Genetic variants of antioxidant enzymes and environmental exposures as molecular biomarkers associated with the risk and aggressiveness of bladder cancer.

Bladder cancer (BC) is one of the top 10 most common tumours worldwide; however, no molecular markers are currently available for tumour management and follow-up. BC could benefit from molecular biomarkers in environmental disease, which provide mechanistic understanding of individual susceptibility to exposure-related cancers and allow characterizing genetic alterations in the molecular pathway for malignancy. This case-control study performed a molecular analysis in 99 BC and 125 controls. Buccal swabs were collected to assess SNPs in eleven genes coding for xenobiotic detoxification enzymes, cellular antioxidant defences, and hormone synthesis and signalling (NAT2 (rs1801280), GPX1 (rs1050450 and rs17650792), TXNRD1 (rs7310505), PRDX3 (rs3740562), PON1 (rs662), SOD1 (rs10432782), SOD2 (rs4880), CAT (rs1001179), CYP17A1 (rs743572) and ESR1 (rs746432)). A structured questionnaire was administered to study participants to assess environmental and dietary chemical exposures. Several miRNAs associated with BC and detoxification/antioxidant pathways were analysed in a subsample of the study population, including miR-93-5p, miR-221-3p, miR-126, miR-27a-3p, miR-193b, and miR-193a-5p. Levels of selected environmental pollutants (polycyclic aromatic hydrocarbons and endocrine disrupting chemicals) were determined in urine from a subsample of BC cases and controls. We found that CYP17A1, CAT, SOD1, ESR1, PON1, and GPX1 (rs17650792) were associated with BC risk. Furthermore, exposure to smoke and/or dust, and alcohol intake were identified as risk factors for BC. Increased urinary levels of benzo[a]pyrene and bisphenol A were observed in BC patients relative to controls, along with an increased expression of miR-193b, miR-27a and miR-93-5p in BC. Nevertheless, further studies with a larger sample size are warranted to confirm these exploratory results. This study also shows that the combination of genetic markers (PON1 and CYP17A1) and miRNA (miR-221-3p and miR-93-5p) open a new scenario in the use of non-invasive biomarkers in the stratification of BC to guide personalized medicine, which is extremely urged in the current clinical setting.

In vitro redox activity of haemozoin and ß-haemozoin interacting with the following antimalarials: artemether, lumefantrine and quinine.

OBJECTIVE: Malaria parasites invade, grow and multiply inside erythrocytes and obtain nourishment from haemoglobin. Then, the released haem group is oxidized to haematin and inert dimeric haemozoin bio-crystals form, which provides the parasite a unique way to avoid the toxicity associated with the haem group. Therefore, antimalarial drugs are designed to inhibit dimer formation; however, recent electrochemical studies indicate that an inert dimer also promotes a toxic oxidizing environment. Therefore, this work explores drug reactivity in the presence of monomers and dimers to evaluate their contribution to redox activity. MATERIALS AND METHODS: Three medicines mixed with haemozoin or ß-haemozoin in carbon paste electrodes were tested using cyclic voltammetry. RESULTS: The data indicated again that the substances modify the natural redox state of haemozoin and ß-haemozoin. This effect could be attributed to the natural oxidation potential of the drugs. In addition, it was found that the oxidation potential decreased through quinine, lumefantrine and artemether with the same tendency in the presence of haemozoin but with less current density. Additionally, it was observed that the oxidation response between the monomer haemozoin and antimalarial drugs is carried out at more negative potentials. CONCLUSIONS: Together, the total results indicate that antimalarials per se can contribute to oxidation processes and that in combination with monomeric or dimeric haemozoin can increase or decrease the oxidizing power of the haemozoin forms. The various oxidizing environments suggest that the cell membranes can also be damaged by the unique presence of the antimalarial.

Is it always necessary to perform an axillary lymph node dissection after neoadjuvant chemotherapy for breast cancer?

