A randomized intraindividual comparative study evaluating the effects of two ultrasound-assisted liposuction devices on the abdomen.

BACKGROUND: Ultrasound-assisted liposuction (UAL) has become popular because of its favorable outcomes in fat emulsification, blood loss reduction, and skin tightening. This study aimed to compare the effects of two UAL devices on the abdomen by assessing postsurgery skin biomechanical properties. METHODS: This single-blind, prospective study (2020-2022) involved 13 liposuction procedures performed on patients without chronic diseases. Each patient's abdomen was divided vertically from the xiphoid to the perineum. Vibration amplification of sound energy at resonance (VASER)-assisted liposuction (Solta Medical, Inc., Hayward, CA) was performed on one half, while the other half underwent liposuction with high-frequency ultrasound energy (HEUS)-assisted technology. Skin biomechanical measurements, including distensibility, net elasticity, biological elasticity, hydration, erythema, melanin, and skin firmness, were taken at 12 and 24 months postsurgery, focusing on the anterior abdomen, 8 cm to the right and left of the umbilicus. RESULTS: Analysis of the above skin biomechanical measurements revealed no significant differences between the HEUS and VASER devices, except for skin firmness, which showed a notable increase following HEUS surgery. Patient-perceived clinical differences were assessed via nonvalidated questionnaires, revealing no distinctions between devices. CONCLUSION: Biomechanical skin results post-UAL surgery with these devices on the abdomen were not significantly different, although HEUS revealed increased skin firmness. This suggests that HEUS-assisted technology, akin to other devices, is a viable option for UAL procedures.

Plasma Catalysis for Hydrogen Production: A Bright Future for Decarbonization.

Thermal approaches have played a dominant role in driving chemical reactions within the chemicals and fuels industries, benefiting from ongoing enhancements in efficiency via heat integration, catalyst development, and process intensification. Nevertheless, these traditional thermal approaches remain heavily reliant on fossil fuels, and there exists an urgent demand for the implementation of renewable energy technologies to synthesize fuels, commodity chemicals, and specialty chemicals. Nonthermal plasmas have gained considerable attention in recent years as a promising solution, and the prospects of combining plasmas with suitable catalysts have become even more appealing. Moreover, the evolution of nonthermal plasma catalysis approaches for the generation of clean hydrogen could be transformative in reducing greenhouse gas emissions. This comprehensive review highlights the influential contributions in plasma catalysis for hydrogen production, discusses recent advancements, and provides future prospects for researchers aiming to advance the production of clean hydrogen.

Cutaneous Horn Presentation in Porokeratotic Eccrine Ostial and Dermal Duct Nevus. A Brief Review and Case Report.

ABSTRACT: Porokeratotic eccrine ostial and dermal duct nevus is a rare adnexal hamartoma characterized by the presence of a cornoid lamella exclusively overlying eccrine acrosyringia. Different clinical presentations have been reported in the literature. Here, we report a case of a 6-year-old girl diagnosed with porokeratotic eccrine ostial and dermal duct nevus confirmed by histopathologic study. Atypical lesions are described as whitish, warty-looking neoformations located in the anterolateral region of the right hip (cutaneous horn).

Buccal Fat Pad Herniation, Repositioning Versus Excision: A New Algorithm of Treatment.

Background: Traumatic herniation of the buccal fat pad can be treated with repositioning or excision. This report describes a case of a child with traumatic herniation of the buccal fat pad treated with excision. A comprehensive review of the literature was performed with the objective of establishing treatment criteria for the decision-making involved in choosing between repositioning versus excision. Methods: A systematic review of the literature was performed through searches of PubMed, Ovid, Elsevier, Cochrane, ResearchGate and Google Scholar for reports published from 1968 through May 2021. The search keywords used were traumatic herniation of the buccal fat pad, buccal fat pad herniation, traumatic pseudolipoma, and traumatic lipoma. We included only those studies that included patients with intraoral buccal fat pad herniation. Results: We found and included 39 articles (44 patients). Time since trauma, size of the fat pad herniated, and presence of necrosis were the most important characteristics considered for treatment decision; on the basis of these factors, we created a treatment algorithm. We present a case report of a 2-year-old boy diagnosed with traumatic herniation of buccal fat pad and, according to our algorithm, the appropriate treatment was to perform excision. A follow-up examination at 11 months showed no complications. Conclusions: Because traumatic herniation of buccal fat pad is very rare, this algorithm can be an easy and effective tool to guide decision-making when choosing between repositioning versus excision.

