Co-axial printing of convoluted proximal tubule for kidney disease modeling.

Despite the increasing incidence of kidney-related diseases, we are still far from understanding the underlying mechanisms of these diseases and their progression. This lack of understanding is partly because of a poor replication of the diseasesin vitro,limited to planar culture. Advancing towards three-dimensional models, hereby we propose coaxial printing to obtain microfibers containing a helical hollow microchannel. These recapitulate the architecture of the proximal tubule (PT), an important nephron segment often affected in kidney disorders. A stable gelatin/alginate-based ink was formulated to allow printability while maintaining structural properties. Fine-tuning of the composition, printing temperature and extrusion rate allowed for optimal ink viscosity that led to coiling of the microfiber's inner channel. The printed microfibers exhibited prolonged structural stability (42 days) and cytocompatibility in culture. Healthy conditionally immortalized PT epithelial cells and a knockout cell model for cystinosis (CTNS-/-) were seeded to mimic two genotypes of PT. Upon culturing for 14 days, engineered PT showed homogenous cytoskeleton organization as indicated by staining for filamentous actin, barrier-formation and polarization with apical markerα-tubulin and basolateral marker Na+/K+-ATPase. Cell viability was slightly decreased upon prolonged culturing for 14 days, which was more pronounced inCTNS-/-microfibers. Finally,CTNS-/-cells showed reduced apical transport activity in the microfibers compared to healthy PT epithelial cells when looking at breast cancer resistance protein and multidrug resistance-associated protein 4. Engineered PT incorporated in a custom-designed microfluidic chip allowed to assess leak-tightness of the epithelium, which appeared less tight inCTNS-/-PT compared to healthy PT, in agreement with itsin vivophenotype. While we are still on the verge of patient-oriented medicine, this system holds great promise for further research in establishing advancedin vitrodisease models.

Lessons Learned After 101 Cases of Single-Site Magnetic-Assisted Cholecystectomy in Children.

BACKGROUND / PURPOSE: The aim of this report is to present our experience with a magnetic-assisted single-site cholecystectomy technique ("magnachole") in pediatric patients. METHODS: We performed a retrospective chart review of all patients who underwent magnachole between 2009 and 2019. We evaluated patients' demographics, diagnosis, operative time, complications, conversion rate and length of stay. Additionally, simple lineal regression analysis was conducted to determine if the surgeon's experience, the patient's age at surgery, the patient's gender or the patient's body weight affected operative time. RESULTS: A total of 101 patients were operated during the analyzed period. The mean age at surgery was 12.6 (range 4 to 19) years, and the mean body weight was 53.7 (range 13.5 to 123) kg. The most frequent indication (91%) was symptomatic cholelithiasis. Mean operative time was 85 (range 45 to 240) min. The mean operative time decreased by 22.7 min (p < 0.001, 95% [CI] 10.35 to 35.13) when we compared the first 51 cases to the last 50 cases. Simple lineal regression showed a reduction of 2.6 min in operative time per year. Age at surgery, gender, and weight did not influence operative time. There were no intraoperative complications. Only 1 case required an additional port to complete the operation. There were no conversions to open cholecystectomy. Median length of stay was 26 h (range 10 to 168). CONCLUSION: The magnachole technique is safe and effective, and has become our preferred surgical approach for children who need a cholecystectomy. As expected, the operative time decreased as surgeons gain experience with the technique. The technique is feasible regardless of the patient's body habitus. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

Physicochemical and microbiological stability of two news oral liquid formulations of clonidine hydrochloride for pediatric patients.

Pediatric patients present changing physiological features. Because of the lack of land suitable for commercial management, pediatric specialties very often need to prepare extemporaneous formulations to improve the dosage and administration of drugs for children. Oral liquid formulations are the most suitable for pediatric patients. Clonidine is widely used in the pediatric population for opioid withdrawal, hypertensive crisis, attention deficit disorders and hyperactivity syndrome, and as an analgesic in neuropathic cancer pain. The objective was to study the physicochemical and microbiological stability and determine the shelf life of an oral solution containing 20 µg/mL clonidine hydrochloride in different storage conditions (5 ± 3 °C, 25 ± 3 °C, and 40 ± 2 °C). Using raw material with excipients safe for all pediatric age groups, two oral liquid formulations of clonidine hydrochloride were designed (with and without preservatives). Solutions stored at 5 ± 3 °C (with and without preservatives) were physically and microbiologically stable for at least 90 days in closed containers and for 42 days after opening. Two oral solutions of clonidine hydrochloride 20 µg/mL were developed for pediatric use from raw materials that are readily available and easy to process, containing safe excipients that are stable over a long period of time.

