Effect of pyridoxine or cobalamin supplementation on apoptosis and cell cycle progression in a human glioblastoma cell line.

Glioblastoma is the most aggressive type of brain tumor, with current therapies failing to significantly improve patient survival. Vitamins have important effects on cellular processes that are relevant for tumor development and progression. AIM: The present study explored the effect of pyridoxine or cobalamin supplementation on the viability and cell cycle progression of human glioblastoma cell line U-87 MG. METHOD: Cell cultures were treated with increasing concentrations of pyridoxine or cobalamin for 24-72 h. After supplementation, cell viability and cell cycle progression were assessed by spectrophotometry and flow cytometry. Analysis of Bcl-2 and active caspase 3 expression in supplemented cells was performed by western blot. RESULT: The results show that pyridoxine supplementation decreases cell viability in a dose and time dependent manner. Loss of viability in pyridoxin-supplemented cells is probably related to less cell cycle progression, higher active caspase 3 expression and apoptosis. In addition, Bcl-2 expression did not appear to be altered by vitamin supplementation, but active caspase 3 expression was significantly increased in pyridoxine-, but not cobalamin-supplemented cells, furthermore, cobalamin inhibited the pyridoxine cytotoxicity in the cell viability assay when combined. CONCLUSION: The results suggest that pyridoxine supplementation promotes apoptosis in human glioblastoma-derived cells and may be useful to enhance the effect of cytotoxic therapies in vivo.

Uso de estudios de laboratorio y gabinete en pacientes con dolor abdominal no traumático, en el servicio de urgencias

Introducción: La evaluación del paciente con dolor abdominal agudo no traumático es un reto diagnóstico. El uso de pruebas de laboratorio y gabinete son herramientas útiles que nos permiten obtener información complementaria sobre cada paciente y con ello confirmar o descartar un diagnóstico y determinar su plan de acción. Objetivo: Estimar la frecuencia de uso de en el servicio de urgencias del Hospital General Regional No.72 en pacientes con dolor abdominal no traumático. Métodos: Se realizó un estudio retrospectivo, observacional, transversal y descriptivo donde se revisaron 126 expedientes clínicos de pacientes ≥20 años, que acudieron a urgencias por, los cuales contaban con una estancia de al menos 8 h y a quienes se practicó alguna; se excluyeron expedientes clínicos de mujeres embarazadas. Los datos se analizaron con estadística descriptiva. Resultados: Se realizaron 827 pruebas a 126 pacientes. Los principales estudios utilizados fueron: biometría hemática (99,2 %), glucosa, urea, creatinina, electrólitos y tiempos de coagulación (en el 100 % de los pacientes). Los estudios de gabinete más utilizados fueron: ultrasonido (31,7 %) y tomografía abdominal (11,9 %). Las cinco patologías más prevalentes fueron: colecistitis, infección urinaria, gastroenteritis, enfermedad ácido péptica y pancreatitis. Conclusiones: El dolor abdominal es una patología de etiología multivariada, por lo que su estudio adecuado es esencial para el manejo de las personas y la implementación de un sistema de gestión de calidad centrado en el paciente.

Introduction: The evaluation of the patient with non-traumatic acute abdominal pain is a diagnostic challenge. The use of laboratory and cabinet tests are useful tools allowing to obtain complementary information about each patient and thereby confirm or rule out a diagnosis and determine its action plan. Objective: To estimate the frequency of use of laboratory and cabinet tests in the emergency department at the Regional General Hospital No.72, in patients with non-traumatic abdominal pain from August to September 2017. Methods: A retrospective, observational, cross-sectional and descriptive study was carried out. One hundred twenty six (126) clinical records of patients ≥20 years old were reviewed, these subjects attended the emergency room for non-traumatic acute abdominal pain, and had a stay of at least 8 hours. They underwent some laboratory and cabinet tests. Clinical records of pregnant women were excluded. The data was analyzed with descriptive statistics. Results: Eight hundred twenty seven (827) tests were performed on 126 patients. The main studies used were blood count (99.2%), glucose, urea, creatinine, electrolytes and coagulation times (in 100% of patients). The most used cabinet studies were ultrasound (31.7%) and abdominal tomography (11.9%). The five most prevalent pathologies were cholecystitis, urinary infection, gastroenteritis, acid peptic disease and pancreatitis. Conclusions: Abdominal pain is a pathology of multivariate etiology, so adequate study is essential for the management of people and the implementation of a quality management system focused on the patient.

