[Natural history of mucopolysaccharidosis type III in a series of Colombian patients]. / Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.

INTRODUCTION: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. CASE REPORTS: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. CONCLUSIONS: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.

TITLE: Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.Introducción. La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos. Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones. La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.

CAR-T Cell Therapy: From the Shop to Cancer Therapy.

Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we describe the limitations and areas of opportunity for this immunotherapy and the current challenges of treating hematological and solid cancer using CAR-T technology as well as its constraints and engineering approaches. We summarize other immune cells that have been using CAR technology, such as natural killer (NK), macrophages (M), and dendritic cells (DC). We conclude that CAR-T cells have the potential to treat not only cancer but other chronic diseases.

Temporalidad y factores de riesgo asociados al desarrollo de un infarto cerebral en pacientes con disección de arterias cervicales / Temporality and factors associated with the development of a cerebral infarction in patients with cervical artery dissection

INTRODUCCIÓN: Las disecciones de arterias cervicales (DAC) son la primera causa de accidente cerebrovascular isquémico (ACVi) en personas jóvenes. Los factores asociados (FA) de ACVi y la relación temporal con la DAC no están bien caracterizados. Tampoco disponemos de una clasificación clínico-radio-lógica que permita conocer el riesgo de ACVi. OBJETIVO: Describir frecuencia y FA y temporalidad de los ACVi en pacientes con DAC. MÉTODOS: Estudio prospectivo de pacientes mayores de 18 años hospitalizados por una DAC carotidea y/o vertebral entre agosto de 2009 y junio de 2017. Las DAC se diagnosticaron clínico-radiológicamente y los ACVi con imagen con infarto. Se utilizo la Clasificación de Borgess para caracterizar radiológicamente las DAC. Se utilizaron análisis de regresión logística uni y multivariable para evaluar las características clínico-radiológicas y los FA. RESULTADOS: 163 pacientes con 182 DAC (60% vertebrales y 40% carotídeas). 73 pacientes (44,8%) tuvieron un ACVi 28 de 68 pacientes (41,2%) tuvieron simultáneamente síntomas de disección y de isquemia. 60 de 68 pacientes (88%) presentan síntomas de isquemia durante la primera semana. FR significativamente asociados a ACVi: Borgess tipo IB (p = 0,001; OR: 4,1; IC: 1,8-9,3), sexo masculino (p < 0,001; OR: 0,2; IC: 0,06-0,8) y anticonceptivos orales (p = 0,02; OR: 0,2; IC: 0,06-0,8). CONCLUSIÓN: Ocurre aproximadamente en la mitad de los pacientes, en su mayoría dentro de la primera semana, no es la forma habitual de presentación inicial y no se relaciona con el tipo de arteria disecada. El principal FA para desarrollar un ACVi fue la oclusión arterial (Borgess tipo IB).

INTRODUCTION: Cervical artery dissections (CAD) are the leading cause of ischemic stroke (CVA) in young people. The risk factors for stroke and the temporal relationship with CAD are not well characterized. Nor do we have a clinical-radiological classification that allows knowing the risk of stroke. OBJECTIVE: To describe the associated factors and temporality of ACVi in patients with CAD. METHODS: We performed a prospective study that included patients over 18 years of age, hospitalized for carotid and/or vertebral CAD between August 2009 and June 2017. CAD cases were diagnosed clinically and radiologically; ACVi was diagnosed when the imaging study demonstrated infarction. The Borgess Classification was used to characterize the CAD radiologically. For correlation studies, we used univariate and multivariate logistic regression analyses. RESULTS: We analyzed 163 patients with 182 CAD (60% vertebral and 40% carotid). 28 of 68 patients (41.2%) simultaneously had symptoms of dissection and ischemia. 60 of 68 patients (88%) presented symptoms of ischemia during the first week. CAD: Borgess type IB (p = 0.001; OR: 4.1; CI: 1.8-9.3), male (p < 0.001; OR: 0.2; CI: 0.06- 0.8) were significantly associated with ischemic strokes and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8). CONCLUSION: Stroke associated with CAD has a relatively low frequency. It is not related to the type of dissected artery. It mainly occurs not simultaneously with CAD and within the first week. The main associated factor for developing a stroke is arterial occlusion (Borgess type IB).1,8-9,3), male sex (p < 0.001; OR: 0.2; CI: 0.06-0.8) and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8).

p16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC. METHODS: Tumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry. RESULTS: Of the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05). CONCLUSION: Our results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC.

