RESUMEN
The treatment of esophageal perforation (EP) remains a significant clinical challenge. While a number of investigators have previously documented efficient approaches, these were mostly single-center experiences reported prior to the introduction of newer technologies: specifically endoluminal stents. This study was designed to document contemporary practice in the diagnosis and management of EP at multiple institutions around the world and includes early clinical outcomes. A five-year (2009-2013) multicenter retrospective review of management and outcomes for patients with thoracic or abdominal esophageal perforation was conducted. Demographics, etiology, diagnostic modalities, treatments, subsequent early outcomes as well as morbidity and mortality were captured and analyzed. During the study period, 199 patients from 10 centers in the United States, Canada, and Europe were identified. Mechanisms of perforation included Boerhaave syndrome (60, 30.1%), iatrogenic injury (65, 32.6%), and penetrating trauma (25, 12.6%). Perforation was isolated to the thoracic segment alone in 124 (62.3%), with 62 (31.2%) involving the thoracoabdominal esophagus. Mean perforation length was 2.5 cm. Observation was selected as initial management in 65 (32.7%), with only two failures. Direct operative intervention was initial management in 65 patients (32.6%), while 29 (14.6%) underwent esophageal stent coverage. Compared to operative intervention, esophageal stent patients were significantly more likely to be older (61.3 vs. 48.3 years old, P < 0.001) and have sustained iatrogenic mechanisms of esophageal perforation (48.3% vs.15.4%). Secondary intervention requirement for patients with perforation was 33.7% overall (66). Complications included sepsis (56, 28.1%), pneumonia (34, 17.1%) and multi-organ failure (23, 11.6%). Overall mortality was 15.1% (30). In contemporary practice, diagnostic and management approaches to esophageal perforation vary widely. Despite the introduction of endoluminal strategies, it continues to carry a high risk of mortality, morbidity, and need for secondary intervention. A concerted multi-institutional, prospectively collected database is ideal for further investigation.
Asunto(s)
Perforación del Esófago/cirugía , Esofagoscopía/métodos , Adulto , Anciano , Canadá , Perforación del Esófago/etiología , Esofagoscopía/efectos adversos , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Stents , Resultado del Tratamiento , Estados UnidosRESUMEN
AIMS: To test a nitric oxide-releasing solution (NORS) as a potential antifungal footbath therapy against Trichophyton mentagrophytes and Trichophyton rubrum during the mycelial and conidial phases. METHODS AND RESULTS: NORS (sodium nitrite citric acid) produces nitric oxide verified by gas chromatography and mass spectrometry (GC-MS). Antifungal activity of this solution was tested against mycelia and conidia of T. mentagrophytes and T. rubrum, using 1-20 mmol l(-1) nitrites and 10-30 min exposure times. The direct effect of the gas released from the solution on the viability of those fungi was tested. NORS demonstrated strong antifungal activity and was found to be dose and time dependent. NO and nitrogen dioxide (NO(2) ) were the only gases detected from this reaction and are likely responsible for the antifungal effect. CONCLUSIONS: This in vitro research suggests that a single 20-min exposure to NORS could potentially be used as an effective single-dose treatment against fungi that are associated with tinea pedis in both mycelia and spore phase. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides the background for developing a user-friendly footbath treatment for Athlete's Foot that will kill both vegetative fungi and its spores.
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Antifúngicos/farmacología , Óxido Nítrico/metabolismo , Trichophyton/efectos de los fármacos , Antifúngicos/química , Antifúngicos/uso terapéutico , Humanos , Tiña del Pie/tratamiento farmacológico , Tiña del Pie/microbiología , Trichophyton/crecimiento & desarrolloRESUMEN
Thermoluminescence dosimeter cards purchased by the US Navy in recent years have different radiation sensitivities, e.g., they exhibit a different amount of light per dose unit. Presented tests indicate that the optical transparency of the Teflon encapsulation is partially responsible for the significant variation of the DT-702/PD radiation sensitivity. It was confirmed also that the Teflon transparency is in fact a primary cause of the radiation sensitivity increase in the most recently produced dosimetric cards. This conclusion is based on the correlation found between the calibrated radiation sensitivity of the dosimeter card element and the optical transparency of its Teflon encapsulation. The transparency measurements were performed at the wavelength of 400 nm within a 10 nm spectral interval effectively covering the spectral range of the thermoluminescence. It is anticipated that the experimentally determined correlation will help to approve the acceptance of new thermoluminescence dosimeter cards in the Naval Dosimetry Center inventory as well as improve the production process.
