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During the pandemic confinement, the WHO changed the term "social distancing" to "physical distancing", to help people deal with the lack of social contact. As a result, there was an increase in mental health problems, including insomnia and stress, with a negative impact on cardiovascular health. The objective of this research was to identify the association between insomnia and stress and cardiovascular risk (CVR) during the pandemic in a sample of the general population in Mexico; the participants were chosen using the non-probabilistic method. The data were obtained from an online questionnaire about medical histories focused on cardiovascular risk, according to the Official Mexican Standards and Regulations for patients' clinical records, NOM-004-SSA3-2012, along with an index for the severity of insomnia, measured with a seven-item guide, and an instrument to measure stress. The data were analyzed with descriptive statistics for several different variables: sociodemographics, stress, insomnia, and cardiovascular risk. Cardiovascular risk was compared to insomnia and stress variables, which led to statistically significant differences and correlations between the variables. Participants were divided into four groups with respect to CVR, from low to very high CVR. This research demonstrated that women were more susceptible to stress and cardiovascular risk. However, stress was a more major indicator of CVR than insomnia, but in the high and very high CVR groups, insomnia contributed along with stress; coping strategies reduced the risk in the high CVR group but did not function as expected with respect to reducing risk in the very high CVR group. These findings suggest that sleep patterns and mental health alterations present during the pandemic may persist even when the pandemic was declared as having ended and may contribute to increases in cardiovascular risk in the long-term.

Chlorophenols (CPs) have been extensively used worldwide as a treatment to prevent the growth and proliferation of different microorganisms, mainly in the wood and farm industries. Chlorine has been used for water disinfection, and phenol groups are water contaminants; these two groups can react with each other to form species such as 2,4-dichlorophenol (2,4-DCP). 2,4-DCP is still used as an herbicide in many countries such as Mexico. CPs have been largely analyzed, like bisphenol A, for their probable endocrine-disrupting effects in humans and aquatic animals. We still do not understand whether these endocrine responses can be manifested as an impairment in sexual behavior in rodents. With the present toxicology study, the endocrine-disrupting effects of 2,4-DCP on male sexual behavior were investigated. Sexually naïve male Wistar rats were used to assess the endocrine-disrupting effects of 2,4-DCP. The rats were divided into two groups: one control group and one experimental group that was administered 1.25 mg/day of 2,4-DCP for 45 days. After completing treatment, the male sexual behavior of the rats was evaluated. The results of this investigation demonstrated that 2,4-DCP affected male sexual behavior. A decrease in mount latency, intromission latency, and post ejaculation period compared with the control animals was found.

In this study, new polyurethanes (PUs) were prepared by using inulin and polycaprolactone as polyols. Their structure and morphology were determined by Fourier transform infrared spectroscopy (FTIR), Raman dispersive spectroscopy, Nuclear magnetic resonance spectroscopy ( 1 H NMR and 13 C NMR), and scanning electron microscopy (SEM), whereas their mechanical properties were evaluated by a universal testing machine. Additionally, their water uptake, swelling behavior, and degradation were evaluated to be used as drug delivery carriers. Therefore, an anti-cancer drug was loaded to these PUs with 25% of loading efficiency and its release behavior was studied using different theoretical models to unveil its mechanism. Finally, the ability of the new PUs to be used as a clip marker in breast biopsy was evaluated. The results clearly demonstrate that these PUs are safe and can be used as intelligent drug release matrices for targeted drug delivery and exhibits positive results to be used for clip marker and in general for breast cancer applications.

