Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico.

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.

Rickettsial Disease Outbreak, Mexico, 2022.

Beginning in 2022, Nuevo Leon, Mexico, experienced an outbreak of rickettsioses that is still ongoing despite multidisciplinary control efforts. A total of 57 cases have been confirmed, particularly affecting children. We report a high mortality rate among hospitalized persons in Nuevo Leon. Continuing efforts are required to control the outbreak.

Perinucleolar Compartment (PNC) Prevalence as an Independent Prognostic Factor in Pediatric Ewing Sarcoma: A Multi-Institutional Study.

The perinucleolar compartment (PNC) is a small nuclear body that plays important role in tumorigenesis. PNC prevalence correlates with poor prognosis and cancer metastasis. Its expression in pediatric Ewing sarcoma (EWS) has not previously been documented. In this study, we analyzed 40 EWS tumor cases from Caucasian and Hispanic patients for PNC prevalence by immunohistochemical detection of polypyrimidine tract binding protein and correlated the prevalence with dysregulated microRNA profiles. EWS cases showed staining ranging from 0 to 100%, which were categorized as diffuse (≥77%, n = 9, high PNC) or not diffuse (<77%, n = 31) for low PNC. High PNC prevalence was significantly higher in Hispanic patients from the US (n = 6, p = 0.017) and in patients who relapsed with metastatic disease (n = 4; p = 0.011). High PNC was associated with significantly shorter disease-free survival and early recurrence compared to those with low PNC. Using NanoString digital profiling, high PNC tumors revealed upregulation of eight and downregulation of 18 microRNAs. Of these, miR-320d and miR-29c-3p had the most significant differential expression in tumors with high PNC. In conclusion, this is the first study that demonstrates the presence of PNC in EWS, reflecting its utility as a predictive biomarker associated with tumor metastasis, specific microRNA profile, Hispanic ethnic origin, and poor prognosis.

Diagnostic Images of the Ocular Fundus Using a Low-Cost Portable Endoscope in Premature Patients at Risk of Developing Retinopathy of Prematurity.

The purpose of this article is to describe how fundus images are obtained using a low-cost device: the "Visual Ear Wax Cleaner Tool" portable endoscope (Soonhua Inc., China) connected to a smartphone, after installation of free applications ("Inskam" and "CameraFI") using the smartphone screen as a monitor and after medication mydriasis, local anesthesia, and blepharostat placement. With this endoscope, video recording and fundus imaging are easily performed, for the case of patients at the risk of developing retinopathy of prematurity (ROP), facilitating timely screening in order to start treatment in patients who require it. This fundus imaging technique shares certain similarities with the RetCam® (Clarity, Pleasaton California) system, which performs real-time fundus imaging providing the ability to record and document findings and capture images from the video footage, with high quality and definition, although with a smaller angle of vision. The capture of images using a smartphone allows storing and sharing the images. These are devices which are generally accessible and portable and which use simplified energy sources, requiring very simple training. The low-cost, easy-to-learn technique and quick sharing of images through communication networks make this a tool to be considered for the practice of telemedicine.

Import and Export of Misfolded α-Synuclein.

In Parkinson's disease, intracellular α-synuclein (α-syn) inclusions form in neurons and are referred to as Lewy bodies. These aggregates spread through the brain following a specific pattern leading to the hypothesis that neuron-to-neuron transfer is critical for the propagation of Lewy body pathology. Here we review recent studies employing pre-formed fibrils generated from recombinant α-syn to evaluate the uptake, trafficking, and release of α-syn fibrils. We outline methods of internalization as well as cell surface receptors that have been described in the literature as regulating α-syn fibril uptake. Pharmacological and genetic studies indicate endocytosis is the primary method of α-syn internalization. Once α-syn fibrils have crossed the plasma membrane they are typically trafficked through the endo-lysosomal system with autophagy acting as the dominant method of α-syn clearance. Interestingly, both chaperone-mediated autophagy and macroautophagy have been implicated in the degradation of α-syn, although it remains unclear which system is chiefly responsible for the removal of α-syn fibrils. The major hallmark of α-syn spreading is the templating of misfolded properties onto healthy protein resulting in a conformational change; we summarize the evidence indicating misfolded α-syn can seed endogenous α-syn to form new aggregates. Finally, recent studies demonstrate that cells release misfolded and aggregated α-syn and that these processes may involve different chaperones. Nonetheless, the exact mechanism for the release of fibrillar α-syn remains unclear. This review highlights what is known, and what requires further clarification, regarding each step of α-syn transmission.