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Politetrafluoroetileno , Dosimetría Termoluminiscente/instrumentación , Fenómenos ÓpticosRESUMEN
Neurofilaments are transported through axons by slow axonal transport. Abnormal accumulations of neurofilaments are seen in several neurodegenerative diseases, and this suggests that neurofilament transport is defective. Excitotoxic mechanisms involving glutamate are believed to be part of the pathogenic process in some neurodegenerative diseases, but there is currently little evidence to link glutamate with neurofilament transport. We have used a novel technique involving transfection of the green fluorescent protein-tagged neurofilament middle chain to measure neurofilament transport in cultured neurons. Treatment of the cells with glutamate induces a slowing of neurofilament transport. Phosphorylation of the side-arm domains of neurofilaments has been associated with a slowing of neurofilament transport, and we show that glutamate causes increased phosphorylation of these domains in cell bodies. We also show that glutamate activates members of the mitogen-activated protein kinase family, and that these kinases will phosphorylate neurofilament side-arm domains. These results provide a molecular framework to link glutamate excitotoxicity with neurofilament accumulation seen in some neurodegenerative diseases.
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Transporte Axonal/fisiología , Ácido Glutámico/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neuronas/enzimología , Transporte Axonal/efectos de los fármacos , Transporte Biológico Activo/efectos de los fármacos , Células Cultivadas , Ácido Glutámico/farmacología , Proteínas Fluorescentes Verdes , Humanos , Proteínas Luminiscentes/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neuritas/metabolismo , Proteínas de Neurofilamentos/genética , Neuronas/citología , Fosforilación/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , TransfecciónRESUMEN
OBJECTIVES: The intractability of renal dysfunction following thoracic and thoraco-abdominal aortic repair leads us to believe that the accepted mechanisms of renal injury - ischaemia and embolism - are incompletely explanatory. We studied postoperative myoglobinaemia and renal dysfunction following aortic surgery. METHODS: Between September 2006 and February 2008, we studied serum myoglobin in 109 patients requiring thoracic/thoraco-abdominal repair for three postoperative days. Forty-two of the 109 (38%) patients were female. The median age was 67 years (range 23-84 years). As we have focussed more attention on renal function, our independent renal consultants have dialysed more aggressively. We divided dialysis into: (1) creatinine indication, (2) non-creatinine indication and (3) no dialysis. RESULTS: Thirteen of the 109 (12%) patients met creatinine indication for dialysis (>4 mg dl(-1)) and an additional 28 (26%) were dialysed for other reasons. Overall mortality was 12 out of 109 (11%) cases: 11 out of 41 (27%) in dialysed patients and one out of 68 (1.5%) in non-dialysed patients. Mortality did not differ between the indications for dialysis. Predictors of mortality were baseline glomerular filtration rate (GFR), postoperative myoglobin and dialysis. The only predictor of dialysis was postoperative myoglobin. CONCLUSION: A strong relationship between postoperative serum myoglobin and renal failure suggests a rhabdomyolysis-like contributing aetiology following thoraco-abdominal aortic repair. We postulate a novel mechanism of renal injury for which mitigation strategies should be developed.
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Lesión Renal Aguda/etiología , Aneurisma de la Aorta Torácica/cirugía , Mioglobina/sangre , Rabdomiólisis/complicaciones , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Adulto , Anciano , Anciano de 80 o más Años , Aorta Abdominal/cirugía , Aorta Torácica/cirugía , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Periodo Posoperatorio , Diálisis Renal , Factores de Riesgo , Adulto JovenRESUMEN
Remarkable progress has been made in the surgical treatment of thoracoabdominal aortic aneurysms. The decline in mortality and complication rates can be attributed to improvements in perioperative care and in surgical technique, particularly the adoption of adjunct distal aortic perfusion and cerebrospinal fluid drainage. Neurologic deficit is no longer a major threat to patients, as the use of adjuncts has brought the incidence down to 2.4% for all thoracoabdominal aortic aneurysms. However, we continue to pursue research to improve organ preservation, particularly for the most troublesome extent II thoracoabdominal aortic aneurysm.