[Temporality and factors associated with the development of a cerebral infarction in patients with cervical artery dissection]. / Temporalidad y factores de riesgo asociados al desarrollo de un infarto cerebral en pacientes con disección de arterias cervicales.

INTRODUCTION: Cervical artery dissections (CAD) are the leading cause of ischemic stroke (CVA) in young people. The risk factors for stroke and the temporal relationship with CAD are not well characterized. Nor do we have a clinical-radiological classification that allows knowing the risk of stroke. OBJECTIVE: To describe the associated factors and temporality of ACVi in patients with CAD. METHODS: We performed a prospective study that included patients over 18 years of age, hospitalized for carotid and/or vertebral CAD between August 2009 and June 2017. CAD cases were diagnosed clinically and radiologically; ACVi was diagnosed when the imaging study demonstrated infarction. The Borgess Classification was used to characterize the CAD radiologically. For correlation studies, we used univariate and multivariate logistic regression analyses. RESULTS: We analyzed 163 patients with 182 CAD (60% vertebral and 40% carotid). 28 of 68 patients (41.2%) simultaneously had symptoms of dissection and ischemia. 60 of 68 patients (88%) presented symptoms of ischemia during the first week. CAD: Borgess type IB (p = 0.001; OR: 4.1; CI: 1.8-9.3), male (p < 0.001; OR: 0.2; CI: 0.06- 0.8) were significantly associated with ischemic strokes and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8). CONCLUSION: Stroke associated with CAD has a relatively low frequency. It is not related to the type of dissected artery. It mainly occurs not simultaneously with CAD and within the first week. The main associated factor for developing a stroke is arterial occlusion (Borgess type IB).1,8-9,3), male sex (p < 0.001; OR: 0.2; CI: 0.06-0.8) and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8).

Molecular epidemiology and drug resistance of Mycobacterium tuberculosis in a tertiary care hospital in northeastern Mexico.

INTRODUCTION: Tuberculosis (TB) is a re-emerging disease considered a public health concern. In the present study, we analyzed the epidemiology and drug resistance of Mycobacterium tuberculosis strains isolated from patients with pulmonary TB. METHODOLOGY: Mycobacterium tuberculosis isolates (n = 190) were obtained from patients with pulmonary TB admitted to Dr. José Eleuterio González University Hospital (UH). Each M. tuberculosis isolate was analyzed by spoligotyping (spacer oligonucleotide typing) and MIRU-VNTR (Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeat). Drug resistance was evaluated using the Anyplex™ II MTB/MDR/XDR assay. RESULTS: The predominant spoligotypes observed were X1 (SIT 119, n = 46), T1 (SIT 53, n = 40), H3 (SIT 50, n = 13), Beijing (SIT 1, n = 11), and EAI2-Manila (SIT 19, n = 8). MIRU-VNTR analysis showed that the locus QUB-26 had the highest allelic variability. The observed drug resistance included monoresistance to rifampicin (2.6%; n = 5), isoniazid (3.2%; n = 6), and fluoroquinolones (1.6%; n = 3) as well as multidrug resistance (5.3%; n = 10). All of the Beijing strains were susceptible. Regarding comorbidities, 13.7% (26/190) of the patients were co-infected with TB and HIV (TB+HIV+), and 31.6% (55/190) had TB along with diabetes (TB + diabetes). CONCLUSIONS: The most prevalent lineages were X1 (SIT 119; 24.3%) and T1 (SIT 53; 21%). An alarming proportion (12.6%) of M. tuberculosis isolates presented drug resistance. To effectively manage TB, continuous surveillance of regional strain dissemination, drug resistance profiles, and TB-associated comorbidities is crucial.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Síndrome de la boca ardiente: revisión de la literatura / Burning mouth syndrome: literature review

