DEHP exposure impairs human skeletal muscle cell proliferation in primary culture conditions: preliminary study.

The plasticizer di (2-ethylhexyl) phthalate (DEHP) inhibits differentiation, impairs glucose metabolism, and decreases mitochondrial function in murine muscle satellite cells; however, if these effects are translated to human cells is unknown. The goal of this study was to evaluate changes in morphology and proliferation of primary human skeletal muscle cells exposed to DEHP. Rectus abdominis muscle samples were obtained from healthy women undergoing programed cesarean surgery. Skeletal muscle cells were isolated and grown under standard primary culture conditions, generating two independent sample groups of 25 subcultures each. Cells from the first group were exposed to 1 mM DEHP for 13 days and monitored for changes in cell morphology, satellite cell frequency and total cell abundance, while the second group remained untreated (control). Differences between treated and untreated groups were compared using generalized linear mixed models (GLMM). Cell membrane and nuclear envelope boundary alterations, loss of cell volume and presence of stress bodies were observed in DEHP-treated cultures. DEHP-treated cultures also showed a significant reduction in satellite cell frequency compared to controls. Exposure to DEHP reduced human skeletal muscle cell abundance. Statistical differences were found between the GLMM slopes, suggesting that exposure to DEHP reduced growth rate. These results suggest that exposure to DEHP inhibits human skeletal muscle cell proliferation, as evidenced by reduced cell abundance, potentially compromising long-term culture viability. Therefore, DEHP induces human skeletal muscle cell deterioration potentially inducing an inhibitory effect of myogenesis by depleting satellite cells.

Dolphin leukocytes exhibit an attenuated cytokine response and increase heme oxygenase activity upon exposure to lipopolysaccharides.

Cetaceans exhibit physiological adaptations that allowed the transition to aquatic life, including a robust antioxidant defense system that prevents injury from repeated exposure to ischemia/reperfusion events associated with breath-hold diving. The signaling cascades that characterize ischemic inflammation in humans are well characterized. In contrast, cetaceans' molecular and biochemical mechanisms that confer tolerance to inflammatory events are poorly understood. Heme oxygenase (HO) is a cytoprotective protein with anti-inflammatory properties. HO catalyzes the first step in the oxidative degradation of heme. The inducible HO-1 isoform is regulated by various stimuli, including hypoxia, oxidant stress, and inflammatory cytokines. The objective of this study was to compare the response of HO-1 and cytokines to a proinflammatory challenge in leukocytes isolated from humans and bottlenose dolphins (Tursiops truncatus). We measured changes in HO activity, and abundance and expression of interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and heme oxygenase 1 (HMOX1) in leukocytes treated with lipopolysaccharide (LPS) for 24 and 48 h. HO activity increased (p < 0.05) in dolphin (48 h) but not human cells. TNF-α expression increased in human (24 h, 48 h), but not dolphin cells following LPS stimulation. LPS-induced cytokine expression was lower in dolphin than in human leukocytes, suggesting a blunted cytokine response in bottlenose dolphin leukocytes treated with LPS. Results suggest species-specific regulation of inflammatory cytokines in leukocytes treated with LPS, which may lead to differential responses to a pro-inflammatory challenge between marine and terrestrial mammals.

"Oxidative stress induced by phthalates in mammals: State of the art and potential biomarkers".

BACKGROUND: Phthalates, plasticizers that are widely used in consumer products including toys, cosmetics, and food containers, have negative effects in liver, kidney, brain, lung and reproductive system of humans and other mammals. OBJECTIVES: To summarize, describe and discuss the available information on the effects of phthalate exposure in mammals, with emphasis on oxidative stress, and to suggest potential biomarkers of the health risks associated with phthalate exposure. METHODS: An assessment of scientific journals was performed using the PRISMA model for systematic reviews. Manuscripts reporting effects of phthalate exposure on mammalian health published in the last decade were selected according to originality, content, and association to health hazards. RESULTS AND DISCUSSION: We identified 25 peer-reviewed articles published between January 1st, 2010 and June 1st, 2021 that fit the aims and selection criteria. Phthalates induce oxidative stress and cell degenerative processes by increasing intracellular reactive species. Antioxidant cytoprotective systems decrease with time of exposure; conversely, oxidative damage markers, including thiobarbituric acid-reactive substances (TBARS), 8-hydroxy-2'-desoxyguanosine (8-OHdG) and malondialdehyde (MDA), increase. Phthalates were associated with endocrine system disfunction, metabolic disorders, infertility, nonviable pregnancy, cell degeneration, growth impairment, tumor development, and cognitive disorders. Phthalates can also aggravate health conditions such as asthma, hepatitis, diabetes, allergies, chronic liver and kidney diseases. Among humans, the more vulnerable subjects to phthalate exposure effects were children and individuals with a prior health condition. CONCLUSION: Chronic exposure to phthalates induces oxidative stress in mammals with concomitant adverse effects in reproductive, respiratory, endocrine, circulatory, and central nervous systems in both in vitro and in vivo trials. Oxidative damage markers and phthalate metabolites levels were the most common biomarkers of phthalate exposure effects. Studies in free-ranging and wild mammals are nil. Further studies on the pathways that lead to metabolic disruption are needed to identify potential treatments against phthalate-induced detrimental effects.