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Aneurisma de la Aorta Torácica/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Aneurisma de la Aorta Torácica/clasificación , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/epidemiología , Humanos , Cuidados Posoperatorios , Cuidados PreoperatoriosRESUMEN
At present, broadband radiometric measurements of LEDs with uniform and low-uncertainty results are not available. Currently, either complicated and expensive spectral radiometric measurements or broadband photometric LED measurements are used. The broadband photometric measurements are based on the CIE standardized V(λ) function, which cannot be used in the UV range and leads to large errors when blue or red LEDs are measured in its wings, where the realization is always poor. Reference irradiance meters with spectrally constant response and high-intensity LED irradiance sources were developed here to implement the previously suggested broadband radiometric LED measurement procedure [1, 2]. Using a detector with spectrally constant response, the broadband radiometric quantities of any LEDs or LED groups can be simply measured with low uncertainty without using any source standard. The spectral flatness of filtered-Si detectors and low-noise pyroelectric radiometers are compared. Examples are given for integrated irradiance measurement of UV and blue LED sources using the here introduced reference (standard) pyroelectric irradiance meters. For validation, the broadband measured integrated irradiance of several LED-365 sources were compared with the spectrally determined integrated irradiance derived from an FEL spectral irradiance lamp-standard. Integrated responsivity transfer from the reference irradiance meter to transfer standard and field UV irradiance meters is discussed.
RESUMEN
BACKGROUND: Many behavioral and physiological studies of laboratory mice employ invasive methods such as radio telemetry to measure key aspects of behavior and physiology. Radio telemetry requires surgical implants, which may impact mouse health and behavior, and thus reduce the reliability of the data collected. NEW METHOD: We developed a method to measure key aspects of thermoregulatory behavior without compromising animal welfare. We examined the thermoregulatory response to heat stress in a custom-built arena that permitted the use of simultaneous and continuous infrared thermography (IRT) and video capture. This allowed us to measure changes in surface body temperature and determine total distance traveled using EthoVision XT animal tracking software. RESULTS: Locomotor activity and surface body temperature differed between heat-stressed mice and mice kept within their thermal comfort zone. The former had an increase in surface body temperature and a decline in locomotor activity, whereas the latter had a stable surface body temperature and showed greater activity levels. METHODS: Surface body temperature and locomotor activity are conventionally quantified by measurements taken at regular intervals, which limit the use and accuracy of the data. We obtained data of high resolution (i.e., recorded continuously) and accuracy that allowed for the examination of key physiological measurements such as energy expenditure and peripheral vasomotor tone. CONCLUSIONS: This novel experimental method for studying thermoregulatory behavior in mice using non-invasive tools has advantages over radio-telemetry and represents an improvement in laboratory animal welfare.
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Actigrafía/métodos , Conducta Animal , Modelos Animales de Enfermedad , Trastornos de Estrés por Calor , Termografía/métodos , Grabación en Video/métodos , Aire , Animales , Conducta Animal/fisiología , Temperatura Corporal , Regulación de la Temperatura Corporal , Femenino , Trastornos de Estrés por Calor/fisiopatología , Trastornos de Estrés por Calor/psicología , Calor , Rayos Infrarrojos , Luz , Ratones Endogámicos C57BL , Actividad Motora/fisiología , Pigmentación/fisiología , Programas InformáticosRESUMEN
