Mortality Prognosis Factors in Patients with Active Cancer Under Treatment, and Severe COVID-19.

BACKGROUND: COVID-19 is associated with systemic inflammation. This inflammatory response is further deregulated by oncological treatments increasing mortality in this population. However, there is conflicting information regarding the clinical factors that increase mortality in patients with severe COVID-19. OBJECTIVE: The aim of this study was to identify prognostic factors associated with mortality during severe COVID-19 in patients with active cancer. In addition, the correlation between oncologic codes and mortality related to severe COVID-19 was evaluated. PATIENTS AND METHODS: We analyzed a cohort of Mexican patients with active cancer and severe COVID-19 between March 2020 and February 2021. We collected information on patient demographic characteristics, COVID-19 symptoms, clinical and laboratory data, and treatments. Patients were classified according to oncologic code. We defined the oncological code based on clinical stage, treatment intention, performance status before COVID-19, and median overall survival with palliative treatment. A log-rank test was performed to determine survival. A multivariate logistic regression model was used to adjust for potential confounders. RESULTS: One hundred fifty-two patients with severe COVID-19 were analyzed. The red oncologic code was associated with an increased risk of mortality OR 22.8 (CI 95% 5.0-105.1, p <0.001), low oxygen saturation OR 5.4 (CI 95% 1.7-17.4, p = 0.005), chronic corticosteriod use OR 4.3 (CI 95% 1.0-18.1, p = 0.050) and high D-dimer level OR 3.2 (CI 95% 1.2-8.2, p = 0.019). CONCLUSIONS: The survival of patients with active cancer and severe COVID-19 was possible to identify, at the time of admission, specific oncological characteristics. Based on this code, decreased oxygen saturation, increased D-dimer levels, and chronic corticosteroid use were the main predictive factors related to mortality.

The Prognostic Significance of HALP Index for Colon Cancer Patients in a Hispanic-Based Population.

Background: Survival and recurrence rates following locoregional colon cancer surgical resection are highly variable. Currently used tools to assess patient risk are still imperfect. In the present work, we evaluate, for the first time, the prognostic value of the recently developed HALP (hemoglobin, albumin, lymphocyte, and platelet) index in Hispanic colon cancer patients. Patients and Methods. We conducted a retrospective cohort study in Mexican patients with a nonmetastatic colon cancer diagnosis who underwent surgical resection. We determined the preoperative HALP score optimal cut-off value by using the X-tile software. We plotted survival curves using the Kaplan-Meier method and performed a multivariate Cox regression analysis to explore the association of preoperative HALP score with two primary endpoints: overall survival (OS) and disease-free survival (DFS). Results: We included 640 patients (49.8% female). The optimal HALP cut-off value was 15.0. A low HALP index was statistically significantly associated with a higher TNM stage. Low HALP score was statistically significantly associated with shorter median OS in the Kaplan-Meier analysis (73.5 vs. 84.8 months) and in the multivariate Cox regression analysis (HR = 1.942, 95% CI = 1.647-2.875). There was no significant association between the HALP score and DFS. Conclusions: Our findings show that the HALP index is an independent factor associated with survival in Hispanic patients, despite recurrence. It seems to reflect both the anatomical extent of the disease and traditionally unaccounted nutritional and inflammatory factors that are significant for prognosis.

Diagnóstico de la organización de la personalidad: una actualización teórico-empírica de la propuesta de Otto F. Kernberg / Diagnosis of personality organization: a theoretical empirical update of Otto F. Kernberg's proposal

Resumen El diagnostico estructural propuesto por el Dr. Otto F. Kernberg y su equipo de trabajo del Instituto de Trastornos de Personalidad en Nueva York ha sido una gran contribución tanto para la comprensión de la personalidad como para el tratamiento de estos casos. El objetivo del presente artículo es realizar una revisión actualizada de este enfoque, abordando una comprensión general de la personalidad, y posteriormente profundizar en el diagnóstico diferencial de la organización neurótica y limítrofe. Además, dentro del espectro limítrofe se distinguirá aquellos cuadros de funcionamiento alto, medio, y bajo, considerando su grado de severidad, y pronostico. Finalmente, se hará una síntesis del proceso de evaluación que consiste en la entrevista estructural.