Pediatric Oncology Palliative Care Programs in Central America: Pathways to Success.

Palliative care offers children who have life-limiting and life-threatening oncologic illnesses and their families improved quality of life. In some instances, impeccable symptom control can lead to improved survival. Cultural and financial barriers to palliative care in oncology patients occur in all countries, and those located in Central America are no exception. In this article, we summarize how the programs participating in the Asociación de Hemato-Oncólogos Pediatras de Centro America (AHOPCA) have developed dedicated oncology palliative care programs. The experience in Guatemala, El Salvador, Costa Rica, Panama, Dominican Republic and Haiti is detailed, with a focus on history, the barriers that have impeded progress, and achievements. Future directions, which, of course, may be impacted by the COVID-19 pandemic, are described as well.

Butirato de sodio como agente coadyuvante de la acción radioprotectora de la amifostina / Sodium butyrate as a coadyuvant agent of the radioprotecting action of amifostine / Butirato de sódio como agente coadjuvante da ação radioprotetora da amifostina

Entre los escasos radioprotectores en uso, la amifostina resulta eficaz para reducir la toxicidad aguda inducida por la radiación ionizante. Sin embargo, presenta efectos tóxicos importantes que impiden su uso repetido o en dosis altas. Es necesario entonces desarrollar radioprotectores menos tóxicos, por sí mismos o como coadyuvantes de la amifostina en dosis bajas. Se expusieron ratas Sprague-Dawley a una dosis de rayos X de 6 Gy (cuerpo entero). Se ensayó el butirato de sodio como mitigante luego de una dosis baja de amifostina previa a la irradiación. A distintos tiempos después de la irradiación se realizó el recuento de eritrocitos, leucocitos y la fórmula leucocitaria. Los efectos genotóxicos se evaluaron en leucocitos de sangre mediante el ensayo Cometa. Se realizaron también estudios de supervivencia a 60 días y la evaluación histológica del duodeno e intestino grueso. El efecto del tratamiento resultó moderadamente protector respecto de la recuperación de los valores normales de eritrocitos, leucocitos y la fórmula leucocitaria en los animales sobrevivientes en ambos sexos, así como de los epitelios intestinales y el ADN de los leucocitos. También aumentó significativamente la sobrevida a 60 días. La radioprotección con amifostina en una dosis baja seguida de una mitigación con butirato fue claramente significativa.

Among the few radioprotectors in use, amifostine is effective in reducing the acute toxicity induced by ionizing radiation. However, it has important toxic effects that prevent its repeated use or in high doses. It is necessary then to develop less toxic radioprotectors, by themselves or as adjuvants of amifostine in low doses. Sprague-Dawley rats were exposed to an X-ray dose of 6 Gy (whole body). Sodium butyrate was tested as a mitigant after a low dose of amifostine prior to irradiation. At different times after the irradiation, the erythrocytes, leukocytes and the leukocyte formula were counted. Genotoxic effects were evaluated in blood leukocytes by the Comet assay. Sixty-day survival studies and histological evaluation of the duodenum and large intestine were also performed. The effect of the treatment was moderately protective with respect to the recovery of the normal values of erythrocytes, leukocytes and the leukocyte formula in the surviving animals in both sexes as well as for the intestinal epithelia and leukocytes DNA. It also significantly increased the 60-day survival. The radioprotection with amifostine in a low dose followed by mitigation with butyrate was clearly significant.

