Organophosphorous (OP) pesticides are considered genotoxic mainly to somatic cells, but results are not conclusive. Few studies have reported OP alterations on sperm chromatin and DNA, and oxidative ...stress has been related to their toxicity. Sperm cells are very sensitive to oxidative damage which has been associated with reproductive dysfunctions. We evaluated the effects of methyl–parathion (Me–Pa; a widely used OP) on sperm DNA, exploring the sensitive stage(s) of spermatogenesis and the relationship with oxidative stress. Male mice (10–12-weeks old) were administered Me–Pa (3–20 mg/kg bw/i.p.) and euthanized at 7- or 28-days post-treatment. Mature spermatozoa were obtained and evaluated for chromatin structure through SCSA (Sperm Chromatin Structure Assay; DNA Fragmentation Index parameters: Mean DFI and DFI%) and chromomycin-A
3 (CMA
3)-staining, for DNA damage through in situ-nick translation (NT-positive) and for oxidative stress through lipid peroxidation (LPO; malondialdehyde production). At 7-days post-treatment (mature spermatozoa when Me–Pa exposure), dose-dependent alterations in chromatin structure (Mean DFI and CMA
3-staining) were observed, as well as increased DNA damage, from 2–5-fold in DFI% and NT-positive cells. Chromatin alterations and DNA damage were also observed at 28-days post-treatment (cells at meiosis at the time of exposure); suggesting that the damage induced in spermatocytes was not repaired. Positive correlations were observed between LPO and sperm DNA-related parameters. These data suggest that oxidative stress is related to Me–Pa alterations on sperm DNA integrity and cells at meiosis (28-days post-treatment) and epididymal maturation (7-days post-treatment) are Me–Pa targets. These findings suggest a potential risk of Me–Pa to the offspring after transmission.
Abstract Analysis of the mechanisms underlying the inflammatory response in amoebiasis is important to understand the immunopathology of the disease. Mucosal associated effector and regulatory T ...cells may play a role in regulating the inflammatory immune response associated to Entamoeba histolytica infection in the colon. A subpopulation of regulatory T cells has recently been identified and is characterized by the expression of the chemokine receptor CCR9. In this report, we used CCR9 deficient (CCR9−/− ) mice to investigate the role of the CCR9+ T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9+/+ , CCR9+/− and CCR9−/− mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9+/+ and CCR9+/− mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9−/− mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-γ, TNF-α, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition, increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in CCR9−/− mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9−/− mice at seven days post infection (pi), whereas in CCR9+/+ mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9−/− mice, was associated with a delayed recruitment of CD4+ CD25+ FoxP3+ T cells to the cecal epithelium and lamina propria, suggesting that this population may play a role in the early regulation of the inflammatory response against E. histolytica , likely through IL-10 production. In support of these data, CCR9+ T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9+ CD4+ CD25+ FoxP3+ T cells may participate in the control and resolution of the inflammatory immune response to E. histolytica infection.
Human paraoxonase 1 (PON1) is A-esterase synthesized in the liver and secreted into the plasma, where it associates with HDL. PON1 acts as an antioxidant preventing lipid oxidation and detoxifies a ...wide range of substrates, including organophosphate compounds. The variability of PON1 (enzyme activity/serum levels) has been attributed to internal and external factors. However, the molecular mechanisms involved in the transcriptional regulation of PON1 have not been well-studied. The aim of this study was to evaluate and characterize the transcriptional activation of PON1 by nuclear receptors (NR) in human hepatoma cells. In silico analysis was performed on the promoter region of PON1 to determine the response elements of NR. Real-time PCR was used to evaluate the effect of specific NR ligands on the mRNA levels of genes regulated by NR and PON1. The results indicated that NR response elements had 95% homology to pregnenolone (PXR), glucocorticoids (GR), retinoic acid (RXR) and peroxisomes proliferator-activated receptor alpha (PPARα). Treatments with Dexamethasone (GR ligand), Rifampicin (PXR ligand) and TCDD (AhR ligand) increased the mRNA levels of PON1 at 24 and 48h. We showed that the activation of GR by Dexamethasone results in PON1 gene induction accompanied by an increase in activity levels. In conclusion, these results demonstrate that GR regulates PON1 gene transcription through directly binding to NR response elements at −95 to −628bp of the PON1 promoter. This study suggests new molecular mechanisms for the transcriptional regulation of PON1 through a process involving the activation of PXR.
•The promoter region of human PON1 has response elements of PXR and GR.•Rifampicin and Dexamethasone ligands of nuclear receptors increased the expression of human PON1 in HepG2 cells.•The results suggest the role of PXR and GR in PON1 activation.
Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect ...against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 −162, −108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (
n = 214) of either gender, 18–52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, −162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 −108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms −108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis.