Strength and biocompatibility of composite materials (using a polymer matrix) are used in medicine for various devices such as prostheses and marker clips (biomarkers). Marker clips indicate the site of a lesion in the body, specifically for breast cancer diagnosis or treatment. In general, marker clips are made of steel or titanium, but lately, materials containing biodegradable polymers had been proposed. Our hypothesis is that a copolymer of polylactic acid and poly(ε-caprolactone) (PLA-PCL) could be used as marker clip material. After evaluating different polymer rates performance, metallic nanoparticles (NPs) were included to enhance the stability of the best copolymer and a marker clip prototype was proposed. Characterization of nanoparticles was made by dynamic light scattering (DLS), X-ray diffraction (XRD) and magnetic measurements. Mechanical, thermal and radiopacity properties were evaluated for composites formulation. In vitro, radiopaque experiments showed that BM-2 composite had the best performance. In vivo experiments showed that, after five months, the marker clip prototype maintained its shape, visibility and contrast properties. In consequence, a novel formulation of composite (PLA-PCL/metallic nanoparticles) is suitable for further studies as an alternative material for marker clips for breast cancer lesions.

We report the combined antibacterial/tissue regeneration responses to thermal burns promoted by functional chitosan/silver nanocomposites (CS/nAg) with ultralow silver content (0.018wt.%, 7-30nm). Our approach allows one to produce CS/nAg nanocomposites without silver nanoparticles (nAg) agglomeration, with bactericide potency higher than 1wt.% of nAg (ca. 10nm) content and, promoting the healing process in controlled thermal burns. CS/nAg films exhibit high antibacterial activity against S. aureus and P. aeruginosa after 1.5h of incubation, demonstrating the bacterial penetration into hydrated films and their interaction with nAg. Additionally, exceptional healing of induced thermal burns was obtained by increasing myofibroblasts, collagen remodeling, and blood vessel neoformation. These factors are associated with epiderma regeneration after 7days of treatment with no nAg release. Our results corroborate the controlled synthesis of nAg embedded in CS matrix with combined antibacterial/biocompatibility properties aiming to produce functional nanocomposites with potential use in wound dressing and health care applications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Several types of dyes or fluorophores are used for the detection of interactions between drug carriers and cells, within biomedicine field. However, many of them have a certain level of toxicity and instability affecting their biological properties. Different studies have demonstrated that nanoparticles (NPs) have interesting properties that could be used to stabilize diverse biomolecules, including dyes. Here, we report the synthesis of a novel nanosystem by the functionalization of silica NPs using biocompounds extracted from Mexican tree "Palo azul" (Eysenhardtia polystachya) and APTES as a coupling agent. Particle size, electrical properties, and morphology of the novel nanosystem were analyzed. The extracted biocompounds presented fluorescence which prevails over time, even after nanosystem formation and apparent cellular internalization. These were detected using MCF-7 cells visualized by confocal laser-scanning microscopy (CLSM), finding that the nanosystem was able to internalize into cells and act as a fluorescent biomarker. By this method, our novel nanosystem opens the possibilities to obtain sensitive data in a noninvasive manner for biological applications, such as early-stage cancer diagnosis, drug delivery, and pathogen detection., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Albendazole (ABZ) is a therapeutic benzimidazole used to treat giardiasis that targets β-tubulin. However, the molecular bases of ABZ resistance in Giardia duodenalis are not understood because β-tubulin in ABZ-resistant clones lacks mutations explaining drug resistance. In previous work we compared ABZ-resistant (1.35, 8, and 250 μM) and ABZ-susceptible clones by proteomic analysis and eight proteins involved in energy metabolism, cytoskeleton dynamics, and antioxidant response were found as differentially expressed among the clones. Since ABZ is converted into sulphoxide (ABZ-SO) and sulphone (ABZ-SOO) metabolites we measured the levels of these metabolites, the antioxidant enzymes and free thiols in the susceptible and resistant clones. Production of reactive oxygen species (ROS) and levels of ABZ-SO/ABZ-SOO induced by ABZ were determined by fluorescein diacetate-based fluorescence and liquid chromatography respectively. The mRNA and protein levels of antioxidant enzymes (NADH oxidase, peroxiredoxin 1a, superoxide dismutase and flavodiiron protein) in these clones were determined by RT-PCR and proteomic analysis. The intracellular sulfhydryl (R-SH) pool was quantified using dinitrobenzoic acid. The results showed that ABZ induced ROS accumulation in the ABZ-susceptible Giardia cultures but not in the resistant ones whilst the accumulation of ABZ-SO and ABZ-SOO was lower in all ABZ-resistant cultures. Consistent with these findings, all the antioxidant enzymes detected and analyzed were upregulated in ABZ-resistant clones. Likewise the R-SH pool increased concomitantly to the degree of ABZ-resistance. These results indicate an association between accumulation of ABZ metabolites and a pro-oxidant effect of ABZ in Giardia-susceptible clones. Furthermore the antioxidant response involving ROS-metabolizing enzymes and intracellular free thiols in ABZ-resistant parasites suggest that this response may contribute to overcome the pro-oxidant cytotoxicity of ABZ.