Rab7A regulates tau secretion.

The axonal microtubule-associated protein TAU, involved in Alzheimer's disease (AD), can be found in the extracellular space where it could be taken up by neurons, an event that is believed to contribute to the propagation of tau pathology in the brain. Since the small GTPase Rab7A is involved in the trafficking of endosomes, autophagosomes, and lysosomes, and RAB7A gene expression and protein levels are up-regulated in AD patients, we tested the hypothesis that Rab7A was involved in tau secretion. We previously reported that both primary cortical neurons and HeLa cells over-expressing human TAU can release tau. Using these two cellular systems, we demonstrated that Rab7A regulates tau secretion. Upon Rab7A deletion, tau secretion was decreased. Consistent with this, the over-expression of a dominant negative and a constitutively active form of Rab7A decreased and increased tau secretion, respectively. A partial co-localization of tau and Rab7-positive structures in both neurons and HeLa cells indicated that a late endosomal compartment could be involved in its secretion. Collectively, the present data indicate that Rab7A regulates tau secretion and therefore the up-regulation of RAB7A reported in AD, could contribute to the extracellular accumulation of pathological TAU species that could result in the propagation of tau pathology in the AD brain.

Enfoque fenomenológico del cuidado humano en estudiantes de enfermería

El cuidado humano, es un proceso reflexivo, afectivo y efectivo, mediante el intercambio de experiencias y conocimientos, a través de una aproximación respetuosa y significativa. Este estudio tuvo como objetivo generar una teoría acerca del cuidado humano como valor fundamental en la formación, derivada de los significados que le asignan estudiantes de la carrera de enfermería de la Universidad de Carabobo, Venezuela. La investigación es de naturaleza cualitativa, bajo el enfoque fenomenológico, utilizando el método de Spiegelberg para el análisis de la información. Como técnica de recolección de información se usó la entrevista a profundidad. Seleccionándose a 12 estudiantes de primero a quinto año de la carrera de enfermería. Los agentes externos participantes fueron cinco docentes de la escuela de enfermería y enfermeras asistenciales, siendo la validación de la información a través de la triangulación de la información obtenida de los sujetos participantes. Resultados: Emergieron cinco categorías: Percibiendo el cuidado humano, Interpretando el significado del cuidado humano, recorriendo la tipología de los valores, interpretando las creencias del cuidado humano y comprendiendo los sentimientos durante la acción del cuidado humano. Como conclusión, emergió la teoría como producto final de la interpretación de los relatos de los sujetos en el estudio y en la cual se señala que la educación en enfermería en la actualidad conduce a la búsqueda de crear un modelo educativo más humanístico y crítico reflexivo, así como considerar al estudiante un ser integral en todas sus dimensiones, haciendo el proceso enseñanza aprendizaje más significativo y creativo.

Phenomenological view of human care in nursing Human care is a reflective, affective and effective process, by sharing experiences and knowledge in a respectful and meaningful way. The aim of this study was to generate a theory about human care as a fundamental value in the educational process, derived from the meanings assigned to it by students of nursing at the University of Carabobo, Venezuela. The is a qualitative research, under a phenomenological approach, using the Spiegelberg method for information analysis. In-depth interviews were done for data collection. 12 students were selected from the first to the fifth year of nursing studies. External participants were five Nursing School teachers and assisstant nurses. Validation of information was done through triangulation of information obtained from participating subjects. Results: Perceiving human care, interpreting the meaning of human care, touring the typology of values, interpreting beliefs on human care, and understanding feelings during the act of human care. As a conclusion, a theory emerged as the final product of interpreting the stories of the studied subjects, which states that presently nursing education aims at creating a more humanistic, critical and reflexive model, as well as viewing the students as comprehensive beings in all their dimensions, thus making the teaching-learning process a more significant and creative one.

