RESUMEN
A new heterogeneous organocatalyst, graft polymer supported dimethylaminopyridine (g-DMAP), is developed. This catalyst has a flexible structure and comprises DMAP anchored to the polyethylene-graft-polyacrylic acid (PE-g-PAA). It exhibits higher activity than DMAP supported on polystyrene cross-linked with divinylbenzene and can be recovered in batch mode acetylation. The activity and stability of this catalyst allow its application in continuous flow systems. Continuous acetylation proceeds with excellent conversion, and a turnover number of 560 can be achieved using g-DMAP. Parallel fixed bed reactors were used to scale up the synthesis of this continuous flow system. Eight parallel fixed bed reactors displayed excellent conversion.
Asunto(s)
Resinas Acrílicas/química , Aminopiridinas/química , Polietilenos/química , CatálisisRESUMEN
AIM: Modest inhibition of the growth hormone (GH) axis by overexpression of the antisense GH gene in male Wistar rats reduced food intake and body weight, and lengthened the lifespan, even if fed ad libitum (AL). These findings were comparable with those induced by 30% calorie restriction (CR) in wild-type (WT) rats, suggesting importance of the GH signal pathway in the effect of CR. The present study evaluated the effects of GH inhibition and CR on mitochondrial oxidative stress and redox state in the liver. METHODS: Transgenic and WT rats were fed AL or 30% CR diets from 6weeks of age. Liver tissues were collected at 6 and 24months of age. The mitochondria fraction was prepared from liver tissue homogenates. The total reactive oxygen species (ROS) generation, the protein levels of glutathione (GSH) and oxidized GSH (GSSG), and the superoxide dismutase 2 activity were measured. RESULTS: The results revealed that CR, but not modest inhibition of GH, decreased mitochondrial ROS generation and increased the mitochondrial GSH redox potential. CONCLUSION: The present study suggests that CR affects mitochondrial function and redox state through a pathway distinct from GH signaling.
Asunto(s)
Restricción Calórica , Hormona del Crecimiento/metabolismo , Mitocondrias Hepáticas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Envejecimiento/genética , Envejecimiento/metabolismo , Análisis de Varianza , Animales , Glutatión/metabolismo , Hormona del Crecimiento/genética , Masculino , Oxidación-Reducción , Ratas , Ratas Transgénicas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
The hypothalamus is organized as a collection of distinct, autonomously active nuclei that regulate discrete functions, such as feeding activity and metabolism. We used suppression subtractive hybridization (SSH) to identify genes that are enriched in the hypothalamus of the rat brain. We screened a subtractive library of 160 clones, and 4 genes that were predominantly expressed in the hypothalamus, compared to other brain regions. The mRNA for a member of the WD-repeat family of proteins, WDR6, was abundantly expressed in the hypothalamus, and we found that WDR6 interacted with insulin receptor substrate 4 (IRS-4) in the rat brain. Interestingly, WDR6 gene expression in the hypothalamic arcuate nucleus was decreased by caloric restriction, and in growth hormone (GH)-antisense transgenic rats, both of which are associated with an increased life span. Insulin-like growth factor (IGF)-I and insulin treatment increased WDR6 gene expression in mouse hypothalamus-derived GT1-7 cells. Our results might suggest that WDR6 participates in insulin/IGF-I signaling and the regulation of feeding behavior and longevity in the brain.
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Encéfalo/fisiología , Proteínas Sustrato del Receptor de Insulina/biosíntesis , Proteínas Sustrato del Receptor de Insulina/genética , Longevidad/fisiología , Envejecimiento/genética , Envejecimiento/metabolismo , Animales , Restricción Calórica/métodos , Línea Celular Transformada , Células Cultivadas , Femenino , Masculino , Ratas , Ratas Mutantes , Ratas Transgénicas , Ratas WistarRESUMEN
AMP-activated protein kinase (AMPK) may act as a key enzyme for metabolic adaptation to calorie restriction (CR) or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling, an experimental intervention for lifespan extension in animals. We investigated the protein levels of AMPKalpha and a downstream enzyme, acetyl-CoA carboxylase (ACC), by immunoblotting of liver and quadriceps femoris muscle (QFM) extracts from 6-month-old wild-type (W) and GH-suppressed transgenic (Tg) Wistar rats fed ad libitum (AL) or 30% CR diets from 6weeks of age. A modified alternate-day feeding regimen for CR yielded a fed-fasted cycle in CR rats, and therefore the effects of overnight fasting in W-AL rats were also evaluated. CR decreased threonine-172-phosphorylated AMPKalpha (p-AMPKalpha; an activated form) levels in the liver, whereas the CR-fed-fasted cycle or overnight fasting did not significantly affect the p-AMPKalpha level. In the QFM, the p-AMPKalpha level was slightly elevated in the CR-fasted phase, but greatly increased in the AL-fasted phase. Suppression of GH did not affect the p-AMPKalpha level. The phosphorylated-ACC levels did not alter in parallel with the p-AMPKalpha level, particularly in the liver. The present results suggest that CR down-regulates the AMPK activity in the liver on a long-term basis.
Asunto(s)
Restricción Calórica , Regulación hacia Abajo , Hígado/metabolismo , Complejos Multienzimáticos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP , Acetil-CoA Carboxilasa/análisis , Acetil-CoA Carboxilasa/metabolismo , Animales , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/genética , Hormona del Crecimiento/metabolismo , Immunoblotting , Hígado/química , Longevidad , Masculino , Complejos Multienzimáticos/análisis , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Organismos Modificados Genéticamente , Proteínas Serina-Treonina Quinasas/análisis , Ratas , Ratas WistarRESUMEN
Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.
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Neoplasias Hepáticas/patología , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Anciano , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/química , Linfoma de Células B Grandes Difuso/química , MasculinoRESUMEN
Although no-reflow phenomenon may occur in patients that experience reperfusion after ischemia, there have been no reports describing the postmortem findings in these patients. We describe the findings of an autopsy in a 56-year-old man who experienced acute coronary syndrome with no-reflow phenomenon after coronary intervention. Macroscopic study demonstrated myocardial infarction with diffuse hemorrhage, and microscopic analysis revealed vascular damage and microembolization in the no-reflow area. In conclusion, coronary microembolization and damage to the small coronary artery may contribute to the pathogenesis of no-reflow phenomenon following coronary intervention in humans.
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Angioplastia Coronaria con Balón , Enfermedad Coronaria/patología , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Angioplastia Coronaria con Balón/efectos adversos , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/terapia , Electrocardiografía , Humanos , Hipertrofia Ventricular Izquierda/patología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatologíaRESUMEN
Ghrelin, a novel acylated peptide and endogenous ligand for growth hormone (GH) secretagogue receptor, was originally isolated from rat and human stomachs. In addition to its GH-releasing activity, ghrelin plays an important role in many physiological functions, including food intake, gastric acid secretion, neonatal development, and so on. In this study, the effect of daily treatment with ghrelin on milk production was investigated in lactating rats and the development of the pups was monitored. Daily subcutaneous injection of ghrelin into nursing dams for 8 days from parturition caused a significant increase in milk yield and litter weight gain. When litters nursed by ghrelin-treated and saline-treated dams were interchanged on day 4 of lactation, the growth curves were reversed. Daily injections of ghrelin also increased plasma GH levels. Northern blot analysis revealed that daily injection of ghrelin significantly increased mammary casein mRNA expression. In addition, RT-PCR analysis showed that a ghrelin receptor was present in the mammary glands of lactating rats. These results suggest that ghrelin may play an important role in milk production in lactating dams.