Entre os poucos radioprotetores em uso, a amifostina é eficaz na redução da toxicidade aguda induzida pela radiação ionizante. No entanto, tem importantes efeitos tóxicos que impedem seu uso repetido ou em altas doses. É necessário, então, desenvolver radioprotetores menos tóxicos, isoladamente ou como coadjuvantes da amifostina em baixas doses. Ratos Sprague-Dawley foram expostos a uma dose de raios X de 6 Gy (corpo inteiro). O butirato de sódio foi testado como mitigante após uma dose baixa de amifostina antes da irradiação. Em diferentes momentos após a irradiação, os eritrócitos, leucócitos e a fórmula de leucócitos foram contados. Os efeitos genotóxicos foram avaliados em leucócitos de sangue pelo ensaio Cometa. Estudos de sobrevida de 60 dias e avaliação histológica do duodeno e do intestino grosso também foram realizados. O efeito do tratamento resultou moderadamente protetor em relação à recuperação de valores normais de eritrócitos, leucócitos e fórmula leucocitária nos animais sobreviventes em ambos os sexos, bem como protegeu epitélios intestinais e o DNA dos leucócitos. Também aumentou significativamente a sobrevida para 60 dias. A radioproteção com amifostina em baixa dose seguida de uma mitigação com butirato foi claramente significativa.

Effects of Short-Term Random Noise Electrical Stimulation on Dissociated Pyramidal Neurons from the Cerebral Cortex.

Transcranial random noise electrical stimulation (tRNS) of the human brain is a non-invasive technique that can be employed to increase the excitability of the cerebral cortex; however, the physiological mechanisms remain unclear. Here we report for the first time the effects of short-term (250 ms) random noise electrical stimulation (RNS) on in-vitro acutely-isolated brain pyramidal neurons from the somatosensory and auditory cerebral cortex. We analyzed the correlation between the peak amplitude of the Na+ current and its latency for different levels of RNS. We found three groups of neurons. The first group exhibited a positive correlation, the second, a negative correlation, and the third group of neurons did not exhibit correlation. In the first group, both the peak amplitude of a TTX-sensitive Na+ current and its inverse of latency followed similar inverted U-like functions relative to the electrical RNS level. In this group, the RNS levels in which the maximal values of the inverted U-like functions occurred were the same. In the second group, the maximal values of the inverted U-like functions occurred at different levels. In the third group, only the peak amplitude of the Na+ current exhibited a clear inverted U-like function, but the inverse of the latency versus the electrical RNS, did not exhibit a clear inverted U-like function. A Hodgkin-Huxley neuron model reproduces our experimental results and shows that the observed behavior in the Na+ current could be due to the impact of RNS on the kinetics of activation and inactivation of the Na+ channels.

Refractive errors among children, adolescents and adults attending eye clinics in Mexico.

AIM: To assess the proportion of refractive errors in the Mexican population that visited primary care optometry clinics in fourteen states of Mexico. METHODS: Refractive data from 676 856 patients aged 6 to 90y were collected from optometry clinics in fourteen states of Mexico between 2014 and 2015. The refractive errors were classified by the spherical equivalent (SE), as follows: sphere+½ cylinder. Myopia (SE>-0.50 D), hyperopia (SE>+0.50 D), emmetropia (-0.50≤SE≤+0.50), and astigmatism alone (cylinder≥-0.25 D). A negative cylinder was selected as a notation. RESULTS: The proportion (95% confidence interval) among all of the subjects was hyperopia 21.0% (20.9-21.0), emmetropia 40.7% (40.5-40.8), myopia 24.8% (24.7-24.9) and astigmatism alone 13.5% (13.4-13.5). Myopia was the most common refractive error and frequency seemed to increase among the young population (10 to 29 years old), however, hyperopia increased among the aging population (40 to 79 years old), and astigmatism alone showed a decreasing trend with age (6 to 90y; from 19.7% to 10.8%). There was a relationship between age and all refractive errors (approximately 60%, aged 50 and older). The proportion of any clinically important refractive error was higher in males (61.2%) than in females (58.3%; P<0.0001). From fourteen states that collected information, the proportion of refractive error showed variability in different geographical areas of Mexico. CONCLUSION: Myopia is the most common refractive error in the population studied. This study provides the first data on refractive error in Mexico. Further programs and studies must be developed to address the refractive errors needs of the Mexican population.

Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species.