Personality Organization Diagnosis, proposed by Dr. Otto F. Kernberg and his team from the Personality Disorder Institute in New York, has been an important contribution to the understanding and treatment of personality disorders. The aim of this article is to make an updated review of this approach, addressing a general understanding of what is personality, and subsequently deepening the differential diagnosis of the neurotic and borderline personality organization. Furthermore, within de borderline spectrum, those high, medium, and low functioning will be distinguished, considering its severity and prognosis. Finally, a synthesis of the personality assessment process will be carried put, which consist of the Structural Interview

Microstructural and physicochemical analysis of collagen in intramuscular pin bones of Bocachico fish (Prochilodus sp.) / Análise microestrutural e físico químico do colágeno presente em espinhos intramusculares do peixe Bocachico (Prochilodus sp.) / Análisis microestructural y fisicoquímico del colágeno presente en espinas intramusculares del pescado Bocachico (Prochilodus sp.)

Background: the presence of intramuscular pin bones hinders the production and commercialization of fish fillet products; however, application of physical processes, such as thermal treatments, offers alternatives for the degradation of said bones. Objective: the present study aimed to conduct a microstructural and physicochemical analysis of Bocachico intramuscular pin bones subjected to a thermal treatment. Methods: collagen extracted from intramuscular pin bones of Bocachico fillets was analyzed using SDS-polyacrylamide gel electrophoresis and viscosity. Pin bones were subjected to 1.5, 2, and 3 minutes heating time and analyzed using electron microscopy and cutting force. Results: intramuscular pin bones contain type I collagen. Threeminute thermal treatment degraded collagen components present in the internal pin bone structure, coinciding with the lowest values of the cutting force test. Conclusions: according to our results, collagen degradation initiates in the internal structure of intramuscular pin bones and moves towards the external layer which does not show the effects of thermal treatment.

Antecedentes: la presencia de espinas intramusculares en filetes de peces impide la obtención y posterior comercialización de estos productos, motivo por el cual la aplicación de procesos físicos antes del tratamiento térmico podría ser una alternativa en la degradación de estas espinas. Objetivo: el alcance del presente estudio fue realizar análisis fisicoquímico y microestructural de espinas intramusculares de Bocachico sometidas a proceso térmico. Métodos: las espinas intramusculares de filetes de Bocachico fueron analizadas a través de electroforesis en gel de SDS-poliacrilamida (SDS-PAGE), temperatura de desnaturalización del colágeno, microscopia electrónica de trasmisión y fuerza de corte. Fueron utilizados tres tiempos de duración del tratamiento térmico (1,5, 2 y 3 min). Resultados: el colágeno presente en espinas intramusculares es tipo l. El tratamiento térmico durante tres minutos degrada los componentes del colágeno en las estructuras internas de la espina, coincidiendo con los valores menores para la prueba de fuerza de corte. Conclusiones: los resultados permiten concluir que la degradación del colágeno es iniciada desde el interior de la estructura de la espina intramuscular hacia la capa externa, sin que esta capa muestre efecto del tratamiento térmico.

Antecedentes: a presença de espinhos intramusculares impede a obtenção de filetes de peixe e posterior comercialização destes produtos, razão pela qual a aplicação de processos físicos antes do tratamento térmico pode ser uma alternativa na degradação desses espinhos. Objetivo: realizar analise físico-químico e microestrutural em espinhos intramusculares do peixe Bocachico submetidos a processo térmico. Métodos: os espinhos intramusculares de filetes do Bocachico foram analisados por eletroforese em gel de SDSpoliacrilamida (SDS-PAGE), temperatura de desnaturação do colágeno, microscopia electrónica de transmissão e força de corte. Foram utilizados três tempos de duração do tratamento térmico (1,5, 2 e 3 min). Resultados: o colágeno presente em espinhos intramusculares é do tipo l. O tratamento térmico por três minutos degrada os componentes do colágeno nas estruturas internas do espinho, coincidindo com os menores valores para o teste de resistência ao corte. Conclusões: os resultados mostram que a degradação do colágeno é iniciado desde o interior do espinho intramuscular até a capa externa, sem que essa capa externa seja afetada pelo tratamento térmico.