In this study we performed proteomic and transcriptional analyses to identify and characterize genes differentially expressed in Giardia duodenalis clones resistant to albendazole. The expression of proteins and their corresponding mRNAs was analyzed in clones resistant in vitro to different concentrations of albendazole (1.35, 8.0 and 250 μM) and these were compared with albendazole-sensitive clones using two approaches: (1) two-dimensional protein electrophoresis to analyze the proteome by the LC-MS/MS technique, and (2) semi-quantitative RT-PCR to assess the mRNA levels of proteins with the highest levels of differential expression .This strategy allowed the identification of eight proteins differentially expressed in albendazole resistant clones with roles in: (a) the cytoskeletal system (alpha 2-giardin and RanBP1), (b) the antioxidant metabolism (NADH oxidase) and (c) energy metabolism (triosephosphate isomerase, phosphoglycerate kinase and ornithine carbamoyltransferase). Gene expression analyses of these genes correlated well with the proteomics results. These observations suggest that resistance to albendazole in Giardia encompasses a complex response involving an altered expression of genes regulated at the transcriptional level that might have an important role in maintaining cell structural stability, coping with oxidative stress and adapting energy supply to a new metabolic status. These molecules are indeed promising targets for drug development., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Angiogenesis is essential for the growth and maturation of the ovarian follicle and its transition into the corpus luteum. In addition to the main proangiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), follicular fluid (FF) contains the hormone prolactin (PRL), which is known to promote angiogenesis in vivo. Here, we show that FF from large follicles, which contains twice the PRL level of FF from small follicles, stimulates endothelial cell proliferation to a greater extent than the latter, and that immunoneutralization of PRL prevents FF from stimulating endothelial cell proliferation. Notably, the FF increases the expression of the short and long PRL receptor isoforms in endothelial cells, and a purified PRL standard stimulates endothelial cell proliferation but only after the cells have been pretreated with FF. However, purified PRL activates the JAK2/STAT3 pathway in endothelial cells in the absence of pretreatment with FF. In summary, PRL present in the FF stimulates the proliferation of endothelial cells. This effect likely involves the upregulation of the short and long PRL receptor isoforms and is independent of PRL-induced JAK2/STAT3 signaling., (Copyright 2009 S. Karger AG, Basel.)

The susceptibility of Giardia duodenalis trophozoites exposed in vitro to sublethal concentrations of metronidazole (MTZ) and albendazole (ABZ) may exhibit inter-culture (variability) and intra-culture (variation) differences in drug susceptibility. It was previously reported that MTZ-resistant trophozoites may display changes in pyruvate:ferredoxin oxidoreductase (PFOR) expression while changes at the beta-tubulin molecule are apparently absent in ABZ-resistant cultures. To assess the levels of gene expression of these molecules, we obtained cloned cultures growing at concentrations up to 23 microM MTZ (WBRM23) and up to 8muM ABZ (WBRA8) and gene sequence and expression of pfor and beta-tubulin loci were compared with these of drug-susceptible clone WB1. Neither the pfor nor the beta-tubulin genes showed changes at sequence level but the MTZ-resistant clones WBRM21 and WBRM23 showed up-regulation of the pfor RNA using the gdh gene as reference. By using WB1 and WBRA8 clones in representational difference analyses of gene expression (RDA) an insert referred to as ARR-VSP was selected and sequenced. It showed the highest homology to one VSP molecule in the Giardia Genome Database (orf GL50803_101765). This isogene was up-regulated in five ABZ-resistant clones and the clone WBRA8 exhibited the highest RNA expression level. When successive progenies of clones WB1, WBRM23 and WBRA8 were analyzed in Northern blot assays to detect pfor and ARR-VSP RNAs respectively, the expression patterns showed variation for both genes but it was much lower in the clone WBRA8. These results suggest that G. duodenalis cultures either susceptible or resistant to MTZ and ABZ may display variability and variation at RNA expression levels albeit these were more marked in the MTZ-resistant parasites. These data might have further implications defining major mechanisms involved in drug resistance of Giardia.