Vibrio is a genus of Gram-negative bacteria, some of which can cause serious infectious diseases. Vibrio infections are associated with the consumption of contaminated food and classified in Vibrio cholera infections and non-cholera Vibrio infections. In the present study, we investigate whether bovine lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences, are able to inhibit the growth or have bactericidal effect against V. cholerae and other Vibrio species. The antibacterial activity of LF and LF-peptides was assessed by kinetics of growth or determination of colony forming unit in bacteria treated with the peptides and antibiotics. To get insight in the mode of action, the interaction between bLF and bLF-peptides (coupled to FITC) and V. cholera was evaluated. The damage of effector-induced bacterial membrane permeability was measured by inclusion of the fluorescent dye propidium iodide using flow cytometry, whereas the bacterial ultrastructural damage in bacteria treated was observed by transmission electron microscopy. The results showed that bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera permeabilized the bacteria which membranes were seriously damaged. Assays with a multidrug-resistant strain of Vibrio species indicated that combination of sub-lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the concentration of the antibiotics to reach 95% growth inhibition. Furthermore, LFchimera were effective to inhibit the V. cholerae counts and damage due to this bacterium in a model mice. These data suggest that LFchimera and bLF are potential candidates to combat the V. cholerae and other multidrug resistant Vibrio species.

Surveillance of Diarrheagenic Escherichia coli Strains Isolated from Diarrhea Cases from Children, Adults and Elderly at Northwest of Mexico.

Diarrheagenic Escherichia coli (DEC) strains are a main cause of gastrointestinal disease in developing countries. In this study we report the epidemiologic surveillance in a 4-year period (January 2011 to December 2014) of DEC strains causing acute diarrhea throughout the Sinaloa State, Mexico. DEC strains were isolated from outpatients of all ages with acute diarrhea (N = 1,037). Specific DEC pathotypes were identified by PCR-amplification of genes encoding virulence factors. The adhesion phenotype and antibiotic resistance were also investigated. DEC strains were detected in 23.3% (242/1037) of cases. The most frequently DEC strain isolated was EAEC [(12.2%), 126/242] followed by EPEC [(5.1%), 53/242], ETEC [(4.3%), 43/242] DAEC [(1.4%), 15/242], STEC [(0.3%), 3/242], and EIEC [(0.2%), 2/242]. EHEC strains were not detected. Overall DEC strains were more prevalent in children ≤2 years of age with EPEC strains the most common of DEC pathotypes. While ∼65% of EAEC strains were classified as typical variant based on the aggregative adherence to in vitro cultures of HEp-2 cells, a high proportion of EPEC strains was classified as atypical strains. EAEC, EPEC, ETEC, and DAEC strains were distributed in the north, central and south regions of Sinaloa state. Among all DEC strains, >90% were resistant to at least one commonly prescribed antibiotic. Strains were commonly resistant to first-line antibiotics such as tetracycline, ampicillin, and sulfamethoxazole-trimethoprim. Furthermore, more than 80% of DEC isolates were multi-drug resistant and EPEC and DAEC were the categories with major proportion of this feature. In conclusion, in nearly one out of four cases of acute diarrhea in Northwestern Mexico a multi-drug resistant DEC strain was isolated, in these cases EAEC was the most prevalent (52%) pathotype.

Efecto radioprotector del piruvato de etilo, solo o como coadyuvante de la amifostina / Radioprotective effect of ethyl pyruvate alone or as a coadyuvant of amifostine / Efeito radioprotetor do piruvato de etila, sozinho ou como um coadjuvante de amifostina

Entre los radioprotectores con uso clínico se destaca la amifostina (WR- 2721), eficaz pero con efectos secundarios que impiden su uso repetitivo. Es interés de los autores desarrollar radioprotectores menos tóxicos, por sí mismos o como coadyuvantes de amifostina. Ratas machos o hembras se expusieron a una dosis de rayos X de 2 Gy. Se ensayó el piruvato de etilo, solo o conjuntamente con amifostina. Cuarenta y ocho horas después de la exposición a la radiación, se realizó el recuento de eritrocitos, de leucocitos y la fórmula leucocitaria. Los efectos genotóxicos se evaluaron en leucocitos de sangre mediante el ensayo Cometa. Se realizaron también estudios de supervivencia a 60 días post-irradiación. En los animales irradiados disminuyeron los eritrocitos, y el recuento de leucocitos se redujo drásticamente respecto al control, presentando además una fórmula alterada. El tratamiento con piruvato de etilo resultó en una protección de los eritrocitos en ambos sexos. El daño genético disminuyó significativamente por el tratamiento con piruvato de etilo solo o combinado con amifostina, y en hembras se observó una mayor supervivencia solo con el tratamiento combinado. El piruvato de etilo mostró una acción radioprotectora significativa, que podría mejorarse aumentando la dosis o el tiempo de tratamiento, ya que tiene muy baja toxicidad.