Risk Factors of Mortality After Liver Transplantation in Uruguay.

INTRODUCTION: Identification of predictive factors of mortality in a liver transplant (LT) program optimizes patient selection and allocation of organs. OBJECTIVE: To determine survival rates and predictive factors of mortality after LT in the National Liver Transplant Program of Uruguay. METHODS: A retrospective study was conducted analyzing data prospectively collected into a multidisciplinary database. All patients transplanted since the beginning of the program on July 2009 to April 2017 were included (n = 148). Twenty-nine factors were analyzed through the univariate Kaplan-Meier model. A Cox regression model was used in the multivariate analysis to identify the independent prognostic factors for survival. RESULTS: Overall survival was 92%, 87%, and 78% at discharge, 1 year, and 3 years, respectively. The Kaplan-Meier survival curves were significantly lower in: recipients aged >60 years, Model for End-Stage Liver Disease score >21, LT due to hepatocellular carcinoma (HCC) and acute liver failure (ALF), donors with comorbidities, intraoperative blood loss beyond the median (>2350 mL), red blood cell transfusion requirement beyond the median (>1254 mL), intraoperative complications, delay of extubation, invasive bacterial, and fungal infection after LT and stay in critical care unit >4 days. The Cox regression model (likelihood ratio test, P = 1.976 e-06) identified the following independent prognostic factors for survival: LT for HCC (hazard ratio [HR] 4.511; P = .001) and ALF (HR 6.346; P = .004), donors with comorbidities (HR 2.354; P = .041), intraoperative complications (HR 2.707; P = .027), and invasive fungal infections (HR 3.281; P = .025). CONCLUSION: The survival rates of LT patients as well as the mortality-associated factors are similar to those reported in the international literature.

Cytogenetic effects of Jacareubin from Calophyllum brasiliense on human peripheral blood mononucleated cells in vitro and on mouse polychromatic erythrocytes in vivo.

Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000µM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC50 at 72h by MTT: 85.9µM) than on G0 phase-PBMCs (IC50 315.6µM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1µM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5µM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G0/G1 phase of the cell cycle (from 5µM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5µM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5µM) and frequency of hypodiploid cells (from 10µM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD50; 0.548g/kg. Approximately to 300µM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.

In-syringe dispersive micro-solid phase extraction using carbon fibres for the determination of chlorophenols in human urine by gas chromatography/mass spectrometry.

In this article, carbon fibres (CFs) are presented as sorbent material for the dispersive micro-solid phase extraction of twelve chlorophenols from urine samples. CFs are synthesized by a reagentless and green procedure consisting of heating raw cotton, a natural precursor, at high temperature (400°C) in an inert atmosphere (Ar) during 2h. The resulting fibres, which present good water dispersibility, are finally loaded on an in-syringe device. This device, which integrates the extraction and final elution of the analytes, is disposable and it is adapted to process low sample volumes. Working at the optimum conditions, the extraction procedure in combination with gas chromatography/mass spectrometry allows the determination of the analytes in urine at the low µg/L range. In fact, the limits of quantification (LOQs) of the analytes were in the interval from 1µg/L to 2.5µg/L with precision values, expressed as relative standard deviations (RSD), better than 13%. Relative recovery values, ranging from 74.5% to 113%, demonstrate the applicability of the proposed method.

Impact of a Multimodal Approach in Prevention of Surgical Site Infection in Hepatic Transplant Recipients.