Deterioro cognitivo, demencia y estado funcional de residentes en un hogar de ancianos: estudio descriptivo de corte transversal con abordaje cuantitativo / Cognitive impairment, dementia and functional status of nursing home residents: cross-sectional study with a quantitative approach

Introducción: la demencia constituye una de las enfermedades con mayor repercusión en la salud individual y familiar, constituyendo un fuerte factor predictivo de institucionalización. Objetivo: determinar los pacientes con deterioro cognitivo y demencia residentes en un hogar de ancianos, así como describir variables biológicas de estos. Métodos: se realizó un estudio descriptivo, correlacional de corte transversal y abordaje cuantitativo en 61 adultos mayores masculinos para determinar la presencia del deterioro cognitivo (DC), demencia, nivel funcional y comorbilidad. La información se obtuvo de las historias clínicas individuales. Resultados: en 35 residentes se encontró DC. La edad media de los pacientes con DC fue de 79,4 (+/-9,81) años frente a un 78,6 (+/-9,79) en los casos sin DC. Fueron diagnosticados 25 ancianos con enfermedad de Alzheimer, 4 con demencia vascular, 3 como frontotemporal y en 1 una demencia por cuerpos de Lewy; dos de los pacientes con deterioro cognitivo no cumplieron criterios de algún tipo de demencia. Existió asociación entre el grado de deterioro cognitivo y el nivel funcional de los pacientes (x2= 25,76; p=0,0001), con una correlación negativa media entre la respuesta al MMSE y al FAQ (Spearman=-0,726; p=0,000). La hipertensión arterial fue la enfermedad crónica no transmisible más frecuente en los residentes y los pacientes con DC presentaron un Índice de Comorbilidad de Charlson superior al grupo sin DC (z=-2,434; p=0,015). Conclusiones: los ancianos con deterioro cognitivo identificados por el estudio tienen una edad media, deterioro funcional y comorbilidad mayor que los pacientes sin deterioro cognitivo. Entre los adultos mayores con trastornos cognitivos predomina la demencia Alzheimer.

Introduction. Dementia is one of the diseases with the greatest impact on the individual and family health, constituting a strong predictor of institutionalization. Objective. To identify cognitive impairment and dementia in residents of a nursing home and to describe these biological variables. Methods. A descriptive, correlational and cross-sectional quantitative approach in 61 elderly male residents was conducted to determine the presence of cognitive impairment (CI), dementia, comorbidities and functional status. Information was obtained from medical records. Results. 35 residents had CI. Mean age of patients with CI was 79.4 (+/- 9.81) years vs. 78.6 (+/- 9.79) in patients without CI. 25 residents were diagnosed with Alzheimer's disease, 4 had vascular dementia, 3 had frontotemporal dementia and 1 resident had Lewy bodies dementia. 2 patients with cognitive impairment did not meet any dementia criteria. Significant association between the degree of cognitive impairment and functional status of patients was found (x2 = 25.76, P = 0.0001), with a mean negative correlation between the response to MMSE and FAQ (Spearman = -0.726, P = 0.000). Hypertension was the most commonly found non communicable disease in residents and patients with CI had a Charlson Comorbidity Index greater than those without CI (z = -2.434, P = 0.015). Conclusions. Mean age, functional impairment, and comorbidities were greater in residents with CI as compared to residents without CI. Among older adults with cognitive impairment, Alzheimer’s was the predominant dementia.

Leptin and fasting regulate rat gastric glucose-regulated protein 58.

The stomach secretes a wide range of peptides with essential metabolic functions, and thereby plays an important role in the regulation of energy homeostasis. Disulfide isomerase glucose-regulated protein 58 (GRp58) is a molecular chaperone member of the endoplasmic reticulum (ER) stress signaling pathway, which is a marker for human gastric cancer. Since GRp58 seems to be regulated by a phosphorylation/dephosphorylation pattern shift, we used the 2DE gel methodology and peptide mass fingerprinting-protein identification by means of MALDI-TOF mass spectrometry. We show that gastric mucosa GRp58 is dephosphorylated by fasting, and this effect is blunted when fasted rats are treated with leptin. Furthermore, we assessed the gene expression of GRp58 under different physiological settings known to be associated with energy homeostasis (fasting, leptin treatment and leptin deficiency). We found that intraperitoneal administration of leptin increases whereas leptin deficiency decreases GRp58 mRNA levels. However, GRp58 expression remains unchanged after fasting, indicating that leptin actions on GRp58 are no direct sensitivity to fasting. Dissection of the molecular pathways mediating the interactions between ER stress-related factors and nutrient availability, as well as their target genes, may open a new avenue for the study of obesity and other metabolic disorders.