The objective of this study was to determine the requirements and interactions between the standardized ileal digestible (SID) Leu and Val levels in low-protein diets, and their effects on ...performance, serum characteristics, carcass yield and diameter of muscle fibers of broiler chickens from d 21 to 42 posthatch. A total of 1,500 21-day-old Cobb 500 male broiler chickens were distributed in a completely randomized design in a 5 × 5 factorial arrangement for a total of 25 treatments with 3 replicates of 20 birds each. Treatments consisted of 5 SID Leu levels (1.0, 1.2, 1.4, 1.6, or 1.8%) and 5 SID Val levels (0.52, 0.67, 0.82, 0.97, or 1.12%). At 42 d of age, there was interaction (P < 0.05) between the SID levels of Leu and Val on feed intake and weight gain. There was a quadratic effect (P < 0.05) of Leu and Val levels on feed conversion, with minimal point estimated at the levels of 1.19 and 0.86%, respectively. Dietary Leu supplementation reduced linearly (P < 0.05) serum concentrations of triglycerides and β-hydroxybutyrate. Dietary Leu increased (P ≤ 0.05) the fiber diameters of the pectoralis major muscle and breast yield at the levels of 1.24 and 1.13%, respectively, while the thigh yield was improved with the level of 0.71% Val. Abdominal fat decreased linearly (P < 0.05) with increasing levels of dietary Leu and Val. The SID Leu and Val levels needed to optimize weight gain and feed conversion in low-CP diets for broiler chickens from d 21 to 42 posthatch were estimated at 1.15 and 0.86%, and 1.19 and 0.86%, respectively. The supplementation of Leu and Val can reduce the abdominal fat deposition in birds fed low-CP diets during the grower phase. Leu and Val interactions can influence the performance but not the serum characteristics, carcass yield and diameter of muscle fibers of broilers fed low-protein diets. Therefore, it is necessary to consider the dietary Leu content to estimate the ideal level of Val in low-CP diets for optimum broiler performance.
Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B
1
(AFB
1
), ochratoxin A (OTA), and fumonisin (FB
1
) in paddy rice, polished rice, ...and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB
1
in 21.21% of paddy rice samples and 11.11% of market maize samples. OTA was present in only 3.03% (one sample) of paddy rice samples. FB
1
was detected in 87.50% and 88.88% of maize samples from field and market, respectively. The estimated human exposure was calculated for FB
1
using the probable daily intake (PDI), which suggested that FB
1
could contribute to the development of diseases through the consumption of contaminated maize. Positive samples indicated that some rice and maize samples were not suitable for human consumption. Further efforts are needed to continue monitoring mycotoxins and update national legislation on mycotoxins accordingly.
In this work, we study a 215-m-long figure-of-eight fiber laser including a double-clad erbium-ytterbium fiber and a nonlinear optical loop mirror based on nonlinear polarization evolution. For ...proper adjustments, self-starting passive mode-locking is obtained. Measurements show that the mode-locked pulses actually are noise-like pulses, by analyzing the autocorrelation, scope traces and the very broad and flat spectrum extending over a record bandwidth of more than 200 nm, beyond the 1750 nm upper wavelength limit of the optical spectrum analyzer. Noise-like pulsing was observed for moderate and high pump power preserving the same behavior, reaching pulse energies as high as 300 nJ, with pulse durations of a few tens of ns and a coherence length in the order of 1 ps. Stable fundamental mode locking as well as harmonic mode locking up to the 6th order were observed. The bandwidth was further extended to more than 450 nm when a 100-m piece of highly nonlinear fiber was inserted at the laser output. The enhanced performances obtained compared to other similar schemes could be related to the absence of a polarizer in the present setup, so that the state of polarization along the cavity is no longer restricted.
Lobomycosis and lobomycosis-like diseases (LLD) (also: paracoccidioidomycosis) are chronic cutaneous infections that affect Delphinidae in tropical and subtropical regions worldwide. In the Americas, ...these diseases have been relatively well-described, but gaps still exist in our understanding of their distribution across the continent. Here we report on LLD affecting inshore bottlenose dolphins Tursiops truncatus from the Caribbean waters of Belize and from the eastern tropical Pacific Ocean off the southwestern coast of Mexico. Photo-identification and catalog data gathered between 1992 and 2017 for 371 and 41 individuals, respectively from Belize and Mexico, were examined for the presence of LLD. In Belize, 5 free-ranging and 1 stranded dolphin were found positive in at least 3 communities with the highest prevalence in the south. In Guerrero, Mexico, 4 inshore bottlenose dolphins sighted in 2014-2017 were affected by LLD. These data highlight the need for histological and molecular studies to confirm the etiological agent. Additionally, we document a single case of LLD in an adult Atlantic spotted dolphin Stenella frontalis in southern Belize, the first report in this species. The role of environmental and anthropogenic factors in the occurrence, severity, and epidemiology of LLD in South and Central America requires further investigation.
Substantial efforts have been devoted to developing and applying biomarkers for ecological risk assessment. Bivalve mollusks, such as mussels and oysters, are commonly used in environmental ...monitoring programs because of their wide geographical distribution, great sensitivity to environmental pollutants, and ability to accumulate anthropogenically derived chemicals at a high rate. Acetylcholinesterase (AChE) activity and metallothionein (MT's) content are representative specific biomarkers that indicate the presence of anticholinesterasic compounds (like organophosphorus and carbamate pesticides) and metals, respectively. The aim of this study was to evaluate AChE activity and MT's content in Crassostrea corteziensis from Boca de Camichín estuary. The results obtained here showed that AChE activity was 65% lower in oysters from Boca de Camichín than in control organisms. In contrast, MT's content in collected organisms was not statistically different from that in control organisms. AChE activity and MT's content in oysters could be used as early biomarkers of effects and exposure to pesticides and heavy metals, respectively, in aquatic environments.
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