Significado de envejecer para profesionales de enfermería en los escenarios de su práctica / Meaning of aging for professional nursing practice scenarios

El envejecimiento es un proceso natural de cambios biológicos, psicoafectivos, sociales y culturales, el cual se inicia con el nacimiento y continua a lo largo de la vida. Este estudio tuvo como objetivo, interpretar el significado de envejecer para el profesional de enfermería en los escenarios de su práctica. Utilizamos la metodología cualitativa con un abordaje fenomenológico hermenéutico. El método para el análisis de datos fue el de Spiegelberg. Los sujetos del estudio fueron cuatro profesionales de enfermería de tres hospitales públicos y tres informantes externos. Seleccionados de manera intencional. Utilizando la entrevista en profundidad para recoger los datos. Obteniendo como resultados cuatro categorías: Interpretando el proceso de envejecimiento humano, vivenciando el cuidado humano del adulto mayor, comprendiendo los sentimientos y emociones del profesional de enfermería e identificando la tipología de los valores de la experiencia cuidadora. Como conclusión, emergió un producto final de la interpretación de los relatos de los sujetos en el estudio, surgiendo la teoría. Los cambios significativos que afectan a los adultos mayores que afrontan las transiciones y perciben pérdidas de identidad y pérdidas en apoyo social se sienten desarraigadas, vulnerables, en desequilibrio e incertidumbre por sus vidas tanto en el presente como en el futuro y hace visualizar en el profesional de enfermería el envejecimiento como una enfermedad y no como un proceso natural.

Aging is a natural process of biological, psycho, social and cultural changes, which begins at birth and continues throughout life. This study aimed to interpret the meaning of aging for professional nursing practice scenarios. Qualitative methodology was used with a hermeneutic phenomenological approach. The method of data analysis was Spiegelberg. The subjects were four professional nurses in three public hospitals and three external informants. Selected intentionally. Using in-depth interviews to collect data. Data analysis showed four categories: Interpreting the human aging process, experiencing human care of the elderly, the feelings and emotions of the nurse in understanding and identifying the type of the values of the caregiver experience. In conclusion emerged a final product of the interpretation of the stories of the subjects in the study, emerging theory. Significant changes affecting older adults facing transitions and perceived loss of identity and loss of social support feel uprooted, vulnerable, imbalance and uncertainty in their lives both in the present and in the future and makes viewing in professional nursing aging as a disease and not as a natural process.

Template-directed synthesis of a small molecule-antisense conjugate targeting an mRNA structure.

The targeting of structural features in mRNA with specificity remains a great chemical challenge. A hairpin structure near exon 10 in the pre-mRNA encoding the tau protein controls its splicing, and dementia-causing mutations that disrupt this structure increase exon 10 splicing. We previously reported the discovery of small molecules, mitoxantrone (MTX) and analogs, which bind to the tau RNA hairpin structure and the design of bipartite antisense oligonucleotides (ASOs) that simultaneously bind to the discontinuous sequences that flank this hairpin. Herein we report the synthesis of a bipartite ASO conjugated to MTX using the tau RNA hairpin and flanking sequences as a template. A set of six MTX analogs, each containing a linker-azide, and a set of ten bipartite ASOs, each containing a branched linker-alkyne, were synthesized and tested in combinatorial fashion for their ability to conjugate in the presence or absence of template RNA. A single template-dependent MTX-ASO conjugate was identified from among the 60 reaction mixtures, demonstrating that the MTX and ASO precursors could simultaneously bind the RNA template and allow proper positioning of azide and alkyne for 1,3-cycloaddition. While the MTX-ASO conjugate proved too cytotoxic for cell-based assays, the conjugate inhibited tau exon 10 splicing under cell-free conditions more effectively than MTX or bipartite ASO alone.

On the performance of trimetazidine and vitamin e as pharmacoprotection agents in cyclosporin a-induced toxicity.

The immunosuppressant drug cyclosporin A (CyA) has been used in diseases with immunological basis and in transplant patients. Nephrotoxicity and hepatotoxicity are the main adverse effects of this drug. To find a protective drug against those effects we assayed the cardioprotector Trimetazidine (TMZ) and vitamin E, used as nutritional supplements to alleviate oxidative stress. Six groups of eight male Wistar rats each were prepared (groups A-F): A, control; B, vitamin E (10 mg/Kg/day); C, TMZ (20 mg/Kg/day); D, 25 mg/Kg/day CyA; E, CyA and vitamin E (25 mg/Kg/day CyA + 10 mg/Kg/day Vit E); F, TMZ for 20 days (20 mg/kg/day); and then CyA (25 mg/kg/day) and TMZ (20 mg/Kg/day). The experiment lasted 120 days. The exposure of rats to CyA promoted nephrotoxicity and hepatotoxicity with an increase in serum urea, creatinine, and glutamate dehydrogenase (GLDH). Structural and ultrastructural studies of liver and kidney were performed. Group D showed adverse effects induced by CyA since statistically significant differences were found with respect to the control group (A). Vitamin E (E) showed no protective effect. Pretreatment with TMZ (F) attenuated the adverse effects of CyA. We conclude that CyA-induced nephrotoxicity and hepatotoxicity are attenuated by the cytoprotective effect of TMZ. TMZ inhibits the reabsorption and, consequently, the accumulation of CyA in the cell. The antioxidant capacity of vitamin E did not improve the effect of CyA.