Human pituitary tumor-transforming gene 1 (PTTG1) encodes a securin protein critically important in regulating chromosome separation. Murine PTTG (mPTTG) is 66% homologous to human PTTG1 and PTTG-null (PTTG-/-) mice exhibit pancreatic beta-cell hypoplasia and abnormal nuclear morphology with resultant diabetes. As we show that ductal beta-cell neogenesis is intact in PTTG-/- mice, we explored mechanism for defective beta-cell replication. We tested whether mPTTG exhibits securin properties in mouse insulin-secreting insulinoma MIN6 cells, using a live-cell system to monitor mitosis in cells transfected with an enhanced green fluorescent protein (EGFP)-tagged mPTTG conjugate (mPTTG-EGFP). To fulfill the criteria for securin properties, the protein should undergo degradation immediately before the metaphase-to-anaphase transition when expression levels are low, and should inhibit metaphase-to-anaphase transition when expression levels are high. EGFP itself did not undergo degradation throughout mitosis and high levels of EGFP per se did not affect normal mitosis progression (n=25). However, mPTTG-EGFP was degraded 2 min before the metaphase-to-anaphase transition when expression levels were low (n=19), and high mPTTG-EGFP levels blocked metaphase-to-anaphase transition in 13 cells. mPTTG-EGFP inhibited MIN6 cell proliferation and caused apoptosis. Immunocoprecipitation demonstrated binding of mPTTG-EGFP and separase. These results show that mPTTG exhibits properties consistent with a murine securin in insulin-secreting mouse cells and mPTTG overexpression inhibits cell proliferation, suggesting that defective beta-cell proliferation observed in PTTG-/- mice is likely due to abnormal cell-cycle progression.

Objectives: We analysed, in a cell-by-cell study, the in vitro susceptibility of Giardia duodenalis strains, including Mexican isolates and their clones to 5-nitroimidazoles and benzimidazoles., Methods: Fluorogenic dye staining (FDA-PI) and cell morphology (CM) assays, two fast and direct techniques, replaced the indirect 'gold standard' method (subculture in liquid medium) in the evaluation of 5-nitroimidazoles and benzimidazoles, respectively., Results: Under these conditions, the activity of several 5-nitroimidazole and benzimidazole derivatives was consistent with their known efficacy, but parasite stocks exhibited a greater variability in response to 5-nitroimidazoles compared with benzimidazoles. Also, consecutive progenies from single stocks maintained in continuous subculture in drug-free media displayed changes (variations) in the proportions of drug resistant (R/T) subpopulations when exposed to sublethal concentrations of 5-nitroimidazoles and benzimidazoles. These were again more variable upon exposure to 5-nitroimidazoles than to benzimidazoles. Variations were not due to drug susceptibility shifts in parent trophozoites since analysis of cytokinetic processes showed a predominant pattern of susceptible/susceptible or resistant/resistant daughters, whereas susceptible/resistant daughters were scarce., Conclusions: Our observations support the idea that G. duodenalis cultures exhibit variations in their response to 5-nitroimidazoles and benzimidazoles as a result of a drug-independent competition between drug-susceptible and drug-resistant subpopulations when parasites are subcultured.

