Influence of demographic parameters and dietary habits on the cytome assay biomarkers in lymphocytes and buccal epithelial cells from a group of argentine adolescents / Influencia de parámetros demográficos y hábitos alimentarios sobre biomarcadores del ensayo citoma en linfocitos y células epiteliales bucales de adolescentes argentinos

ABSTRACT The use of the cytome assay in monitoring studies on children has increased in recent years. For this reason, it is necessary to know the role of possible confounding factors that could affect its outcomes. The objective was to evaluate the influence of some demographic variables and diet on the baseline values of the cytome assay biomarkers in lymphocytes and buccal mucosa cells from a group of Argentine adolescents. Following the calculation of the biomarkers, a multivariate regression analysis including confounders was performed. In lymphocytes it was observed that micronuclei (MNi) had a negative association with a moderate consumption of roots and tubers, while the number of nuclear buds (NBUDs) was higher in minors not exposed to second-hand smoke (SHS). Regarding epithelial cells, MNi had a negative relationship with the intake of tropical fruits and red meat; on the contrary, this parameter increased with the moderate ingestion of legumes. In addition, oral NBUDs had a positive association with citrus and red meat consumption, whereas cereals and oil decreased its frequency. Furthermore, an increased number of binucleated cells was observed for adolescents who ate white meat and an increase in pyknotic cells for those exposed to SHS. These results revealed that in adolescents the baseline level of the cytome assay biomarkers, especially of those related to genotoxicity, can be influenced by exogenous variables, for instance, dietary habits. Thus, such factors need to be considered when carrying out biomonitoring studies on child populations.

RESUMEN El uso del ensayo de citoma en estudios de seguimiento en niños se ha incrementado en los últimos años y resulta necesario conocer el papel de posibles factores de confusión que podrían afectar sus resultados. El objetivo fue evaluar la influencia de algunas variables demográficas y de la dieta en los valores basales de los biomarcadores de este ensayo en linfocitos y células de mucosa bucal de un grupo de adolescentes argentinos. Luego del cálculo de los biomarcadores, se realizó un análisis de regresión multivariada incluyendo factores de confusión. En linfocitos se observó que los micronúcleos (MN) se asociaron negativamente con un consumo moderado de raíces y tubérculos, mientras que los brotes nucleares (BrN) aumentaron en los menores no expuestos al humo de segunda mano (HSM). En células epiteliales, los MN tuvieron una relación negativa con el consumo de frutas tropicales y carnes rojas, aunque aumentaron con el consumo moderado de legumbres. Los BrN orales tuvieron una asociación positiva con el consumo de cítricos y carnes rojas, mientras que los cereales y el aceite disminuyeron su frecuencia. Además, se encontró un mayor número de células binucleadas para quienes comieron carne blanca y un aumento de células picnóticas para los expuestos a HSM. Estos resultados revelaron que en los adolescentes el nivel basal de los biomarcadores del ensayo de citoma, especialmente de aquellos relacionados con la genotoxicidad, puede verse influenciado por variables exógenas como los hábitos alimentarios. Por lo tanto, dichos factores deben considerarse al realizar estudios de biomonitoreo en poblaciones infantiles.

A Study of Zn-Ca Nanocomposites and Their Antibacterial Properties.

This study aimed to develop Ca2+ doped ZnO nanoparticles (NPs) and investigate their antibacterial properties against microorganisms of dental interest. Zn-Ca NPs were synthesized by the sol-gel method with different concentrations of Ca2+ (1, 3, and 5 wt. %) and subsequently characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-vis spectroscopy and Fourier transform infrared spectroscopy (FT-IR). The Kirby-Bauer method was used to measure antibacterial effects. NPs showed the wurzite phase of ZnO and bandgap energies (Eg) from 2.99 to 3.04 eV. SEM analysis showed an average particle size of 80 to 160 nm. The treatments that presented the best antibacterial activity were Zn-Ca 3% and Zn-Ca 5%. ZnO NPs represent an alternative to generate and improve materials with antibacterial capacity for dental applications.