Targeting a pre-mRNA structure with bipartite antisense molecules modulates tau alternative splicing.

Approximately 15% of human genetic diseases are estimated to involve dysregulation of alternative pre-mRNA splicing. Antisense molecules designed to alter these and other splicing events typically target continuous linear sequences of the message. Here, we show that a structural feature in a pre-mRNA can be targeted by bipartite antisense molecules designed to hybridize with the discontinuous elements that flank the structure and thereby alter splicing. We targeted a hairpin structure at the boundary between exon 10 and intron 10 of the pre-mRNA of tau. Mutations in this region that are associated with certain forms of frontotemporal dementia, destabilize the hairpin to cause increased inclusion of exon 10. Via electrophoretic mobility shift and RNase protection assays, we demonstrate that bipartite antisense molecules designed to simultaneously interact with the available sequences that immediately flank the tau pre-mRNA hairpin do indeed bind to this structured region. Moreover, these agents inhibit exon 10 splicing and reverse the effect of destabilizing disease-causing mutations, in both in vitro splicing assays and cell culture. This general bipartite antisense strategy could be employed to modulate other splicing events that are regulated by RNA secondary structure.

Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1.

Kinesin light chain 1 (KLC1) binds to the intracellular cytoplasmic domain of the type-1 membrane-spanning protein calsyntenin-1 (also known as alcadein-α) to mediate transport of a subset of vesicles. Here, we identify serine 460 in KLC1 (KLC1ser460) as a phosphorylation site and show that mutation of KLC1ser460 influences the binding of KLC1 to calsyntenin-1. Mutation of KLC1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residue, to mimic permanent phosphorylation, reduced the binding. Mutation of KLC1ser460 did not affect the interaction of KLC1 with four other known binding partners: huntingtin-associated protein 1 isoform A (HAP1A), collapsin response mediator protein-2 (CRMP2), c-Jun N-terminal kinase-interacting protein-1 (JIP1) and kinase-D-interacting substrate of 220 kDa (Kidins220). KLC1ser460 is a predicted mitogen-activated protein kinase (MAPK) target site, and we show that extracellular-signal-regulated kinase (ERK) phosphorylates this residue in vitro. We also demonstrate that inhibition of ERK promotes binding of calsyntenin-1 to KLC1. Finally, we show that expression of the KLC1ser460 mutant proteins influences calsyntenin-1 distribution and transport in cultured cells. Thus, phosphorylation of KLC1ser460 represents a mechanism for selectively regulating the binding and trafficking of calsyntenin-1.

An X11alpha/FSBP complex represses transcription of the GSK3beta gene promoter.

X11alpha is a neuronal adaptor protein that interacts with the amyloid precursor protein (APP) through a centrally located phosphotyrosine binding domain to inhibit the production of Abeta peptide that is deposited in Alzheimer's disease brains. X11alpha also contains two C-terminal postsynaptic density-95, large discs, zona occludens 1 (PDZ) domains, and we show here that through its PDZ domains, X11alpha interacts with a novel transcription factor, fibrinogen silencer binding protein. Moreover, we show that an X11alpha/fibrinogen silencer binding protein complex signals to the nucleus to repress glycogen synthase kinase-3beta promoter activity. Glycogen synthase kinase-3beta is a favoured candidate kinase for phosphorylating tau in Alzheimer's disease. Our findings show a new function for X11alpha that may impact on Alzheimer's disease pathogenesis.

Attenuation of gentamicin-induced nephrotoxicity: trimetazidine versus N-acetyl cysteine.

