Chronic exposure to low concentrations of chlorpyrifos affects normal cyclicity and histology of the uterus in female rats.

Chlorpyrifos (CPF), the most used insecticide in Argentina, can act as an endocrine disruptor at low doses. We previously demonstrated that chronic exposure to CPF induces hormonal imbalance in vivo. The aim of this work was to study the effects of low concentrations of CPF (0.01 and 1 mg/kg/day) on the reproductive system of virgin adult rats. In the ovary, we studied the effects of CPF on steroidogenesis by determining steroid hormone content by RIA and CYP11 and CYP19 enzyme expression by qRT-PCR. The estrous cycle was evaluated by microscopic observation of vaginal smear, as well as by changes in uterine histology. In endometrium, we determined the fractal dimension and expression of PCNA, ERα and PR by IHC. Our results showed that chronic exposure to CPF affects ovarian steroid synthesis, causing alterations in the normal cyclicity of animals. In addition, CPF induced proliferative changes in the uterus, suggesting that it could affect reproduction or act as a risk factor in the development of uterine proliferative pathologies.

AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG.

Breast cancer is the most common cancer type in females worldwide. Environmental exposure to pesticides affecting hormonal homeostasis does not necessarily induce DNA mutations but may influence gene expression by disturbances in epigenetic regulation. Expression of long interspersed nuclear element-1 (LINE-1) has been associated with tumorigenesis in several cancers. In nearly all somatic cells, LINE-1 is silenced by DNA methylation in the 5́'UTR and reactivated during disease initiation and/or progression. Strong ligands of aryl hydrocarbon receptor (AhR) activate LINE-1 through the transforming growth factor-ß1 (TGF-ß1)/Smad pathway. Hexachlorobenzene (HCB) and chlorpyrifos (CPF), both weak AhR ligands, promote cell proliferation and migration in breast cancer cells, as well as tumor growth in rat models. In this context, our aim was to examine the effect of these pesticides on LINE-1 expression and ORF1p localization in the triple-negative breast cancer cell line MDA-MB-231 and the non-tumorigenic epithelial breast cell line NMuMG, and to evaluate the role of TGF-ß1 and AhR pathways. Results show that 0.5 µM CPF and 0.005 µM HCB increased LINE-1 mRNA expression through Smad and AhR signaling in MDA-MB-231. In addition, the methylation of the first sites in 5́'UTR of LINE-1 was reduced by pesticide exposure, although the farther sites remained unaffected. Pesticides modulated ORF1p localization in MDA-MB-231: 0.005 µM HCB and 50 µM CPF increased nuclear translocation, while both induced cytoplasmic retention at 0.5 and 5 µM. Moreover, both stimulated double-strand breaks, enhancing H2AX phosphorylation, coincidentally with ORF1p nuclear localization. In NMuMG similar results were observed, since they heighten LINE-1 mRNA levels. CPF effect was through AhR and TGF-ß1 signaling, whereas HCB action depends only of AhR. In addition, both pesticides increase ORF1p expression and nuclear localization. Our results provide experimental evidence that HCB and CPF exposure modify LINE-1 methylation levels and induce LINE-1 reactivation, suggesting that epigenetic mechanisms could contribute to pesticide-induced breast cancer progression.

Espondilodiscitis: análisis de 19 casos internados en un hospital de tercer nivel / Spondylodiscitis: analiysis of 19 inpatients at a referral hospital in Rosario, Argentina

Introducción: la espondilitis representa un desafío diagnóstico, ya que el dolor lumbar, su principal manifestación clínica, constituyeun motivo de consulta muy frecuente en la práctica cotidiana y carece de especificidad. Por lo tanto, resulta indispensablemantener una elevada sospecha clínica. Objetivo: Analizar las características clínicas, analíticas, microbiológicas e imagenológicas,el tratamiento, la evolución y los factores pronósticos de pacientes internados por espondilodiscitis en el Hospital Provincial delCentenario, desde enero de 2011 a marzo de 2015, excluyéndose los casos postquirúrquicos. Resultados: Se analizaron 19 pacientescon una edad media 48±11 años, 63% varones. Se identificaron como comorbilidades: diabetes (37%), obesidad (16%), etilismo(21%), insuficiencia renal crónica en hemodiálisis (16%), HIV (11%), adicción EV (11%). Los gérmenes más frecuentes fueron losestafilococos (52%). Al ingreso el 94% presentó dolor, 73% fiebre y 36% foco neurológico. La media de tiempo de evolución desíntomas hasta ingreso fue 62±80 días (rango 4-360 días). La velocidad de eritrosedimentación fue elevada en todos los pacientes,y sólo 37% presentaban leucocitosis. La vancomicina fue el antibiótico más utilizado. El 37% de los pacientes presentaba infeccióndiseminada. La mortalidad fue del 26%. Los pacientes que tuvieron un tiempo de evolución al ingreso mayor a 25 días presentaronpeor evolución (colecciones, foco neurológico o muerte) (p<0,05). Conclusiones: en esta serie, la asociación de la consulta tardíacon la mala evolución destaca la importancia de considerar las pautas de alarma en centros de atención primaria para posibilitar undiagnóstico más temprano.

Introduction: Spondylodiscitis represents a diagnostic challenge since the main clinical manifestation, low back pain, is very frequent andnonspecific, and often impedes a timely diagnosis. Clinical suspicion is essential. Objective: to analyze the clinical, analytical, microbiological,and radiological features, as well as outcome and prognostics factors, in patients with spondylodiscitis admitted to the Hospital Provincialdel Centenario (Rosario, Argentina), from January 2011 to March 2015. Postsurgical cases were excluded. Results: Nineteen patients wereincluded. Mean age was 48±11 years, 63% were males. We identified the following comorbid diseases: diabetes (37%), obesity (16%),alcoholism (21%), hemodialysis-dependent chronic kidney disease (16%), HIV (11%), intravenous drug abuse (11%). The most frequentcausative organism was Staphylococcus sp. (52%). Upon admission 94% of patients presented pain, 73% fever, and 36% neurologicalinvolvement. The average time from the onset of symptoms to diagnosis was 62±80 days (range 4-360). The erythrocyte sedimentation ratewas raised in all the patients, and only 37% had leukocytosis. Vancomycin was the most frequently prescribed antibiotic. Disseminatedinfection was present in 37% of patients. The mortality rate was 26%. Patients with a time lag to diagnosis higher than 25 days had worseoutcome (suppurative collections, neurological involvement, or death) compared to those with earlier diagnosis (p <0.05). Conclusions:The association of late consultation with poor outcome in this study emphasizes the importance of educating the general population toencourage attendance to medical centers. Physicians in primary care settings must be trained to identify pain pattern, and incorporateclinical perspectives capable of recognizing a defined syndrome at first contact, in other to achieve a better outcome.Key words: Spondylodiscitis, comorbid conditions, diagnostic delay, outcome.