INTRODUCTION: Recent prospective studies support the feasibility of performing sentinel lymph node biopsy following neoadjuvant chemotherapy in initially fine-needle aspiration cytology or ultrasound-guided biopsy-proven node-positive breast cancer. The main aid is to identify preoperative features that help us predict a complete axillary response to neoadjuvant chemotherapy in these patients and thus select the candidates for sentinel lymph node biopsy post-neoadjuvant chemotherapy to avoid unnecessary axillary lymphadenectomy. MATERIALS AND METHODS: A retrospective observational study with a total of 150 patients, biopsy-proven node-positive breast cancer who underwent neoadjuvant chemotherapy followed by breast surgery and axillary lymphadenectomy were included and retrospectively analysed. A predictive model was generated by a multivariate logistic regression analysis for pathological complete response-dependent variable. RESULTS: The response of the primary lesion to neoadjuvant chemotherapy according to post-treatment magnetic resonance imaging, Her2/neu overexpression and a low estrogen receptor expression are associated with a higher rate of nodal pathologically complete response. The multivariant model generated a receiver operating characteristic curve with an area under the curve of 0.79 and a confidence interval of 0.72-0.87 at a 95% level of significance. CONCLUSIONS: This model could be a helpful tool for the surgeon to help in predicting which cases have a higher likelihood of achieving a pathologically complete response and therefore selecting those who may benefit from a post-neoadjuvant chemotherapy sentinel lymph node biopsy and avoid unnecessary axillary lymphadenectomy.

Usefulness of surgical complexity classification index in cataract surgery process. / Utilidad del índice de complejidad quirúrgica en el proceso de cirugía de catarata.

OBJECTIVE: To evaluate the usefulness of surgical complexity classification index (SCCI) to predict the degree of surgical difficulty in cataract surgery. MATERIAL AND METHODS: This retrospective study includes data collected between January 2013 and December 2014 from patients who underwent cataract extraction by phacoemulsification at our hospital. A sample size of 159 patients was obtained by simple random sampling (P=.5, 10% accuracy, 95% confidence). The main variables were: recording and value of SCCI in electronic medical record (EMR), presence of exfoliation syndrome (XFS), criteria for inclusion in surgical waiting list (SWL), and functional results. SCCI was classified into 7 categories (range: 1-4) according to predictors of technical difficulty, which was indirectly estimated in terms of surgical time (ST). All statistical analyses were performed using SPSS v15.0 statistical software. RESULTS: Prevalence of XFS was 18.2% (95%CI: 11.9-24.5). In terms of quality indicators in the cataract surgery process, 96.8% of patients met at least one of the criteria to be included in SWL, and 98.1% gained ≥2 Snellen lines. The SCCI was recorded in EMR of 98.1% patients, and it was grouped for study into 2 categories: High and low surgical complexity. Statistically significant differences in the distribution of ST were found depending on the assigned SCCI (P<.005) and the presence of XFS (P<.005). CONCLUSIONS: The SCCI enables to estimate the degree of surgical complexity in terms of ST in cataract surgery, which is especially useful in those areas with high prevalence of XFS, because of the higher theoretical risk of surgical complications.

Evaluation of the genotoxic activity of dicamba and atrazine herbicides in several Mexican and South American varieties of sweetcorn (Zea mays L.).

Corn is a major crop and various herbicides are used to maximize its production, which include a dicamba-atrazine mixture. This has great advantages, but can also induce DNA damage. Genotoxic activity was assessed by comet assay following application of two concentrations of dicamba-atrazine: 1000-2000 and 2000-4000 ppm. Apical meristem leaf nuclei from 119 varieties of sweetcorn plants from Mexico and South America, and from five commercial sweetcorn hybrids were used. Each accession comprised two individuals per concentration and two controls. Significant genotoxic activity (P < 0.001) was observed following treatment with 1000-2000 and 2000-4000 ppm compared to the negative control. There was no difference in the genotoxic activity induced by both 1000-2000 and 2000-4000 ppm concentrations in plants from Mexico and South America (P > 0.05) except (P < 0.05) in the 2000-4000 ppm treated plants from Mexico and the 1000-2000 ppm treated plants from South America. Sweetcorn hybrids showed significant genetic damage (P < 0.01) at all concentrations compared to the negative controls. Thus, the dicamba-atrazine mixture caused genetic damage to corn plants, and it suggested that Mexican sweetcorn is more sensitive to dicamba-atrazine than the maize varieties from South America. Neither hybrid status nor the origin avoids DNA damage caused by Marvel. Thus, maize can be useful as a biomonitor of genetic damage induced by chemicals and to identify possible phenotypes based upon the amount of genetic damage induced by herbicides and selection of resistant genotypes.