Isoprene emitted by vegetation is an important precursor of secondary organic aerosol (SOA), but the mechanism and yields are uncertain. Aerosol is prevailingly aqueous under the humid conditions typical of isoprene-emitting regions. Here we develop an aqueous-phase mechanism for isoprene SOA formation coupled to a detailed gas-phase isoprene oxidation scheme. The mechanism is based on aerosol reactive uptake coefficients (γ) for water-soluble isoprene oxidation products, including sensitivity to aerosol acidity and nucleophile concentrations. We apply this mechanism to simulation of aircraft (SEAC4RS) and ground-based (SOAS) observations over the Southeast US in summer 2013 using the GEOS-Chem chemical transport model. Emissions of nitrogen oxides (NOx ≡ NO + NO2) over the Southeast US are such that the peroxy radicals produced from isoprene oxidation (ISOPO2) react significantly with both NO (high-NOx pathway) and HO2 (low-NOx pathway), leading to different suites of isoprene SOA precursors. We find a mean SOA mass yield of 3.3 % from isoprene oxidation, consistent with the observed relationship of total fine organic aerosol (OA) and formaldehyde (a product of isoprene oxidation). Isoprene SOA production is mainly contributed by two immediate gas-phase precursors, isoprene epoxydiols (IEPOX, 58% of isoprene SOA) from the low-NOx pathway and glyoxal (28%) from both low- and high-NOx pathways. This speciation is consistent with observations of IEPOX SOA from SOAS and SEAC4RS. Observations show a strong relationship between IEPOX SOA and sulfate aerosol that we explain as due to the effect of sulfate on aerosol acidity and volume. Isoprene SOA concentrations increase as NOx emissions decrease (favoring the low-NOx pathway for isoprene oxidation), but decrease more strongly as SO2 emissions decrease (due to the effect of sulfate on aerosol acidity and volume). The US EPA projects 2013-2025 decreases in anthropogenic emissions of 34% for NOx (leading to 7% increase in isoprene SOA) and 48% for SO2 (35% decrease in isoprene SOA). Reducing SO2 emissions decreases sulfate and isoprene SOA by a similar magnitude, representing a factor of 2 co-benefit for PM2.5 from SO2 emission controls.
RESUMEN
Hypoxia-induced delayed neuronal death is known to require de novo gene expression; however, the molecular mediators that are involved remain undefined. The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha), in addition to promoting the expression of adaptive genes under conditions of hypoxia, has been implicated as being a necessary component in p53-mediated cell death in tumors. Using herpes amplicon-mediated gene transfer in cortical neuronal cultures, we demonstrate that delivery of a dominant-negative form of HIF-1alpha (HIFdn), capable of disrupting hypoxia-dependent transcription, reduces delayed neuronal death that follows hypoxic stress. In contrast, hypoxia-resistant p53-null primary cultures are not protected by HIFdn expression. These data indicate that, in hypoxic neurons, HIF-1alpha and p53 conspire to promote a pathological sequence resulting in cell death.
Asunto(s)
Muerte Celular/fisiología , Hipoxia de la Célula/fisiología , Proteínas de Unión al ADN/fisiología , Genes p53 , Neuronas/fisiología , Proteínas Nucleares/fisiología , Factores de Transcripción/fisiología , Animales , Células Cultivadas , Genes Dominantes , Humanos , Factor 1 Inducible por Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones , Ratones Noqueados , Factores de Tiempo , Transcripción Genética , Células Tumorales CultivadasRESUMEN
In order to elucidate the metabolic fate of eicosapentaenoic acid (20:5 (n-3], a major n-3 fatty acid constituent of fish oil, resident and casein-elicited mouse peritoneal macrophages were incubated with [3H]20:5 (n-3). Comparative experiments with arachidonic acid (20:4 (n-6] were also conducted. After 4, 8 and 18 h incubation, [3H]20:5 (n-3) was extensively elongated into [3H]22:5(n-3) while [3H]20:4(n-6) was only moderately elongated into [3H]22:4(n-6) in both resident and elicited macrophages. No measurable conversion of [3H]22:5(n-3) into [3H]22:6(n-3) (delta 4 desaturation) could be demonstrated. These data demonstrate that the highly active chain elongation of 20:5(n-3) by macrophage elongase, as well as the lack of detectable delta 4 desaturase activity, are responsible for the accumulation of 22:5(n-3) in this cell.