Among the currently available radioprotectors, only amifostine (WR-2721) has shown in clinical trials to reduce radiation-induced toxicity. This compound is an efficient radioprotector but it exhibits some undesirable side effects which prevent its repetitive use. Efforts are directed to develop radioprotective agents with lower toxicity, with their own protective potential or suitable as coadyuvants of amifostine. The present study describes the results obtained by repetitive oral administration of ethyl pyruvate. Male or female rats were exposed to an X-ray dose of 2 Gy. Forty-eight hours after exposure to radiation, erythrocyte count, leukocyte and differential count were performed. Genotoxic effects were assessed in blood leukocytes by the Comet assay. Survival studies were also performed at 60 days post-irradiation. Eritrocyte and leukocyte were reduced in animals exposed to radiation compared to the control, also presenting an altered formula. Treatment with ethyl pyruvate resulted in a protection on erythrocytes of both sexes. Genetic damage was significantly decreased by ethyl pyruvate alone or combined with amifostine, and in females, higher survival was observed only with combined administration. Ethyl pyruvate showed a significant radioprotective action, which could be improved by increasing the dose or time of treatment because it has low toxicity.

Entre os radioprotetores com uso clínico destaca-se a amifostina (WR-2721) eficaz mas com efeitos secundários que impedem seu uso repetitivo. O interesse dos autores é desenvolver radioprotetores menos tóxicos, por si mesmos ou como coadjuvantes de amistofina. Ratos machos ou fêmeas foram expostos a doses de raios X de 2Gy. Ensaiou-se o piruvato de etila, só ou junto com amifostina. Quarenta e oito horas após a exposição à radiação foi realizada a contagem de eritrócitos, de leucócitos e da fórmula leucocitária. Efeitos genotóxicos foram avaliados em leucócitos do sangue pelo Ensaio Cometa. Estudos de sobrevivência foram também realizados a 60 dias pós-irradiação. Nos animais irradiados diminuíram os eritrócitos, e a contagem de leucócitos se reduziu drasticamente em comparação com o controle, apresentando também uma fórmula alterada. O tratamento com piruvato de etila resultou numa proteção dos eritrócitos em ambos os sexos. O dano genético diminuiu significativamente pelo tratamento com piruvato de etila sozinho ou combinado com amifostina, e nas fêmeas se observou maior sobrevivência só com o tratamento combinado. O piruvato de etila mostrou uma ação radioprotetora significativa, que poderia ser melhorada pelo aumento da dose ou do tempo de tratamento, visto que tem baixa toxicidade.

Mecanismos involucrados en el cáncer de mama por consumo de alcohol y alternativas para su prevención / Mechanisms involved in breast cancer induced by alcohol drinking and alternatives for prevention / Mecanismos envolvidos no câncer de mama por consumo de álcool e alternativas para sua prevenção

El consumo de alcohol se asocia con un riesgo incrementado para el cáncer de mama, aumentando linealmente incluso con un consumo moderado y con independencia del tipo de bebida alcohólica. El mecanismo está aún lejos de haberse establecido. Los estudios realizados por este laboratorio sugieren que el acetaldehído producido in situ y acumulado en el tejido mamario podría desempeñar un papel en los eventos mutacionales y de promoción del proceso carcinogénico. Estudios posteriores indicaron la producción de especies reactivas de oxígeno, acompañada de la disminución en los contenidos de vitamina E y de glutatión y de la actividad glutatión transferasa. El estrés oxidativo resultante también podría desempeñar un papel relevante en varias etapas del proceso carcinogénico. Por otra parte, está demostrado que los niveles plasmáticos de los estrógenos aumentan significativamente después del consumo de alcohol y que el riesgo de cáncer de mama inducido por beber alcohol guarda mayor relación con los tumores mamarios con receptores de estrógeno (ER)- positivo en comparación con los ER-negativos. Los estrógenos pueden producir cáncer de mama por acciones sobre el ER y también como auténticos carcinógenos químicos, como consecuencia de su oxidación que conduce a metabolitos reactivos. En este trabajo se presenta una hipótesis que integra los efectos del acetaldehído y del estrés oxidativo con los que implica un aumento de los niveles de estrógeno. Se analizan posibles acciones preventivas accesibles.