Difteria: Experiencia en el servicio de enfermedades infecciosas del Hospital Universitario de Caracas

Difteria es una enfermedad infecciosa bacteriana producida por Corynebacterium diphtheriae, es altamente contagiosa, prevenible por vacunas, con importantes complicaciones agudas y alta mortalidad. Objetivo: Describir las características clínicoepidemiológicas y el manejo médico de los pacientes con diagnóstico de Difteria ingresados en el Servicio de Enfermedades Infecciosas del Adulto del Hospital Universitario de Caracas (HUC) en los años 2017 y 2018. Metodología: Estudio de casos, analítico, retrospectivo, de revisión de historias clínicas. Resultados: Ingresaron 27 pacientes de los cuales se encontraron 22 historias clínicas y se excluyeron 2. De los 20 pacientes 13 (65 %) ingresaron en el año 2017 y 7 (35 %) hasta mayo del 2018. Predominó el género masculino 11 (55 %). La mayoría eran procedentes del Distrito Capital 9 (45 %), seguido del estado Miranda 8 (40 %). El promedio de edad fue de 26 años. La mayoría 8 (40 %) no tenían reportes de datos epidemiológicos en la historia clínica, 7 (35 %) negaron viajes recientes, 3 (15 %) estaban vacunados. La mayoría de los pacientes consultaron por fiebre, odinia y odinofagia 13 (65 %), seguido de fiebre y odinia 6 (30 %), el 100 % tuvo membrana blanco grisácea como clínica primaria, seguido de edema de cuello 10 (50 %). La ubicación de las membranas fue más frecuente en amígdalas palatinas 15 (75 %), con 9 casos (45 %) de formas extensivas a úvula, paladar blando y paredes de orofaringe. Las complicaciones al ingreso fueron respiratorias 9 (45 %) y neurológicas 1 (5 %). El tratamiento fue penicilina cristalina en 12 casos (60 %) y antitoxina diftérica (ATD) en el 100 %, la mayoría administrada en las primeras 24 hrs 9 (45 %). Un paciente presentó polineuropatía y 1 falleció por insuficiencia respiratoria. Conclusiones: El HUC es un centro de referencia y es pertinente determinar las características clínico-epidemiológicas y el manejo médico de los pacientes hospitalizados con diagnóstico de difteria, en el contexto de la actual epidemia.

Diphtheria is a bacterial infectious disease caused by Corynebacterium diphtheriae, it is highly contagious, preventable by vaccines, with important acute complications and high mortality. Objective: To describe the clinical-epidemiological characteristics and medical management of patients diagnosed with Diphtheria admitted to the Adult Infectious Diseases Service of the Hospital Universitario de Caracas (HUC) in the years 2017 and 2018. Methodology: Case study, analytical , retrospective, review of medical records. Results: 27 patients were admitted, of which 22 clinical records were found and 2 were excluded. Of the 20 patients, 13 (65%) entered in 2017 and 7 (35%) up to May 2018. The male gender predominated 11 (55 %). Most were from Distrito Capital 9 (45%), followed by Miranda 8 (40%). The average age was 26 years. The majority 8 (40%) had no reports of epidemiological data in the clinical history, 7 (35%) denied recent trips, 3 (15%) were vaccinated. The majority of patients consulted for fever, odinia and odynophagia 13 (65%), followed by fever and odinia 6 (30%), 100% had grayish white membrane as primary clinic, followed by neck edema 10 (50%) . The location of the membranes was more frequent in palatine tonsils 15 (75%), with 9 cases (45%) of extensive forms to the uvula, soft palate and walls of the oropharynx. Complications at admission were respiratory 9 (45%) and neurological 1 (5%). The treatment was crystalline penicillin in 12 cases (60%) and diphtheria antitoxin (DAT) in 100%, the majority administered in the first 24 h 9 (45%). One patient presented polyneuropathy and 1 died due to respiratory failure. Conclusions: The HUC is a reference center and it is pertinent to determine the clinical-epidemiological characteristics and medical management of hospitalized patients diagnosed with diphtheria, in the context of the current epidemic.