The Extracellular Vesicles from the Commensal Staphylococcus Epidermidis ATCC12228 Strain Regulate Skin Inflammation in the Imiquimod-Induced Psoriasis Murine Model.

Extracellular vesicles (EVs) are evaginations of the cytoplasmic membrane, containing nucleic acids, proteins, lipids, enzymes, and toxins. EVs participate in various bacterial physiological processes. Staphylococcus epidermidis interacts and communicates with the host skin. S. epidermidis' EVs may have an essential role in this communication mechanism, modulating the immunological environment. This work aimed to evaluate if S. epidermidis' EVs can modulate cytokine production by keratinocytes in vitro and in vivo using the imiquimod-induced psoriasis murine model. S. epidermidis' EVs were obtained from a commensal strain (ATC12228EVs) and a clinical isolated strain (983EVs). EVs from both origins induced IL-6 expression in HaCaT keratinocyte cultures; nevertheless, 983EVs promoted a higher expression of the pro-inflammatory cytokines VEGF-A, LL37, IL-8, and IL-17F than ATCC12228EVs. Moreover, in vivo imiquimod-induced psoriatic skin treated with ATCC12228EVs reduced the characteristic psoriatic skin features, such as acanthosis and cellular infiltrate, as well as VEGF-A, IL-6, KC, IL-23, IL-17F, IL-36γ, and IL-36R expression in a more efficient manner than 983EVs; however, in contrast, Foxp3 expression did not significantly change, and IL-36 receptor antagonist (IL-36Ra) was found to be increased. Our findings showed a distinctive immunological profile induction that is dependent on the clinical or commensal EV origin in a mice model of skin-like psoriasis. Characteristically, proteomics analysis showed differences in the EVs protein content, dependent on origin of the isolated EVs. Specifically, in ATCC12228EVs, we found the proteins glutamate dehydrogenase, ornithine carbamoyltransferase, arginine deiminase, carbamate kinase, catalase, superoxide dismutase, phenol-soluble ß1/ß2 modulin, and polyglycerol phosphate α-glucosyltransferase, which could be involved in the reduction of lesions in the murine imiquimod-induced psoriasis skin. Our results show that the commensal ATCC12228EVs have a greater protective/attenuating effect on the murine imiquimod-induced psoriasis by inducing IL-36Ra expression in comparison with EVs from a clinical isolate of S. epidermidis.

Heptapeptide HP3 acts as a potent inhibitor of experimental imiquimod­induced murine psoriasis and impedes the trans­endothelial migration of mononuclear cells.

During the progression of psoriatic lesions, abundant cellular infiltration of myeloid cells, such as macrophages and activated dendritic cells, occurs in the skin and the infiltrating cells interact with naive lymphoid cells to generate a T helper (Th)1 and Th17 environment. Therapies to treat psoriasis include phototherapy, non­steroidal and steroidal drugs, as well as antibodies to block tumor necrosis factor­α, interleukin (IL)­17­A and IL­12/IL­23, which all focus on decreasing the proinflammatory hallmark of psoriasis. The present study obtained the heptapeptide HP3 derived from phage display technology that blocks mononuclear cell adhesion to endothelial cells and inhibits trans­endothelial migration in vitro. The activity of the heptapeptide in a murine model of psoriasis was also assessed, which indicated that early administration inhibited the development of psoriatic lesions. Therefore, the results suggested that HP3 may serve as a potential therapeutic target for psoriasis.

Idiopathic Lead Migration: Concept and Variants of an Uncommon Cause of Cardiac Implantable Electronic Device Dysfunction.