Assessing the genotoxicities of sparteine and compounds isolated from Lupinus mexicanus and L. montanus seeds by using comet assay.

The genus Lupinus is widely distributed. Its seeds are used for animal and human food, and Lupinus possesses pharmacological potential because of its high content of quinolizidine alkaloids and flavonoids; however, there is little available information about its genotoxicity. We used the comet assay and staminal nuclei of Tradescantia (clone 4430) to evaluate the in vitro genotoxicity of 4 concentrations (0.01, 0.1, 0.5, and 1.0 mM) of alkaloid extracts of Lupinus mexicanus and Lupinus montanus, flavonoids of L. mexicanus, and commercial sparteine; nitrosodiethylamine was used as a positive control and untreated nuclei were used as a negative control. All concentrations of L. mexicanus and L. montanus showed significant genotoxic activity (P ≤ 0.05). A similar behavior was observed for flavonoid extracts of L. montanus except the 1.0 mM concentration. Sparteine showed genotoxic activity only at 0.5 mM. The order of genotoxicity of the compounds studied was as follows: L. mexicanus > L. montanus > flavonoids of L. montanus > sparteine. There is evident genotoxic activity in the compounds that were studied, particularly at lower concentrations (0.01 and 0.1 mM). Given the limited information about the genotoxicity of the compounds of L. mexicanus and L. montanus, further studies are necessary.

Tumoraciones quísticas intracraneales. A propósito de un caso / Intracranial cystic tumors. A case report

Los quistes aracnoideos son lesiones benignas, de origen congénito, formadas por una membrana aracnoidea, que contienen líquido cefalorraquídeo en su interior. Presentamos el caso de un niño de cinco años con una asimetría craneal con abombamiento frontoparietotemporal derecho. Refería vómitos ocasionales de un año de evolución y cefalea que no le despertaba por la noche desde hacía dos años, acompañada algunas veces de sonofobia y fotofobia. En las pruebas de imagen se visualizaba un gran quiste aracnoideo en la fosa craneal media derecha con desplazamiento de la línea media y colapso de las astas ventriculares adyacentes. Dado el tamaño del quiste y la clínica, se decidió tratamiento con cistocisternostomía endoscópica comunicando el quiste aracnoideo con las cisternas basales (AU)

Arachnoid cysts are benign, congenital malformations formed by an arachnoid membrane containing cerebrospinal fluid inside. We report the case of a 5 year old child with cranial asymmetry with right fronto-parieto-temporal bulging. Occasional vomiting a year of evolution and sometimes headache are refered, which did not wake him at night, accompanied by sonophobia and photophobia for two years. The imaging displays large arachnoid cyst in right middle cranial fossa with midline shift and collapse of adjacent ventricular horns. Because of the size of the cyst and the clinic, endoscopic treatment was selected, communicating arachnoid cyst and basal cisterns (AU)

Hematocolpos por himen imperforado; causa infrecuente de dolor abdominal y retención aguda de orina / Hematocolpos secondary to imperforate hymen; an uncommon cause of abdominal pain and acute urinary retention

El hematocolpos constituye una patología poco prevalente en nuestro medio, secundaria a alteraciones en la génesis del aparato genitourinario femenino, entre las cuales el himen imperforado es la malformación congénita más frecuente. La sintomatología suele ser variable e inespecífica, y el dolor abdominal es la forma de presentación clínica más frecuente. En este artículo se exponen dos casos clínicos de adolescentes afectas de esta patología. Ambas presentaron abdominalgia y síntomas miccionales. La realización de una historia clínica detallada junto con la inspección de los genitales, así como la visualización en la ecografía abdominal de una colección sanguínea localizada en la vagina, fueron fundamentales para llegar al diagnóstico. En este artículo se pretende destacar la importancia de la anamnesis y la exploración genital ante una sintomatología tan inespecífica como son el dolor abdominal y la clínica miccional, ya que puede orientarnos al diagnóstico de forma sencilla, evitando pruebas innecesarias, medidas terapéuticas erróneas y aparición de complicaciones (AU)

Hematocolpos constitutes an unusual pathology in our environment, secondary to alterations in the genesis of female genitourinary tract, being the imperforate hymen the most common congenital malformation. The symptomatology is usually variable and nonspecific with abdominal pain as the most frequent clinical presentation. In this paper we present the description of two cases of teenagers affected by this disease. Both presented abdominal pain and urinary symptoms. Besides a detailed medical history along with the inspection of the genitalia as well as the visualization in the abdominal echography of a blood collection located in the vagina, were fundamental in order to make a diagnosis. Throughout this article we intend to emphasize the relevance of the medical history and genital examination before symptoms as nonspecific as abdominal pain and urinary symptoms because of it can help us to guide the diagnosis in an easy way avoiding unnecessary tests, erroneous therapeutic measures and appearance of complications (AU)

Comminuted simultaneous bilateral tibial tubercle avulsion fractures: a case report.

A 16-year-old male had simultaneous bilateral tibial tubercle avulsion fractures after making a sudden stop while running at full speed. The left knee injury (type V) was minimally displaced, was treated conservatively with closed reduction, and the patient recovered uneventfully. The right tibial tubercle injury was unusual. The tuberosity and anterior aspect of the proximal epiphysis remained as one, but there was severe intra-articular comminution posterior to the displaced tubercle fragment. The right knee injury (type III) required open reduction and internal fixation to reduce the apophyseal fragment and 2 intra-articular displaced fragments. The patient's recovery was complicated by a severe, persistent flexion deformity on the right side. Eventually, the patient required manipulation under anaesthesia, extensive continuous passive mobilisation and a turnbuckle extension splint. A residual 5-degree flexion deformity remained at 16 months post-injury. This case highlights the importance of identifying any intra-articular fragments, their careful anatomical reduction, and aggressive mobilisation when treating tibial tubercle avulsion fractures.

Intragraft cytokine expression in heart transplants with mild or no histological rejection.

UNLABELLED: The study of pro-inflammatory cytokines produced in situ in heart allografts may help to understand the mechanisms of rejection and open new possibilities to control graft rejection. METHODS: A total of 23 endomyocardial biopsies obtained from 16 transplanted patients treated with triple-drug therapy (azathioprine, prednisone, and cyclosporine) were studied. mRNA expression for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-10, IL-12, IL-15, transforming growth factor (TGF)-beta, and beta-actin was determined by reverse transcription polymerase chain reaction (RT-PCR) and Southern blotting. Semiquantitative analysis was done by establishing the ratio between densitometric integrated value of each cytokine with the beta-actin and correlated with the histopathologic findings. RESULTS: Three groups of biopsies were determined according to the International Society for Heart and Lung Transplantation criteria: grade 0 (control group, n=12), grade 1A (sub-clinical rejection, n=6) and 'quilty effect' (n=5). An increased expression of mRNA for TNF-alpha and IL-6 (p=0.0091 and 0.0075, respectively) was found associated with rejection grade 1A episodes, mRNA for IL-1 beta was nonspecifically expressed in all the study groups, while IL-10 mRNA was not detected in any of the biopsies studied. mRNA for IL-12 and IL-15 was not associated with rejection. Interestingly, TGF-beta was not detected in any of the biopsies with the 'quilty pattern'. CONCLUSION: The association of TNF-alpha and IL-6 mRNA in situ expression with mild histologically probed rejection episodes may be used in the monitoring of heart transplants.

[Coronary fibrinolysis: quality care]. / Fibrinolisis coronaria: cuidados de calidad.