Two novel frameshift mutations in BRCA2 gene detected by next generation sequencing in a survey of Spanish patients of breast cancer.

PURPOSE: To analyze BRCA1 and BRCA2 genes using a cost-effective and rapid approach based on next generation sequencing (NGS) technology. METHODS: A population of Spanish cancer patients with a personal or familial history of breast and/or ovarian cancer was analyzed for germline mutations in BRCA1 and BRCA2 genes. The methodology relies on a 5 multiplex PCR assay coupled to NGS. RESULTS: Ten pathogenic mutations (four in BRCA1 and six in BRCA2 gene) were identified in a Spanish population. The deletion c.1792delA, in exon 10, and the duplication c.5869dupA, in exon 11 of BRCA2 gene were not previously reported and should be considered as pathogenic due to its frameshift nature. CONCLUSION: Two novel frameshift mutations in BRCA2 gene were detected using the multiplex PCR-based assay following by NGS.

The life cycle and geographical distribution of the monorchiid Proctotrema bartolii (Digenea) in the clam Darina solenoides from the Patagonian coast, Argentina.

The life cycle of Proctotrema bartolii Carballo, Laurenti & Cremonte 2011 (Digenea: Monorchiidae) at Fracasso Beach (the type locality) (42°25'S, 64°07'W), Península Valdés, Argentina, was investigated. This digenean uses the clam Darina solenoides (Mactridae) as both the first and second intermediate hosts in the natural environment. The metacercariae were located mainly at the tip of the incurrent siphon, with an infection prevalence of 100%. Experimental infections in other macroinvertebrates, such as the clam Tellina petitiana and the polychaete Glycera americana, were successful, but these and other invertebrates are not naturally infected. Silversides Odontesthes smitti and Odontesthes nigricans (Pisces: Atherinopsidae) and the mullet Eleginops maclovinus (Eleginopidae) act as the definitive hosts of both experimentally and naturally obtained adults. Fish acquire infection by eating either the siphon or the entire clam. Proctotrema bartolii seems to be endemic to the Magellan Region and is distributed where its intermediate clam host is present, from the San José Gulf in Península Valdés to the southern tip of South America.

Similarity in parasite community structure may be used to trace latitudinal migrations of Odontesthes smitti along Argentinean coasts.

The aims of this study were to determine the existence of migratory movements and to identify ecological stocks of the silverside Odontesthes smitti along its distribution in the Southern Atlantic Ocean, using metazoan parasites as biological tags. Samples were obtained from San José Gulf (SJ) (42° 25' S; 64° 07' W) and Nuevo Gulf (NG) (42° 47' S; 65° 02' W) in north Patagonia during winter and summer and in waters off Mar del Plata (MDP) (38° 03' S; 57° 32' W), Bonaerense region, during winter. Fifteen parasite species were collected. Multivariate statistical procedures on parasite community data showed strong effect of host size on the structure of parasite assemblages. Taking into account the variations among samples due to host size, the differential structure of parasite communities between SJ and NG suggests that fish inhabiting these localities could belong to different ecological stocks. Fish from MDP and SJ caught in summer showed similar composition in their parasite assemblages, which is congruent with a migratory cycle that implies that fish caught in MDP during winter inhabit SJ during summer. Further evidence of the Patagonian origin of MDP O. smitti is the presence of the digenean Proctotrema bartolii in fish from both regions. Proctotrema bartolii is acquired by O. smitti only in the Magellanic province, where its intermediate host, Darina solenoides, is distributed. The analyses suggest that O. smitti inhabiting north Patagonian gulfs could belong to different ecological stocks and that O. smitti caught in MDP could have come from SJ.

Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months.

BACKGROUND: Stereotactic thermocoagulative lesions of the subthalamic nucleus (STN) have been shown to induce significant motor improvement in patients with Parkinson's disease (PD). PATIENTS AND METHODS: 89 patients with PD were treated with unilateral subthalamotomy. 68 patients were available for evaluations after 12 months, 36 at 24 months and 25 at 36 months. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor scores improved significantly contralaterally to the lesion in the "off" and "on" states throughout the follow-up, except for the "on" state at the last evaluation. Axial features and signs ipsilateral to the lesion progressed steadily throughout the study. Levodopa daily doses were significantly reduced by 45%, 36% and 28% at 12, 24 and 36 months post-surgery. 14 patients (15%) developed postoperative hemichorea-ballism which required pallidotomy in eight. These 14 patients had significantly higher dyskinesia scores (levodopa induced) preoperatively than the entire cohort. CONCLUSION: Unilateral subthalamotomy was associated with significant and sustained motor benefit contralateral to the lesion. Further work is needed to ascertain what factors led to severe, persistent chorea-ballism in a subset of patients. Subthalamotomy may be considered an option in circumstances when deep brain stimulation is not viable.

Increased organ donations from people born outside Spain.

Organs donated from persons born outside Spain are becoming increasingly numerous. These persons now account for 26.1% of all donors in the "Malaga sector," an area of tourism with a high percentage of immigrants. Acceptance to donation among persons from Europe and South America is similar to that of Spanish persons but lower among those born in Africa. We must recognize the great help that cultural mediators provided not only by assistance with the language barrier but also by generating confidence among families and understanding their emotions, feelings, and traditions, mainly during interviews with families from different social and cultural miliere. To be efficient, the interpreters or cultural mediators need to have received specific training in the organ donation process and to be involved and convinced that organ donation and transplantation is the best solution for severe health problems.

DNA damage in workers occupationally exposed to pesticide mixtures.

Pesticides are used in agriculture to protect crops but represent at the same time a potential risk to farmers and environment. The aim of this work is the evaluation of 54 subjects occupationally exposed to pesticides and 30 subjects as a control group using the quantification of DNA damage level by means of the alkaline Comet assay and the evaluation of repair processes. Damage index Comet assay (DICA) and damage index repair assay (DIRA) were studied in 27 pesticide applicator workers, 27 non-pesticide applicators and controls. Our results show that both exposed groups revealed significant increase in DICA when compared with controls (P < 0.0001), as well as in DIRA (P < 0.0001). However, the spraying group exhibited a marginally significant difference in DICA (P = 0.05) when years of exposure are considered and a significant difference (P < 0.05) when the personal protective equipment used by individuals was taken as a comparison factor. The influence of confounding factors on the genotoxic effects of occupational exposure to pesticides was investigated and no significant differences were observed considering age, gender, smoking and alcohol consumption in relation to DICA and DIRA. Since DNA damage is an important step in events leading from carcinogen exposure to cancer disease, our study highlights the potential health risk associated with agrochemical exposure in developing countries with vast cultivated areas, such as Argentina.

Genotoxicity and cell death induced by tinidazole (TNZ).

