Exergy Optimization of a Moving Bed Heat Exchanger

The MBHE proposed can be analyzed as a crossflow heat exchanger where one of the phases is a moving granular medium. In the present work the exergy analysis of the MBHE is carried out over operation data of the exchanger obtained in two ways: a numerical simulation of the stationary problem and a simplified analysis. The numerical simulation is carried over the two steady state energy equations (fluid and solid), involving (for the fluid) the convection heat transfer to the solid and the diffusion term in the flow direction, and (for the solid) only the convection heat transfer to the fluid. The simplified analysis followed the well-known e-NTU method, taking the equipment as a crossflow heat exchanger with both fluids unmixed.Publicad

Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis

Personalized medicine; Responder and non-responderMedicina personalizada; Respondedor y no respondedorMedicina personalitzada; Contestador i no contestadorBackground The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition to inhibiting T cell egress from lymph nodes, fingolimod promotes the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), whose monocytic subset (M-MDSCs) can be used as a biomarker of disease severity, as well as the degree of demyelination and extent of axonal damage in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the present study, we have assessed whether the abundance of circulating M-MDSCs may represent a useful biomarker of fingolimod efficacy in EAE and in the clinical context of MS patients. Methods Treatment with vehicle or fingolimod was orally administered to EAE mice for 14 days in an individualized manner, starting the day when each mouse began to develop clinical signs. Peripheral blood from EAE mice was collected previous to treatment and human peripheral blood mononuclear cells (PBMCs) were collected from fingolimod to treat MS patients’ peripheral blood. In both cases, M-MDSCs abundance was analyzed by flow cytometry and its relationship with the future clinical affectation of each individual animal or patient was assessed. Results Fingolimod-treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e., patients who met at least two of the criteria used to define non-evidence of disease activity-3 (NEDA-3) 12 months after treatment. Conclusion Our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod.This work was supported by the Instituto de Salud Carlos III (PI18/00357, RD16-0015/0019, PI21/00302, all co-funded by the European Union), the Fundación Merck Salud (FMS_2020_MS), Esclerosis Múltiple España (REEM-EME-S5 and REEM-EME_2018), ADEMTO, ATORDEM and AELEM. CC-T holds a predoctoral fellowship from the Instituto de Salud Carlos III (FI19/00132, co-funded by the European Union). LC and JG-A were hired under PI18/00357 and RD16/0015/0019, respectively. DC, MCO and IM-D were hired by SESCAM

Comparative in vivo and in vitro models to approach the cellular basis of endotoxic shock. The role of sinusoidal liver cells

During endotoxic shock, the liver exerts a lipopolysaccharide (LPS) clearance function with the participation of both parenchymal and sinusoidal cells. Liver damage could be caused by LPS direct action, hypoxia and/or inflammatory mediators released by Kupffer cells. The aim of this study is to establish an experimental model that could allow us to understand the direct E. coli O1 1 l:B4 LPS action on sinusoidal cells. A comparative study was carried out, in vivo and in vitro, using either a rat reversible endotoxic shock model or sinusoidal cell cultures. The LPS was found to induce important and similar morphological alterations both in vivo and in vitro, specially in Kupffer cells. These cells present mitochondrial damage, nuclear membrane swelling, and increased number of phagosomes, including lamellar bodies. An immunocolloidal gold technique shows, in vitro, the LPS mainly located on Kupffer cell membrane and in phagosomes. The LPS binding to membrane, as a primary step of Kupffer cell activation, increases the phagocytosis. This effect could be related to a decrease of fluidity on the externa1 membrane portion

Climate Variability and land-use changes since medieval times inferred from the laguna Zoñar sedimentary record (Andalucia, Spain)

3 páginas.-- Comunicación presentada a la Asamblea General de la European Geosciences Union celebrada en Viena (Austria) del 24 al 29 de Abril del 2005.Peer reviewe

LIMNOCLIBER: a transect of high-resolution lacustrine records of climate and environmental variability in Spain since the Last Glacial Maximum

1 Poster with 6 Fig., 1 Tabl.The LIMNOCLIBER project represents a multidisciplinary, international effort to recover, for the first time, long paleoenvironmental and paleoclimate records from relatively deep lakes in Spain. New records from the Iberian Peninsula during the last decade have changed our views on Holocene history from a generally benign climate punctuated by dry mid Holocene period and an amelioration afterwards, to a complex fluctuation of arid and humid periods. Lateglacial reconstructions have also shown large variability and a multifaceted regional pattern in the Iberian Peninsula. The fact that the maximum extent of mountain glaciers occurred much earlier than the global LGM, also underlines the differences in timing of the main climatic events in Southwestern Europe. To resolve the contradictory interpretations of available records and to reconstruct the effective moisture history of the region since the Last Global Glacial Maximum (LGM), long, high resolution, well-dated records from hydrologically-sensitive regions in Spain are needed. Although deep lakes are not common in Spain, numerous, relatively deep (up to 20 m), karstic lakes with carbonate-rich sediments occur in the Iberian Range and the Pyrenees, and deep terminal-moraine lakes occur in the mountains of northern and western Spain.The LIMNOCLIBER project is funded by the Spanish government (ref: REN 2003-09130-C02-02/CLI).Peer reviewe