Morphometric characteristics of human skeletal muscle cells in primary culture / Características morfométricas de células musculares esqueléticas humanas en cultivo primario

SUMMARY: The study of cell morphology has contributed to the innovation of clinical techniques and biomedical research. Primary cell culture techniques are well standardized; however, knowledge about morphometric parameters under cell culture conditions is scarce. Variations in morphology can affect cell physiology and responses. The aim of this study was to use morphometric tools to describe the growth and development of skeletal muscle cells under standard cell culture conditions. A photographic database was generated, and morphometric data was obtained for nine cell characteristics (n = 559 cells). Four muscular cell shapes (spherical, irregular outline, triangular and spindle/fusiform) were characterized with wide ranges in variation. The maximum cell length (110-262 µm), width (35-66 µm), area (2,642 - 9,480 µm2), projection lengths (45 - 127 µm), and nucleus diameter (28 ± 11 µm) were obtained by day 23 of culture. A single centrally positioned nucleus was observed in each cell; nucleoli diameter (5 ± 2 µm) and number (1 - 5) varied. In general, cyclic changes in cell sizes were identified during culture, whereas cell length, width, and area increased in spurts. These results suggest that morphometric parameters can be used to monitor skeletal muscle cell development under standard culture conditions.

RESUMEN: A partir de células madre musculares, surgen los mioblastos que se dividen y fusionan entre sí para formar a los miocitos. Estas células ya diferenciadas son precursoras de miocitos que maduran en fibras musculares y posteriormente forman los músculos. La implementación de cultivos celulares de mioblastos ha permitido obtener conocimiento detallado del tejido muscular. Particularmente, algunas de las aportaciones morfológicas fueron el punto de partida de técnicas clínicas, terapias o investigaciones biomédicas. Sin embargo, los estudios morfométricos en condiciones de cultivo celular son escasos. Por lo cual, realizamos seguimientos fotográficos a cultivos desarrollados bajo condiciones estándar, registramos datos para nueve características celulares y aplicamos técnicas morfométricas para analizar estas células (n = 559). Se caracterizaron cuatro formas celulares adoptadas por los mioblastos (esférica, irregular, triangular y huso) y se registraron intervalos amplios de variación en los caracteres. Hacia el día 23 de cultivo se presentaron los valores máximos en la longitud (110-262 µm), el ancho (35-66 µm) y el área celular (2,642-9,480 µm2), así como en el tamaño máximo de las proyecciones celulares (45-127 µm) y el diámetro del núcleo (28±11 µm). El núcleo se observó como único y en posición central; los nucleolos variaron poco en diámetro (5±2 µm), aunque no en número (1 a 5). En términos generales, se identificaron cambios cíclicos en la talla de las células durante los cultivos, esto es, períodos intercalados de incremento y decremento en el largo, ancho y área celular. Debido a que estas características reflejaron los cambios generales sufridos por los mioblastos durante el cultivo, se proponen para monitorear sus etapas de desarrollo en cultivo.

Morphological alterations in human skeletal muscle cells exposed to di-(2-Ethylhexyl) Phthalate (dehp) in primary cell culture conditions / Alteraciones morfológicas en células musculares esqueléticas humanas expuestas a Ftalato de di-(2-etilhexilo) (dehp) en condiciones de cultivo celular primario

SUMMARY: Di-(2-ethylhexyl) phthalate (DEHP) is among the most common plasticizer additives that humans are in contact with daily. DEHP can be released from plastic and enter the human body, whereby it is metabolized and transformed into oxidative hydrophilic molecules. Clinical follow-ups in patients exposed to this phthalate and investigations in cultures of several cell types have provided information on its effects. For example, it is associated with inhibition of diploid human cell development and morphological changes in cultured germ cells. Although skeletal muscle represents around 50 % of the human body mass, knowledge about the effects of DEHP on this tissue is poor. Cultured skeletal muscle cells were exposed to DEHP (1 mM) for 13 days with the aim of exploring and evaluating some of the potential morphological effects. Three culture development parameters and nine cell characteristics were monitored during the bioassay. At 13 days, growth area, cell viability, and concentration of total proteins were lower in DEHP exposed than in control cells. Cell width and area, as well as the diameter of the nucleus and nucleolus, were greater in exposed cells than in control cells. These are interpreted as signs of cytotoxicity and suggest potential adverse effects on the development of skeletal muscle cells from DEHP exposure, as reported for other cell types.

RESUMEN: Diariamente los seres humanos tenemos contacto con aditivos plastificantes, el di-(2-etilhexil) ftalato (DEHP) se encuentra entre los más comunes. El DEHP puede liberarse del plástico e ingresar al cuerpo humano, donde es metabolizado y transformando en moléculas hidrofílicas oxidativas. Seguimientos en pacientes expuestos a este ftalato e investigaciones en cultivos de varios tipos celulares han aportado información sobre sus efectos. El DEHP es asociado con la inhibición del desarrollo de células humanas diploides y cambios morfológicos en células germinales en cultivo. Sin embargo, aún es poco lo que se sabe sobre los efectos en el músculo esquelético, a pesar de que este tejido representa alrededor del 50 % de la masa corporal del humano. Para explorar y evaluar algunos efectos morfológicos en células de músculo esquelético, cultivos primarios fueron expuestos a DEHP (1 mM) durante 13 días. Se dio seguimiento a tres parámetros de desarrollo del cultivo y nueve características celulares. Al término de 13 días de exposición, los valores del área de crecimiento, viabilidad celular y concentración de proteínas totales fueron inferiores con respecto a los cultivos control. Se observaron cambios morfométricos en las células expuestas. Particularmente, el ancho y área celular, así como los diámetros del núcleo y nucleolos, fueron mayores a los registros en las células control. Estos resultados se interpretan como signos de citotoxicidad y sugieren efectos potencialmente adversos en el desarrollo de las células del músculo esquelético ante una exposición al DEHP, como se ha registrado para otros tipos celulares.