El polimetilmetacrilato en la reconstrucción craneofacial / The polymethylmethacrylate in the craniofacial repair

La reconstrucción de defectos craneofaciales constituye un reto para el cirujano maxilofacial. Si bien existe una amplia gama de materiales para la reconstrucción, cada cual tiene ventajas y desventajas además de indicaciones para su utilización. Por lo que nos hemos dado a la tarea de emplear el polimetilmetacrilato como una opción económica y efectiva en la reconstrucción de defectos craneofaciales. Con este objetivo se realizó un estudio descriptivo, retrospectivo, no comparativo, en el Servicio de Cirugía Maxilofacial del Hospital Universitario Miguel Enríquez en el periodo comprendido desde enero de 2006 a diciembre de 2008. Se incluyeron un total de 14 pacientes, los cuales recibieron tratamiento quirúrgico para la reconstrucción craneofacial mediante el empleo del polimetilmetacrilato. El mayor número de pacientes que recibieron tratamiento quirúrgico para la reconstrucción craneofacial con polimetilmetacrilato se encontró en el grupo de 16 a 25 años de edad, con un predominio del sexo masculino y mayor afectación de los pacientes de color de piel blanca. En todos los casos estudiados la etiología de la deformidad fue traumática; dentro de ellos el mayor por ciento le correspondió a los accidentes viales, seguido de los causados por violencia. El diagnóstico que predominó fue el de las fracturas orbitomalares de grado IV. El piso de órbita fue la localización o estructura más reconstruida. Se presentaron únicamente como complicaciones, la infección y la colección subcutánea. El polimetilmetacrilato es un material económico y efectivo que permite obtener excelentes resultados estéticos y funcionales en la reconstrucción de defectos craneofaciales adquiridos(AU)

The repair of craniofacial defects is a challenge for the maxillofacial surgeon. There are a great range of materials for reconstruction, where each has advantages and disadvantages as well as indications for its use. Polymethylmethacrylate is an economic and effective option in the reconstruction of craniofacial defects. The objective of present paper is to conduct a non-comparative, retrospective and descriptive study in the Maxillofacial Surgery Service of the Miguel Enriquez University Hospital from January, 2006 to December, 2008 including a total of 14 patients operated on to repair a craniofacial defect using polymethylmethacrylate. The great number of patients operated on to repair a craniofacial defect using polymethylmethacrylate included the 16-25 age groups. There was predominance of male sex and a great involvement in white patients. In all the study cases the deformity origin was of traumatic origin; where the traffic accidents were the more prevalent ones, followed by those caused by violence. The predominant diagnosis was that of the IV grade orbitomalar fractures being the orbital floor the more repaired structure. The only complications present were the infection and the subcutaneous collection. The polymethylmethacrylate is an economic and effective material allowing obtaining of excellent esthetic and functional results in the repair of acquired craniofacial defects(AU)

Differential regulation of hepatic apoptotic pathways by dietary olive and sunflower oils in the aging rat.

In this work we have studied how dietary fat affects aging-related changes in a number of factors that regulate rat hepatic apoptosis. Animals were fed lifelong with two experimental diets containing either virgin olive oil or sunflower oil as dietary fat. Caspases of the intrinsic and extrinsic pathways of apoptosis, Bcl-2 and Bax polypeptide levels, and plasma membrane neutral sphingomyelinase activity were determined at 6, 12, and 24 months of age. Caspase-8/10 activity (a marker of the extrinsic pathway) was not affected by either aging or dietary fat, but activities of both caspase-9 (a marker of the intrinsic pathway) and caspase-3 (an executioner caspase) were significantly depressed in liver from animals fed on a sunflower oil-based diet. These decreases were not observed in animals fed with a diet based on virgin olive oil, which also resulted in significantly lower Bcl-2/Bax ratios. On the other hand, in comparison with sunflower, dietary olive oil decreased oxidative stress in liver from aged rats, resulting in lower levels of membrane hydroperoxides and higher coenzyme Q levels in plasma membrane. Plasma membrane Mg(2+)-dependent neutral sphingomyelinase was strongly activated in aged rats fed on the sunflower oil diet, but no aging-related increase was observed in animals fed on the olive oil diet. Our results support that dietary oil can alter significantly the susceptibility of hepatocytes to different apoptotic stimuli by altering both pro- and anti-apoptotic mediators, which reinforces the importance of the diet in aging studies. Because virgin olive oil may increase susceptibility of hepatocytes to apoptosis induced through the intrinsic pathway under conditions of decreased oxidative stress, our results may have important implications to understand the potential beneficial effects of that edible oil against liver carcinogenesis during aging.

