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Rare earth elements (REEs) are important raw materials for green technologies. However, REE mining and production uses techniques that are often not environmentally sustainable. Life cycle assessment (LCA) is a well-recognized method for evaluating the environmental impacts of products and technologies. This article provides an overview of the environmental impacts based on published LCA results of primary REE production. Existing major REE deposits (Bayan Obo in China, Mountain Pass in the United States, Mount Weld in Australia, ion-adsorption deposits in several Chinese southern provinces) and currently possible production routes are compared. Alternative minerals, such as eudialyte, are also discussed. The article shows which environmental effects can be minimized by technology optimization and environmental safety strategies. Additionally, some of the environmental impacts discussed, may be difficult to mitigate, as they depend on the mineral type. Activities along the complex process chain of REEs production that have particularly high environmental impacts are identified.
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Rare earth elements (REEs) are one of the most important elements used for transformation of the fossil era into a decarbonized future. REEs are essential for wind, electric and hybrid vehicles, and low-energy lighting. However, there is a general understanding that REEs come along with multiple environmental problems during their extraction and processing. Life cycle assessment (LCA) is a well-established method for a holistic evaluation of environmental effects of a product system considering the entire life cycle. This paper reviews LCA studies for determining the environmental impacts of rare earth oxide (REO) production from Bayan Obo and ion adsorption clays (IAC) in China, and shows why some studies lead to over- and underestimated results. We found out that current LCA studies of REE production provide a good overall understanding of the underlying process chains, which are mainly located in China. However, life cycle inventories (LCI) appear often not complete. Several lack accuracy, consistency, or transparency. Hence, resulting environmental impacts are subject to great uncertainty. This applies in particular to radioactivity and the handling of wastewater and slurry in tailing ponds, which have often been neglected. This article reviews 35 studies to identify suitable LCAs for comparison. The assessment covers the world's largest REO production facility, located in Bayan Obo, as well as in-situ leaching of IACs in the Southern Provinces of China. A total of 12 studies are selected, 8 for Bayan Obo and IACs each. The LCIs of these studies are reviewed in detail. The effects of over- and underestimated LCIs on the life cycle impact assessment (LCIA) are investigated. The partly controversial results of existing LCAs are analyzed thoroughly and discussed. Our results show that an increased consistency in LCA studies on REO production is needed.
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Metales de Tierras Raras , Animales , China , Ambiente , Estadios del Ciclo de Vida , Metales de Tierras Raras/análisis , InvestigaciónRESUMEN
AIMS: To test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors. METHODS: Male rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3 mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5 µg rimonabant (CB1 antagonist) or 5 µg SR144528 (CB2 antagonist) were studied in awake rats. RESULTS: After administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH. CONCLUSIONS: Urodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. © 2015 Wiley Periodicals, Inc.
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Amidohidrolasas/antagonistas & inhibidores , Médula Espinal/metabolismo , Obstrucción del Cuello de la Vejiga Urinaria/tratamiento farmacológico , Urodinámica/efectos de los fármacos , Animales , Canfanos/farmacología , Masculino , Ácidos Oléicos/farmacología , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor Cannabinoide CB2/antagonistas & inhibidores , Rimonabant , Médula Espinal/efectos de los fármacos , Obstrucción del Cuello de la Vejiga Urinaria/metabolismoRESUMEN
AIMS: Stromal growth is critical for prostate enlargement during benign prostatic hyperplasia (BPH). While responses of prostate cells to single growth factors have been well characterized, responses to multiple growth factors at once are poorly understood. Here, we examined the effects of combinations between epidermal growth factor (EGF), fibroblast growth factor (FGF), and transforming growth factor-ß1 (TGF-ß1) in human prostate stromal cells. MAIN METHODS: EGF, FGF, and TGF-ß1 were applied to WPMY-1 cells, an immortalized, non-malignant line of stromal cells from the human prostate. Hypertrophic responses were assessed by protein/DNA ratio, and cyclin D1 mRNA by RT-PCR. Expression of EGF, FGF, and TGF-ß1 and their receptors in human prostate tissue was analyzed by RT-PCR, Western blot, and fluorescence staining. KEY FINDINGS: Hypertrophic responses to single growth factors and combinations were similar. Combinations showed additive effects on cyclin D1 mRNA. Combination of EGF with TGF-ß1, but not EGF or TGF-ß1 alone, caused assembly of cells to a new two-dimensional structure, being characterized by dense aggregates connected by branches of few cells. EGF and TGF-ß1 were detected together in human prostates. Receptors for EGF and TGF-ß colocalized on stromal cells in human prostates. SIGNIFICANCE: Responses of prostate stromal cells to combinations of EGF, FGF, and TGF-ß1 may be quantitatively different, qualitatively different, or similar to responses to single growth factors. The combination of EGF and TGF-ß1, but not EGF or TGF-ß1 alone, induces aggregation of prostate stromal cells, which may be relevant for morphogenesis.