Antioxidant response to cadmium exposure in primary skeletal muscle cells isolated from humans and elephant seals.

Cadmium (Cd) occurs naturally; however, its concentration can increase with anthropogenic activities. Excess Cd increases reactive oxygen species (ROS) production and oxidative damage, which can lead to pathological conditions. Marine mammals accumulate Cd in the liver and the kidney; yet, there are no reports of Cd-associated tissue damage in whales, seals or dolphins. Response to Cd exposure (0-5.0 µM CdCl2 for 1-12 h) was analyzed and compared in primary skeletal muscle cells isolated from northern elephant seals (Mirounga angustirostris) and humans (Homo sapiens). Antioxidant enzyme activities (glutathione S-transferase, glutathione reductase, glutathione peroxidase), glutathione concentration, and protein carbonyl levels (an indicator of oxidative damage) were quantified. Glutathione levels were higher in northern elephant seal than in human cells. Protein carbonyl content in cells exposed to Cd was lower and had a smaller variability range in elephant seals than in humans. Generalized linear models (GLIM) identified Cd exposure and antioxidant defenses as significant contributors to protein carbonyl variability in human but not in elephant seal cells. These results suggest that the previously observed differences in circulating and tissue glutathione levels between marine and terrestrial mammals are maintained under cell culture conditions and that northern elephant seal and human muscle cells respond differently to Cd exposure. The results also suggest that the observed differences could potentially be associated with the protective mechanisms that allow northern elephant seals to tolerate extreme conditions that result in increased ROS generation (e.g. diving, sleep apnea, fasting) with no oxidative damage.

Oxidative damage to proteins related to metals and antioxidant defenses in breastmilk.

INTRODUCTION: Breast milk contains molecules needed for the development of children; the integrity and function of these molecules is affected by the presence of pro-oxidants. Protein carbonyls are mainly produced as a result of the interaction of metals with reactive oxygen species (ROS), which may initiate a chain reaction that promotes molecular oxidation. OBJECTIVE: This study aimed to determine the association between the concentration of protein carbonyls with the concentration of trace elements (lead [Pb], cadmium [Cd] and selenium [Se]), superoxide radical (O2•-) production, and glutathione (GSH) content, as well with the activity of the main antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], glutathione reductase [GR] and glutathione S-transferase [GST]) in breast milk. METHODS: In this study 108 transitional milk samples (7-10 days) were analyzed. Antioxidant enzyme activities, O2•-production, protein carbonyl and GSH concentrations were analyzed by spectrophotometry. Trace element concentration was quantified by atomic absorption spectrophotometry. Generalized linear modelling was used to assess the relationship between protein carbonyls concentration with oxidative stress indicators and trace elements concentration. RESULTS: Cd and Pb were detected in 21.3 and 55.6% of breast milk samples, respectively. The median concentration of Cd was 0.01 µg L-1 (0.01-3.52 µg L-1) and Pb concentration was 2.61 µg L-1 (0.08-195.20 µg L-1). According to the best-fit model, the main factors contributing to protein carbonyl concentrations were the activity of GPx, GR, and concentration of GSH, Se, Pb and Cd. CONCLUSIONS: According to the generalized linear model, the activity of GPx and GR, could help explain protein oxidation induced by Pb and Cd in breast milk.

Plasma Hypoxanthine-Guanine Phosphoribosyl Transferase Activity in Bottlenose Dolphins Contributes to Avoiding Accumulation of Non-recyclable Purines.

Marine mammals are exposed to ischemia/reperfusion and hypoxia/reoxygenation during diving. During oxygen deprivation, adenosine triphosphate (ATP) breakdown implies purine metabolite accumulation, which in humans is associated with pathological conditions. Purine recycling in seals increases in response to prolonged fasting and ischemia. Concentrations of metabolites and activities of key enzymes in purine metabolism were examined in plasma and red blood cells from bottlenose dolphins (Tursiops truncatus) and humans. Hypoxanthine and inosine monophosphate concentrations were higher in plasma from dolphins than humans. Plasma hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity in dolphins suggests an elevated purine recycling rate, and a mechanism for avoiding accumulation of non-recyclable purines (xanthine and uric acid). Red blood cell concentrations of hypoxanthine, adenosine diphosphate, ATP and guanosine triphosphate were lower in dolphins than in humans; adenosine monophosphate and nicotinamide adenine dinucleotide concentrations were higher in dolphins. HGPRT activity in red blood cells was higher in humans than in dolphins. The lower concentrations of purine catabolism and recycling by-products in plasma from dolphins could be beneficial in providing substrates for recovery of ATP depleted during diving or vigorous swimming. These results suggest that purine salvage in dolphins could be a mechanism for delivering nucleotide precursors to tissues with high ATP and guanosine triphosphate requirements.

[Not Available]. / Antioxidantes, especies reactivas de oxígeno y daño oxidativo asociado a la presencia de plaguicidas organoclorados en la leche materna.

Introducción: los plaguicidas organoclorados (POC) pueden incrementar la producción de especies reactivas de oxígeno (ERO). Tales efectos pueden ser contrarrestados por el sistema antioxidante, el cual se encuentra también en la leche materna. Objetivo: evaluar los indicadores de estrés oxidativo en leche materna asociados a la presencia de POC y su relación con la ingesta de alimentos marinos. Métodos: la leche materna fue colectada de 108 mujeres lactantes. Los indicadores de estrés oxidativo (actividad enzimática antioxidante, concentración de glutatión, producción de radical superóxido [O 2•- ], concentración de peroxidación de lípidos y carbonilos proteicos) se analizaron por espectrofotometría. Las concentraciones de POC se midieron por cromatografía de gases. Resultados y discusión: la producción de O 2•- no presentó relación significativa con las concentraciones de POC. Se encontraron correlaciones significativas entre las concentraciones de POC y la actividad de las enzimas antioxidantes (actividad de glutatión reductasa [GR] y concentración de aldrín [r = - 0,5], actividad de superóxido dismutasa [SOD] y concentración de α-HCH [r = 0,45]). El daño oxidativo mostró baja correlación con el contenido de POC (r < 0,30, p < 0,05). Es posible que los niveles de POC no sean suficientes para incrementar la producción de O 2•- , ya sea que el incremento en la producción de ERO se deba a especies reactivas diferentes a O 2•- o debido a que la capacidad antioxidante es suficiente para evitar el daño oxidativo en leche materna. Conclusión: los resultados de este estudio sugieren que la dieta marina no es un factor determinante en el nivel de contaminación por POC, ni en el daño oxidativo presente en leche materna.

The Neuroprotective Effect of Erythropoietin in Rat Hippocampus in an Endotoxic Shock Model.

BACKGROUND: Sepsis is characterized by an early systemic inflammation in response to infection. In the brain, inflammation is associated with expression of pro-inflammatory cytokines (e.g. tumor necrosis factor-α, interleukin-1ß and interleukin-6, among others) that may induce an overproduction of reactive oxygen and nitrogen species. The constitutive expression of cytokines in the brain is low, but may be induced by various stimuli, including lipopolysaccharide, which causes neuronal damage. Erythropoietin, among other effects, acts as a multifunctional neurotrophic factor implicated in neurogenesis, angiogenesis, vascular permeability, and immune regulation in the central nervous system. In an experimental model of endotoxic shock, we studied the neuroprotective capacity of erythropoietin in the rat hippocampus and compared with melatonin, a neurohormone with an important antioxidant and immunomodulatory effect. METHODS: In 21-day-old male Wistar rats divided into eight groups, we administered by intraperitoneal injection lipopolysaccharide, erythropoietin, melatonin, or combinations thereof. The hippocampus was dissected and morphological (histological analysis) and biochemical (cytokine levels) studies were conducted. RESULTS: The number of dead neuronal cells in histological sections in groups treated with lipopolysaccharide was higher compared to the erythropoietin group. There was a greater decrease (70%) in interleukin-1ß concentrations in rats with endotoxic shock that received erythropoietin compared to the lipopolysaccharide group. CONCLUSIONS: The neuronal cell loss caused by endotoxic shock and interleukin-1ß levels were reduced by the administration of the hematopoietic cytokine erythropoietin in this experimental model.

Purine nucleoside phosphorylase and the enzymatic antioxidant defense system in breast milk from women with different levels of arsenic exposure.

Purine nucleoside phosphorylase (PNP) is an ubiquitous enzyme which plays an important role in arsenic (As) detoxification. As is a toxic metalloid present in air, soil and water; is abundant in the environment and is readily transferred along the trophic chain, being found even in human breast milk. Milk is the main nutrient source for the growth and development of neonates. Information on breast milk synthesis and its potential defense mechanism against As toxicity is scarce. In this study, PNP and antioxidant enzymes activities, as well as glutathione (GSH) and total arsenic (TAs) concentrations, were quantified in breast milk samples. PNP, superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) activities and GSH concentration were determined spectrophotometrically; TAs concentration ([TAs]) was measured by atomic absorption spectrometry. Data suggest an increase in PNP activity (median = 0.034 U mg protein-1) in the presence of TAs (median = 1.16 g L(-1)). To explain the possible association of PNP activity in breast milk with the activity of the antioxidant enzymes as well as with GSH and TAs concentrations, generalized linear models were built. In the adjusted model, GPx and GR activities showed a statistically significant (p<0.01) association with PNP activity. These results may suggest that PNP activity increases in the presence of TAs as part of the detoxification mechanism in breast milk.

Purina nucleósido fosforilasa (PNP) es una enzima ubicua que desempeña un papel importante en la desintoxicación del arsénico (As). As es un metaloide tóxico presente en el aire, el suelo y el agua; es abundante en el medio ambiente y se transfiere fácilmente a lo largo de la cadena trófica, encontrándose incluso en la leche materna humana. Información sobre la síntesis de la leche materna y su potencial mecanismo de defensa contra tóxicos es escasa. En este estudio, se cuantificó la actividad de PNP y de las enzimas antioxidantes así como la concentración de glutatión (GSH) y de arsénico total ([TAs]) en muestras de leche materna. La actividad de PNP, superóxido dismutasa (SOD), catalasa (CAT), glutatión S-transferasa (GST), glutatión peroxidasa (GPx), glutatión reductasa (GR) y la concentración de GSH se determinaron por espectrofotometría; la [TAs] se midió por espectrometría de absorción atómica. Los datos sugieren un incremento en la actividad de PNP (mediana= 0.034 U mg proteína-1) con la presencia de TAs (mediana= 1.16 g L-1). Para explicar la posible asociación de la actividad de las enzimas antioxidantes y la concentración de GSH, así como [TAs], con la actividad de PNP en la leche materna, se construyeron modelos lineales generalizados. En el modelo ajustado, la actividad de GPx y GR presentó una asociación estadística (p.

Oxidative stress in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is an autoimmune disease of unknown etiology, characterized by articular inflammation. Oxidative damage induced by reactive oxygen species has been related to the pathophysiology of rheumatoid arthritis in several studies, although results have been inconsistent and contradictory. OBJECTIVE: To determine oxidative stress markers in patients with rheumatoid arthritis. METHODS: Descriptive cross-sectional study in rheumatoid arthritis patients and healthy controls. In peripheral blood samples from all study subjects, lipid peroxide (thiobarbituric acid reactive substances) and protein carbonyl levels were quantified as oxidative damage markers; superoxide dismutase and glutathione peroxidase activities, glutathione concentration, and the reduced glutathione/oxidized glutathione ratio were analyzed as antioxidant defense indicators. Mann-Whitney U tests were run. Statistical significance (a) was 0.05%. RESULTS: We included 29 rheumatoid arthritis patients, 10 with active disease, and 41 healthy controls. Age was higher in the rheumatoid arthritis group; there were no differences in female:male ratio between groups. Oxidative damage was higher in rheumatoid arthritis patients; however, there was no difference between patients with active or inactive rheumatoid arthritis. Antioxidant enzyme activities, glutathione concentration, and reduced glutathione/oxidized glutathione ratio were higher in rheumatoid arthritis patients than in controls. CONCLUSIONS: Antioxidant levels were higher in rheumatoid arthritis patients than in healthy controls; however, they were insufficient to prevent oxidative damage. This suggests an active oxidative process in rheumatoid arthritis patients.

[Antioxidant defences in breast milk in relation to number of pregnancies and age of mothers]. / Defensas antioxidantes en leche materna en relación al número de gestas y a la edad de las madres.

INTRODUCTION: Breast milk is a specific combination of nutrients and immunologic factors; however, milk components may be exposed to oxidation processes, which can in turn be counteracted by antioxidant molecules such as vitamins and antioxidant enzymes, amongst others. Both antioxidant defences and oxidative damage can be affected by age, number of pregnancies and other factors. OBJECTIVE: To compare antioxidant defences and oxidative damage indicators in breast milk, according to age of women and number of pregnancies. METHOD: Activity of the main antioxidant enzymes, glutathione concentration, oxidative damage to lipids (thiobarbituric acid reactive substances, TBARS) and oxidative damage to proteins (protein carbonyls) was measured in breast milk using spectrophotometric techniques. Data were grouped according to number of pregnancies (1, 2 and 3 or more) and were related to the age of mothers. RESULTS: Significant differences among groups according to number of pregnancies were found in TBARS levels (p = 0.04) and GST activity (p < 0.01). Also linear correlations between age, lipid peroxidation and GST activity were found. CONCLUSION: The age and number of pregnancies apparently increase lipid oxidation in milk due to increased metabolism and production of reactive oxygen species. However, TBARS levels remain relatively low probably because of the mother's antioxidant defenses, particularly GST.

Introducción: La leche materna es una combinación específica de nutrientes y factores inmunológicos; sin embargo, sus componentes pueden estar expuestos a procesos de oxidación, mismos que pueden ser contrarrestados por moléculas antioxidantes como vitaminas y enzimas, entre otros. Tanto las defensas antioxidantes como el daño oxidativo pueden ser afectados por la edad, número de gestas y otros factores. Objetivo: Comparar el contenido de antioxidantes e indicadores de daño oxidativo en leche materna de acuerdo a la edad de las mujeres y el número de gestas. Metodología: Se midió la actividad de las principales enzimas antioxidantes, la concentración de glutatión, el daño oxidativo a lípidos (sustancias reactivas al ácido tiobarbitúrico, TBARS) y daño a proteínas (carbonilos proteicos) en leche materna utilizando técnicas espectrofotométricas. Se agruparon los datos de acuerdo al número de gestas (1, 2 y 3 o más) y se correlacionó con la edad de las madres. Resultados: Se encontraron diferencias significativas en los niveles de TBARS (p = 0.04) y la actividad de glutatión S-transferasa (GST, p < 0.01) entre los grupos de acuerdo al número de gestas. Así mismo, se encontraron correlaciones lineales entre la edad, el daño oxidativo a lípidos y la actividad de GST. Conclusión: La edad y el número de gestas al parecer incrementan la oxidación de los lípidos presentes en leche materna debido al aumento en el metabolismo y la producción de especies reactivas de oxígeno. Sin embargo, los niveles de TBARS se mantienen relativamente bajos posiblemente debido a las defensas antioxidantes, particularmente GST, de la madre.

Marine diet and tobacco exposure affects mercury concentrations in pregnant women (I) from Baja California Sur, Mexico.

Seafood provides essential polyunsaturated fatty acids (PUFA) and other nutrients to pregnant women and their fetus(es) while a diet rich in finfish can be a major pathway of monomethyl mercury (MeHg+) exposure. We measured total mercury concentration ([THg]) in hair samples provided by 75 women in Baja California Sur (BCS) to assess its relationship with age, parity, tobacco smoke exposure, and diet based on survey methodologies. Generalized linear models (GLM) were used to explain the possible association of the different variables with [THg] in hair. Median [THg] in hair was 1.52 µgg-1, ranging from 0.12 to 24.19 µgg-1 and varied significantly by segment. Approximately 72% (54/75) of those evaluated exceed 1 µgg-1 [THg] and 8% (6/75) exceed 5 µgg-1 [THg] in hair. Although frequency of fish consumption contributed significantly to explaining hair [THg], fish consumption only explained 43% of [THg] in a GLM incorporating tobacco exposure and body mass index. This study establishes possible relationships among multiple potential sources of exposure and other factors related to [THg] in hair of women in the prenatal period. A more detailed examination of other sources of exposure and factors contributing to [THg] is warranted.