INTRODUCTION: In liver transplant (LT) recipients, surgical site infection (SSI) represents an important cause of morbidity and mortality. OBJECTIVE: This study measures the impact of a multimodal approach to the incidence of surgical site infection in LT recipients. MATERIALS AND METHODS: All of the LT recipients in our department were registered on the national database in solid organ transplant. A study was performed in two analytical-interventional phases. Phase 1 took place between July 14, 2009, and February 20, 2014. Phase 2 took place between February 21, 2014, and July 15, 2015. The multimodal change implemented during phase 1 was that 0.5% alcoholic chlorhexidine and ether were applied to the surgical field; surgical prophylaxis was primarily with ampicillin/sulbactam plus cefazolin. In phase 2, 2% alcoholic chlorhexidine alone was applied to the surgical field. The prior standard prophylaxis was changed to piperacillin tazobactam administered during surgery as a continuous infusion of 13.5 g over 8 hours with a pre-incision loading dose of 4.5 g. The loading dose of piperacillin tazobactam was combined with a single dose of gentamicin of 5 mg/kg. RESULTS: One hundred eight patients have received transplants since the start of the program: 82 patients during phase one and 26 patients during phase two. During phase 1, 13 cases of SSI were recorded, representing a rate of 15.85 per 100 transplants. Sixteen micro-organisms were isolated during phase 1, of which 12 corresponded to gram-negative bacilli. With regard to resistance profiles, 13 showed multidrug resistant and extensively drug resistant profiles. During phase 2, no cases of SSI were recorded (relative risk = 0.158 [95% confidence interval 0.0873-0.255], P = .0352]. CONCLUSION: A multimodal approach allowed for the reduction of the incidence of SSI in LTs and offered a protective strategy.

First report of linezolid dependence in methicillin-resistant Staphylococcus aureus.

Linezolid is used to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We describe the first report of linezolid dependence in MRSA. The strain was isolated from a respiratory sample of a cystic fibrosis patient, and it showed a thymidine-dependent small-colony variant phenotype. The effect was not related to any known mechanisms implicated in S. aureus resistance to linezolid. The clinical significance of this phenomenon needs further investigation.

Assessing the impact of As-Cd-Pb metal mixture on cell transformation by two-stage Balb/c 3T3 cell assay.

Human beings are exposed to metals as a consequence of various industrial activities, including glass production, agrochemical production, metallurgy and battery manufacture. New data about the possible mechanisms involved in the carcinogenic activity of these metals are constantly being reported. Exposure to complex mixtures of metals is more likely to occur than exposure to a single metal alone. Among these elements, arsenic, cadmium and lead are ubiquitous air and water pollutants that continue to threaten the quality of public health around the world. The aim of the present study was to evaluate the capability of a mixture of 2 µM NaAsO2, 2 µM CdCl2 and 5 µM Pb(C2H3O2)2·3H2O at relevant epidemiological concentrations to induce cell transformation processes. Transforming potential was determined by a murine two-stage Balb/c 3T3 cell assay. Cell viability, reactive oxygen species (ROS), DNA damage, cell cycle analysis, senescence, generation time and metallothionein expression were also evaluated. The results showed that the metal mixture induced morphological cell transformation only when acting as initiator stimuli of the process. A decrease in cell viability was observed at the promotion stage, a time during which ROS increase, especially when a metal mixture was applied as a promoter stimulant. Changes in DNA damage were not observed throughout the assay; however, we observed G1 cell cycle arrest. The metal mixture, acting as a promoter, is capable of inducing senescence, but metals employed as initiators with 12-O-tetradecanoylphorbol-13-acetate as a promoter are capable of causing avoidance of senescence and triggering the transformation potential of the cells.

Seminoma with bronchial involvement and superior vena cava syndrome: a rare combination.

We describe the case of a 45-year-old male who was admitted with clinical signs of superior vena cava syndrome (SVCS). Physical examination showed collar of Stokes and extensive collateral circulation in the neck and anterosuperior thoracic region, as well as a large testicular mass. Fibrobronchoscopy revealed an endobronchial tumour, histopathologically diagnosed as seminoma, with the same characteristics as the testicular biopsy. Treatment was initiated with surgery, chemotherapy and radiotherapy, resulting in a major clinical improvement. We indicate the importance of considering SVCS as an entity related with less common neoplasms such as germ cell tumours.

MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects.