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Factor de Crecimiento Epidérmico/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Próstata/citología , Hiperplasia Prostática/metabolismo , Células del Estroma/fisiología , Factor de Crecimiento Transformador beta1/metabolismo , Western Blotting , Línea Celular , Fluorescencia , Humanos , Indoles , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Células del Estroma/metabolismoRESUMEN
PURPOSE: Smooth muscle contraction and prostate growth are important targets for medical therapy of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia. Honokiol and Magnolol are lignan constituents of Magnolia species, which are used in traditional Asian medicine. Here, we examined effects of honokiol and magnolol on contraction of human prostate tissue and on growth of stromal cells. METHODS: Prostate tissues were obtained from radical prostatectomy. Contraction of prostate strips was examined in organ bath studies. Effects in stromal cells were assessed in cultured immortalized human prostate stromal cells (WPMY-1). Ki-67 mRNA was assessed by reverse transcription-polymerase chain reaction, and proliferation by a fluorescence 5-ethynyl-2'-deoxyuridine assay. RESULTS: Honokiol (100µM) reduced noradrenaline-induced contractions, which was significant at 10 to 100µM noradrenaline. Honokiol reduced phenylephrine-induced contractions, which was significant at 3 to 100µM phenylephrine. Honokiol reduced electric field stimulation-induced contractions very slightly. In WPMY-1 cells, honokiol (24 hours) induced cell death. Magnolol (100µM) was without effects on contraction, and cellular viability. CONCLUSIONS: Honokiol inhibits smooth muscle contraction in the human prostate, and induces cell death in cultured stromal cells. Because prostate smooth muscle tone and prostate growth may cause LUTS, it appears possible that honokiol improves voiding symptoms.
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Smooth muscle contraction may be critical for lower urinary tract symptoms (LUTS) in patients with benign prostate hyperplasia and requires stable anchorage of the cytoskeleton to the cell membrane. These connections are regulated by focal adhesion kinase (FAK). Here, we addressed the involvement of FAK in the regulation of smooth muscle contraction in hyperplastic human prostate tissues. Prostate tissues were obtained from radical prostatectomy. Expression of FAK and focal adhesion proteins was assessed by Western blot analysis and immunohistochemical stainings. Effects of the FAK inhibitors PF-573228 and Y-11 on contraction of prostate strips were examined in the organ bath. Expression of FAK and focal adhesion proteins (integrin-5α, paxilin, and c-Src) was detected by Western blot analysis in prostate samples. By double immunofluorescence staining with calponin and pan-cytokeratin, expression of FAK was observed in stromal and epithelial cells. Immunoreactivity for FAK colocalized with integrin-5α, paxilin, talin, and c-Src. Stimulation of prostate tissues with the α1-adrenergic agonist phenylephrine increased the phosphorylation state of FAK at Tyr³97 and Tyr9²5 with different kinetics, which was blocked by the α1-adrenoceptor antagonist tamsulosin. Norepinephrine and phenylephrine induced concentration-dependent contractions of prostate strips. Both FAK inhibitors PF-573228 and Y-11 significantly inhibited norepinephrine- and phenylephrine-induced contractions. Finally, PF-573228 and Y-11 inhibited contractions induced by electric field stimulation, which was significant at the highest frequency. In conclusion, α1-adrenergic smooth muscle contraction or its regulation involves FAK in the human prostate. Consequently, FAK may be involved in the pathophysiology of LUTS and in current or future LUTS therapies.