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Ácido Eicosapentaenoico/metabolismo , Macrófagos/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Ácidos Grasos Insaturados/metabolismo , Femenino , Ratones , Ratones Endogámicos C57BL , Cavidad Peritoneal/citologíaRESUMEN
This study examined the metabolism of dihomo-gamma-linolenic acid (20:3(n-6] in casein-elicited murine peritoneal macrophages. Cells were incubated with [14C]20:3(n-6) in the presence of 1% fetal bovine serum (FBS) or 0.025% bovine serum albumin (BSA), and the distribution and identity of membrane-bound and soluble products were determined. Approx. 70-80% of the [14C]20:3(n-6) was recovered in membrane phospholipids. The distribution of radiolabel in individual cellular phospholipids revealed a time-dependent (6 vs. 16 h) increase in the percentage of radiolabel esterified to phosphatidylethanolamine (PE). Analysis of cellular total lipids following transmethylation indicated that approx. 4, 2 and 9% of the incorporated 20:3(n-6), respectively, had been desaturated and elongated into 20:4(n-6), 22:4(n-6) and 22:3(n-6). When cells prelabeled for 16 h were incubated in the presence of the divalent cation ionophore, A23187, or zymosan for 30-60 min, two radiolabeled metabolites were isolated in the incubation supernatant. These metabolites were identified as 12-hydroxy-8,10,14- and 15-hydroxy-8,11,13-eicosatrienoic acids, as determined by reverse-phase and normal-phase high-performance liquid chromatography. The generation of monohydroxy fatty acids was notably absent in prelabeled quiescent cells and A23187-stimulated cells incubated with BW755C, a dual cyclooxygenase and lipoxygenase inhibitor. We conclude that casein-elicited murine peritoneal macrophages can extensively metabolize 20:3(n-6) through delta 5-desaturase, elongase and oxygenation reactions.
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Ácido 8,11,14-Eicosatrienoico/metabolismo , Ácidos Grasos Insaturados/metabolismo , Macrófagos/metabolismo , Animales , Líquido Ascítico/citología , Calcimicina/farmacología , Células Cultivadas , Cromatografía Líquida de Alta Presión , Femenino , Cinética , Lípidos/análisis , Ratones , Ratones Endogámicos C57BLRESUMEN
Spinal bulbar muscular atrophy (SBMA) is one of a family of inherited neurodegenerative diseases caused by expansion of CAG encoding polyglutamine repeats; in SBMA the affected gene is the androgen receptor. To understand further the mechanisms that lead to neuronal cell death in SBMA, we generated SHSY5Y neuroblastoma cell lines that stably express identical levels of wild-type (19 polyglutamine repeat) or SBMA (52 polyglutamine repeat) androgen receptor. Parental SHSY5Y cells do not express detectable levels of the androgen receptor. In the absence of androgen, the transfected cell lines have similar phenotypes and growth characteristics to parental SHSY5Y cells. However, upon treatment with androgen, both cell lines undergo a marked dose-dependent loss of viability; this loss was significantly greater in cells expressing the SBMA receptor. Morphological analyses of the androgen treated cells revealed that cell death bore hallmarks of apoptosis involving altered nuclear morphology and cleavage of poly(ADP-ribose) polymerase and of caspase 3 in both wild-type and SBMA cell lines. The caspase inhibitor VAD-fmk was able to decrease loss of viability of both cell lines on exposure to androgen.
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Apoptosis , Metribolona/farmacología , Enfermedad de la Neurona Motora/patología , Neuroblastoma/patología , Receptores Androgénicos/efectos de los fármacos , Congéneres de la Testosterona/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Vectores Genéticos , Humanos , Inmunohistoquímica , Enfermedad de la Neurona Motora/genética , Mutación , Neuroblastoma/genética , Neuroblastoma/metabolismo , Receptores Androgénicos/biosíntesis , Receptores Androgénicos/genética , Transfección , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
BACKGROUND: Extensive aortic aneurysms (ascending aorta, aortic arch, and descending or thoracoabdominal aorta) require innovative surgical techniques. Some surgeons advocate a single procedure with long periods of profound hypothermia, whereas others use a staged approach. We adopted a two-staged procedure (elephant trunk technique) in 1991 for elective repair of extensive aortic aneurysms. METHODS AND RESULTS: Between February 1991 and May 2000, we performed a total of 1146 aortic aneurysm operations. Of these, 182 (15.9%) operations were first- or second-stage elephant trunk procedures, performed in a total of 117 patients. Stage 1 was completed in all 117 patients. Stage 2 was completed in 65 (55.6%) of 117 patients. Thirty-day mortality rate for the first stage was 5.1% (6 of 117). Mortality rate during the interval between operations was 3.6% (4 of 111), of which 75% (3 of 4) were the result of aneurysm rupture. Thirty-day mortality rate for the second stage was 6.2% (4 of 65). A total of 43 patients did not return for second-stage repair. Among these patients, within an average period of 3.4 years (range, 1.5 months to 4.9 years), 13 of 43 (30.2%) died, 4 of 13 (30.8%) as the result of rupture. Two of 117 (1.7%) first-stage patients had postoperative stroke. No spinal cord dysfunction occurred in second-stage patients. CONCLUSIONS: Extensive aortic aneurysms can be repaired with acceptable morbidity and mortality rates through the use of the elephant trunk technique. Death was most commonly the result of rupture, both in interval patients awaiting scheduled second-stage repair and in patients who did not return. After the first stage, prompt treatment of the remaining segment is crucial to the success of staged repair.