Metals are a threat to human health by increasing disease risk. Experimental data have linked altered miRNA expression with exposure to some metals. MiRNAs comprise a large family of non-coding single-stranded molecules that primarily function to negatively regulate gene expression post-transcriptionally. Although several human populations are exposed to low concentrations of As, Cd and Pb as a mixture, most toxicology research focuses on the individual effects that these metals exert. Thus, this study aims to evaluate global miRNA and mRNA expression changes induced by a metal mixture containing NaAsO2, CdCl2, Pb(C2H3O2)2·3H2O and to predict possible metal-associated disease development under these conditions. Our results show that this metal mixture results in a miRNA expression profile that may be responsible for the mRNA expression changes observed under experimental conditions in which coding proteins are involved in cellular processes, including cell death, growth and proliferation related to the metal-associated inflammatory response and cancer.

Effect of aluminum sulfate on litter composition and ammonia emission in a single flock of broilers up to 42 days of age.

New alternatives are necessary if the environmental impact linked to intensive poultry production is to be reduced, and different litter handling methods should be explored. Among these, acidifying amendments added to poultry litters has been suggested as a management practice to help reduce the potential environmental effect involved in multiple flock cycles. There have been several studies on the use of aluminum sulfate (alum) and its benefits, but almost no data are available under farm conditions in Europe. An experiment with Ross 308 broilers from 1 to 42 days of age was conducted to evaluate the effect of alum on litter composition, the solubility of some mineral elements and NH3 emission during a single flock-rearing period in commercial houses located in southeast Spain. Broilers were placed on clean wood shavings in four commercial houses, containing 20 000 broilers each. Before filling, alum was applied at a rate of 0.25 kg/m2 to the wood shavings of two poultry houses, whereas the remaining two were used as control. Litter from each poultry house was sampled every 3 to 5 days. Ammonia emissions from the poultry houses were monitored from 37 to 42 days of age. In comparison with the control group, alum treatment significantly reduced the pH level of the litter (P < 0.001) with an average difference of 1.32 ± 0.24 units. Alum-treated litter showed, on average, a higher electrical conductivity than the control litter (5.52 v. 3.63 dS/m). The dry matter (DM) and total N and P contents did not show differences between the treatments (P > 0.05). Regarding the NH4 +-N content, alum-treated litter showed a higher value than the untreated litter, with an average difference of 0.16 ± 0.07% (on a DM basis). On average, alum-treated litter had lower water-soluble P, Zn and Cu contents than the untreated litter. Alum noticeably reduced the in-house ammonia concentration (P < 0.001), with an average of 4.8 ppm at 42 days of age (62.9% lower than the control), and ammonia emissions from 37 to 42 days of age were significantly reduced by the alum treatment (P < 0.001), representing a reduction of 73.3%. The lower pH values might have reduced ammonia volatilization from the litter, with a corresponding positive effect on the building environment and poultry health. For these reasons, litter amendment with alum could be recommended as a way of reducing the pollution potential of European broiler facilities during a single flock cycle.

Differential DNA damage response to UV and hydrogen peroxide depending of differentiation stage in a neuroblastoma model.

DNA is a frequent target of oxidative damage, and DNA damage removal is therefore a crucial process in prevention of or recovery from degenerative diseases. DNA repair is an essential system for maintaining the inherited nucleotide sequence of genomic DNA over time. Cells engage in efficient DNA repair mechanisms, the activity of which can vary depending on the type of lesion and the developmental stage. Base excision repair (BER) and nucleotide excision repair (NER) are the major repair pathways addressed in this study. BER is the principal mechanism for repair of DNA oxidative lesions, while NER is the mechanism for repair of a variety of helix-distorting lesions such as those caused by UV radiation. Recent studies suggest that NER plays a cooperative role in removal of oxidative lesions. Little is known about the roles of DNA damage sensors and repair factors in terminally differentiated, non-proliferating cells such as neurons, which are vulnerable to oxidative damage from reactive oxygen species generated by endogenous or exogenous agents. We used the human neuroblastoma MSN cell model to investigate whether terminally differentiated neuronal cells respond to lesions cause in the DNA helix, such as UV-induced CPD and the major DNA oxidative lesion 8OHdG, and thereby clarify the role of NER capacity. We observed differences in DNA damage removal depending on the challenge insult and the differentiation state. Differentiated MSN cells, compared with undifferentiated cells, showed greater sensitivity to UVC and decreased DNA damage over time. In contrast, undifferentiated cells displayed genotoxicity induced by oxidative insult and tended to accumulate DNA damage and 8OHdG lesions over time. Our findings suggest the participation of GG-NER, TC-NER and BER proteins in the removal of 8-OHG and CPDs indicating a dynamic role in overall response to damage.