Alcohol consumption is associated with an increased risk of breast cancer, increasing linearly even with a moderate consumption and irrespective of the type of alcoholic beverage. The precise mechanism is still far from being established. Studies by this laboratory suggest that acetaldehyde produced in situ and accumulated in mammary tissue because of poor detoxicating mechanisms might play a role in mutational and promotional events. Additional studies indicated the production of reactive oxygen species accompanied by decreases in vitamin E and glutathione contents and of glutathione transferase activity. The resulting oxidative stress might also play a relevant role in several stages of the carcinogenic process. Studies reported in the literature show that plasmatic levels of estrogens significantly increased after alcohol drinking and that breast cancer risk by alcohol is more related to ER-positive tumors than to ER-negative tumors. Estrogens are known to likely produce breast cancer by actions on ER and also act as chemical carcinogens as a result of their oxidation leading to reactive metabolites. In this review, a working hypothesis is introduced, integrating the effects of acetaldehyde and oxidative stress with those involving increased estrogen levels. Potential preventive actions are also analysed.

O consumo de álcool está associado a um risco elevado de câncer de mama aumentando linearmente mesmo com o consumo moderado e independentemente do tipo de bebida alcoólica. O mecanismo está ainda longe de ter-se estabelecido. Estudos realizados por esse laboratório sugerem que o acetaldeído produzido in situ e acumulado no tecido mamário, poderia desempenhar um papel nos eventos mutacionais e de promoção do processo carcinogênico. Estudos posteriores indicaram a produção de espécies reativas de oxigênio, juntamente com uma diminuição nos conteúdos de vitamina E e de glutationa e da atividade glutationa transferase. O estresse oxidativo resultante também poderia desempenhar um papel importante em vários passos do processo carcinogênico. Aliás, está demonstrado que os níveis plasmáticos dos estrogênios aumentam significativamente após o consumo de álcool e que o risco de câncer de mama induzido por beber álcool guarda maior relação com os tumores mamários com receptores de estrogênio (ER)-positivo em comparação com os (ER)-negativos. Os estrogênios podem causar câncer de mama por ações sobre o ER e também como autênticos carcinógenos químicos, como resultado de sua oxidação que leva a metabólitos reativos. Neste trabalho apresenta-se uma hipótese que integra os efeitos do acetaldeído e do estresse oxidativo que envolvem um aumento nos níveis de estrogênio. Ações preventivas possíveis também são discutidas.

Enfermedad de Chagas: Contribuciones del Centro de Investigaciones Toxicológicas / Chagas disease: The contribution of the Center for Toxicological Research

La quimioterapia de la enfermedad de Chagas cuenta en la actualidad con el empleo de dos fármacos solamente: Nifurtimox y Benznidazol. Nifurtimox es un nitrofurano y Benznidazol es un compuesto nitroimidazólico. El uso de estas drogas para tratar la fase aguda de la enfermedad se acepta ampliamente. Sin embargo, su utilización en el tratamiento de la fase crónica no está exenta de cuestionamientos serios. Los efectos colaterales de ambas son un inconveniente mayor en su uso, y frecuentemente fuerza a los médicos a detener el tratamiento. Los estudios de toxicidad experimentales con Nifurtimox evidenciaron neurotoxicidad, daño testicular, toxicidad ovárica y efectos deletéreos en corazón, tejido mamario, adrenales, colon y esófago. Para el Benznidazol, se observaron efectos deletéreos en adrenales, colon y esófago. También inhibe el metabolismo de varios xenobióticos transformados por el sistema del citocromo P450 y sus metabolitos reaccionan con los componentes fetales in vivo. Ambas drogas exhibieron efectos mutagénicos significativos y se demostró en algunos estudios que eran carcinogénicas o tumorigénicas. Los efectos tóxicos de ambos fármacos dependen de la reducción enzimática de su grupo nitro. En este trabajo se resume la actividad de este laboratorio en el esfuerzo por comprender los mecanismos de la acción tóxica de estos fármacos...