OBJECTIVES: This cumulative case study was performed to properly address the possible mechanisms, forms, and consequences of "twiddler's," "reel," and "ratchet" syndromes. BACKGROUND: Twiddler's, reel, and ratchet syndromes are rare entities responsible for lead displacement of cardiac implantable electronic devices (CIED). METHODS: From 2007 to 2012, 1,472 CIED were implanted at our center. Eighty-nine cases were reviewed for failure of pacing circuit integrity. Only 9 met the inclusion criteria for idiopathic lead migration (ILM) and were grouped as ILM (twiddler) or ILM (reel). For a pooled analysis of cases, a review of the literature from 1990 to 2012 was performed, and the authors identified 78 cases from 64 publications. RESULTS: The study population consisted of 87 cases (45 women; median age, 66 years; 46 with ILM [twiddler] and 41 with ILM [reel]). Migration affected only 1 lead in 65% of 46 devices with more than 1 lead. None of the previously reported risk factors-manual manipulation of the device, elderly age, obesity, oversized pocket, and psychiatric history-correlated with the risk of ILM. CONCLUSIONS: Neither manual manipulation of the device nor the other traditional risk factors reported in the literature for ILM syndrome correlated with the risk of ILM.

Reuse of pacemakers: comparison of short and long-term performance.

BACKGROUND: In developing economies, there are patients in whom pacemaker implantation is delayed because they cannot afford one. Reused devices have been a solution. To address concerns about safety, a cohort of consecutive patients implanted with a reused pacemaker was compared with a control group. METHODS AND RESULTS: A cohort of 603 consecutive patients from 2000 to 2010 was studied in an ambispective noninferiority study. The study group patients (n=307) received resterilized pacemakers, and the control group patients (n=296) received a new pacemaker. A combined end point of 3 major outcomes-unexpected battery depletion, infection, and device dysfunction-was analyzed. A total of 85 pacemakers had to be explanted, 31 in the control group (10.5%) and 54 in the study group (17.6%; relative risk, 1.68; 95% confidence interval, 1.1-2.5; P=0.02). Forty-three reached the primary end point, 16 in the control group (5.5%) and 27 in the study group (7.2%; relative risk, 1.3; 95% confidence interval, 0.70-2.45; P=0.794). In terms of individual outcomes, 5 new pacemakers (1.7%) and 11 resterilized pacemakers (3.6%) had unexpected battery depletion (relative risk, 2.12; 95% confidence interval, 0.75-6; P=0.116); 3.7% new pacemakers and 3.2% reused pacemakers had a procedure-related infection (relative risk, 0.87; 95% confidence interval, 0.38-2.03; P=0.46); and 1 pacemaker in the study group malfunctioned. CONCLUSIONS: Pacemaker reuse is feasible and safe and is a viable option for patient with bradyarrhythmias. Other than the expected shorter battery life, reuse of pacemaker generators is not inferior to the use of new devices.

Predictores clínicos de tormenta arrítmica en pacientes con cardiomiopatía Chagásica con un desfibrilador automático implantable / Clinical predictors of ventricular arrhythmia storms in Chagas cardiomyopathy patients with implantable defibrillators

OBJECTIVES: To define the predictive factors of electrical storm (ES) in patients with Chronic Chagas Heart Disease (CCh) with an implantable cardioverter defibrillator (ICD). MATERIAL AND METHODS: We retrospectively studied 21 consecutive patients with CCh in whom an ICD was implanted between April 2005 and December 2008, with a mean follow up of 867 days. Patients were classified into two groups according to the presence of electrical storm episodes. We compared baseline characteristics, medical treatment and determinants of ventricular function. P values less than 0.05 were considered statistically significant. RESULTS: Of the 21 patients with CCh there were eight women (37%), mean age 61 years and an EF of 30%. It was noted at least one episode of arrhythmic storm in 9 cases (incidence of 43%). The total number of episodes of arrhythmic storm was 13 and the number of ventricular arrhythmias in each episode of arrhythmic storm was 15.6 (range 3-61). A trigger was identified in only two cases (pulmonary infectious process and decompensation of chronic heart failure). After analyzing the possible predictors of arrhythmic storm was found that a greater percentage of subjects with this complication had an EF <35% (89% vs. 50%, p = 0.01) and NYHA functional class III (66% vs. 8.3%, p = 0.001). In contrast, a lower percentage of subjects with arrhythmic storm were under beta-blocker treatment (55% vs. 100%, p = 0.01). CONCLUSIONS: In subjects with CCh with an ICD, the following variables are predictive of arrhythmic storm: EF <35%, NYHA functional class III-IV and absence of beta-blocker treatment.