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Aneurisma de la Aorta/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aorta Abdominal/patología , Aorta Abdominal/cirugía , Aorta Torácica/patología , Aorta Torácica/cirugía , Aneurisma de la Aorta/epidemiología , Aneurisma de la Aorta/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Alzheimer's disease is the most common form of senile dementia and is predicted to become even more prevalent as the proportion of elderly in the population increases over the next few decades. As yet, there are no effective treatments for the disorder. A major limitation to identifying new drugs and therapeutic targets for Alzheimer's disease has been the absence of an animal model displaying typical Alzheimer's pathology. Transgenic technology is now providing a powerful new approach for the development of animal models of Alzheimer's disease.
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Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/terapia , Animales Modificados Genéticamente , Precursor de Proteína beta-Amiloide/genética , Animales , Modelos Animales de Enfermedad , Síndrome de Down/genética , HumanosRESUMEN
Reversal of essential fatty acid deficiency (EFA) induced epidermal hyperproliferation was recently suggested to require linoleic acid and an active lipoxygenase product. Because the nature of this lipoxygenase product is unknown, we employed a model of n-3 polyunsaturated fatty acid (PUFA) induced hyperproliferation in guinea pig skin to test a possible reversal of the hyperproliferation by an oxidative metabolite of linoleic acid. Topical applications of two n-3 PUFA: 0.5% of eicosapentaenoic acid (20:5n-3) and/or of docosahexaenoic acid (22:6n-3) for 5 d induced severe epidermal hyperproliferation. Development of the epidermal hyperproliferation paralleled a marked decrease in the major epidermal linoleic acid lipoxygenase product (13-hydroxyoctadecadienoic acid; 13-HODE). The application of 0.1% of 13-HODE to the n-3 PUFA-induced guinea pig hyperproliferative skin resulted in the restoration of normal epidermal histology and reversal of hyperproliferation as determined by epidermal uptake of 3H-thymidine. These data support the view that 13-HODE may represent the endogenous cutaneous mediator necessary for full restoration of cutaneous symptoms of essential fatty acid deficiency. Furthermore, the topical use of n-3 PUFA for the disruption of normal metabolism of skin n-6 EFA (linoleic acid) does serve as a useful tool for further investigations into the regulatory mechanisms of in vivo epidermal proliferation/differentiation.
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Ácidos Grasos Insaturados/farmacología , Ácidos Linoleicos/metabolismo , Piel/patología , Administración Tópica , Animales , Ácido Araquidónico , Ácidos Araquidónicos/metabolismo , División Celular/efectos de los fármacos , Fenómenos Químicos , Química , ADN/antagonistas & inhibidores , ADN/biosíntesis , Epidermis/efectos de los fármacos , Epidermis/metabolismo , Epidermis/patología , Ácidos Grasos/metabolismo , Cobayas , Ácido Linoleico , Piel/efectos de los fármacos , Piel/metabolismoRESUMEN
Clinical reports have attributed the amelioration of chronic inflammatory skin disorders to the presence of certain polyunsaturated fatty acids (PUFA) in dietary oils. To test the hypothesis of a local modulatory effect of these PUFA in the epidermis, the basal diet of normal guinea pigs was supplemented with ethyl esters of either fish oil [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] or borage oil [rich in gamma-linolenic acid (GLA)]. Our data demonstrated that dietary oils influence the distribution of PUFA in epidermal phospholipids and the epidermal levels of PUFA-derived hydroxy fatty acids. Specifically, animals supplemented with ethyl esters of fish oil markedly incorporated EPA and DHA into epidermal phospholipids, which paralleled the epidermal accumulation of 15-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDoHE). Similarly, animals supplemented with esters of borage oil preferentially incorporated dihomogammalinolenic acid (DGLA), the epidermal elongase product of GLA, into the epidermal phospholipids, which also was accompanied by epidermal accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE). By factoring the epidermal levels of the 15-lipoxygenase products and their relative inhibitory potencies, we evolved a measure of the overall potential of dietary oils to exert local anti-inflammatory effect. For example, the leukotriene inhibition potentials (LIP) of both fish oil and borage oil were greatly enhanced when compared to controls. Thus, the altered profiles of epidermal 15-lipoxygenase products generated from particular dietary oils may be responsible, at least in part, for reported ameliorative effects of oils on chronic inflammatory skin disorders.