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Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Contracción Muscular , Músculo Liso/fisiología , Próstata/enzimología , Receptores Adrenérgicos alfa 1/metabolismo , Proteína-Tirosina Quinasas de Adhesión Focal/antagonistas & inhibidores , Compuestos Heterocíclicos de Anillo en Puente , Humanos , Técnicas In Vitro , Masculino , Cadenas Ligeras de Miosina/metabolismo , Fenilefrina , Fosforilación , Quinolonas , SulfonasRESUMEN
The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.
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Factor Natriurético Atrial/metabolismo , Hipertensión Renovascular/metabolismo , Hipertensión Renovascular/fisiopatología , Péptido Natriurético Encefálico/metabolismo , Renina/metabolismo , Animales , Factor Natriurético Atrial/deficiencia , Factor Natriurético Atrial/genética , Presión Sanguínea/fisiología , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores del Factor Natriurético Atrial/deficiencia , Receptores del Factor Natriurético Atrial/genética , Receptores del Factor Natriurético Atrial/metabolismo , Sistema Renina-Angiotensina/fisiología , Instrumentos Quirúrgicos , Vasoconstricción/fisiología , Vasodilatación/fisiologíaRESUMEN
Inhibition of prostate smooth muscle contraction is an important strategy for medical treatment of lower urinary tract symptoms (LUTS). Besides α1-adrenoceptors, prostate smooth muscle contraction is induced by activation of thromboxane (TXA2) receptors (TXA2-R). Here, we examined the effects of the TXA2-R antagonist picotamide on contraction of human prostate tissue. Prostate tissues were obtained from radical prostatectomy. The effects of picotamide (300 µM), L-665,240 (3 µM), and seratrodast (3 µM) on U46619-, electric field stimulation- (EFS-), phenylephrine-, and norepinephrine-induced contractions were studied in organ baths. Expression of TXA2-R and TXA2 synthase (TXS) was examined by fluorescence stainings. Picotamide, seratrodast, and L-655,240 inhibited concentration-dependent contractions induced by the TXA2 analog U46619. Picotamide, but not seratrodast or L-655,240, inhibited frequency-dependent contractions induced by EFS. Picotamide inhibited concentration-dependent contractions induced by norepinephrine or by the selective α1-adrenoceptor agonist phenylephrine. In prostate strips, where only submaximal contraction by a low dose of phenylephrine was induced, application of U46619 raised tone to maximum phenylephrine-induced tension. Immunoreactivity for TXA2-R and TXS was observed in the stroma and in epithelial cells of glands. Colocalization of both immunoreactivites was observed with the smooth muscle markers calponin and α-smooth muscle actin, with the epithelial marker pan-cytokeratin, and with prostate-specific antigen in the stroma and glands. The receptor antagonist picotamide inhibits α1-adrenergic, TXA2-mediated, and EFS-induced contractions in the human prostate. To the best of our knowledge, this is the first antagonist able to inhibit two different contraction systems in the prostate.
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Agonistas Adrenérgicos/farmacología , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Ácidos Ftálicos/farmacología , Antagonistas de Prostaglandina/farmacología , Próstata/efectos de los fármacos , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Receptores de Tromboxano A2 y Prostaglandina H2/antagonistas & inhibidores , Tromboxanos/farmacología , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Humanos , Masculino , Músculo Liso/inervación , Músculo Liso/metabolismo , Próstata/inervación , Próstata/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Receptores de Tromboxano A2 y Prostaglandina H2/metabolismo , Transducción de Señal/efectos de los fármacos , Tromboxano-A Sintasa/metabolismoRESUMEN
Determination of glomerular filtration rate (GFR) in conscious mice is cumbersome for the experimenter and stressful for the animals. Here we report on a simple new technique allowing the transcutaneous measurement of GFR in conscious mice. This approach extends our previously developed technique for rats to mice. The technique relies on a miniaturized device equipped with an internal memory that permits the transcutaneous measurement of the elimination kinetics of the fluorescent renal marker FITC-sinistrin. This device is described and validated compared with FITC-sinistrin plasma clearance in healthy, unilaterally nephrectomized and pcy mice. In summary, we describe a technique allowing the measurement of renal function in freely moving mice independent of blood or urine sampling as well as of laboratory assays.
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Fluoresceínas , Tasa de Filtración Glomerular , Riñón/fisiología , Oligosacáridos , Animales , Estado de Conciencia , Colorantes Fluorescentes , Ratones , Miniaturización , Oligosacáridos/orina , Fenómenos Fisiológicos del Sistema UrinarioRESUMEN
Severe sepsis is often accompanied by acute renal failure with renal tubular dysfunction. Albuminuria is a common finding in septic patients and we studied whether it was due to an impairment of proximal tubular endocytosis of filtered albumin. We studied the regulation of megalin and cubilin, the two critical multiligand receptors responsible for albumin absorption, during severe experimental endotoxemia. Lipopolysaccharide (LPS) caused a time- and dose-dependent suppression of megalin and cubilin expression that was paralleled by a decrease in plasma albumin levels and an increase in the urine concentration of albumin in mice. Incubation of rat renal cortical slices with LPS also reduced the mRNA expression of megalin and cubilin. Further, LPS suppressed megalin and cubilin mRNA expression in murine primary proximal tubule cells and decreased the uptake of FITC albumin in these cells. In addition, the increase in urine levels of albumin in response to ischemia/reperfusion-induced acute renal failure was paralleled by a decrease in the expression of megalin and cubilin. Thus, our data indicate that the expression of megalin and cubilin is decreased during experimental endotoxemia and in response to renal ischemia/reperfusion injury. This downregulation may contribute, in part, to an increase in urine levels of albumin during acute renal failure.
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Albuminuria/etiología , Endotoxemia/complicaciones , Túbulos Renales Proximales/metabolismo , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Receptores de Superficie Celular/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Albuminuria/sangre , Albuminuria/genética , Albuminuria/fisiopatología , Albuminuria/orina , Animales , Biomarcadores/sangre , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo , Endocitosis , Endotoxemia/sangre , Endotoxemia/inducido químicamente , Endotoxemia/genética , Endotoxemia/fisiopatología , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Capacidad de Concentración Renal , Túbulos Renales Proximales/fisiopatología , Lipopolisacáridos , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Masculino , Ratones , Ratones Endogámicos BALB C , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Superficie Celular/genética , Daño por Reperfusión/complicaciones , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Albúmina Sérica/metabolismo , Factores de TiempoRESUMEN
The sympathetic nervous system stimulates renin release from juxtaglomerular cells via the ß-adrenoreceptor-cAMP pathway. Recent in vitro studies have suggested that the calcium-inhibited adenylyl cyclases (ACs) 5 and 6 possess key roles in the control of renin exocytosis. To investigate the relative contribution of AC5 and AC6 to the regulation of renin release in vivo we performed experiments using AC5 and AC6 knockout mice. Male AC5(-/-) mice exhibited normal plasma renin concentrations, renal renin synthesis (mRNA and renin content), urinary volume, and systolic blood pressure. In male AC6(-/-) mice, plasma renin concentration (AC6(-/-): 732 ± 119; AC6 (+/+): 436 ± 78 ng of angiotensin I per hour*mL(-1); P<0.05), and renin synthesis were stimulated associated with an increased excretion of dilute urine (1.55-fold; P<0.05) and reduced blood pressure (-10.6 mm Hg; P<0.001). Stimulation of plasma renin concentration by a single injection of the ß-adrenoreceptor agonist isoproterenol (10 mg/kg IP) was significantly attenuated in AC5(-/-) (male: -20%; female: -33%) compared with wild-type mice in vivo. The mitigation of the plasma renin concentration response to isoproterenol was even more pronounced in AC6(-/-) (male: -63%; female: -50% versus AC6(+/+)). Similarly, the effects of isoproterenol, prostaglandin E2, and pituitary adenylyl cyclase-activating polypeptide on renin release from isolated perfused kidneys were attenuated to a higher extent in AC6(-/-) (-51% to -98% versus AC6(+/+)) than in AC5(-/-) (-31% to 46% versus AC5(+/+)). In conclusion, both AC5 and AC6 are involved in the stimulation of renin secretion in vivo, and AC6 is the dominant isoforms in this process.