Resumen El síndrome de la boca ardiente (SBA) es una condición de dolor crónico en la cavidad oral, que se presenta mayoritariamente en mujeres de edad media. Diversas causas locales y sistémicas pueden producirlo en forma secundaria, o bien, puede representar un cuadro primario, sin etiología específica identificable. Su etiopatogenia y evolución clínica es poco comprendida. Las opciones terapéuticas son variadas y en general es necesario un tratamiento multidisciplinario. A continuación, se presenta una revisión de la literatura respecto a esta patología para difusión en nuestro medio.

Abstract Burning mouth syndrome (BMS) is a chronic pain condition of the oral cavity, which occurs more frequently in middle-aged women. It can be secondary to different local and systemic causes, or represent a primary condition, with no specific identifiable etiology. Its etiopathogenesis and clinical evolution are poorly understood. Therapeutic options are multiple and a multidisciplinary treatment is necessary. We present a review of the literature regarding BMS, to provide information relevant to our area of expertise.

Electroencefalograma cuantitativo en la predicción precoz de la isquemia cerebral tardía en hemorragia subaracnoidea aneurismática: reporte de un caso / Quantitative electroencephalogram for prediction of delayed ischemia in subarachnoid haemorrhage: report of one case

Subarachnoid hemorrhage (SAH) is a devastating disease, with a mortality rate of 35%. Among patients who survive the initial bleeding, the leading cause of morbidity and mortality is delayed cerebral ischemia (DCI). Electroencephalography (EEG) can detect cerebral ischemia in the early stages. We report a 66-year-old female patient who consulted for ictal headache and impaired consciousness. On admission, she was confused, dysarthric, and with meningeal signs. Brain angio-CT showed SAH FISHER IV and an aneurysm of the left posterior cerebral artery. After excluding the aneurysm (by coiling), the patient recovered the altered consciousness. Continuous EEG monitoring was initiated. On the sixth day of follow up, she had a transient headache and apathy. The brain MRI showed low cerebral blood flow in the left frontotemporal area, without ischemic lesions. On the seventh day, she presented expression aphasia and right facial-brachial paresis. Angiography confirmed severe vasospasm in M1 and M2 segments bilaterally. Pharmacological angioplasty with nimodipine was performed, with an excellent radiological response, although not clinical. A second MRI was carried out on the eighth day, which showed a left insular infarction and generalized vasospasm. A second therapeutic angiography was performed; the patient persisted with aphasia and left central facial paresis. The quantitative EEG analysis performed retrospectively showed a generalized reduction in the spectral edge frequency 95 (SEF95; meaning slowing in the EEG signal) at the fourth day of follow up, three days earlier than the clinical and imaging diagnosis of DCI was established.

[Quantitative electroencephalogram for prediction of delayed ischemia in subarachnoid haemorrhage. Report of one case]. / Electroencefalograma cuantitativo en la predicción precoz de la isquemia cerebral tardía en hemorragia subaracnoidea aneurismática.Reporte de un caso.

Subarachnoid hemorrhage (SAH) is a devastating disease, with a mortality rate of 35%. Among patients who survive the initial bleeding, the leading cause of morbidity and mortality is delayed cerebral ischemia (DCI). Electroencephalography (EEG) can detect cerebral ischemia in the early stages. We report a 66-year-old female patient who consulted for ictal headache and impaired consciousness. On admission, she was confused, dysarthric, and with meningeal signs. Brain angio-CT showed SAH FISHER IV and an aneurysm of the left posterior cerebral artery. After excluding the aneurysm (by coiling), the patient recovered the altered consciousness. Continuous EEG monitoring was initiated. On the sixth day of follow up, she had a transient headache and apathy. The brain MRI showed low cerebral blood flow in the left frontotemporal area, without ischemic lesions. On the seventh day, she presented expression aphasia and right facial-brachial paresis. Angiography confirmed severe vasospasm in M1 and M2 segments bilaterally. Pharmacological angioplasty with nimodipine was performed, with an excellent radiological response, although not clinical. A second MRI was carried out on the eighth day, which showed a left insular infarction and generalized vasospasm. A second therapeutic angiography was performed; the patient persisted with aphasia and left central facial paresis. The quantitative EEG analysis performed retrospectively showed a generalized reduction in the spectral edge frequency 95 (SEF95; meaning slowing in the EEG signal) at the fourth day of follow up, three days earlier than the clinical and imaging diagnosis of DCI was established.

Malformaciones vasculares linfáticas de cabeza y cuello en pacientes pediátricos: revisión de la literatura

Resumen Los linfangiomas son malformaciones vasculares linfáticas de etiología no completamente precisada, que se manifiestan principalmente en edad pediátrica. Su localización más frecuente es en cabeza y cuello, donde pueden potencialmente generar compromiso de vía aérea. En el diagnóstico, la sospecha clínica juega un rol fundamental y debe ser considerado dentro del diagnóstico diferencial de masa cervical. Para el estudio resulta útil la ecografía como enfrentamiento inicial, y la resonancia magnética debiese ser de elección en estos casos. Actualmente, también es posible contar con diagnóstico antenatal debido a los avances imagenológicos en obstetricia. El manejo es controvertido y no existen protocolos terapéuticos mundialmente validados. Las opciones terapéuticas incluyen el manejo quirúrgico, la administración de agentes esclerosantes, terapia sistémica o una combinación de éstos. Debido a sus potenciales implicancias estéticas y funcionales en el área de cabeza y cuello, el otorrinolaringólogo debe estar familiarizado con esta patología, motivo por el cual presentamos este artículo de revisión.

Abstract Lymphangiomas are lymphatic vascular malformations of unclear etiology that generally manifest in pedriatic-age patients. The most frequent localization is in the head and neck, where they can potentially generate airway compromise. Clinical suspicion plays a fundamental role in its diagnosis, and should be considered in the differential diagnosis of pediatric head and neck masses. Imaginologic investigations include the use of ultrasound as an initial approach, with magnetic resonance imaging being the modality of choice. Currently, it is also possible to establish an antenatal diagnosis due to imaging advances in obstetrics. Treatment is challenging and there is still not a protocol that is universally accepted. Op- tions include surgery, sclerotherapy, systemic agents, or a combination of the above. Due to its potential esthetic and functional implications in the head and neck region, the otolaryn- gologist must be aware of this pathology, reason for which we present this review.

[Primary lymphocytic hypophysitis. Report of one case]. / Hipofisitis linfocitaria primaria. Caso clínico.

Primary lymphocytic hypophysitis is an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland, with a higher incidence during late pregnancy and the postpartum period. It causes glandular destruction, mass effect and symptoms such headache, visual field defects, ophthalmoplegia and symptoms of hypopituitarism. We report a 38-year-old postpartum woman who, after giving birth presented decreased left visual acuity associated with a non ictal headache. Magnetic resonance imaging demonstrated a sellar mass associated with decreased free thyroxine and cortisol levels. Suspecting a primary lymphocytic hypophysitis, she was treated with prednisone 60 mg/day and hormonal replacement therapy. One month later, size of the pituitary gland decreased, and the visual field defect improved. Steroidal treatment was maintained for 36 months and progressively tapered. After two years of follow-up, the imaging studies show a normal sized pituitary gland.

IMMUNEPOTENT CRP induces DAMPS release and ROS-dependent autophagosome formation in HeLa and MCF-7 cells.

BACKGROUND: IMMUNEPOTENT CRP (ICRP) can be cytotoxic to cancer cell lines. However, its widespread use in cancer patients has been limited by the absence of conclusive data on the molecular mechanism of its action. Here, we evaluated the mechanism of cell death induced by ICRP in HeLa and MCF-7 cells. METHODS: Cell death, cell cycle, mitochondrial membrane potential and ROS production were evaluated in HeLa and MCF-7 cell lines after ICRP treatment. Caspase-dependence and ROS-dependence were evaluated using QVD.oph and NAC pre-treatment in cell death analysis. DAMPs release, ER stress (eIF2-α phosphorylation) and autophagosome formation were analyzed as well. Additionally, the role of autophagosomes in cell death induced by ICRP was evaluated using SP-1 pre-treatment in cell death in HeLa and MCF-7 cells. RESULTS: ICRP induces cell death, reaching CC50 at 1.25 U/mL and 1.5 U/mL in HeLa and MCF-7 cells, respectively. Loss of mitochondrial membrane potential, ROS production and cell cycle arrest were observed after ICRP CC50 treatment in both cell lines, inducing the same mechanism, a type of cell death independent of caspases, relying on ROS production. Additionally, ICRP-induced cell death involves features of immunogenic cell death such as P-eIF2α and CRT exposure, as well as, ATP and HMGB1 release. Furthermore, ICRP induces ROS-dependent autophagosome formation that acts as a pro-survival mechanism. CONCLUSIONS: ICRP induces a non-apoptotic cell death that requires an oxidative stress to take place, involving mitochondrial damage, ROS-dependent autophagosome formation, ER stress and DAMPs' release. These data indicate that ICRP could work together with classic apoptotic inductors to attack cancer cells from different mechanisms, and that ICRP-induced cell death might activate an immune response against cancer cells.

Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines.

Immunotherapies strengthen the immune system to fight multiple diseases such as infections, immunodeficiencies, and autoimmune diseases, and recently, they are being used as an adjuvant in cancer treatment. IMMUNEPOTENT-CRP (I-CRP) is an immunotherapy made of bovine dialyzable leukocyte extract (bDLE) that has chemoprotective and immunomodulatory effects in different cellular populations of the immune system and antitumor activity in different cancer cell lines. Our recent results suggest that the antineoplastic effect of I-CRP is due to the characteristics of cancer cells. To confirm, we evaluated whether the selectivity is due to cell lineage or characteristics of cancer cells, testing cytotoxicity in T-acute lymphoblastic leukemia cells and their cell death mechanism. Here, we assessed the effect of I-CRP on cell viability and cell death. To determine the mechanism of cell death, we tested cell cycle, mitochondrial and nuclear alterations, and caspases and reactive oxygen species (ROS) and their role in cell death mechanism. Our results show that I-CRP does not affect cell viability in noncancer cells and induces selective cytotoxicity in a dose-dependent manner in leukemic cell lines. I-CRP also induces mitochondrial damage through proapoptotic and antiapoptotic protein modulation (Bax and Bcl-2) and ROS production, nuclear alterations including DNA damage (γ-H2Ax), overexpression of p53, cell cycle arrest, and DNA degradation. I-CRP induced ROS-dependent apoptosis in leukemic cells. Overall, here, we show that I-CRP cytotoxicity is selective to leukemic cells, inducing ROS-dependent apoptosis. This research opens the door to further exploration of their role in the immune system and the cell death mechanism that could potentially work in conjunction with other therapies including hematological malignances.

Reduction in CYP1A1 and 2B2 activity at low oxygen tension.

The Cytochrome P450 (CYP) enzyme family comprises a wide array of monooxygenases involved in the oxidation of endobiotic and xenobiotic molecules. The active site of a CYP enzyme contains an iron protoporphyrin center coordinated to a cysteine thiolate, and then, molecular oxygen is associated with the iron to be converted into dioxygen complex plus substrate. Reduction by CYP reductase expedites hydroxylation of the compound. In this oxidation reaction, insufficient oxygen molecules would affect enzyme catalysis. Nevertheless, biochemical data about CYP kinetics at low oxygen concentrations are not available. In this work, we present the results on the variation in rat liver microsomal CYP Vmax app and Km app under normal and hypoxic conditions. Using alkoxyresorufin molecules as substrates, the Vmax/Km ratios for resorufin production decreased from 426 to 393 for CYP1A1 and from 343 to 202 for CYP2B1 at a low oxygen concentration (4.1 ppm) compared to the ratios observed at a normal oxygen concentration (6.5 ppm). Additionally, the bacterial mutagenicity of 2-aminoanthracene and cyclophosphamide, decreased by 32% and 42%, respectively, at low oxygen concentrations. These results support the hypothesis that low oxygen availability is implicated in the low efficiency of substrate oxidation by CYP.