[Ollier disease: benign tumours with risk of malignant transformation. A review of 17 cases]. / Enfermedad de Ollier: tumores benignos con riesgo de malignización. Revisión de 17 casos.

AIM: To review Ollier disease, an uncommon disease, in order to understand the clinical symptoms, diagnosis, correct treatment, and risk factors in order to prevent malignant transformation. MATERIALS AND METHODS: Seventeen cases of Ollier disease were treated between 1976 and 2006. The variables studied included: age at diagnosis and onset of malignant transformation, location of the lesion, family association with other tumours, radiological findings, treatment for the different lesions, metastatic lesions and survival. We excluded patients with Chondrosarcoma without previous diagnosis of Ollier disease. All malignant transformations were assessed by histopathology studies and radiological images. RESULTS: We include 16 cases of Ollier's and 1 of Maffucci's syndrome. The median age at diagnosis for patients having malignant transformation was 45 years, whereas the average age at diagnosis for patient without progression to malignancy was 11 years. Pathological fractures, dysmetria and deformities led to the diagnosis in young people. Benign lesions were treated with minor surgery. There were five malignancy transformations in four patients (23.5%), with the distal femur being the most frequent location for transformation to grade I chondrosarcoma. Surgery was the treatment in all of them. We found no family association with other tumours. CONCLUSIONS: Multiple enchondromatosis is a benign disease with a high risk of malignant transformation above 40 years old. Bone scintigraphy is the best tool for detecting multiple lesions and malignant transformation. Radical surgery is the only way to improve survival, and this is the reason why early diagnosis is essential.

Prevalence and impact of fibromyalgia on function and quality of life in individuals from the general population: results from a nationwide study in Spain.

OBJECTIVE: To estimate the prevalence of fibromyalgia (FM) and to compare some descriptive epidemiological and quality of life data between persons with and without FM criteria in a representative sample of the general Spanish population. METHODS: Cross sectional study of 2,192 Spaniards aged 20 or above, selected by cluster sampling. Subjects were invited to a structured interview carried out by trained rheumatologists to ascertain various musculoskeletal disorders. The visit included screening and examination, validated instruments for measuring function (HAQ) and quality of life (SF-12) and questions about socio-demographic characteristics and musculoskeletal, mental, and other general symptoms. FM was suspected in subjects with widespread pain for more than three months. FM was defined by theAmerican College of Rheumatology classification criteria. All estimates are adjusted to sampling scheme. RESULTS: The prevalence of FM in Spain is 2.4% (95% CI: 1.5-3.2). FM is significantly more frequent in women (4.2%) than in men (0.2%), with an OR for women of 22.5 (95%CI: 7.2- 69.9), mainly in the 40-49 years age interval. It is more frequent in rural (4.1%) than in urban settings (1.7%), with an OR for rural settings of 2.5 (95%CI: 1.03-5.9). FM is associated with a low educational level, to a low social class, and to self-reported depression. The scores in the HAQ and in the SF-12 were significantly lower in FM subjects, despite adjustment by covariates. CONCLUSION: FM has a high prevalence in the general population. FM is associated to female gender, comorbidities, age between 40 and 59 years, and a rural setting. Persons fulfilling FM criteria show impaired functioning and quality of life.

DNA damage in outdoor workers occupationally exposed to environmental air pollutants.

BACKGROUND: Health concerns about the exposure to genotoxic and carcinogenic agents in the air are particularly significant for outdoor workers in less developed countries. AIMS: To investigate the association between personal exposure to a group of air pollutants and severity of DNA damage in outdoor workers from two Mexican cities. METHODS: DNA damage (Comet assay) and personal exposure to volatile organic compounds, PM(2.5), and ozone were investigated in 55 outdoor and indoor workers from México City and Puebla. RESULTS: In México City, outdoor workers had greater DNA damage, reflected by a longer tail length, than indoor workers (median 46.8 v 30.1 mum), and a greater percentage of highly damaged cells (cells with tail length > or =41 microm); in Puebla, outdoor and indoor workers had similar DNA damage. There were more alkali labile sites in outdoor than indoor workers. The DNA damage magnitude was positively correlated with PM(2.5) and ozone exposure. Outdoor and indoor workers with > or =60% of highly damaged cells (highly damaged workers) had significantly higher exposures to PM(2.5), ozone, and some volatile organic compounds. The main factors associated with the highly damaged workers were ozone, PM(2.5), and 1-ethyl-2-methyl benzene exposure. CONCLUSIONS: With this approach, the effects of some air pollutants could be correlated with biological endpoints from the Comet assay. It is suggested that the use of personal exposure assessment and biological endpoints evaluation could be an important tool to generate a more precise assessment of the associated potential health risks.