Artrocentesis: evaluación clinico-terapeutica en las disfunciones temporo-mandibulares / Arthrocentesis: clinical and therapeutical evaluation in temporomandibular disfunctions

Se realizó un estudio de casos descriptivo-prospectivos, en 34 pacientes elegidos al azar, diagnósticados de disfunciones dolorosas temporo-mandibulares con desplazamientos discales en grados variables, con el objetivo de evaluar clínicamente la eficacia de la artrocentesis temporo- mandibular. Cada paciente se sometió a terapia con férulas miorelajantes 15 días antes y 3 semanas después del proceder terapéutico. El lavado articular se efectuó con jeringa a presión, con 200 ml de solución de lactato ringer, difenhidramina y betametasona. Se realizó medición de Máxima Apertura Bucal (MAO), excursión protusiva, y laterotrusiva, grado de deflexión, y síntoma dolor por escala VAS (pretratamiento y postratamiento) y se evaluó la eficacia del proceder. Se encontró que a las 72 horas postratamiento, la MAO alcanzó cifras promedio de 37mm, la excursión protusiva promedio 8mm y la laterotrusiva 9 mm. El 86por ciento de los proce-deres resultaron exitosos a las 72 horas y a los 6 meses, 95 por ciento

Proteomic analysis of acute myeloid leukemia: Identification of potential early biomarkers and therapeutic targets.

The main goal of this study was to analyze, using proteomic techniques, changes in protein expression of acute myeloid leukemia (AML) cells that could give insights into a better early prognosis for tumor pathophysiology. Proteomic analysis of different subtypes of AML cells was carried out using 2-DE and MALDI-TOF PMF analysis. Proteins identified as more significantly altered between the different AMLs belonged to the group of suppressor genes, metabolic enzymes, antioxidants, structural proteins and signal transduction mediators. Among them, seven identified proteins were found significantly altered in almost all the AML blast cells analyzed in relation to normal mononuclear blood cells: alpha-enolase, RhoGDI2, annexin A10, catalase, peroxiredoxin 2, tromomyosin 3, and lipocortin 1 (annexin 1). These differentially expressed proteins are known to play important roles in cellular functions such as glycolysis, tumor suppression, apoptosis, angiogenesis and metastasis, and they might contribute to the adverse evolution of the disease. Proteomic analysis has identified for the first time novel proteins that may either help to form a differential prognosis or be used as markers for disease outcome, thus providing potential new targets for rational pathogenesis-based therapies of AML.

Dicoumarol relieves serum withdrawal-induced G0/1 blockade in HL-60 cells through a superoxide-dependent mechanism.

This work was set to study how dicoumarol affects the cell cycle in human myeloid leukemia HL-60 cells. Cells were accumulated in G0/1 after serum deprivation. However, when cells were treated with 5 microM dicoumarol in serum-free medium, a significant increment in the number of cells in S-phase was observed. Inhibition of G0/1 blockade was confirmed by the increase of thymidine incorporation, the phosphorylation of retinoblastoma protein, and the promotion of cell growth in long-term treatments in the absence of serum. Dicoumarol treatment increased superoxide levels, but did not affect peroxide. Increase of cellular superoxide was essential for inhibition of G0/1 blockade, since scavenging this reactive species with a cell-permeable form of SOD and the SOD mimetics 2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine (ambroxol, 100 microM) and copper[II]diisopropyl salicylate (CuDIPS, 10 microM) completely abolished the effect of dicoumarol. However, N-acetyl-cysteine, overexpression of Bcl-2 or a cell-permeable form of catalase were not effective. 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenol)methyl]-indole-4,7-dione (ES936), a mechanism-based irreversible inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1), did not promote S phase entry, and dicoumarol still inhibited G0/1 blockade in the presence of ES936. We demonstrate that dicoumarol inhibits the normal blockade in G0/1 in HL-60 cells through a mechanism involving superoxide, but this effect is not dependent solely on the inhibition of the NQO1 catalytic activity. Our results send a precautionary message about use of dicoumarol to elucidate cellular processes involving oxidoreductases.