Doença de Ebstein: ausência de bloqueio de ramo direito como preditor de via anômala manifestada / Ebstein disease: absence of right branch block as a predictor of manifested anomalous way

O desenvolvimento anormal da válvula tricúspide na doença de Ebstein resulta em uma série de anormalidades na ativação, que inclui condução intra-atrial demorada, bloqueio de ramo direito(BRG) e pré-excitação ventricular. O objetivo desse tabalho era definir as características do ECG antes e depois da ablação de uma via anômala atrioventricular. De 226 pacientes consecutivos com anomalia de Ebstein, 64 apresentavam taquicardia documentada...

[Clinical predictors of ventricular arrhythmia storms in Chagas cardiomyopathy patients with implantable defibrillators]. / Predictores clínicos de tormenta arrítmica en pacientes con cardiomiopatía Chagásica con un desfibrilador automático implantable.

OBJECTIVES: To define the predictive factors of electrical storm (ES) in patients with Chronic Chagas Heart Disease (CCh) with an implantable cardioverter defibrillator (ICD). MATERIAL AND METHODS: We retrospectively studied 21 consecutive patients with CCh in whom an ICD was implanted between April 2005 and December 2008, with a mean follow up of 867 days. Patients were classified into two groups according to the presence of electrical storm episodes. We compared baseline characteristics, medical treatment and determinants of ventricular function. P values less than 0.05 were considered statistically significant. RESULTS: Of the 21 patients with CCh there were eight women (37%), mean age 61 years and an EF of 30%. It was noted at least one episode of arrhythmic storm in 9 cases (incidence of 43%). The total number of episodes of arrhythmic storm was 13 and the number of ventricular arrhythmias in each episode of arrhythmic storm was 15.6 (range 3-61). A trigger was identified in only two cases (pulmonary infectious process and decompensation of chronic heart failure). After analyzing the possible predictors of arrhythmic storm was found that a greater percentage of subjects with this complication had an EF <35% (89% vs. 50%, p = 0.01) and NYHA functional class III (66% vs. 8.3%, p = 0.001). In contrast, a lower percentage of subjects with arrhythmic storm were under beta-blocker treatment (55% vs. 100%, p = 0.01). CONCLUSIONS: In subjects with CCh with an ICD, the following variables are predictive of arrhythmic storm: EF <35%, NYHA functional class III-IV and absence of beta-blocker treatment.

Electrocardiographic characteristics of patients with Ebstein's anomaly before and after ablation of an accessory atrioventricular pathway.

UNLABELLED: The abnormal development of the tricuspid valve in patients with Ebstein's anomaly results in several activation abnormalities including delayed intraatrial conduction, right bundle branch block (RBBB), and ventricular preexcitation. The aim of the present study was to define the ECG characteristics before and after ablation of an accessory A-V pathway (AP) in patients with Ebstein's anomaly. METHODS: A series of 226 consecutive patients with Ebstein's anomaly was studied. Sixty-four patients (28%) had documented tachycardia. Thirty-three patients with recurrent tachycardia were found to have a single right-sided AP that was successfully ablated (study group). Thirty patients without tachycardia served as the control group. RESULTS: Only 21 of 33 patients (62%) had a typical ECG pattern of preexcitation. In addition, none of the patients had an ECG pattern of RBBB during sinus rhythm. In contrast, 28 of 30 (93%) patients in the control group had RBBB (P < 0.001). Radiofrequency catheter ablation resulted in appearance of RBBB in 31 of 33 (94%) patients. The absence of RBBB in patients with Ebstein's anomaly and recurrent tachycardia had a 98% sensitivity and 92% specificity for the diagnosis of an AP. The positive predictive value was 91% (0.77, 0.97 CI 95%) and the negative predictive value was 98% (0.85, 0.99 CI 95%). CONCLUSION: One-third of patients with Ebstein's anomaly and symptomatic tachyarrhythmias have minimal or absent ECG features of ventricular preexcitation. In these patients, the absence of RBBB pattern is a strong predictor of an AP.

Familial vasovagal syncope.

Vasovagal syncope (VVS) is a common clinical problem characterized by transient episodes of loss of consciousness due to abnormal autonomic activity. This paper describes two groups of monozygotic twins, from different families, affected by VVS and a family with several members with this condition. Their clinical characteristics, haemodynamic response to tilt, treatment, and outcome are described.