Physical inactivity and excessive sucrose consumption are associated with higher serum lipids in subjects with Taq1B CETP polymorphism.

BACKGROUND: Dyslipidaemias result from the interaction between genetic and environmental factors, including diet disequilibrium and physical inactivity. Among the genetic factors associated with serum lipids, the Taq1B CETP polymorphism has been investigated. The B1 allele has been considered as a risk factor for dyslipidaemia because of its association with greater CETP levels and higher serum triglycerides. The present study aimed to determine the role of the Taq1B polymorphism with lipid and anthropometric variables and its interaction with diet and physical activity. METHODS: In total, 215 subjects were enrolled in this cross-sectional study. Diet intake was evaluated using a 3-day food consumption record and physical activity was determined in accordance with World Health Organization recommendations. The Taq1B CETP polymorphism was determined by allelic discrimination. RESULTS: Subjects with the B1B2/B2B2 genotype, who had a sucrose consumption ≥5% of the total kcal day-1 , had higher levels of total cholesterol (TC) [165.55 (142.21-188.89) mg dL-1 versus 200.19 (184.79-215.60) mg dL-1 ; P for interaction = 0.034] and low-density lipoprotein [99.29 (75.52-123.05) mg dL-1 versus 128.64 (113.59-143.69) mg dL-1 ; P for interaction = 0.037] than subjects with the B1B1 genotype. Subjects who did not perform physical activity and had the B1B2/B2B2 genotype showed significantly higher levels of TC [177.48 (161.36-193.60) mg dL-1 versus 194.49 (185.43-203.56) mg mL-1 ; P for interaction = 0.033] than subjects with the B1B1 genotype. CONCLUSIONS: We provide evidence that subjects with inadequate environmental factors carriers of the polymorphic genotype had higher serum lipid levels than subjects with the B1B1 genotype.

Hipofisitis linfocitaria primaria. Caso clínico / Primary lymphocytic hypophysitis. Report of one case

Primary lymphocytic hypophysitis is an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland, with a higher incidence during late pregnancy and the postpartum period. It causes glandular destruction, mass effect and symptoms such headache, visual field defects, ophthalmoplegia and symptoms of hypopituitarism. We report a 38-year-old postpartum woman who, after giving birth presented decreased left visual acuity associated with a non ictal headache. Magnetic resonance imaging demonstrated a sellar mass associated with decreased free thyroxine and cortisol levels. Suspecting a primary lymphocytic hypophysitis, she was treated with prednisone 60 mg/day and hormonal replacement therapy. One month later, size of the pituitary gland decreased, and the visual field defect improved. Steroidal treatment was maintained for 36 months and progressively tapered. After two years of follow-up, the imaging studies show a normal sized pituitary gland.

Genetic and serologic surveillance of canine (CIV) and equine (EIV) influenza virus in Nuevo León State, México.

BACKGROUND: Despite the uncontrolled distribution of the Influenza A virus through wild birds, the detection of canine influenza virus and equine influenza virus in Mexico was absent until now. Recently, outbreaks of equine and canine influenza have been reported around the world; the virus spreads quickly among animals and there is potential for zoonotic transmission. METHODS: Amplification of the Influenza A virus matrix gene from necropsies, nasal and conjunctival swabs from trash service horses and pets/stray dogs was performed through RT-PCR. The seroprevalence was carried out through Sandwich enzyme-linked immunosorbent assay system using the M1 recombinant protein and polyclonal antibodies anti-M1. RESULTS: The matrix gene was amplified from 13 (19.11%) nasal swabs, two (2.94%) conjunctival swabs and five (7.35%) lung necropsies, giving a total of 20 (29.41%) positive samples in a pet dog population. A total of six (75%) positive samples of equine nasal swab were amplified. Sequence analysis showed 96-99% identity with sequences of Influenza A virus matrix gene present in H1N1, H1N2 and H3N2 subtypes. The phylogenetic analysis of the sequences revealed higher identity with matrix gene sequences detected from zoonotic isolates of subtype H1N1/2009. The detection of anti-M1 antibodies in stray dogs showed a prevalence of 123 (100%) of the sampled population, whereas in horses, 114 (92.68%) positivity was obtained. CONCLUSION: The results unveil the prevalence of Influenza A virus in the population of horses and dogs in the state of Nuevo Leon, which could indicate a possible outbreak of equine and Canine Influenza in Mexico. We suggest that the prevalence of Influenza virus in companion animals be monitored to investigate its epizootic and zoonotic potential, in addition to encouraging the regulation of vaccination in these animal species in order to improve their quality of life.