Tinidazole (TNZ), a second-generation 5-nitroimidazole compound chemically related to metronidazole (MTZ), has been widely used throughout Europe and developing countries for the treatment of amoebic and parasitic infections. Despite TNZ's increasing use in therapeutics, scarce experimental reports are available in literature on its potential genotoxicity in human cells. Therefore, the aim of the present study was to achieve a precise characterization of the cytotoxic and genotoxic activities of this nitroimidazole in cultured human lymphocytes at therapeutic concentrations (0.1, 1, 10 and 50 microg/ml of culture) and evaluate the possible cell death mechanism associated with it. The endpoints analyzed included: mitotic index (MI), replication index (RI), sister chromatid exchange (SCE) and chromosomal aberrations (CA). A significant decrease (p<0.0001) in MI as well as an increase in SCE (p<0.0001) and CA (p<0.0001) frequencies were observed. No modifications in RI were found. The results suggest a genotoxic and cytotoxic effect of TNZ related with cell death process. Therefore, we evaluated this mechanism by DNA fragmentation (laddering), fluorescence microscopy using acridine orange/ethidium bromide (AO/EB) staining and flow cytometry propidium iodide (PI). DNA extracts of TNZ-treated cells resulted in nucleosomal DNA ladder pattern after 48 h of cell treatment; meanwhile no differences were detected in untreated cells. This pattern correlated with the observed decrease in cellular viability (p<0.05), morphological evidence of apoptosis and increase in the percentage of nuclei with hypodiploid DNA content of TNZ exposed cultures compared with control (p<0.05). We concluded that TNZ is genotoxic, cytotoxic and is able to modulate cell death through apoptotic mechanisms in the experimental design employed.

[Microbiological isolates in patients with febrile neutropenia and hematological neoplasias]. / Aislamientos microbiologicos en pacientes con neutropenia febril y neoplasias hematologicas.

We studied the frequency of culture isolation, type of microorganism isolated and local pattern of resistance in 309 adult febrile neutropenic inpatients with hematological neoplasm, who were hospitalized between January 1998 and December 2003, in Caracas University Hospital (Hospital Universitario de Caracas), in Venezuela. There were 576 febrile neutropenic episodes. Organisms were isolated in 41% of 940 cultures. The most common organisms involved were gram-negative bacilli (48%), followed by gram-positive cocci (35.1%), fungal (11.5%) and other agents (5.4%). Coagulase-negative staphylococci (22.4%) and Escherichia coli (13.4%) were the most isolated; 58.5% of 479 agents isolated had an antibiogram; 62.2% of coagulase-negative staphylococci and 23.1% coagulase-positive staphylococci were oxacillin-resistant. We did not find any vancomycin-resistant organisms. The gram-negative antimicrobial sensitivity for imipenem was 96.2%, cefepime 81%, and ceftazidime 57.5%. Tazobactam-piperacillin and sulbactam-cefoperazone were tested in 26% of antibiograms and had activity of 57.1% and 77.5%, respectively. Fungi were not characterized. Betalactamases producing gram-negative bacilli were found. In general, micro-biological identification and local vigilance of antibacterial resistance pattern must be done routinely in these patients, in order to improve empiric therapy guidelines.

Genotoxic and aneugenic properties of an imidazole derivative.

To contribute to a more accurate characterization of the mutagenic and aneugenic effects of thiabendazole (TBZ), a widely used antiparasitic and food preservative drug, the induction of sister chromatid exchanges (SCEs) and mitotic spindle anomalies as cytogenetic end-points were investigated. Studies were carried out in Chinese hamster ovary (CHO) cells and human peripheral blood lymphocytes. A significant dose-dependent increase in SCE frequency was observed in CHO cells with S9-Mix (P < 0.01) in the 50-100 microg ml(-1) dose-range, while in the absence of S9-Mix, an enhancement of the SCE frequency was exhibited at the highest dose (P < 0.01). In CHO-K1 cells a significant increase in mitotic spindle anomalies (P < 0.01) was observed with the highest concentration assayed reflecting the specific effect of TBZ formulation at the microtubule level. Cell proliferation kinetics (CPK) were not modified by the addition of this pharmaceutical product. In human lymphocyte cultures, exposure to 100 microg ml(-1) TBZ formulation resulted in a significant decrease of the mitotic index (MI) (P < 0.003) and changes in the replication index (RI) (P < 0.05).

Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced DNA damage as shown by the comet assay technique.

Aloysia triphylla a perennial, bushy plant originally from South America has long been used in traditional medicine. Its aqueous extract contains considerable amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view of the interest in natural phenolic compounds as antioxidant in preventive medicine, this study was undertaken to investigate the chemoprotective effects of cedron leaves infusion against the genetic damage induced by acrylamide (AA) by using the alkaline version of the comet assay technique. Mice were separated in nine groups (eight animals each): (I) untreated, (II) negative control, (III) treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30 mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally evaluated per animal from three different slides (100 each). Media of tail moment (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were found between untreated animals, negative control and infusion-treated mice. A single dose of AA-induced genetic damage as revealed by a statistically significant increase in TM values (p<0.01). Pretreatment with infusion prior to AA injection significantly reduces the capacity of AA to induce genetic damage. In these conditions, tail moments values did not differ from data obtained in negative control (p>0.05) and exhibit statistical differences from animals treated only with AA (p<0.01). Cell viability was at least 90% in all cases as measured by the trypan blue exclusion method. The ferric reducing ability of plasma (FRAP) method reveals that the plasma of infusion-treated mice has a significantly higher antioxidant capacity than plasma from controls (p<0.01). The results suggest that the infusion could exerts an in vivo chemo protective action, probably due to its scavenging potency towards free radicals.

Argentine folk medicine: genotoxic effects of Chenopodiaceae family.

Chenopodium ambrosioides L. and Chenopodium multifidum L. (Chenopodiaceae), common name: Paico, are medicinal plants. They are aromatic shrubs growing in South America. For centuries, they have been used due to its medicinal properties. However, there are few reports in literature about the genotoxic effects of these plants. There for, the aim of these work is the evaluation of genetic damage induced by decoction and infusion of this plants which were assayed in different concentrations (1, 10, 100, 1,000 microL extract/mL culture), by addition of the extract to human lymphocyte cell cultures, negative controls were included. The endpoints evaluated were chromosomal aberrations (CA), sister chromatid exchanges (SCE), cell proliferation kinetics (CPK) and mitotic index (MI). The repeated measure analysis of variance was used for statistic evaluation of the results. The results showed: (a) statistical increase in the percentage of cells with CA and in the frequency of SCE when cultures were exposed to both aromatic plants, (b) a decrease in MI of both Paicos assayed, although no modification in the CPK values was observed, (c) no effect was noticed in the analysis of Chenopodium album L., which was used as negative control of the essential oil. These results suggest a cyto and genotoxic effect of Chenopodium ambrosioides and Chenopodium multifidum aqueous extracts related to the essential oil of the plant (as Chenopodium album did not perform).

Accuracy of frozen-section analysis in the diagnosis of ovarian tumors: a systematic quantitative review.

A quantitative systematic review was performed to estimate the diagnostic accuracy of frozen sections in ovarian tumors. Studies that compared frozen sections and paraffin sections within subjects for diagnosis of ovarian tumors were included. Fourteen primary studies were analyzed, which included 3 659 women. For benign ovarian vs borderline/malignant tumor cases, the occurrence of a positive frozen-section result for benignity (pooled likelihood ratio [LR], 8.7; 95% confidence interval [CI], 7.3-10.4) and posttest probability for benign diagnosis was 95% (95% CI, 94-96%). A positive frozen-section result for malignant vs benign diagnosis (pooled LR, 303; 95% CI, 101-605) increased the probability of ovarian cancer to 98% (95% CI, 97-99%). In borderline vs benign ovarian tumor cases, a positive frozen-section result (pooled LR, 69; 95% CI, 45-106) increased the probability of borderline tumors to 79% (95% CI, 71-85%). In borderline vs malignant ovarian tumor cases, a positive frozen-section result (pooled LR, 18; 95% CI, 13-26) increased the probability of borderline tumors to 51% (95% CI, 42-60%). We conclude that diagnostic accuracy rates for frozen-section analysis is high for malignant and benign ovarian tumors, but the accuracy rates in borderline tumors remain relatively low.