Gentamicin (G) is a highly nephrotoxic aminoglucoside. It was used to experimentally induce nephrotoxicity in male Wistar rats. To find a drug capable of protecting the nephron we assayed a cardioprotector (trimetazidine, TMZ) and a hepatoprotector (N-acetyl cysteine, NAC). The rats were divided into six groups (n = 8): (A) control without drugs; (B) treated with 50 mg kg(-1) per day (i.p.) of G for 7 days; (C) diet supplemented with 20 mg kg(-1) per day of TMZ for 7 days; (D) treated with 10 mg kg(-1) per day (i.p.) of NAC for 7 days; (E) pretreated for 7 days with 20 mg kg(-1) per day of TMZ and during the following 7 days with G + TMZ; (F) pretreated for 7 days with 10 mg kg(-1) per day (i.p.) of NAC and during the following 7 days with G + NAC. Urea and creatinine as well as the excretion of urinary gamma-glutamyl transpeptidase (GGT(u)) and urinary N-acetyl-glucosaminidase (NAG(u)) were determined and structural and ultrastructural studies were carried out. Group B was used as a G-induced nephrotoxicity control. Pretreatment with TMZ (E) showed a protector effect against induced nephrotoxicity, with no biochemical or functional changes nor alterations in histoarchitecture or ultrastructure. Pretreatment with NAC (F) showed no protector effect against G-induced nephrotoxicity since no statistically significant differences were found with respect to the control group with G. We conclude that G-induced nephrotoxicity is attenuated by the cytoprotective effect of TMZ. We may infer that TMZ inhibits the reabsorption and consequently the accumulation of G in the proximal tubule cell.

Efecto de trimetazidina en la nefrotoxicidad por gentamicina / Trimetazidine effect on nephrotoxicity by gentamicyn

La Trimetazidina (TMZ) es una droga utilizada como cardioprotector, ya que previene la muerte celular secundaria a la isquemia miocárdica. Algunos investigadores le atribuyeron efecto reno-protector, actividad antioxidante y scavenger de radicales libres del oxígeno. El objetivo del presente trabajo es mostrar el efecto citoprotector de TMZ en las alteraciones inducidas por Gentamicina (G) a nivel de la célula del túbulo renal. Se diseñaron esquemas en animales de experimentación tratados con ambas drogas. Ratas macho Wistar de 180 a 200 g de peso fueron distribuidas en 5 grupos (n=8) y tratadas con: dieta estándar (A); suplementada con 20 mg/Kg/día de TMZ durante 27 días (B); suplementada con 50 mg/Kg/día de G durante 7 días(C); pretratadas 20 días con 20 mg/Kg/día de TMZ y los últimos 7 días con G (D) y tratadas simultáneamente durante 7 días con 20 mg/Kg/día de TMZ y 50 mg/Kg/día de G(E). Se midieron los compuestos nitrogenados urea y creatinina, la excreción de gamma glutamiltranspeptidasa urinaria y se efectuaron estudios estructurales con tinción de hematoxilina-eosina y ultraestructurales. Se utilizó el grupo C como testigo de nefrotoxicidad inducida por G. El pretratamiento durante 20 días con TMZ demostró el efecto protector para la nefrotoxicidad inducida, sin cambios bioquímicos-funcionales, ni alteración de la histoarquitectura, ni de la ultraestructura. El tratamiento simultáneo con TMZ y G no mostró efecto protector. Se concluye que en el modelo de ratas macho Wistar se demuestra el efecto citoprotector de TMZ en tratamiento previo por 21 días. El estudio histológico del tejido renal, bajo estas condiciones, presenta histoarquitectura conservada y función renal normal. Se infiere que el efecto citoprotector de TMZ que impide la nefrotoxicidad inducida por G se debe a la inhibición de la reabsorción y acumulación de Gentamicina en la célula del túbulo proximal del nefrón.

Trimetazidine (TMZ) is a drug used as a cardioprotector since it prevents cell death secondary to myocardial ischemia. Some investigators have attributed protective effect, antioxidant activity and oxygen free radical scavenging abilityt to TMZ. The aim of the present work is to show the cytoprotective effect of TMZ on Gentamicin (G)-induced alterations at the level of the renal tubular cell. Schemes were designed in experimental animals treated with both drugs. Male Wistar rats weighing 200 to 260 g were divided into 5 groups (n=8) and treated with: standard diet (A); standard diet supplemented with 20 mg/Kg/day of TMZ for 27 days (B); standard diet supplemented with 50 mg/Kg/day of G for 7 days (C), pretreated for 20 days with 20 mg/Kg/day of TMZ and for the last 7 days with G (D), and treated simultaneously for 7 days with 20 mg/Kg/day of TMZ and 50 mg/Kg/day of G (E). The nitrogen compounds urea and creatinine were measured and so was the excretion of urinary gamma-glutamyl transpeptidase. Structural studies with hematoxilin and eosin staining and ultrastructural studies were also performed. Gentamicin was used as a control for nephrotoxicity (group C). Pretreatment with TMZ showed a protective effect against induced nephrotoxicity, with no biochemical changes or alterations in the histoarchitecture. Simultaneous treatment with TMZ and G (group E) showed no protective effect. Conclusions: the cytoprotective effect of TMZ on G-induced nephrotoxicity would take place at the level of the proximal tubular cell of the brush border by inhibiting G reabsorption and accumulation.