Ecmo pediátrico: una puesta al día / Pediatric ecmo up to date

Extracorporeal membrane oxygenation (ECMO) is an ever more available technique for reversible catastrophic heart or pulmonary failure that requires permanent training and actualization. This article reviews inclusion criteria, basic concepts, anticoagulation management, use of vasoactive drugs, respiratory support, laboratory tests and weaning. An up to date and easy to use reference material we hope will facilitate the study and implementation of ECMO in centers that are, or look to be, providers. The authors have made an exhaustive review of published literature and have also referenced the Extracorporeal Life Support Organization (ELSO) guidelines.

La oxigenación de membrana extracorpórea (ECMO) es una técnica indicada para falla cardiológica y/o pulmonar catastrófica de etiología recuperable, cada vez más disponible, lo que hace necesario que los prestadores de cuidados intensivos estén actualizados en esta técnica. Este artículo repasa conceptos, criterios de inclusión, manejo de anticoagulación, uso de drogas vasoactivas, apoyo ventilatorio, exámenes paraclínicos y destete de la asistencia. El tener una referencia actualizada, fácil y concreta facilita el estudio e implementación de ECMO en centros que van a disponer del mismo o que ya la están desarrollando. Los autores hicieron una revisión exhaustiva de la literatura publicada y de la normativa internacional disponible de la Organización del soporte de vida extracorpóreo (ELSO por su sigla en inglés Extracorporeal Life Support Organization).

[Emergency endovascular management of ischemic stroke. Experience in 104 patients]. / Experiencia en el tratamiento endovascular del accidente cerebrovascular isquémico agudo en un centro chileno.

BACKGROUND: Recently, five randomized controlled trials confirmed the efficacy and safety of endovascular treatment with or without intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. AIM: To report patients with ischemic stroke treated with endovascular methods. MATERIAL AND METHODS: Retrospective analysis of 104 patients aged 61 ± 15 years (54% males) with ischemic stroke who received endovascular treatment at a single medical center between 2009 and 2017. RESULTS: Sixty one percent were treated with intravenous thrombolysis plus endovascular procedures and 39% with endovascular procedures alone. The median door-to needle time was 61 minutes and door-to femoral puncture was 135 minutes. The median National Institute of Health Stroke Scale (NIHSS) scores on admission, 24 hours later and at discharge were 12,4 and 1 points, respectively. Middle cerebral artery was occluded in 60% of cases. Other frequent localizations where distal carotid artery in 17% and vertebro-basilar artery in 14%. Thrombolysis in cerebral infarction (TICI) scale flow score after the procedure was 3 or 2b in 58% of cases and significantly correlated with NIHSS scores at 24 hours and discharge. Fifty percent of patients had a mRankin score < = 1 and ten patients died (9.6%). Eight percent had a symptomatic intracerebral hemorrhage. CONCLUSIONS: The clinical improvement of these patients 24 hours after the procedure and at discharge demonstrate the effectiveness of endovascular treatment in ischemic stroke. The presence neurologists able to interpret multimodal images at the emergency room, the use of local guidelines, the availability of an experienced neuro-interventional team engaged with the workflow and the use of stent retrievers are strongly associated with good outcomes.