Relationship between self-reported fish and shellfish consumption, carbon and nitrogen stable isotope values and total mercury concentrations in pregnant women (II) from Baja California Sur, Mexico.

Seafood is a valuable source of nutrients important for fetal development. However, seafood consumption is the main route of exposure to monomethyl mercury (MeHg+) for humans. MeHg+ is highly bioavailable and potentially adversely affects fetal neurodevelopment. MeHg+ exposure from fish consumption varies significantly by age and trophic level of fish consumed as well as the frequency and amount of fish consumed. This study investigates total Hg concentrations ([THg]) in hair segments of pregnant Mexican women in relation to (1) self-reported frequency of fish and shellfish consumption, (2) maternal trophic level and marine diet contributions, determined using hair carbon (C) and nitrogen (N) stable isotopes, and (3) relates [THg] to various hair advisory thresholds. We also examined whether variation in C and N isotope values is explained by self-reported frequency of fish and shellfish consumption. A significant proportion of hair samples had [THg] higher than suggested agency thresholds and, for women within the range of the various advisory thresholds (1-20 µg g-1), the specific statistic used and threshold applied are important considerations for assessing and communicating risk. Individuals enriched in 15N (δ15N values) had higher [THg] as did individuals that reported consuming fish and shellfish more frequently, suggesting that variation in [THg] can be explained by both consumer reported diet and diet as determined by C and N stable isotope assessment. However, at higher reported fish consumption levels the trophic level is maintained while [THg] is paradoxically lower. This suggests that THg exposure and assimilation are more complicated in higher fish frequency consumption categories. [THg] is more variable at the higher concentrations, possibly indicating some exposure to non-dietary Hg, heritable variations affecting Hg toxicodynamics, and BMI and tobacco exposure factors as outlined in our companion paper.

Incremento de la temperatura ambiental y su posible asociación al suicidio en Baja California Sur (BCS) 1985-2008 / Environmental temperature increase and its possible association with suicide in the population of Baja California Sur (BCS) 1985-2008

Introduction During the last decade we have observed important climate changes, especially in environmental temperatures. There is considerable information linking the increase in hot weather and human health. For example, hot weather is associated with an increased risk of suicide in different countries around the world. Objective To evaluate the relationship between suicide rates and the environmental temperature in Baja California Sur, Mexico, from 1985 to 2008. Method Suicide mortality data for Baja California Sur (BCS) were obtained for the years 1985-2008 from the Instituto Nacional de Estadística, Geografía e Informática (INEGI). The selected codes were: E950-E959 (ICD-9) and X60-X84, Y87.0 (ICD-10) for BCS. The BCS weather data used was the maximum temperature from 1985 to 2008, obtained from the Extractor Rápido de Información Climatológica (ERIC III). Lineal and quadratic models were used to assess the annual rate changes of suicide and generalized lineal models (GLM) to assess the effect of the climatological variables to the suicide rate. The p≤0.05 was considered significant. Results In BCS, 582 suicide deaths were reported from 1985 to 2008. The 9% (53) of the total reported were women with a yearly average rate 1.6/100 000; 91% (529) were men with a yearly average rate 16.3/100 000. Lineal and quadratic models explained the tendency of the annual increment observed in the number of suicides in both seasons. The quadratic model better explained such increment during the warmer months (R²=0.64 p<0.01). The temperature was positively correlated with the rate of suicides in both seasons (p<0.01). Two predictive GLMs were created by season. Discussion These results suggest a potential link between an increase in environmental temperature and the rates of suicide during 24 years in BCS. This relationship is clear during the hot season; however, a positive trend was found during the cold season, perhaps due to the result of warmer winters.

Introducción Durante las últimas décadas se ha podido apreciar un cambio en las variables climáticas, en especial en la temperatura ambiental. Hay evidencias que asocian el aumento de la temperatura ambiental con el incremento en las tasas de mortalidad por suicidio. Objetivo Evaluar la relación entre la tasa de suicidio y la temperatura ambiental en Baja California Sur (BCS) durante los años 1985-2008. Método Los datos de suicidio fueron obtenidos de las bases de Mortalidad del INEGI de 1985-2008. Se tabularon los registros con códigos: E950-E959 CIE-9 y X60-X84, Y87.0 CIE-10 para BCS. En el análisis climático se usaron las temperaturas máximas de 1985 al 2008 para BCS del Extractor Rápido de Información Climatológica (ERIC III). Para evaluar la tendencia, se utilizaron modelos de regresión lineal y cuadráticos. Los modelos lineales generalizados (GLM) se utilizaron para evaluar el efecto de las variables ambientales sobre la tasa de suicidios, con una significancia de p≤0.05. Resultados Un total de 582 suicidios ocurrieron en BCS de 1985 a 2008. Las mujeres representaron el 9% (53), con tasa anual promedio de 1.6/100 000. Los hombres 91% (529), con tasa promedio anual de 16.3/100 000. La tendencia de incremento anual se explicó con modelos lineales simples y cuadráticos en ambas temporadas. En los meses cálidos el modelo cuadrático explicó mejor dicho incremento (R²=0.64 p<0.01). La temperatura se correlacionó positivamente con la tasa en ambas temporadas (p<0.01). Se generaron dos modelos GLM predictivos por temporada. Discusión En este trabajo se observó una posible relación entre el incremento de la temperatura ambiental y el número de suicidios registrados durante 24 años en BCS. Esta relación se encuentra bien definida en los meses cálidos, pero con una tendencia en aumento para los meses fríos.

