Sperm Quality in Mouse After Exposure to Low Doses of TCDD.

BACKGROUND: In the last decade, the harmful use of dioxin has been demonstrated in human health and in the whole environment. It is well known among scientists that 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin (TCDD) is an environmental pollutant that causes endocrine disruption, which causes male reproductive toxicity. OBJECTIVE: The objective of the present study was to evaluate the toxicity effect of low doses of TCDD in male CD1 mice. MATERIALS AND METHODS: Three concentrations of TCDD (0.375, 0.75, 1.5 mg / kg) were analyzed and the effects on spermatozoa were evaluated 10 days after oral administration of the product. As bioindicators of TCDD toxicity, an exhaustive analysis of several spermatic parameters including motility, vitality, count, morphology and viability, flow cytometry was used to determine the affected sperm population by cytotoxicity and apoptosis. In addition, a morphometric analysis of testicles was performed. RESULTS: The results show that the body weight of the treated animals was reduced in medium and high doses (0.75, 1.5 mg / kg) with respect to the control groups. In the groups treated with TCDD, the abnormal head of the sperm increased by 52.5% more than the control group. Significant differences in apoptosis were observed between the negative control and vehicle control, including the median dose (0.75 mg / kg). CONCLUSION: It is concluded that at these low doses there was an impact on the quality of the mouse sperm, adding an effect on apoptosis and cytotoxicity of sperm exposed to these doses of TCDD.

Detection of Quinolone Resistance in Salmonella typhimurium Pig Isolates Determined by gyrA Gene Mutation Using PCR- and Sequence-Based Techniques within the gyrA Gene.

BACKGROUND: The emergence of reduced susceptibility to fluoroquinolones among Salmonella enterica serotype Typhimurium isolates leading to clinical failure of treatment poses a great therapeutic challenge. METHODS: The current study is focused on the evaluation of the minimum inhibitory concentration (MIC) of quinolones in 29 Salmonella typhimurium of 86 Salmonella spp. strains, obtained from pigs from the State of Mexico. The MIC was performed with the Kirby-Bauer method. On the other hand, the GyrA gene was sequenced. The present study was undertaken to describe the resistance profiles and fluoroquinolone resistance mechanism of Salmonella Typhimurium. RESULTS: The DNA sequence of the gyrA genes from Salmonella enterica serovar typhimurium revealed strong similarity between gyrA and its counterpart in Escherichia coli. The sequencing of quinolone resistance-determining region (QRDR) of the gyrA gene showed the presence of mutation at either S83 or at D87 in almost all the Salmonella typhimurium isolates. CONCLUSION: This mutation, although phenotypically expressed as decreased susceptibility to fluoroquinolones goes undetected by the disk diffusion method using the present method of Kirby-Bauer. Hence, it can increase morbidity and mortality due to delay in appropriate antibiotic treatment.

Experimental-Theoretic Approach to Drug-Lymphocyte Interactome Networks with Flow Cytometry and Spectral Moments Perturbation Theory.

We can combine experimental techniques like Flow Cytometry Analysis (FCA) with Chemoinformatics methods to predict the complex networks of interactions between organic compounds and targets in the immune system. In this work, we determined experimentally the values of EC50 = 17.82 µg/mL and Cytotoxicity = 20.6 % for the anti-microbial / anti-parasite drug Dermofural over Balb/C CD9 lymphocytes using flow cytometry. After that, we developed a new Perturbation-theory model for Drug-Cell Target Interactome in Lymphocytes based on dispersion-polarization moments of drug structure. The models correctly classifies 34591 out of 42715 (Accuracy = 80.9%) cases of perturbations in assay endpoints of 11492 drugs (including both train and validation series). Each endpoint correspond to one out of 2616 assays, 38 molecular and cellular targets, 77 standard type measures, in four possible (human and rodents).

QSPR and flow cytometry analysis (QSPR-FCA): review and new findings on parallel study of multiple interactions of chemical compounds with immune cellular and molecular targets.

The immune system helps to halt the infections caused by pathogenic microbial and parasitic agents. The ChEMBL database lists very large datasets of cytotoxicity of organic compounds but notably, a large number of compounds have unknown effects over molecular and cellular targets in the immune system. Flow Cytometry Analysis (FCA) is a very important technique to determine the effect of organic compounds over these molecular and cellular targets in the immune system. In addition, multi-target Quantitative Structure- Property Relationship (mt-QSPR) models can predict drug-target interactions, networks. The objectives of this paper are the following. Firstly, we carried out a review of general aspects and some examples of applications of FCA to study the effect of drugs over different cellular targets. However, we focused more on methods, materials, and experimental results obtained in previous works reported by our group in the study of the drug Dermofural. We also reviewed different mt-QSPR models useful to predict the immunotoxicity and/or the effects of drugs over immune system targets including immune cell lineages or proteins. Secondly, we included new results not published before. Initially, we used ChEMBL data to train and validate a new model but with emphasis in the effect of drugs over lymphocytes. Lastly, we report unpublished results of the computational and FCA study of a new nitro-vinyl-furan compound over thymic lymphocytes T helpers (CD4+) and T cytotoxic (CD8+) population.