The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats

Liver growth factor (LGF), a mitogen for liver cells, behaves as an anti-fibrotic agent even in extrahepatic sites, but its mechanistic basis is unknown. We aimed to determine the intrahepatic expression pattern of key modulators of liver fibrosis in bile ductligated rats (BDL) after injection of LGF. BDL rats received either LGF (4.5 μg/ratXdose, two doses/week, at time 0 or 2 or 5w after operation, depending on the group (BDL+LGF groups, n=20) or saline (BDL+S groups, n=20). Groups were compared in terms of fibrosis (histomorphometry), liver function (aminopyrine breath test), matrix metalloproteinases MMP-2 and MMP-9, transforming growth factor beta 1 (TGF-ß1) and liver endoglin content (Western blotting), and serum tissue inhibitor of metalloproteinases 1 (TIMP-1) levels (ELISA). In BDL+LGF rats, the fibrotic index was significantly lower at 5w, p=0.006, and at 8w, p=0.04, than in BDL+S rats. Liver function values in BDL+LGF rats were higher than those obtained in BDL+S rats (80% at 5w and 79% at 8w, versus 38% and 29%, p<0.01, taking healthy controls as 100%). Notably, in BDL+LGF rats the intrahepatic expression levels of both MMPs were lower at 2w (MMP-2, p=0.03; MMP-9, p=0.05) and 5w (MMP-2, p=0.05, MMP-9, p=0.04). In addition, the hepatic TGF-ß1 level in BDL+LGF rats was lower at 2w (36%, p=0.008), 5w (50%) and 8wk (37%), whereas intrahepatic endoglin expression remained constant in all BDL rats studied. LGF ameliorates liver fibrosis and improves liver function in BDL rats. The LGF-induced anti-fibrotic effect is associated with a decreased hepatic level of MMP-2, MMP-9 and TGF-ß1 in fibrotic rats

Liver growth factor antifibrotic activity in vivo is associated with a decrease in activation of hepatic stellate cells

The antifibrotic activity of Liver Growth Factor (LGF), a liver mitogen, was previously demonstrated in several models of rat liver fibrosis and even in extrahepatic sites, such as carotid artery in hypertensive rats and rat CdCl2-induced lung fibrosis. In the present study, we have attempted to examine in depth its mechanism of antifibrotic action in bile duct-ligated (BDL) rats, with special emphasis on its activity in fibrogenic liver cells. BDL rats received either LGF 9 μg/week for 2 or 3 weeks (BDL+LGF, n=20/group) or saline (BDL+S, n=20/group), at times 0, week 2, or week 5 after operation. Groups were compared in terms of liver a- smooth muscle actin (SMA) content (western blotting and immunohistochemistry), hepatic apoptosis, liver desmin content (western blotting), and serum endothelin-1 (ELISA). LGF produced a marked decrease in liver a-SMA content compared with saline-injected rats, especially evident at longer times (5w and 8w; p<0.05), accompanied by a decrease in hepatic a-SMA+ cells. This decrease was not due to the killing of activated hepatic stellate cells (HSC) or myofibroblasts by LGF, since there was a slight decrease in hepatic apoptosis that was more evident at 2w (p<0.05). Moreover, LGF did not seem to influence HSC proliferation, as shown by measuring liver desmin content. The antifibrotic activity exerted by LGF seems to be closely related to a modulation of the activation state of fibrogenic liver cells (activated HSC and myofibroblasts) in BDL rats

Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis

The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition to inhibiting T cell egress from lymph nodes, fingolimod promotes the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), whose monocytic subset (M-MDSCs) can be used as a biomarker of disease severity, as well as the degree of demyelination and extent of axonal damage in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the present study, we have assessed whether the abundance of circulating M-MDSCs may represent a useful biomarker of fingolimod efficacy in EAE and in the clinical context of MS patients. Treatment with vehicle or fingolimod was orally administered to EAE mice for 14 days in an individualized manner, starting the day when each mouse began to develop clinical signs. Peripheral blood from EAE mice was collected previous to treatment and human peripheral blood mononuclear cells (PBMCs) were collected from fingolimod to treat MS patients' peripheral blood. In both cases, M-MDSCs abundance was analyzed by flow cytometry and its relationship with the future clinical affectation of each individual animal or patient was assessed. Fingolimod-treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e., patients who met at least two of the criteria used to define non-evidence of disease activity-3 (NEDA-3) 12 months after treatment. Our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod. The online version contains supplementary material available at 10.1186/s12974-022-02635-3

Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6C -cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6C -cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6C -cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS