological aspects for the optimization of the assay for monitoring studies.
Autoradiography↗
AS-101: a modulator of in vitro T-cell proliferation.
AS-101 is a tellurate compound originally designed as a drug with cytostatic activity. Nevertheless, in vivo it was found to be an immunomodulator agent due to a stimulation of cytokine production. Mitotic Index (MI) as an indicator of cytotoxicity and cell proliferation kinetics (CPK) in lymphocytes cultures are parameters used in the evaluation of the antineoplastic activity of drugs, such as mitomycin-C and cisplatin. For this reason, we evaluated the effects of AS-101 upon these two parameters. The results show that AS-101 produces an inhibition of MI in proliferating lymphocytes higher than the inhibition mediated by cisplatin. When CPK was evaluated, AS-101 induced a retardation not related with dose, while cisplatin produced a stepwise inhibition. This effect contrasts with the stimulation observed when AS-101 was added to non-proliferating lymphocytes which was measured as an increased [3H]thymidine incorporation in culture. The results confirm the mode of action of AS-101 as a real modulating agent of cell proliferation.
Adjuvants, Immunologic↗
Biological monitoring of workers at a recently opened hazardous waste disposal site.
A health assessment was performed in a recently opened landfill for toxic waste. The site has received 14,000 tons of hazardous waste, confined in drums or deposited as bulk material, which were left outdoors for seven months. The analysis in some samples showed that the waste is rich in heavy metals, however we did not find high levels of contaminates in air or surface soil in different areas on-site. When compared to a control group, high-risk workers show higher levels of arsenic in urine and hair, and non-specific symptoms (irritability and insomnia). But among groups, we did not find statistical differences in urinary mercury, blood lead, phenol in urine, cadmium in hair or blood, sister chromatid exchange values, lymphocytes proliferation kinetics, liver function tests, and other non-specific symptoms. We considered this project as a background study for human exposure to hazardous waste, providing useful results for the future evaluation of chronic effects in the same population.
Adult↗
Effects of progesterone and estradiol on the proliferation of phytohemagglutinin-stimulated human lymphocytes.
In this paper we report on a study to elucidate whether the response of human lymphocytes to mitogenic stimulation was modified by physiological changes which occur during the menstrual cycle. Experiments with untreated cultures showed intra-individual variation to mitogen stimulation in female lymphocyte cultures, but a significant correlation between the menstrual cycle and the proliferation kinetics of lymphocytes was not found. Consequently, we performed experiments in which two of the hormones that regulate the menstrual cycle in women, estradiol and progesterone, were added to cultured human lymphocytes obtained from both men and women. The results indicate that both hormones at physiological concentrations have the capacity to modify the proliferation of PHA-stimulated human lymphocytes. Therefore, both hormones could play a role in the induction of the intra-individual variation observed in the untreated female cultures. However, in vivo other factors could also modify the proliferation kinetics of human lymphocytes preventing the demonstration of the effects of a single factor, such as the hormonal changes occurring during the menstrual cycle.
Adult↗
Are mitotic index and lymphocyte proliferation kinetics reproducible endpoints in genetic toxicology testing?
Lymphocyte proliferation kinetics is an endpoint used in genetic toxicology which has recently been proposed as an alternative for the screening of new cytostatic drugs. Although great variability for this parameter has been reported, there are few reports about the intra- and inter-individual variation of the effects of chemicals on this endpoint. For this reason, experiments were conducted to evaluate the reproducibility of the effects of a well-known cytostatic, mitomycin C (MMC), on the proliferation of PHA-stimulated human lymphocytes, both over time and among samples from several donors. Although inter-individual variability was shown in both parameters in untreated and treated cultures, this variation was not significant. Intra-individual variation was significantly detected only in cultures treated with 0.1 microM MMC.
Adult↗