Mecanismos involucrados en el cáncer de mama por consumo de alcohol y alternativas para su prevención / Mechanisms involved in breast cancer induced by alcohol drinking and alternatives for prevention / Mecanismos envolvidos no cÔncer de mama por consumo de álcool e alternativas para sua prevenþÒo

El consumo de alcohol se asocia con un riesgo incrementado para el cáncer de mama, aumentando linealmente incluso con un consumo moderado y con independencia del tipo de bebida alcohólica. El mecanismo está aún lejos de haberse establecido. Los estudios realizados por este laboratorio sugieren que el acetaldehído producido in situ y acumulado en el tejido mamario podría desempeñar un papel en los eventos mutacionales y de promoción del proceso carcinogénico. Estudios posteriores indicaron la producción de especies reactivas de oxígeno, acompañada de la disminución en los contenidos de vitamina E y de glutatión y de la actividad glutatión transferasa. El estrés oxidativo resultante también podría desempeñar un papel relevante en varias etapas del proceso carcinogénico. Por otra parte, está demostrado que los niveles plasmáticos de los estrógenos aumentan significativamente después del consumo de alcohol y que el riesgo de cáncer de mama inducido por beber alcohol guarda mayor relación con los tumores mamarios con receptores de estrógeno (ER)- positivo en comparación con los ER-negativos. Los estrógenos pueden producir cáncer de mama por acciones sobre el ER y también como auténticos carcinógenos químicos, como consecuencia de su oxidación que conduce a metabolitos reactivos. En este trabajo se presenta una hipótesis que integra los efectos del acetaldehído y del estrés oxidativo con los que implica un aumento de los niveles de estrógeno. Se analizan posibles acciones preventivas accesibles.(AU)

Alcohol consumption is associated with an increased risk of breast cancer, increasing linearly even with a moderate consumption and irrespective of the type of alcoholic beverage. The precise mechanism is still far from being established. Studies by this laboratory suggest that acetaldehyde produced in situ and accumulated in mammary tissue because of poor detoxicating mechanisms might play a role in mutational and promotional events. Additional studies indicated the production of reactive oxygen species accompanied by decreases in vitamin E and glutathione contents and of glutathione transferase activity. The resulting oxidative stress might also play a relevant role in several stages of the carcinogenic process. Studies reported in the literature show that plasmatic levels of estrogens significantly increased after alcohol drinking and that breast cancer risk by alcohol is more related to ER-positive tumors than to ER-negative tumors. Estrogens are known to likely produce breast cancer by actions on ER and also act as chemical carcinogens as a result of their oxidation leading to reactive metabolites. In this review, a working hypothesis is introduced, integrating the effects of acetaldehyde and oxidative stress with those involving increased estrogen levels. Potential preventive actions are also analysed.(AU)

O consumo de álcool está associado a um risco elevado de cÔncer de mama aumentando linearmente mesmo com o consumo moderado e independentemente do tipo de bebida alcoólica. O mecanismo está ainda longe de ter-se estabelecido. Estudos realizados por esse laboratório sugerem que o acetaldeído produzido in situ e acumulado no tecido mamário, poderia desempenhar um papel nos eventos mutacionais e de promoþÒo do processo carcinogÛnico. Estudos posteriores indicaram a produþÒo de espécies reativas de oxigÛnio, juntamente com uma diminuiþÒo nos conteúdos de vitamina E e de glutationa e da atividade glutationa transferase. O estresse oxidativo resultante também poderia desempenhar um papel importante em vários passos do processo carcinogÛnico. Aliás, está demonstrado que os níveis plasmáticos dos estrogÛnios aumentam significativamente após o consumo de álcool e que o risco de cÔncer de mama induzido por beber álcool guarda maior relaþÒo com os tumores mamários com receptores de estrogÛnio (ER)-positivo em comparaþÒo com os (ER)-negativos. Os estrogÛnios podem causar cÔncer de mama por aþ§es sobre o ER e também como autÛnticos carcinógenos químicos, como resultado de sua oxidaþÒo que leva a metabólitos reativos. Neste trabalho apresenta-se uma hipótese que integra os efeitos do acetaldeído e do estresse oxidativo que envolvem um aumento nos níveis de estrogÛnio. Aþ§es preventivas possíveis também sÒo discutidas.(AU)