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Adenilil Ciclasas/metabolismo , Agonistas Adrenérgicos beta/farmacología , Isoproterenol/farmacología , Riñón/metabolismo , Renina/metabolismo , Adenilil Ciclasas/genética , Análisis de Varianza , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Dinoprostona/farmacología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Inmunohistoquímica , Riñón/efectos de los fármacos , Masculino , Ratones , Ratones Noqueados , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Renina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Dogs and humans acquire Blastomyces dermatitidis infections from the same incompletely defined habitat. Studies of blastomycosis cases have not consistently demonstrated seasonality or significant antecedent climate effects. To determine the distribution of disease by season, we studied over 18 years 219 dogs with blastomycosis from a single veterinary practice in Northern Wisconsin. The 202 Vilas County dog addresses were compared to 200 random-number selected addresses from the practice registry. Street addresses were geocoded and mapped using ArcGIS, including ratio of cases/random addresses to construct a control chart. Stepwise and linear regression was used to model case counts by season and by 6 month warm (April-September) and cold periods, using lagged local weather data. The geographic distribution of cases was found to be similar regardless of season and time period, and no season exceeded control chart limits. Seasonal distribution of cases was; winter (n = 53, 24%), spring (39, 18%), summer (79, 36%), fall (48, 22%), p = 0.002. When cases were considered by 6-month warm/cold periods, 67% of variation is explained by the total precipitation which occurred two periods prior, and lower average temperature, but higher maximum temperature one period prior (p = 0.000). Weather parameters along with fixed and variable environmental factors likely determine the occurrence of B. dermatitidis, perhaps as part of a 'grow and tolerate change' model.
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Blastomyces/aislamiento & purificación , Blastomicosis/veterinaria , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/microbiología , Animales , Blastomicosis/epidemiología , Blastomicosis/microbiología , Perros , Factores de Riesgo , Estaciones del Año , Tiempo (Meteorología) , Wisconsin/epidemiologíaRESUMEN
The second messenger cAMP plays an important role in the regulation of renin gene expression. Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) is known to stimulate renin gene transcription acting through PPARγ-binding sequences in renin promoter. We show now that activation of PPARγ by unsaturated fatty acids or thiazolidinediones drastically augments the cAMP-dependent increase of renin mRNA in the human renin-producing cell line Calu-6. The underlying mechanism involves potentiation of agonist-induced cAMP increase and up-regulation of adenylate cyclase 6 (AC6) gene expression. We identified a palindromic element with a 3-bp spacer (Pal3) in AC6 intron 1 (AC6Pal3). AC6Pal3 bound PPARγ and mediated trans-activation by PPARγ agonist. AC6 knockdown decreased basal renin mRNA level and attenuated the maximal PPARγ-dependent stimulation of the cAMP-induced renin gene expression. AC6Pal3 decoy oligonucleotide abrogated the PPARγ-dependent potentiation of cAMP-induced renin gene expression. Treatment of mice with PPARγ agonist increased AC6 mRNA kidney levels. Our data suggest that in addition to its direct effect on renin gene transcription, PPARγ "sensitizes" renin gene to cAMP via trans-activation of AC6 gene. AC6 has been identified as PPARγ target gene with a functional Pal3 sequence.
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Adenilil Ciclasas/genética , AMP Cíclico/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , PPAR gamma/metabolismo , Renina/genética , Adenilil Ciclasas/deficiencia , Adenilil Ciclasas/metabolismo , Animales , Secuencia de Bases , Sitios de Unión , Línea Celular , Secuencia de Consenso , Sinergismo Farmacológico , Activadores de Enzimas/farmacología , Humanos , Intrones/genética , Ratones , Datos de Secuencia Molecular , Oligonucleótidos/farmacología , PPAR gamma/agonistas , Pioglitazona , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Regiones Promotoras Genéticas/genética , Renina/metabolismo , Rosiglitazona , Tiazolidinedionas/administración & dosificación , Tiazolidinedionas/farmacologíaRESUMEN
We recently found that endogenous (free fatty acids) and pharmacological (thiazolidinediones) agonists of nuclear receptor Peroxisome proliferator-activated receptor (PPAR)gamma stimulate renin transcription. In addition, the renin gene was identified as a direct target of PPARgamma. The mouse renin gene is regulated by PPARgamma through a distal enhancer direct repeat closely related to consensus PPAR response element (PPRE). In vitro studies demonstrated that PPARgamma knockdown stimulated PPRE-driven transcription. These data predicted that deficiency of PPARgamma would upregulate mouse renin expression. Consistent with these observations knockdown of PPARgamma increased the transcription of a reporter gene driven by the mouse renin PPRE-like motif in vitro. To study the impact of PPARgamma on renin production in vivo, we used a cre/lox system to generate double-transgenic mice with disrupted PPARgamma locus in renin-producing juxtaglomerular (JG) cells of the kidney (RC-PPARgamma(fl/fl) mice). We provide evidence that PPARgamma expression was effectively reduced in JG cells of RC-PPARgamma(fl/fl) mice. Fluorescent immunohistochemistry showed stronger renin signal in RC-PPARgamma(fl/fl) than in littermate control RC-PPARgamma(wt/wt) mice. Renin mRNA levels and plasma renin concentration in RC-PPARgamma(fl/fl) mice were almost 2-fold higher than in littermate controls. Arterial blood pressure and pressure control of renal vascular resistance, which play decisive roles in the regulation of renin production were indistinguishable between RC-PPARgamma(wt/wt) and RC-PPARgamma(fl/fl) mice. These data demonstrate that the JG-specific PPARgamma deficiency results in increased mouse renin expression in vivo thus corroborating earlier in vitro results. PPARgamma appears to be a relevant transcription factor for the control of renin gene in JG cells.
