Cytotoxic and estrogenic activity of chlorpyrifos and its metabolite 3,5,6-trichloro-2-pyridinol. Study of marine yeasts as potential toxicity indicators

Chlorpyrifos (CP) is one of the organophosphate insecticides most used worldwide today. Although the main target organ for CP is the nervous system triggering predominantly neurotoxic effects, it has suggested other mechanisms of action as cytotoxicity and endocrine disruption. The risk posed by the pesticide metabolites on non-target organisms is increasingly recognized by regulatory agencies and natural resource managers. In the present study, cytotoxicity and estrogenic activity of CP, and its principal metabolite 3,5,6-trichloro-2-pyridinol (TCP) have been evaluated by in vitro assays, using two mammalian cell lines (HEK293 and N2a), and a recombinant yeast. Results indicate that TCP is more toxic than CP for the two cell lines assayed, being N2a cells more sensitive to both compounds. Both compounds show a similar estrogenic activity being between 2500 and 3000 times less estrogenic than 17β-estradiol. In order to find new toxicity measurement models, yeasts isolated from marine sediments containing CP residues have been tested against CP and TCP by cell viability assay. Of the 12 yeast strains tested, 6 of them showed certain sensitivity, and a concentration-dependent response to the tested compounds, so they could be considered as future models for toxicity tests, although further investigations and proves are necessary.

     

The Potential Effects of New Stent Platforms for Coronary Revascularization in Patients With Diabetes

Coronary artery disease in patients with diabetes mellitus (DM) is characterized by extensive atherosclerosis, longer lesions, and diffuse distal disease. Consequently, these patients have worse outcomes after coronary revascularization, regardless of the modality used. Traditionally, coronary artery bypass grafting (CABG) has been regarded as more effective than percutaneous coronary intervention (PCI) in patients with DM, likely because of more complete revascularization and protection against disease progression in the bypass segment. Revascularization with balloon angioplasty, bare-metal stents, and first-generation drug-eluting stents have all been shown to be inferior to CABG in patients with DM. Current professional society guidelines reflect these findings, strongly recommending CABG over PCI in this setting. Newer stent platforms, however, have challenged this notion. The use of thinner struts, biocompatible polymer coating, and newer antiproliferative agents have improved the rates of cardiovascular events in patients with DM revascularized percutaneously. Since the publication of current guidelines, new studies suggested acceptable outcomes in patients with DM revascularized with second-generation drug-eluting stents, even though these conclusions are drawn from small subgroup analyses or nonrandomized studies. Robust registry data suggest similar mortality with lower rates of stroke after PCI compared with surgery, at the expense of increased rates of repeat revascularization. If complete revascularization can be achieved, similar rates of myocardial infarction are also observed. Therefore, contemporary revascularization in patients with DM with multivessel coronary artery disease should involve a multidisciplinary approach, in which interventional cardiologists and cardiac surgeons involve their patients to individualize treatment choices, and balance the risks and effectiveness of each modality.     

Dermoscopy applied to pediculosis corporis diagnosis

We report the case of a 47-year-old homeless male with a massive infestation of Pediculus humanus corporis on his entire body. Dermoscopy helped to diagnose pediculosis by showing the involvement of scalp, beard and the genital region in this disease.     

Apoptosis in eosinophilic nasal polyps treated in vitro with Mitomycin C

The etiopathogenesis of eosinophilic nasal polyps is yet to be explained. Eosinophils are key components in the inflammatory infiltrate and are related to the perpetuation of the inflammatory process in chronic rhinosinusitis with nasal polyps.ObjectiveThis paper aims to evaluate the in vitro action of mitomycin upon the apoptotic index of nasal polyps.Materials and MethodsThis is a self-paired prospective experimental study using biopsy fragments from 15 patients with eosinophilic nasal polyps. Biopsy fragments were divided into two groups. In the case group, the fragments were treated with 400 µg/ml of mitomycin for five minutes. The control group fragments were treated with culture medium. The pair of fragments contained in the two first compartments - control and case - were immediately sent to the histopathologist. The other pair of samples containing control and case fragments was incubated for 12 hours. The fragments were then taken to the histopathologist for testing. The apoptotic index was determined by the morphometry in hematoxylin and eosin staining and DNA fragmentation analysis (TUNEL reaction).ResultsThe comparison between the two groups showed a statistically significant difference (p < 0,001) in the apoptotic index of the 12-hour incubated cultures.ConclusionMitomycin acts in vitro upon the eosinophilic nasal polyps inducing the rise of the eosinophilic apoptotic index.     

Pharmacogenomic predictors of citalopram treatment outcome in major depressive disorder

Objectives. A significant proportion of patients with major depressive disorder (MDD) do not improve following treatment with first-line antidepressants and, currently, there are no objective indicators of predictors of antidepressant response. The aim of this study was to investigate pre-treatment peripheral gene expression differences between future remitters and non-responders to citalopram treatment and identify potential pharmacogenomic predictors of response. Methods. We conducted a gene expression study using Affymetrix HG-U133 Plus2 microarrays in peripheral blood samples from untreated individuals with MDD (N = 77), ascertained at a community outpatient clinic, prior to an 8-week treatment with citalopram. Gene expression differences were assessed between remitters and non-responders to treatment. Technical validation of significant probesets was carried out by qRT-PCR. Results. A total of 434 probesets displayed significant correlation to change in score and 33 probesests were differentially expressed between eventual remitters and non-responders. Probesets for SMAD 7 (SMA- and MAD-related protein 7) and SIGLECP3 (sialic acid-binding immunoglobulin-like lectin, pseudogene 3) were the most significant differentially expressed genes following FDR correction, and both were down-regulated in individuals who responded to treatment. Conclusions. These findings point to SMAD7 and SIGLECP3 as candidate predictive biomarkers of antidepressant response.     

The Orthogeriatrics Model of Care: Systematic Review of Predictors of Institutionalization and Mortality in Post-Hip Fracture Patients and Evidence for Interventions

Hip fracture is a common serious complication of osteoporosis, which is associated with high morbidity and mortality. In nursing home residents, incidence rates of hip fractures are at least twice to three times higher than in community-dwellers of the same age and sex. Older adults with hip fracture have a 5- to 8-fold increased risk for all-cause mortality and much higher risk of institutionalization. Therefore, interventions to prevent institutionalization, prevent a second fracture in institutionalized patients, and decrease mortality after a hip fracture are highly needed. The orthogeriatrics model of care is a shared-care approach to patients after suffering a hip fracture. This program, which has been studied in models run by geriatricians with the assistance of a multidisciplinary team, includes a comprehensive medical and nursing admission assessment focusing on the patient’s premorbid function, cognition, comorbidities, and risks is followed by a comprehensive care plan design. This systematic review describes and analyzes the interrelation between hip fracture and nursing home placement taking into consideration those evidence-based interventions to prevent later complications and future institutionalization.