[Mercury concentration in breast milk of women from northwest Mexico; possible association with diet, tobacco and other maternal factors]. / Concentraciones de mercurio en leche de mujeres del noroeste de México; posible asociación a la dieta, tabaco y otros factores maternos.

OBJECTIVE: To determine THg levels in milk of women from Northwest Mexico and its potential association with maternal factors such as diet and tobacco smoke. METHOD: The study was performed in 108 milk samples donated by women in Baja California Sur. Data were stratified into three groups of 36 donors by number of pregnancies. General data, smoking, exposure to environmental tobacco smoke and seafood intake were explored. THg levels were measured using atomic absorption spectrophotometry. The difference between groups was evaluated with non-parametric statistics. To explain the possible association of the different variables with THg concentrations in milk, generalized linear models were performed. RESULTS: THg levels ranged from 1.23 µg/L in single-pregnancy women (GI) to 2.96 µg/L for women with 3 or more pregnancies (GIII) (p = 0.07). In the GI group THg concentration was 175% higher (p = 0.02) in women who do not eat fish, compared to those who eat fish. In the generalized linear model to adjust THg concentrations, the variables were: age, number of pregnancies, breastfeeding duration and exposure to tobacco smoke (p ≤ 0.05). CONCLUSIONS: Fish consumption was the factor that better adjusted models, relative to THg levels. The contribution associated to this factor was low; therefore, consumption of fish from the coast of Baja California Sur is safe. Tobacco increased Hg concentrations in breast milk; it is necessary to avoid the smoking habit during pregnancy and breast-feeding.

Objetivo: Determinar los niveles de mercurio total (THg) en leche de mujeres del Noroeste de México y su posible asociación con factores maternos, la dieta y el tabaco. Método: El estudio se realizó en leches donadas por 108 mujeres de Baja California Sur. Se estratificaron en tres grupos de 36 donantes según el número de gesta. Se exploraron datos generales, hábito tabáquico, exposición al humo de tabaco ambiental, ingesta de mariscos y pescados. Los niveles de THg fueron cuantificados utilizando espectrofotometría de absorción atómica. La diferencia entres grupos se evaluó con estadística no paramétrica. Para explicar la posible asociación de las diferentes variables estudiadas y las concentraciones de THg en la leche, se realizaron modelos lineales generalizados. Resultados: Los niveles de THg fueron desde 1.23 ?g/L en las primigestas (GI) a 2,96 ?g/L para las mujeres con 3 o más gestas (GIII) (p = 0,07). En el grupo de GI encontramos una concentración del THg 175% mayor (p = 0,02) entre las mujeres que no comen pescado, en comparación con las que si comen pescado. En el modelo lineal generalizado ajustado por las concentraciones de THg, las variables fueron: edad, número de embarazos, duración de la lactancia y exposición al tabaco (p =?0,05). Conclusiones: El consumo de pescado fue el factor que mejor ajustó los modelos en relación a los niveles de THg. El aporte de Hg por la dieta que se pudo asociar fue bajo, por lo que el consumo de pescado de las costas de Baja California Sur es seguro. El tabaco, incrementa las concentraciones de Hg en la leche materna, por lo que debe de limitarse su hábito durante el embarazo y la lactancia.

[Lipid peroxidation and the response of the antioxidant defense system in the obese type 2 diabetic compared with the non-obese type 2 diabetic]. / Peroxidación de lípidos y la respuesta del sistema de defensa antioxidante en el diabético tipo 2 obeso en comparación al diabético tipo 2 sin obesidad.

INTRODUCTION: Diabetes is associated with increased lipid peroxidation, quantified as the levels of thiobarbituric acid reactive substances (TBARS). In parallel, the antioxidant defense system (ADS) reacts to diminish the oxidative damage. OBJECTIVE: To determine the levels of lipid peroxidation and the activity of antioxidant enzymes in obese type 2 diabetic (DM2) individuals compared to non-obese DM2 individuals. METHODS: Lipid peroxidation was quantified by measuring TBARS and the ADS response by measuring the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). RESULTS: Two groups of 30 subjects were studied. The obese DM2 group had a mean body mass index (BMI) 38.6 ± 3.5 kg m(-2) compared to the control group 24.7 ± 3.6 kg m(-2) (p<0.01). TBARS levels in the study group were higher compared to the control group (p <0.01). Multiple linear regression analysis suggested that activities of SOD and CAT adjusted to lipid peroxidation (TBARS) in the obese DM2 individuals. CONCLUSION: TBARS levels suggest greater oxidative damage in obese DM2 subjects with a diminished response of ADS.

Introducción: La diabetes se asocia a un incremento en la peroxidación de lípidos, cuantificada a partir del nivel de sustancias reactivas al ácido tiobarbitúrico (TBARS). En paralelo, se activa el sistema de defensa antioxidante (SDA) para delimitar el daño. Objetivo: Determinar el grado de peroxidación de lípidos en individuos obesos diabéticos tipo 2 (DM2) y la respuesta del SDA en comparación con individuos con DM2 sin obesidad. Método: Se evaluó el daño a lípidos a través de la medición de las TBARS en dos grupos de 30 individuos. Se evaluó la respuesta del SDA por medio de la medición de la actividad de las enzimas catalasa (CAT), superóxido dismutasa (SOD) y glutatión peroxidasa (GPx). Resultados: El grupo de DM2 obesos presentó un índice de masa corporal (IMC) promedio de 38.6 ± 3.5 kg m-2 en comparación con el grupo control 24.7 ± 3.6 kg m-2 (p.