Atendimento às mulheres vítimas de violência sexual: um estudo qualitativo / The services for women victims of sexual violence: a qualitatif study

OBJETIVO: Avaliar o funcionamento de serviços públicos de atendimento a mulheres vítimas de violência sexual. MÉTODOS: Estudo de natureza qualitativa realizado em dois serviços públicos de atendimento às mulheres vítimas da violência sexual. Foram realizadas entrevistas com 42 mulheres, sendo 13 que buscaram os serviços e 29 profissionais que trabalhavam nas equipes. A avaliação teve por referência as categorias: acolhimento, acesso, resolutividade e responsabilidade sanitária. RESULTADOS: A análise das entrevistas por categorias revelou haver acolhimento em ambos os serviços, dificuldade de acesso por falta de informação da existência desses serviços, resolutividade de qualidade com equipe multiprofissional. Quanto à responsabilidade sanitária, ela existe nesses serviços especializados, mas é deficiente nos pronto-socorros e unidades básicas de saúde. Muitas mulheres desconhecem os direitos que lhes garantem serviço especializado. Muitas vezes chegam tardiamente aos serviços comprometendo sua eficácia. Há deficiência na referência e contra-referência. CONCLUSÕES: As conclusões permitem ratificar a importância desses serviços de atendimento, a necessidade de sua ampliação descentralizada e a inserção da temática da violência sexual nas graduações dos cursos de saúde.

Drug targeting of estrogen receptor signaling in the cardiovascular system: preclinical and clinical studies.

Atherosclerosis and associated coronary heart disease events have lower prevalence in women than in men, especially during young adult years. Although multiple lines of evidence suggest that estrogens contribute to this difference, the efficacy of hormone replacement therapy for the prevention of cardiovascular disease in postmenopausal women is controversial. The protective action of estrogen in the cardiovascular system appears to be mediated indirectly by an effect on serum lipoprotein and triglyceride profiles and on the expression of coagulant and fibrinolytic proteins, and by a direct effect on the vessel wall itself. Estrogen has both rapid effects involving alteration of membrane ionic permeability and activation of membrane-bound enzymes and increases in endothelial cell nitric oxide synthase activity, as well as longer-term effects on gene expression that are mediated, at least in part, by the ligand-activated transcription factors, estrogen receptor alpha and beta. Compounds with pure antiestrogenic activity and selective estrogen receptor modulators that regulate estrogen receptor function in a tissue-specific manner have been developed in an attempt to achieve the cardioprotective effects of estrogens while minimizing the undesirable risks associated with hormone replacement therapy (e.g., endometrial and breast cancer). In this review, we will discuss recent developments on the mechanisms of estrogen action in the cardiovascular system. The results of clinical trials testing the long-term efficacy of hormone replacement therapy for the treatment of cardiovascular disease will also be discussed.

Genotoxic differences by sex in nasal epithelium and blood leukocytes in subjects residing in a highly polluted area.

We describe differences by sex in genotoxic damage found in a population of medical students exposed to a highly oxidative atmosphere, compared with a control group, measured by the single-cell gel electrophoresis assay and histological changes in nasal epithelium smears. Cells were obtained from the nasal epithelium and blood leukocytes. Higher DNA damage in nasal cells and leukocytes was found in males compared to females and control subjects. The percentage of squamous metaplastic changes in the nasal epithelium was also higher in males compared with females and controls. The co-mutation of normal nasal epithelium by squamous cells might modify its protective function in the nose, increasing the risk of damage to the lower respiratory tract. Although, as medical students, males and females were exposed to the same environment and activity patterns, male genotoxicity damage was higher in control and exposed subjects. More research should be done in order to identify direct or indirect sexual hormone intervention.