Caracterización del cáncer de piel facial: Pinar del Río, 2007 / Characterization of the facial skin cancer: Pinar del Rio, 2007

Se realizó un estudio descriptivo, transversal a todos los pacientes que acudieron a una consulta provincial de Maxilofacial del Hospital Clínico Quirúrgico Abel Santamaría a los que se les diagnosticó cáncer de piel facial, con el objetivo de caracterizar esta patología en nuestro medio en el año 2007, motivados por su alta frecuencia. Se le aplicó una encuesta a cada paciente, previo consentimiento informado y que cumplieron los criterios de inclusión. Los datos se plasmaron en un formulario y procesaron utilizando el sistema Epinfo 2002 y el método estadístico porcentual. Todos los resultados fueron expresados en cuadros y posteriormente analizados según los conocimientos previos de los autores y la información científica consultada. Predominó el carcinoma basal y de este la forma clínica nóduloulcerada. Los más afectados fueron los hombres de más de 55 años, con fototipo II, residentes en zonas rurales, de ocupación campesinos, la región de la cara que prevaleció fue la nasal y un alto porciento de los pacientes presentaron queratosis actínicas. La mayoría de los pacientes tuvieron antecedentes patológicos personales y/o familiares de cáncer de piel y el medio de protección más usado por nuestros pacientes fue el sombrero. Concluimos que el cáncer de piel facial más frecuente en nuestro medio fue el carcinoma basal y que su incidencia se relacionó con variables como la edad, sexo, fototipo, zona de residencia, ocupación, fotoprotección, presencia de lesiones premalignas en piel y antecedentes familiares y personales positivos de cáncer cutáneo...(AU)

A descriptive cross sectional study was performed in all patients attending to the provincial dental surgeon office in Abel Santamaría Cuadrado General hospital, they were diagnosed as facial skin malignancy in order to characterize this disease in our enviroment in 2007 being motivated by its high frequency.A survey was applied to every patient having the informed consent previously and meeting the criteria for inclusion.Data were recorded in a form and processed with Epinfo 2002 system and the percentage statistical method was used. All the results were shown in pictures and were analyzed later taking into account the previous author´s knowledge and the scientific information predominating the basal carcinomas being the clinical ulcer nodule the most frequent. 55 year-old peasants were the most affected showing phototype II and coming from rural areas . The nasal aspect was predominating as well as a high percent of actinic keratosis in patiens, most of them presented personal y/or family pathological backgrounds of skin malignancy and the hat was the most used protection . It is concluded that the basal carcinoma was the most frequent facial skin malignancy in our enviroment and its incidence was related to the following variables: age, sex, phototype, living area , occupation, photoprotection,skin premalignant lesions and positive family and personal skin malignancy...(AU)

Caracterización del cáncer de piel facial. Pinar del Río. 2007 / Characterization of the facial skin cancer .Pinar del Rio. 2007

Se realizó un estudio descriptivo, transversal a todos los pacientes que acudieron a una consulta provincial de Maxilofacial del Hospital Clínico Quirúrgico Abel Santamaría a los que se les diagnosticó cáncer de piel facial, con el objetivo de caracterizar esta patología en nuestro medio en el año 2007, motivados por su alta frecuencia. Se le aplicó una encuesta a cada paciente, previo consentimiento informado y que cumplieron los criterios de inclusión. Los datos se plasmaron en un formulario y procesaron utilizando el sistema Epinfo 2002 y el método estadístico porcentual. Todos los resultados fueron expresados en cuadros y posteriormente analizados según los conocimientos previos de los autores y la información científica consultada. Predominó el carcinoma basal y de este la forma clínica nóduloulcerada. Los más afectados fueron los hombres de más de 55 años, con fototipo II, residentes en zonas rurales, de ocupación campesinos, la región de la cara que prevaleció fue la nasal y un alto porciento de los pacientes presentaron queratosis actínicas. La mayoría de los pacientes tuvieron antecedentes patológicos personales y/o familiares de cáncer de piel y el medio de protección más usado por nuestros pacientes fue el sombrero. Concluimos que el cáncer de piel facial más frecuente en nuestro medio fue el carcinoma basal y que su incidencia se relacionó con variables como la edad, sexo, fototipo, zona de residencia, ocupación, fotoprotección, presencia de lesiones premalignas en piel y antecedentes familiares y personales positivos de cáncer cutáneo.