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Aparato Yuxtaglomerular/fisiología , PPAR gamma/genética , PPAR gamma/metabolismo , Renina/sangre , Renina/genética , Animales , Presión Sanguínea/fisiología , Línea Celular , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica/fisiología , Hematócrito , Humanos , Integrasas/genética , Luciferasas/genética , Ratones , Ratones Noqueados , ARN Mensajero/metabolismo , Transducción de Señal/fisiología , Transcripción Genética/fisiología , Regulación hacia Arriba/fisiologíaRESUMEN
OBJECTIVE: To perform a novel geographic analysis of Attention-Deficit/ Hyperactivity Disorder (ADHD) diagnosis in Midwest United States. METHOD: Primary care children age 5-17 with ADHD diagnosis (N = 6833; 13.5%) were compared to those receiving well child care without ADHD diagnosis (N = 43,630) in a Wisconsin integrated medical system. Street addresses, demographic, and block group level U.S. Census 2000 data were mapped and analyzed using ArcGIS, CrimeStat III, and SaTScan. Lead levels from a State database were linked to 2,837 subjects. Univariate analysis was done by chi-square test or Mann-Whitney U test, multivariate analysis by logistic regression. RESULTS: ADHD cases were 74% male (p = 0.0001), and more frequently diagnosed in White children (17.3%) than Blacks (10.6%), Hispanics (9.4%), or Asians (3.7%; all p values < 0.001). Overall, male gender, white race, lower block group median household income and population density, and greater distance to nearest park and airport were more predictive of ADHD (p values < 0.001). In urban Milwaukee County (865 cases/10,493 controls) male gender, white race, suburban residence, and younger age were more predictive of ADHD (p values < 0.01). Among children with ADHD diagnosis and linked lifetime lead values, those with a maximum level of 10 microg/dl or more differed significantly from controls (9.3% vs. 5.6%; p = 0.003); elevated lead remained a significant predictor of ADHD diagnosis in multivariate analysis. CONCLUSIONS: Further studies are needed to determine if geographic distribution of ADHD diagnosis can be partially explained by differential efficiency of referral for diagnosis by school districts, by race/ethnicity, and/or built environment.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adolescente , Factores de Edad , Trastorno por Déficit de Atención con Hiperactividad/etnología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Preescolar , Estudios Transversales , Prestación Integrada de Atención de Salud/estadística & datos numéricos , Etnicidad/psicología , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Análisis Multivariante , Densidad de Población , Atención Primaria de Salud/estadística & datos numéricos , Factores de Riesgo , Factores Sexuales , Medio Social , WisconsinRESUMEN
Historically, the most significant non-HIV viral infection of salivary glands has been, and remains, mumps. Despite the widespread administration of mumps vaccines worldwide, sporadic outbreaks continue to be reported. Epidemiologic studies are invaluable in understanding the etiology of these outbreaks. Information gleaned from these studies, coupled with advances in immunology, virology, and DNA/RNA testing will hopefully result in the development of vaccination regimens to ensure eradication of the disease.