Arrhythmic storm responsive to quinidine in a patient with Brugada syndrome and vasovagal syncope.

A 37-year-old man with Brugada syndrome (BrS) and arrhythmic storm is described. One month after implantation of a cardioverter-defibrillator he presented with recurrent appropriate shocks for spontaneous ventricular fibrillation (VF). Because of this arrhythmic storm, quinidine therapy was initiated with total suppression of all spontaneous arrhythmias. He had remained free of arrhythmias for 22 months since quinidine initiation. Two episodes of VF occurred after the patient stopped taking the medication. The patient resumed quinidine and has been free of VF for the last 3 months. This response to quinidine in a patient with symptomatic BrS supports its role in the prophylaxis of arrhythmic events in BrS.

Dynamic electrocardiographic changes after aborted sudden death in a patient with Brugada syndrome and rate-dependent right bundle branch block.

A 37-year-old man with Brugada syndrome and dynamic changes of the ST-segment morphology observed after an episode of aborted sudden death is described. On admission, after 3 syncopal episodes during nighttime, his electrocardiogram showed right bundle branch block (RBBB) with a J-point elevation of 0.6 mV in lead V 2 . Changes observed in the following days included a diminished J-point elevation and intermittent "saddle-back" type of morphology. During a previous 2-year follow-up, intermittent, complete, acceleration-dependent RBBB was documented. Right ventricular intracavitary tracings showed an RS pattern with a broad S wave in the unipolar electrogram; the time of onset of intrinsic deflection in this electrogram was 60 milliseconds. To our knowledge, this is the first report of an intracavitary demonstration of complete RBBB in Brugada syndrome.

[Direct cryothermal ablation eliminates conduction of the slow pathway without inducing ectopic rhythms]. / La ablación criotérmica percutánea directa elimina la conducción a través de la vía lenta intranodal sin inducir ritmos ectópicos.

Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia is based on the elimination of conduction of slow or fast intranodal pathway. To avoid potential atrioventricular (AV) block, a new technology has been developed, cryothermal ablation. We report a case of AV nodal reentrant tachycardia in whom direct cryoablation, without previous ice mapping, was successfully performed. Interestingly and as previously described, cryotherapy did not induce ectopic rhythms, the conventional surrogate during radiofrequency ablation.

[Infrequent electrocardiographic changes during exercise stress test in a patient with Brugada's syndrome]. / Alteraciones electrocardiográficas infrecuentes durante la prueba de tolerancia al ejercicio en un paciente con síndrome de Brugada.

38 year old patient with a syncope history and family background of sudden death had an electrocardiogram compatible with the "Brugada Syndrome". When an exercise stress testing with Bruce protocol was done, we found that during the effort phase and at maximum effort, contrary to a ST segment normalization, a discreet increase of the ST segment elevation of 2 mm in V1 and V2 occurred. During recovery phase a decrease in the ST segment elevation was observed, at a normal level as before the test.

[ Segmental ostial ablation to interrupt electrical conduction in a single pulmonary vein for the prevention of idiopathic paroxysmal atrial fibrillation]. / Ablación segmentaria del ostium de la vena pulmonar superior izquierda para eliminar actividad eléctrica anormal generadora de fibrilación atrial paroxística idiopática.

Several studies have shown the role of focal trigers in the pulmonary veins initiating episodes of atrial fibrillation. Radiofrequency catheter ablation of this foci is a curative therapy for paroxysmal atrial fibrillation. We report a case of idiopathic paroxysmal atrial fibrillation triggered by abnormal electrical activity in a single pulmonary vein. Mapping was performed during sinus rhythm with a 4F decapolar catheter (Spiral Supreme, Daig, St. Jude Medical) positioned near the ostium by a transseptal approach. Pulmonary vein potentials were only identified in the left superior pulmonary vein. Segmental ostial ablation (30 W) performed during left atrial pacing resulted in complete cesation of conduction in the pulmonary vein. There were no complications. The clinical response (suppression of the paroxysms of atrial fibrillation in a 9-month follow-up) observed in this patient imply that atrial fibrillation was triggered by this pulmonary vein. This case report illustrates several aspects of catheter-based ablation of pulmonary vein foci for the treatment of paroxysmal atrial fibrillation and demonstrates its efficacy.