Tendencia de la mortalidad por picaduras de alacrán en México, 1979-2003 / Trends in mortality from scorpion stings in Mexico, 1979-2003

OBJETIVO: Describir la tendencia de la mortalidad por picaduras de alacrán en México y sus estados federativos en el período de 1979 a 2003. MÉTODOS: Se estimaron las tasas crudas y estandarizadas de mortalidad por picaduras de alacrán y las tendencias durante el período estudiado a partir de los datos oficiales de mortalidad en México, según la 9.ª y la 10.ª revisiones de la Clasificación Internacional de Enfermedades (códigos E905.2 y X22, respectivamente). Los resultados se estratificaron por grupos de edad. Las frecuencias de muertes por picaduras de alacrán se compararon mediante el riesgo relativo (RR) y sus intervalos de confianza de 95 por ciento (IC95 por ciento). RESULTADOS: Entre 1979 y 2003, en México se registraron 6 077 muertes por picaduras de alacrán. Se observó una tendencia descendente estadísticamente significativa en la mortalidad estandarizada (beta = -0,195; P < 0,001), con una reducción total de 86,5 por ciento entre los períodos 1979-1982 y 2001-2003. La mayor mortalidad en el trienio 2001-2003 se observó en varones (0,81 por 1 000 000 de habitantes) y en los menores de 1 año (7,07 por 1 000 000 de habitantes), seguidos por los grupos de 1 a 4 años (3,78 por 1 000 000 de habitantes) y de 60 años o más (0,84 por 1 000 000 de habitantes). Las poblaciones con menos de 2 500 habitantes presentaron una mortalidad por picaduras de alacrán superior en 11,8 (IC95 por ciento: 7,86 a 17,72) veces la observada en las de más de 20 000 habitantes. Los estados con mayor mortalidad por picaduras de alacrán se encuentran en la región occidental y central del país. CONCLUSIONES: A pesar de la sostenida tendencia descendente en el número de muertes por picaduras de alacrán en los últimos 20 años en México, este sigue siendo un importante problema de salud pública. Los grupos de edad más afectados son los niños menores de 5 años y los ancianos. Se deben tomar medidas para que en todas las comunidades, principalmente en las pequeñas, se disponga de los recursos y la información adecuados para la atención oportuna de las personas que sufren una picadura de alacrán.

OBJECTIVE: To describe the trends in mortality from scorpion stings in Mexico as a whole and in each of its states for the period of 1979 to 2003. METHODS: We estimated the crude and standardized mortality rates due to scorpion stings and the trends during the period studied based on official mortality data for Mexico, using the codes (E905.2 and X22, respectively) from the 9th and 10th editions of the International Classification of Diseases. The results were stratified by age group. The frequencies of deaths from scorpion stings were compared using relative risk (RR), with 95 percent confidence intervals (CIs). RESULTS: Between 1979 and 2003 in Mexico, 6 077 deaths from scorpion stings were registered. A statistically significant downward trend was found in standardized mortality rates (beta = -0.195; P < 0.001), with a total reduction of 86.5 percent for the period of 2001-2003 versus 1979-1982. For the 2001-2003 period, the highest mortality rates were in children under 1 year of age (7.07 per 1 000 000), children 1 to 4 years old (3.78 per 1 000 000), persons 60 and older (0.84 per 1 000 000), and males (0.81 per 1 000 000). Persons in communities with fewer than 2 500 inhabitants had a relative risk that was 11.8 times (95 percent CI: 7.86 to 17.72) that found in communities with more than 20 000 inhabitants. The states with the highest mortality rates were in the central and western regions of the country. CONCLUSIONS: Despite the sustained decline in the number of deaths from scorpion stings in the last 20 years in Mexico, there is still an important public health problem. The groups that are most affected are children under 5 and the elderly. Measures should be taken so that in all communities, especially small ones, adequate resources and information are available to provide for the prompt care of persons who suffer a scorpion sting.

[Measurement of the development of psychomotor abilities in surgical endoscopy training with the use of a simulator and biological pieces]. / Método de medición del desarrollo de habilidades psicomotoras en las enseñanza de la cirugía endoscópica, con el uso de simulador y piezas biológicas.

INTRODUCTION: Learning laparoscopic surgery skills using a simulator board is one of the new acquired teaching methods. This work seeks an evaluation method to assess, by objective means, the development of psychometric skills during a simulated workshop with biological pieces. MATERIAL AND METHODS: During a 2-month period, 15 students from an endoscopic surgery seminar were evaluated using a simulator board with the objective to assess four specific skills: object mobilization, cutting pattern, sutures and intracorporeal knots. Eight practice procedures with biological pieces were performed in the simulator. Time and precision were measured in the four assignments. RESULTS: Students improved significantly in object mobilization (p = 0.02), precision in cutting pattern (p < 0.01) and suture (p = 0.02), and time and precision to realize intracorporeal knots (p < 0.01). CONCLUSIONS: This method allows the objective evaluation of the degree of development of surgical skills using a simulator board. It is inexpensive and easy to perform, which makes it useful for other institutions.