This study evaluates metabolic and hormonal factors influencing extrarenal buffering of an acute acid load. Phosphate deprivation of 2 weeks duration was associated with enhanced extrarenal acid buffering. The enhanced extrarenal buffering capacity of phosphate deprivation was not dependent on the presence of parathyroid glands. Parathyroid hormone administration to phosphate-deprived rats promoted a further enhancement of the buffering capacity of an acid load. Blood pH and HCO3 during acid loading were not significantly different between control and diphosphonate-treated rats and between phosphate-deprived rats and phosphate-deprived rats treated with diphosphonate. The mortality rate, however, was significantly higher in diphosphonate-treated rats than in rats not receiving the drug suggesting that diphosphonate blunts the buffering of an acid load in both control and phosphate-deprived rats. Chronic vitamin D administration and acute administration of arginine vasopressin in pharmacologic doses were associated with significant enhancement of buffering capacity as compared to control rats. Thyrocalcitonin administration to intact but not thyroparathyroidectomized rats was associated with diminished capacity to buffer an acid load. These data demonstrate that the buffering of an acute acid load is influenced by a number of dietary and hormonal factors probably acting at the level of the bone.

Complete papillary necrosis in rats can be induced within 1 month following a single injection of 2-bromoethylamine hydrobromide (BEA) (50 mg, i.v.). Utilizing a combination of clearance and balance techniques the effects of complete absence of the papilla was examined as regards urinary acidification, whole kidney glomerular filtration rate (GFR), single nephron GFR, and morphology. Whole kidney GFR was not different from control, however, the percent filtering juxtamedullary nephrons was markedly diminished (87.2 +/- 2.1 vs. 31.5 +/- 3.6% filtering, control vs. BEA, respectively, P less than 0.001) and significantly reduced in the superficial nephrons (80.6 +/- 3.6 vs. 62.2 +/- 6.1% filtering, control vs. BEA, respectively, P less than 0.05). There was a significant decrease in juxtamedullary single nephron GFR and an increase in the superficial single nephron GFR as assessed by the quantitative Hanssen's technique in the animals with chronic papillary necrosis. Complete papillary necrosis was associated with normal arterial bicarbonate concentration, pH, and plasma electrolyte concentrations. At the same degree of acidemia (induced by NH4Cl administration) minimal urinary pH, ammonium excretion, and titratable acid excretion were not different than seen in age matched controls. The response to Na2SO4 infusion and phosphate infusion was the same in both groups of animals. The urine-blood (U-B)pCO2, and index of urinary acidification, was identical in BEA and control animals. Scanning electron microscopy showed scarring of the juxtamedullary glomeruli one month after BEA. The papilla was sloughed and lying free in the renal pelvis in every experimental animal. These data demonstrate that complete papillary necrosis is not associated with acidosis nor a defect in urinary acidification.

The present study was designed to indirectly localize the tubular sites of carbonic anhydrase independent bicarbonate reabsorption in the rat. Papillary necrosis was induced in rats by intravenous administration of bromoethyleneamine hydrobromide (BEA) 6 weeks prior to the study, in order to assess the role of deep nephrons in this process. Acetazolamide alone, acetazolamide plus amiloride, and acetazolamide, amiloride plus furosemide were infused into rats with intact papillae (groups I, III, V) and rats with BEA-induced papillary necrosis (groups II, IV, VI). Our results show that chronic papillary necrosis does not alter carbonic anhydrase independent bicarbonate reabsorption, since the fractional excretion of bicarbonate (FEHCO3) was not significantly higher when acetazolamide was infused into animals with BEA-induced papillary necrosis as compared to those rats with intact papillae (FEHCO3 group I vs. group II: NS). The addition of amiloride hydrochloride, a blocker of distal acidification at the administered doses, increased FEHCO3 significantly in both, animals with intact papillae and those with papillary necrosis, to a similar degree. The addition of furosemide to acetazolamide and amiloride further induced a significant increase in FEHCO3 only in the group of animals with papillary necrosis (FEHCO3 group V 43.0 +/- 2.9% vs. group VI 52.1 +/- 0.9%; p less than 0.05). It appears from our study that deeper nephrons and papillary structures are not indispensable for carbonic anhydrase independent bicarbonate reabsorption in the rat on a chronic basis. The cortical collecting duct appears to have a significant capacity to reabsorb bicarbonate independent of carbonic anhydrase which can be blocked by amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)