[A clinical and epidemiological description of a series of patients diagnosed as suffering from progressive supranuclear palsy]. / Descripción clínica y epidemiológica de una serie de pacientes con diagnóstico de parálisis supranuclear progresiva.

INTRODUCTION: Progressive supranuclear palsy is a disease that normally presents only sporadically in adults and courses in a progressive, chronic manner. It is characterised by the presence of supranuclear ophthalmoplegia, postural instability, a Parkinsonian syndrome, pseudobulbar affect, cervical dystonia and cognitive impairment. PATIENTS AND METHODS: We conducted a descriptive study of clinical and epidemiological features in a series of 18 patients who satisfied the mandatory NINDS-SPSP clinical eligibility criteria for the likely diagnosis of progressive supranuclear palsy, using the scale developed by Golbe et al. RESULTS AND CONCLUSIONS: The mean age of onset of the disease was 58.6 +/- 8.2 years, 55.5% of the patients were males, the average history of the disease at the time of diagnosis was 4.39 +/- 2.3 years, and there was a diagnostic subregister in the first 4 years of the disease. Gait disorders, falls and slowness were the most frequently observed presenting forms of the disease. During their first four years with the disease, 75% of the patients were totally independent when it came to carrying out activities of daily living, whereas after the fourth year there was a predominance of the need for aid and absolute dependence. Dysphagia was more frequent in the later stages of the disease. Ocular motility disorders and impaired cognitive functioning were obvious in the initial stages of the disease, and there was a strong correlation between the length of time the disease had been coursing and the severity of the ocular and cognitive disorders.

Teratogenic evaluation of metronidazole and ornidazole using Drosophila melanogaster as an experimental model.

BACKGROUND: Drosophila and vertebrates show similarities that suggest that the mechanisms involved in the induction of developmental defects may be similar in both. Therefore, Drosophila has been proposed as a useful, rapid, and economical model in the preliminary screening for teratology studies. The objective of the present study was to investigate the effect of metronidazole (MTZ) and ornidazole (ONZ) on the developmental stages of Drosophila melanogaster. METHODS: Samarkand wild-type females were allowed to lay eggs for 24 hr in media containing MTZ or ONZ at concentrations of 0, 500, 1000, and 2000 microg/ml. When larvae completed their development, the emerging flies were counted and examined for morphological abnormalities. RESULTS: After the analysis of 400-1000 flies for each concentration, ONZ-treated flies did not show an incidence of malformations above control values, although a significant high number of individuals with reduced body size was observed (p < 0.005, chi2 test). On the other hand, the 1000- and 2000-microg/ml MTZ-treated series presented higher frequencies of total abnormalities than did concurrent and historic controls (p < 0.05, chi2 test), indicating an MTZ effect during developmental morphogenesis. CONCLUSIONS: These findings contribute to the characterization of both nitroimidazoles, which are widely used, especially in underdeveloped countries. At the same time, this Drosophila bioassay is sensitive enough to detect differential effects of MTZ and ONZ (abnormalities vs. growth effects), showing specificity and selectivity.

Toxicogenetic evaluation of metronidazole in the treatment of women infected with Trichomonas vaginalis.

Samples of peripheral blood were collected once from non-smoking women who were healthy (controls) and twice (immediately before and immediately after 7 days of treatment with metronidazole at 500 mg/day) from non-smoking women infected with Trichomonas vaginalis. Lymphocyte cultures were prepared and used, in toxicogenetic studies, to determine the frequency of sister-chromatid exchange (SCE), the mitotic index (MI), and the replication index (RI) for each sample. MTZ treatment of the infected women led to an increase in the frequency of SCE (P <0.001), a decrease in the MI (P <0.003), and a modification in the kinetics of cell proliferation, with a decrease in the RI (P <0.0006). The differences seen between the results for the controls and those for the infected women, before and after MTZ treatment, may be attributed to the presence of the parasite, to the treatment itself, and/or to variation in the host's response to infection with T. vaginalis.