A descriptive cross - sectional study was performed in all patients attending to the provincial dental surgeon office in Abel Santamaría Cuadrado General hospital, they were diagnosed as facial skin malignancy in order to characterize this disease in our enviroment in 2007 being motivated by its high frequency. A survey was applied to every patient having the informed consent previously and meeting the criteria for inclusion.Data were recorded in a form and processed with Epinfo 2002 system and the percentage statistical method was used. All the results were shown in pictures and were analyzed later taking into account the previous author´s knowledge and the scientific information predominating the basal carcinomas being the clinical ulcer nodule the most frequent. 55 year-old peasants were the most affected showing phototype II and coming from rural areas. The nasal aspect was predominating as well as a high percent of actinic keratosis in patiens, most of them presented personal y/or family pathological backgrounds of skin malignancy and the hat was the most used protection. It is concluded that the basal carcinoma was the most frequent facial skin malignancy in our enviroment and its incidence was related to the following variables: age, sex, phototype, living area, occupation, photoprotection,skin premalignant lesions and positive family and personal skin malignancy.

Hedgehog signaling is a principal inducer of Myosin-II-driven cell ingression in Drosophila epithelia.

Cell constriction promotes epithelial sheet invagination during embryogenesis across phyla. However, how this cell response is linked to global patterning information during organogenesis remains unclear. To address this issue, we have used the Drosophila eye and studied the formation of the morphogenetic furrow (MF), which is characterized by cells undergoing a synchronous apical constriction and apicobasal contraction. We show that this cell response relies on microtubules and F-actin enrichment within the apical domain of the constricting cell as well as on the activation of nonmuscle myosin. In the MF, Hedgehog (Hh) signaling is required to promote cell constriction downstream of cubitus interruptus (ci), and, in this context, Ci155 functions redundantly with mad, the main effector of dpp/BMP signaling. Furthermore, ectopically activating Hh signaling in fly epithelia reveals a direct relationship between the duration of exposure to this signaling pathway, the accumulation of activated Myosin II, and the degree of tissue invagination.

Cambios en el sistema de defensa antioxidante inducido por Ciclosporina A / Changes in the antioxidant defence system induced by Cyclosporin A

La Ciclosporina A (CyA) es un inmunosupresor que presenta efectos adversos como la hepatotoxicidad. Se estudió el efecto de CyA sobre el sistema de defensa antioxidante (SDA), su relación con la lipoperoxidación y la función hepática. Ratas machos wistar de 200-260 g de peso fueron tratadas durante 7 días (agudo) y 120 días (crónico) con dosis orales de CyA de 5 y 20 mg/kg/ día. Se estudió el SDA midiendo el contenido hepático total de glutatión (GSH), glutatión peroxidasa (GPx) y catalasa (CAT); el perfil de funcionamiento hepático (PFH) se realizó determinando aspartato aminotransferasa (AST), alanín aminotransferasa (ALT) y bilirrubina total (Bt) y para la lipoperoxidación se midieron las sustancias reactivas al ácido tiobarbitúrico (SRAT). Los resultados fueron confirmados con estudios histológicos. El tratamiento agudo con 20 mg/kg/día de CyA mostró aumento significativo de SRAT (30,51±1,97 nmol/g), pérdida de GSH (2,47±0,06 µmol/g), incremento significativo de GPx (663,25±1,88 mU/mg) y CAT (290,65±3,31 mU/mg). El tratamiento crónico con 5 mg/kg/día de CyA mostró disminución tiempo-dependiente del SDA con disminución de GSH (3,19±0,05 µmol/g), GPx (569,6±2,67 mU/mg) y CAT (223,3±2,78 mU/mg), sin cambios en SRAT. Los resultados del tratamiento crónico y agudo con 20 mg/kg/día de CyA son coincidentes y sólo en esta dosis se observaron alteraciones de la histo-arquitectura del parénquima hepático. Se concluye que dosis de 20 mg/kg/día de CyA en tratamiento agudo y crónico provocan lipoperoxidación con compromiso del SDA y alteración del hepatocito; dosis de 5 mg/kg/día de CyA en tratamiento crónico producen deterioro reversible del SDA sin lipoperoxidación. La inmunosupresión aplicada en clínica con dosis de 3 a 8 mg/kg/día produciría disminución del SDA sin cambios en la histo-arquitectura del parénquima hepático.