Coenzyme Q and the regulation of intracellular steady-state levels of superoxide in HL-60 cells.

The present work was set to study how CoQ concentrations affected steady-state levels of superoxide in a cellular model of partial CoQ(10) deficiency in cultured human myeloid leukemia HL-60 cells. Culturing HL-60 cells in the presence of p-aminobenzoate, a competitive inhibitor of polyprenyl-4-hydroxybenzoate transferase (Coq2p), produced a significant decrease of CoQ(10) levels without affecting cell viability. Concomitant decreases in CoQ-dependent electron transport activity and mitochondrial membrane potential were observed under these conditions. Intracellular superoxide was significantly elevated in cells treated with p-aminobenzoate, both under serum-containing and serum-free conditions, and this effect was reversed by exogenous CoQ(10). A slight increase of superoxide was also observed in CoQ(10)-supplemented cells in the absence of serum. Our results support a requirement for CoQ(10) to control superoxide levels in HL-60 cells. The importance of extramitochondrial sources of superoxide in cells with impaired CoQ(10) biosynthesis is discussed.

Antioxidant response induced by serum withdrawal protects HL-60 cells against inhibition of NAD(P)H:quinone oxidoreductase 1.

We have previously shown that inhibition of NAD(P)H:quinone acceptor oxidoreductase 1 with dicoumarol decreases growth and viability of HL-60 cells in the absence of serum. Here we demonstrate that culturing HL-60 cells in serum-free medium in the presence of dicoumarol results in a significant potentiation of apoptosis. However, when cells were preincubated for 24 h without serum before they were treated with dicoumarol, the effect of the inhibitor on cell growth and death was much lower. We have investigated cellular changes induced in HL-60 cells by removal of serum that could account for protection against the effects of dicoumarol. Serum removal induced significant increases of NAD(P)H:quinone acceptor oxidoreductase 1, particularly at 32 h after serum withdrawal. Total amounts of ubiquinone in cells were unchanged but, its reduction state paralleled the observed increase in quinone reductase activity. Levels of the antiapoptotic protein Bcl-2 were also significantly increased after serum removal. Our results indicate that removal of serum evokes an antioxidant protective response that make HL-60 cells less sensitive to cell death induced by inhibition of NAD(P)H:quinone acceptor oxidoreductase 1 with dicoumarol.

Hydrogen peroxide- and cell-density-regulated expression of NADH-cytochrome b5 reductase in HeLa cells.

Environmental conditions regulate the expression of different antioxidant enzymes in cell culture. We have studied the effect of cell density and hydrogen peroxide on the expression of NADH-cytochrome b5 reductase in HeLa cells. Polypeptide levels of the NADH-cytochrome b5 reductase increased about three fold in confluent HeLa cells compared to sparse cells. Addition of H2O2 to HeLa cells altered expression levels of the NADH-cytochrome b5 reducatase in a concentration-dependent way, being sparse cells more sensitive to H2O2 addition than confluent cells. The presence of pyruvate, a H2O2 scavenger, produced a significant increment (200%) in the levels of NADH-cytochrome b5 reductase in sparse cells, but less increase (25%) in confluent cells, suggesting that generation of endogenous H2O2 could repress NADH-cytochrome b5 reductase expression, particularly in sparse cultures. Accordingly, confluent HeLa cells showed significantly lower levels of reactive oxygen species than cells in sparse cultures. Addition of tert-butylhydroquinone, a compound which generates reactive oxygen species through redox cycling, also reduced expression of the NADH-cytochrome b5 reductase. Increments in several antioxidant enzymes taking place during confluency could participate in the increase of NADH-cytochrome b5 reductase expression by reducing reactive oxygen species levels in cells. Overall, our results support that acute oxidative stress caused by H2O2 inhibits the expression levels of NADH-cytochrome b5 reductase, most likely due to inhibition of SP1 transcriptional activity. On the other hand, adaptation to H2O2 involved increased expression of the cytochrome b5 reductase, supporting the existence of additional regulatory mechanisms.