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Grasas de la Dieta/metabolismo , Epidermis/metabolismo , Ácidos Grasos Insaturados/metabolismo , Aceites de Pescado/metabolismo , Animales , Araquidonato 15-Lipooxigenasa/metabolismo , Línea Celular , Cobayas , Hidroxiácidos/aislamiento & purificación , Hidroxiácidos/metabolismo , Masculino , Valores de ReferenciaRESUMEN
We have previously described a rat model that responds to repetitive episodic hypoxia (FiO2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia-exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia.
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Presión Sanguínea , Hipoxia/fisiopatología , Simpatectomía , Animales , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Epinefrina/sangre , Epinefrina/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Hipoxia/sangre , Hipoxia/patología , Masculino , Miocardio/metabolismo , Norepinefrina/sangre , Norepinefrina/metabolismo , Oxidopamina/farmacología , Periodicidad , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
An association between chronic high blood pressure and obstructive sleep apnea has been described. We hypothesized that repetitive episodic hypoxia patterned after the hypoxia seen in sleep apnea could contribute to diurnal elevation of blood pressure. Using 12-second infusions of nitrogen into daytime sleeping chambers, four groups of male rats (250-375 g) were subjected to intermittent hypoxia (3-5% nadir ambient oxygen) every 30 seconds, 7 hours per day for up to 35 days. In one group, blood pressure was measured weekly by the tail-cuff method in conscious animals during 5 weeks of episodic hypoxia. In the other three groups, blood pressure was measured in conscious animals via femoral artery catheters at baseline and after 20, 30, or 35 days of exposure. Additional groups served as controls: two sham groups housed in identical "hypoxia" chambers received compressed air instead of nitrogen (35 days) while two other groups remained unhandled in their usual cages (35 days). Both groups challenged with 35 days episodic hypoxia showed significant increases in blood pressure compared with controls: the tail-cuff rats showed a 21 mm Hg increase in systolic pressure (p less than 0.05) and the intra-arterially measured rats a 13.7 mm Hg increase in mean arterial pressure (p less than 0.05). The 30-day exposed rats also showed a 5.7 mm Hg increase in mean pressure over baseline (p less than 0.05). Blood pressure did not change significantly from baseline in the control groups. Left ventricle-to-body weight ratio was higher in both 35-day exposed groups than in unhandled or sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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Presión Sanguínea , Ritmo Circadiano , Hipoxia/fisiopatología , Periodicidad , Animales , Determinación de la Presión Sanguínea/métodos , Hipoxia/patología , Masculino , Miocardio/patología , Tamaño de los Órganos , Ratas , Ratas Endogámicas , Valores de ReferenciaRESUMEN
Transgenic mice expressing the oncogenic protein-serine/threonine kinase Mos at high levels in the brain display progressive neuronal degeneration and gliosis. Gliosis developed in parallel with the onset of postnatal transgene expression and led to a dramatic increase in the number of astrocytes positive for GFAP, vimentin, and possibly tau. Interestingly, vimentin is normally expressed only in immature or neoplastic astrocytes, but appears to be induced to high levels in Mos-transgenic, mature astrocytes. Mos can activate mitogen activated protein kinase (MAPK) and MAPK has been implicated in Alzheimer-type tau phosphorylation. In the Mos-transgenic brain we found increased levels of phosphorylation at one epitope on tau containing serines 199 and 202 (numbering according to human tau), a pattern similar but not identical to that found in Alzheimer's disease. In addition, Mos-transgenic mice express a novel neurofilament-related protein that might be a proteolytic neurofilament heavy chain degradation product. These results suggest that activation of protein phosphorylation in neurons can result in changes in cytoskeletal proteins that might contribute to neuronal degeneration.