Cyclosporin A (CyA), an immunosuppressive agent, exerts adverse effects such as hepatotoxicity. The effect of CyA on the Antioxidant Defence System(ADS), its relation to lipoperoxidation, and liver function were studied. Assays were performed on male wistar rats weighing 200-260 g during acute (7 days) and chronic (120 days) treatment with oral doses of CyA of 5 and 20 mg/kg/day. ADS was studied in rat liver homogenate by measuring the liver content of total glutathion (GSH), glutathion peroxidase(GPx) and catalase (CAT); the Liver Profile Test (LPT) was measured by determining aspartate amino transferase (AST), alanin amino transferase (ALT) and total bilirubin (TB), and lipoperoxidation by determining thiobarbituric acid reactive substances (TRAS). The results were confirmed by histological studies. In the acute treatment, 20 mg/kg/day with CyA, a significant increase in TRAS (30.51±1.97 nmol/g), a loss of GSH (2.47±0.06 µmol/g) and a significant increase in GPx (663.25±1.88 mU/mg) and CAT (290.65±3.31 mU/mg) were observed. In the chronic treatment, 5 mg/kg/day with CyA, a time-dependent decrease in the ADS with a diminution in GSH (3.19±0.05 µmol/g), GPx (569.6±2.67 mU/mg) and CAT (223.3±2.78 mU/mg) were observed, with no changes in TRAS. The results for the chronic and acute treatment with 20 mg/kg/day of CyA are coincident, only this dose causing alterations in liver parenchyma histoarchitecture. CyA doses of 20 mg/kg/day during acute and chronic treatment cause lipoperoxidation with ADS involvement and hepatocyte alteration. CyA doses of 5 mg/kg/day during chronic treatment cause deterioration in the ADS with no lipoperoxidation, hepatotoxicity being reversible. Immunosuppression in human patients with 3 to 8 mg/kg/day doses, would cause a decrease in the ADS with no structural or functional changes in the hepatocyte.

Hepatotoxic effect of cyclosporin A in the mitochondrial respiratory chain.

UNLABELLED: Cyclosporin A (CyA), a potent immunosuppressant, was used to determine the hepatotoxic effect in long-term treatments. Male Wistar rats were used in these experiments. They were given CyA chronically at doses used in patients for 120 days, and at doses of 5, 10, 15 and 20 mg kg(-1) day(-1). These doses amount to CyA values in blood of 200 +/- 24, 314 +/- 40, 445 +/- 33 and 598 +/- 53 ng ml(-1), respectively. A significant increase in glutamate dehydrogenase (GLDH) was found in the groups treated with 15 and 20 mg kg(-1) day(-1), which would point to mitochondria as the potential target of the toxic action of CyA. The mitochondrial respiratory chain of rat livers was studied in enzyme complexes I and II. Enzyme complex I was determined by spectrophotometry at 340 nm using NADH oxidase with the respirable substrate 10 mm NADH; enzyme complex II was determined by monitoring succinate dehydrogenase by oxymetry using the respirable substrate 10 mm succinate. The results show the inhibition of NADH oxidase in the groups treated with 10, 15 and 20 mg kg(-1) day(-1), an effect dependent both on time and on CyA concentration. Enzyme complex II showed a decrease in oxygen consumption. These findings were confirmed by histological studies (hematoxylin-eosin technique). CONCLUSIONS: Long-term treatment with CyA at doses of 15 and 20 mg kg(-1) day(-1), amounting to concentrations in blood of 445 +/- 33 and 598 +/- 53 ng ml(-1), causes alterations in the mitochondria, revealed by the increase in serum GLDH and by the functional alteration of enzyme complexes I and II of the mitochondrial respiratory chain.