Enfermedad de Chagas: Contribuciones del Centro de Investigaciones Toxicológicas / Chagas disease: The contribution of the Center for Toxicological Research / Doenþa de Chagas: Contribuiþ§es do Centro de Investigaþ§es Toxicológicas

La quimioterapia de la enfermedad de Chagas cuenta en la actualidad con el empleo de dos fármacos solamente: Nifurtimox y Benznidazol. Nifurtimox es un nitrofurano y Benznidazol es un compuesto nitroimidazólico. El uso de estas drogas para tratar la fase aguda de la enfermedad se acepta ampliamente. Sin embargo, su utilización en el tratamiento de la fase crónica no está exenta de cuestionamientos serios. Los efectos colaterales de ambas son un inconveniente mayor en su uso, y frecuentemente fuerza a los médicos a detener el tratamiento. Los estudios de toxicidad experimentales con Nifurtimox evidenciaron neurotoxicidad, daño testicular, toxicidad ovárica y efectos deletéreos en corazón, tejido mamario, adrenales, colon y esófago. Para el Benznidazol, se observaron efectos deletéreos en adrenales, colon y esófago. También inhibe el metabolismo de varios xenobióticos transformados por el sistema del citocromo P450 y sus metabolitos reaccionan con los componentes fetales in vivo. Ambas drogas exhibieron efectos mutagénicos significativos y se demostró en algunos estudios que eran carcinogénicas o tumorigénicas. Los efectos tóxicos de ambos fármacos dependen de la reducción enzimática de su grupo nitro. En este trabajo se resume la actividad de este laboratorio en el esfuerzo por comprender los mecanismos de la acción tóxica de estos fármacos.(AU)

Chemotherapy of Chagas disease is currently performed by the use of only two drugs: Nifurtimox and Benznidazole. Nifurtimox is a nitrofurane and Benznidazole is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is now widely accepted. However, their use in the treatment of the chronic phase is not without serious consequences. The side effects of both drugs are a major drawback in their use and often force physicians to stop treatment. In the case of Nifurtimox, experimental toxicity studies showed neurotoxicity, testicular damage, ovarian toxicity and deleterious effects in heart, breast tissue, adrenals, colon and esophagus. Benznidazole deleterious effects were observed in adrenals, colon and esophagus. It also inhibits the metabolism of various xenobiotics transformed by cytochrome P450 and its metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and in some studies, they demonstrated to be carcinogenic or tumorigenic. Toxic effects of both drugs are dependent on the enzymatic reduction of the nitro group. This paper summarizes this laboratory’s activity in an effort to understand the mechanisms of these drugs’ toxic action.(AU)

A quimioterapia da doenþa de Chagas tem atualmente com o uso de apenas dois medicamentos: nifurtimox e benzonidazol. Nifurtimox é um nitrofuran e benzonidazol é um composto nitroimidazólico. A utilizaþÒo destes fármacos para o tratamento da fase aguda da doenþa é agora amplamente aceite. No entanto, a sua utilizaþÒo no tratamento da fase crónica nÒo é sem dúvida graves. Os efeitos colaterais de ambas sÒo uma grande desvantagem na sua utilizaþÒo, e frequentemente médicos forþa para interromper o tratamento. Estudos experimentais com Nifurtimox mostraram neurotoxicidade, lesÒo testicular, toxicidade ovariana e efeitos deletérios no coraþÒo, tecido mamário, adrenal, cólon e es¶fago. Para benzonidazole efeitos deletérios foram observadas em supra-renal, cólon e esofágica. Também inibe o metabolismo de vários xenobióticos transformadas pelo citocromo P450 e seus metabolitos reagem com componentes fetal in vivo. Ambos os fármacos apresentaram efeitos mutagÛnicos significativos demonstrado em alguns estudos que eram cancerígenas ou tumorigenic. Os efeitos tóxicos de ambas as drogas sÒo dependentes da reduþÒo enzimática do grupo nitro. Neste trabalho a atividade do nosso laboratório no esforþo para compreender os mecanismos de aþÒo tóxica dessas drogas é resumida.(AU)