Coronary fibrinolysis through intravenous via is a usual technique in ICU worldwide, it is a procedure of controlled risk which provides great benefits to patients who undergo such technique. The role of nursing in the administration and control of the fibrinolytic treatment is essential. Despite that, the plans for fibrinolysis specific care are very scarce, if not inexistent, in the bibliography reviewed. The main objective of this work is identify the complications derived from the administration of fibrinolytic medicines through intravenous via. Using a chart of collected data, which goes from the admission of the patient to their discharge from ICU, 178 cases are studied. After the analysis of results, a standardization of intensive care units orientated to increase the assistance quality is suggested.

Effect of ethanol on insulin-stimulated glucose uptake in the isolated rat diaphragm.

Insulin-stimulated (0.16 and 2.56 nM) glucose uptake (GU) was studied in isolated rat diaphragms in the presence of ethanol (EtOH) 21, 42 and 84 mM as well as in diaphragms removed from rats orally treated with the drug (1.5 or 4.5 g/kg/day) for 10 or 30 days. In spite of inhibiting the base-line GU, the addition of EtOH to the incubation medium gave rise to a potentiation of the insulin effect. In the orally intoxicated series, the low-dose EtOH increased the response to 0.16 nM insulin after 10 or 30 days, no changes being observed in that induced by 2.56 nM insulin. On the other hand, the high-dose EtOH caused an increase of the base-line GU which remained practically unmodified in the presence of insulin. The precise molecular basis for these phenomena is unknown.

Quinovic acid glycosides from Uncaria guianensis.

From the bark of Uncaria guianensis, two new quinovic acid glycosides, quinovic acid 3 beta-O-beta-D-quinovopyranoside and quinovic acid 3 beta-O-beta-D-fucopyranosyl-(27----1)-beta-D-glucopyranosylester, have been isolated, in addition to known quinovic acid 3 beta-O-[beta-D-glucopyranosyl-(1----3)-beta-D-fucopyranosyl]-(27----1)- beta-D-glucopyranosylester and quinovic acid 3 beta-O-beta-D-fucopyranoside. Their structures were elucidated by spectral and chemical studies.

[Congenital and neonatal varicella. A report on 9 cases]. / Varicela congénita y neonatal. Presentación de nueve casos.

Varicella infection in the first month of life is rare. Neonates may be infected through the placenta or in the perinatal period. In Mexico, the experience with neonatal varicella infection is limited; on the other hand this disease may be misdiagnosed in the neonate. The purpose of this work is to inform nine patients which presented varicella in the neonatal period; in six cases the disease was observed after the 10th but before the 30th day of life; in the remaining cases, the disease was present before the 10th day. Only one patient was premature. Five patients developed varicella in the hospital; in three cases, the mother presented the disease nine, eight, and one day prior delivery; one patient was exposed to varicella in his home. Four patients died but only in one case the death was attributed to varicella.

Development of the esophageal muscles in embryos of the sea urchin Strongylocentrotus purpuratus.

Development of the esophageal muscles in embryonic sea urchins is described using light- and electron microscopy. The muscles develop from processes of about 14 cells of the coelomic epithelium that become immunoreactive to anti-actin at about 60 h (12-14 degrees C). Initially, each myoblast extends a single process with numerous fine filopodia around the esophagus. By 72 h the processes have reached the midline and fused with those from cells of the contralateral coelomic sac. Myoblasts begin to migrate out of the coelomic epithelium between 72 and 84 h. By 72 h the processes stain with the F-actin specific probe NBD-phallacidin. The contractile apparatus is not evident in transmission electron-microscopic preparations of embryos at 70 h, but by 84 h the contractile apparatus is present and the muscle cells are capable of contraction. Because the myoblasts migrate free of the coelomic epithelium and are situated on the blastocoelar side of the basal lamina, it is suggested that that they should be considered as a class of mesenchymal cells.

Mandibular advancement combined with horizontal advancement genioplasty for the treatment of obstructive sleep apnea in an edentulous patient. A case report.

Orthognathic surgical procedures have been used in the past for the treatment of obstructive sleep apnea. The treatment becomes more complicated when the patient has edentulous upper and lower arches. A treatment plan that provided a good surgical result and resolution of all symptoms was devised for such a patient.