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Paperas/diagnóstico , Paperas/epidemiología , Sialadenitis/virología , Brotes de Enfermedades , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/epidemiología , Salud Global , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Incidencia , Paperas/complicaciones , Paperas/prevención & control , Vacuna contra la Parotiditis , Cuidados Paliativos , Sialadenitis/complicaciones , Sialadenitis/diagnóstico , Sialadenitis/epidemiologíaRESUMEN
PURPOSE: A previous study revealed a non-random distribution of blastomycosis cases by home site in urban Milwaukee County. This study was conducted to determine the proportion of cases with likely exposures solely in urban areas. METHODS: Records of 68 urban southeastern Wisconsin individuals, including 45 residents of Milwaukee, 19 from suburban Milwaukee County, and 4 from outside Milwaukee County, diagnosed with blastomycosis between January 2002 and July 2007 were studied using medical record reviews, case reports, and telephone interviews. Geographic Information Systems (GIS) proximity analysis was then used to compare the distance between case and control home sites to environmental risk factors. RESULTS: Of patients reporting their exposure history, 41 of 49 (84%) participated in outdoor work or leisure activities, and 12 of 47 (26%) engaged in fishing, hunting, camping, or hiking. Of the urban cases, 64 occurred among Milwaukee County residents; of those, 25 of 49 (51%) denied traveling, which suggests local urban exposure, and 8 of 11 (73%) specifically recalled urban waterway exposure prior to diagnosis. The 45 Milwaukee cases were concentrated on the north side of town and were closer to inland waterways than a random sample of 6528 controls (median 690 versus 1170 meters; P=0.003), but not closer to parks. CONCLUSION: Southeastern Wisconsin residents may acquire blastomycosis solely in their local urban area, sometimes without specific outdoor exposures. Proximity to inland waterways is associated with blastomycosis cases in urban areas, similar to rural areas of Wisconsin. Clinicians should include blastomycosis in appropriate differential diagnoses of symptomatic individuals, even in urban residents without travel history or history of significant outdoor exposures.
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Blastomicosis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Femenino , Sistemas de Información Geográfica , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Población Urbana , Wisconsin/epidemiologíaRESUMEN
This article focuses on the pathogenesis of the gender gap of autoimmune disease. Specifically, the discussion characterizes the role of sex hormones in the immune response and a female predilection for the common diseases seen in daily practice (ie, lupus erythematosus, myasthenia gravis, and other autoimmune diseases). A comparison between the sexes, with respect to autoimmune disease mechanisms, is presented to give oral and maxillofacial surgeons a better insight as to the role of sex and successful surgical treatment outcomes in this population of patients.
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Enfermedades Autoinmunes/inmunología , Síndrome Antifosfolípido/inmunología , Femenino , Hormonas Esteroides Gonadales/inmunología , Humanos , Lupus Eritematoso Sistémico/inmunología , Esclerosis Múltiple/inmunología , Procedimientos Quirúrgicos Orales , Factores Sexuales , Resultado del TratamientoRESUMEN
Twenty-nine specimens of calcareous sponges (Class Calcarea, Phylum Porifera), covering thirteen representative species of the families Soleneiscidae, Leucaltidae, Levinellidae, Leucettidae, Clathrinidae, Sycettidae, Grantiidae, Jenkinidae, and Heteropiidae were analysed for their fatty acids. The fatty acids of Calcarea generally comprise saturated and monounsaturated linear (n-), and terminally methylated (iso-, anteiso-) C(14)-C(20) homologues. Furthermore, polyunsaturated C(22) fatty acids and the isoprenoic 4,8,12-trimethyltridecanoic acid were found. The most prominent compounds are n-C(16), iso-C(17), iso-C(18), n-C(18), n-C(20). In addition, a high abundance of the exotic 16-methyloctadecanoic acid (anteiso-C(19)) appears to be a characteristic trait of Calcarea. Long-chain 'demospongic acids', typically found in Demospongiae and Hexactinellida, are absent in Calcarea. The completely different strategy of calcarean fatty acid synthesis supports their phylogenetic distinctiveness from a common Demospongiae/Hexactinellida taxon. Both intraspecific and intraclass patterns of Calcarea showed great similarity, suggesting a conserved fatty acid composition that already existed in the last common ancestor of Calcinea and Calcaronea, i.e. before subclasses diverged.